Neonatal watershed brain injury on magnetic resonance imaging correlates with verbal IQ at 4 years.
We have previously described patterns of neonatal brain injury that correlate with global cognitive and motor outcomes. We now examine, in survivors of neonatal encephalopathy (presumed secondary to hypoxia-ischemia) without functional motor deficits, whether the severity and neuroanatomical involvement on neonatal MRI are associated with domain-specific cognitive outcomes, verbal and performance IQ, at 4 years of age. In this prospective study, neonatal MRIs of 81 term infants with neonatal encephalopathy were scored for degree of injury in 2 common patterns: watershed distribution and basal ganglia distribution. Follow-up evaluation at 4 years of age by examiners blinded to clinical history and MRIs included a 5-point neuromotor score and the Wechsler Preschool and Primary Scale of Intelligence-Revised. In 64 subjects with no functional motor impairment, test of trend was used to examine the association of ordered watershed-distribution and basal ganglia-distribution MRI scores with mean verbal and performance IQ. Lower verbal and performance IQs were seen with increasing degree of injury on both watershed-distribution and basal ganglia-distribution scales in univariate analyses. When each MRI pattern score was adjusted for the other, only the association of decreasing verbal IQ with increasing watershed-distribution injury remained significant. A suggestion of decreasing verbal IQ with increasing basal ganglia-distribution injury was also seen in the multivariate model, whereas no association was seen between performance IQ and severity of injury in either MRI pattern. In survivors of neonatal encephalopathy without functional motor deficits at 4 years of age, an increasing severity of watershed-distribution injury is associated with more impaired language-related abilities.


[Central serous chorioretinopathy].
Central serous chorioretinopathy (CSC) is the fourth most common disease of the macula after age-related macular degeneration, diabetic retinopathy and retinal vein occlusion and a cause of irreversible visual loss. This article gives an overview of the epidemiology, risk factors, pathophysiology, clinical presentation, multimodal imaging and discusses current therapeutic options for CSC.


Crystal structure of bis-[1-(naphthalen-1-ylmeth-yl)pyridinium] bis-(2,2-di-cyano-ethene-1,1-di-thiol-ato-κ(2) S,S')nickelate(II).
A new ion-pair complex, (C16H14N)2[Ni(C4N2S2)2] or (1-NaMePy)2[Ni(imnt)2], where 1-NaMePy is 1-(4-naphthyl-methyl-ene)pyridinium and imnt is 2,2-di-cyano-ethene-1,1-di-thiol-ate, was obtained by the direct reaction of NiCl2, K2imnt and (1-NaMePy)(+)Br(-) in H2O. The asymmetric unit contains a [1-NaMePy](+) cation and one half of an Ni(imnt)2 (2-) anion. The Ni(II) ion lies on an inversion centre and adopts a square-planar configuration with Ni-S bond lengths of 2.200 (1) and 2.216 (1) Å. In the [1-NaMePy](+) cation, the naphthyl ringsystem and the pyridinium ring make a dihedral angle of 90.0 (2)°. In the crystal, C-H⋯N and C-H⋯Ni hydrogen bonds, as well as π-π inter-actions between the chelate ring and the pyridinium ring [centroid-centroid distance = 3.675 (2) Å] link the ions into a three-dimensional network.


Flexible sigmoidoscopy screening for colorectal neoplasia in average-risk people: evaluation of a five-year rescreening interval.
To determine the prevalence of colorectal neoplasia detected by rescreening people with average risk five years after initial screening by flexible sigmoidoscopy. Prospective survey of results of a colorectal cancer screening program. People aged 55-64 years with no symptoms or family history of colorectal cancer who were recruited from the community for flexible sigmoidoscopy screening five years previously (July 1995 to December 1996) and had no colorectal neoplasms detected. Fremantle Hospital, Western Australia, a community-based teaching hospital, December 2000 to June 2001. Number and size of colorectal neoplasms (adenomas or cancer) compared between rescreened patients and initial screening population (all 982 people screened between July 1995 and December 1996). 803 people were eligible for rescreening; 138 were no longer at the recorded address, and 361 of the remaining 665 (54%) were rescreened. Rescreening found a significantly lower prevalence of colorectal adenomas than initial screening (8% [95% CI, 5%-11%] versus 14% [95% CI, 13%-15%]; P < 0.05) and also a lower percentage of adenomatous polyps over 5 mm in diameter (32% [95% CI, 15%-49%] versus 51% [95% CI, 46%-56%]; no significant difference). Average-risk people who have been screened for colorectal neoplasms, with none found, have a low prevalence of neoplastic lesions five years later. Longer rescreening intervals need to be considered.


Guiding farnesyltransferase inhibitors from an ECLiPS library to the catalytic zinc.
Farnesyltransferase inhibitors identified from an ECLiPS library were optimized using solution-phase synthesis. X-ray crystallography of inhibited complexes was used to identify substructures that coordinate to the active site zinc. The X-ray structures were ultimately used to guide the design of second-generation analogs with FTase IC(50)s of less than 1.0 nM.


Linear and undulating periodized strength plus aerobic training promote similar benefits and lead to improvement of insulin resistance on obese adolescents.
The present study compares the effectiveness of three types of physical training for obesity control in adolescents submitted to a long-term interdisciplinary therapy. Forty-five post-puberty obese adolescents (15-18yo) were randomly placed in three different groups of physical trainings: aerobic training (AT n=20), aerobic plus strength training with linear periodization (LP n=13) and aerobic plus strength training with daily undulating periodization (DUP n=12). The body composition was evaluated by air-displacement plethysmography; the rest metabolic rate was measured by indirect calorimetry; serum analysis was collected after an overnight fasting. The most important finding of this study was that both LP and DUP groups improved lipid profile, insulin sensitivity and adiponectin concentration (p<0.01). The linear regression showed a negative association between delta (%) adiponectin and delta (%) insulin (p<0.05). Each group presented a significant reduction in body mass, body mass index and fat mass (kg) after short and long-term intervention (p<0.01). However, the AT group reduced the fat-free mass after short-term intervention (p<0.01) and enhanced protein oxidation (p<0.01), whereas only LP group was able to increase the fat-free mass and maintain the rest metabolic rate (RMR). There was a negative correlation between percentage of protein oxidation and RMR (r=-0.75) in all groups. The interdisciplinary therapy models that included aerobic plus strength training were more effective than only aerobic training to improve lipid profile and insulin sensitivity, as well as the inflammatory state by increasing adiponectin. In all groups were observed an improvement on anthropometric profile.


Measuring Mechanical and Adhesive Properties of Single Cells Using an Atomic Force Microscope.
Atomic force microscopy allows the determination of both mechanical and adhesive properties of living single cells and generation of high-resolution surface images. Here, we describe a method to determine the Young's modulus of a cell and adhesion between a coated cantilever and a cell, as well as an overview of the analysis of the data obtained. Additionally, we point out typical and important pitfalls during the measurement and analysis.


Glucocorticoid receptors.
Glucocorticoid receptors are found in most mammalian tissues and have been studied in detail in a number of tissue culture systems. With cells that have not been exposed to steroids, the receptors are found in the cytoplasmic fraction from which they can be isolated and studied. Methods for studying glucocorticoid receptors depend on their high-affinity specific binding of radioactive steroids. The reversible interaction is intracellular. It follows Michaelian kinetics, at least in cell-free cytosol, and involves a thermodynamically homogeneous population of about 10 000 sites per cell. The receptor is an asymmetric, slightly acidic protein of about 100 000 daltons. It is very labile, especially in the unbound form. Binding activity depends on the integrity of thiol groups and perhaps on phosphorylation of amino acid residues. Although indirect, the evidence is overwhelmingly convincing that this protein is the physiologic glucocorticoid receptor. The time-kinetics of binding and dissociation are consistent with the sequence of events in glucocorticoid action. Various steroid analogs display binding characteristics predictable from their glucocorticoid activity. Loss of the binding protein from certain cultured cell lines is accompanied by unresponsiveness to glucocorticoids. The extensive tissue distribution of receptors parallels the extensive role of glucocorticoids in regulation. Finally, there is a strong correlation between nuclear binding of receptors and nuclear effects of the steroid. The glucocorticoid receptor can be distinguished from other glucocorticoid-binding proteins, based on their steroid specificity and physicochemical properties. There is no clear-cut demonstration that the receptor differs from tissue to tissue, and it is in fact very similar in various species. Unlike in other systems, receptor concentration does not seem to be regulated by its ligand or by other hormones. However, certain cases of hypo- as well as hypersensitivity to glucocorticoids appear to result from changes at the receptor level. The data indicate that the receptor can exist in inactive and active forms. The former predominate in the absence of steroid or when an angatonist is bound. Glucocorticoid agonists bind the active form, allowing it to be "activated" and subsequently bound to the nucleus. All of the receptors in isolated cytosol do not appear to be available for immediate occupancy by an agonist and this may be due to the time required for conversion of the receptors from inactive to active forms. The correlations between receptor binding and the glucocorticoid response indicate that the receptor is a rate-limiting factor in the magnitude and kinetics of the response, and this finding has important implications regarding mechanisms.


A novel fluorescent probe for more effective monitoring of nanosized drug delivery systems within the cells.
To improve visualization of nanoparticles within the cells' compartments, we synthesized a coumarin based fluorescent derivative, tetradecyl diethylamino coumarin amid, 14-DACA. In this compound the coumarin chromophore is linked with a tetradecyl alkyl chain that contributes to lipophilicity and slightly amphiphilic character of this probe. 14-DACA exhibits good biocompatibility, its solubility and emission spectrum are not sensitive to changes in pH value. Solid lipid nanoparticles (SLN) labeled with 14-DACA (SLN-D) and frequently used 6-coumarin (SLN-C) were utilized to evaluate probes' properties in the trafficking and intracellular localization of nanoparticles. SLN-D were seen as distinct blue dots in the cellular environment in contrast to SLN-C which were hardly to recognize due to the self-quenching of 6-coumarin, its leakage and distribution in intracellular compartments. Spectra of 14-DACA indicated the possibility of spectral resolution from both green and red fluorophores allowing clear multicolor imaging of organelles in both fixed and living cells. The results showed valuableness of new probe for trafficking of the drug nanocarriers intracellularly in a kinetic and sensitive manner. Such studies are of great importance in investigations aimed to clarify subcellular targeted drug delivery, controlled release and even to identify toxicological changes.


Evaluation of histoplasmin for the presence of H and M antigens: some difficulties encountered in the production and evaluation of a product suitable for the immunodiffusion test.
The development of a single histoplasmin suitable for use in immunodiffusion testing of a variety of human histoplasmosis sera depends not only upon the presence of both antigens, but on relative concentration of one to the other, and perhaps on the chemical characteristics of the H and M antigens of a given strain.


[The importance of vitamin B 6 for development of the infant. Human medical and animal experiment studies].
Vitamin B-6 is an important coenzyme in the biosynthesis of the neurotransmitters GABA, dopamine and serotonin and is therefore required for the normal perinatal development of the central nervous system. In rat studies, biochemical and morphological abnormalities (decreased dendritic arborization and reduced numbers of myelinated axons and synapses) in the brains of pups from vitamin B-6 deficient dams were associated with behavioral changes such as epileptiform seizures and movement disorders. In severely vitamin B-6 deficient human infants, similar behavioral abnormalities have been described. Marginally deficient neonates were found to have a lower birthweight and to display less mature reactive and adaptive behavior in the Brazleton Neonatal Assessment Scale than well-fed infants. While it is not yet possible to define the exact amount of vitamin B-6 required to support optimal brain development, pregnant and lactating women should be encouraged to consume a diet that is rich in vitamin B-6.


Design, synthesis, docking, and anticancer evaluations of phthalazines as VEGFR-2 inhibitors.
Twenty new N-substituted-4-phenylphthalazin-1-amine derivatives were designed, synthesized, and evaluated for their anticancer activities against HepG2, HCT-116, and MCF-7 cells as VEGFR-2 inhibitors. HCT-116 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 7f was found to be the most potent derivative among all the tested compounds against the three cancer cell lines, with 50% inhibition concentration, IC50 = 3.97, 4.83, and 4.58 µM, respectively, which is more potent than both sorafenib (IC50 = 9.18, 5.47, and 7.26 µM, respectively) and doxorubicin (IC50 = 7.94, 8.07, and 6.75 µM, respectively). Fifteen of the synthesized derivatives were selected to evaluate their inhibitory activities against VEGFR-2. Compound 7f was found to be the most potent derivative that inhibited VEGFR-2 at an IC50 value of 0.08 µM, which is more potent than sorafenib (IC50 = 0.10 µM). Compound 8c inhibited VEGFR-2 at an IC50 value of 0.10 µM, which is equipotent to sorafenib. Moreover, compound 7a showed very good activity with IC50 values of 0.11 µM, which is nearly equipotent to sorafenib. In addition, compounds 7d, 7c, and 7g possessed very good VEGFR-2-inhibitory activity, with IC50 values of 0.14, 0.17, and 0.23 µM, respectively.


A New Biodegradable Stent to Improve the Management of Biliary Strictures in Pediatric Split Liver Transplantation.
Cholestasis due to benign biliary strictures is the most common biliary complication after pediatric split liver transplantation (SLT), decreasing graft survival, but consensus about its management lacks. Percutaneous transhepatic cholangiography, bilioplasty and internal-external biliary drainage (IEBD) are standard treatments. The aim of this report is to present the preliminary experience with a new biodegradable biliary stent in the management of post-SLT biliary strictures. Between September 2020 and April 2021, SLT patients with a single anastomotic benign biliary stricture underwent percutaneous transhepatic implantation of an innovative 10F helical-shaped biodegradable biliary stent, featuring a slow degradation profile, in addition to the standard treatment with bilioplasty and IEBD. The device is unique and the first to be CE-marked for the use in this indication. Six pediatric patients (4 males; median age 8.6 years, interquartile range 3.7 years) underwent percutaneous stent implantation, without complications nor clinical cholestasis during a median follow-up of 271 days (IQR 120.25). Stent dislodgement occurred in one case. Preliminary data suggest that implantation of a new biodegradable biliary stent may be considered in the management of post-SLT cholestasis in pediatric patients. Some technical tips are useful during implantation. This device may prolong biliary drainage, potentially relieving the discomfort of long-term IEBD.


Examining current physical activity interventions in Black school-age children and parents: A systematic review.
Obesity is prevalent in Black children and adults; increasing physical activity (PA) can aid in reducing childhood obesity in both age groups. The purpose of this systematic review is to examine current research on PA interventions in school-age Black children. Adhering to PRISMA guidelines, a systematic search was conducted in six databases for PA interventions in Black children. A total of 13 articles met inclusion criteria (n = 7 randomized controlled trial, n = 5 quasi-experimental, n = 1 cross-sectional). The majority of the articles were on a combination of diet and PA programs (n = 9). Four articles targeted PA and parental role modeling of PA as the outcome showing positive intervention effects. Nine additional studies included PA as an outcome variable along with at least one additional obesity-related predictor. PA interventions for Black school-age children typically use a parent-child dyadic approach (n = 13), are guided by theory (n = 11) and are high quality. However, continued investigation is warranted to draw definitive conclusions and determine how to best involve parents within the PA interventions. Theory-driven higher quality trials that clearly describe the structured PA component and outcomes among Black parent-child dyads are needed.


Thymic Immunosuppressive Pentapeptide (TIPP) Shown Anticancer Activity in Breast Cancer and Chronic Myeloid Leukemia Both In Vitro and In Vivo.
Being the common cause and major burden of deaths globally, timely cancer management is crucial. Thymic immunosuppressive pentapeptide (TIPP) is a novel pentapeptide originally obtained from calf thymic immunosuppressive extract. Previously, TIPP has been proved to suppress the allergic and inflammatory responses in allergic mice via blocking MAP kinases/NF-κB signaling pathways. In this study, in vitro anticancer activity of TIPP was tested on two different types of cancers using MCF-7 and K562 cell lines. Tumor xenograft models for breast cancer and chronic myeloid leukemia were designed. In vivo anticancer activity of TIPP was investigated on both cancer types. The liver and tumor tissues of the mice were preserved for immunohistochemistry analysis. In vitro anticancer activity of TIPP showed significant inhibition on cell viability of both breast cancer and chronic myeloid leukemia. In vivo anticancer effect of TIPP in both types of cancer models further proved the potent anticancer nature of TIPP. Immunohistochemistry analysis assured that TIPP is a safe drug for normal organs such as the liver. Our present study revealed that TIPP is a potent anticancer drug and an important treatment option for various diseases. Further work is needed to test the flexible and proficient activity of the novel peptide.


Prenatal ethanol exposure permanently reduces the number of pyramidal neurons in rat hippocampus.
The effect of prenatal ethanol exposure in the rat on the development of dorsal hippocampal pyramidal and dentate gyrus granule cells was examined. Ethanol was administered in a nutritionally adequate liquid diet to pregnant rats during days 10--21 of gestation. Control groups were either pair-fed the same liquid diet, except for equicaloric substitution of sucrose for ethanol, or received free access to pelleted laboratory food. The brains of 60-day-old offspring exposed to ethanol during gestation were found to have 20% fewer dorsal hippocampal pyramidal cells than did those of controls. Prenatal ethanol exposure, however, did not affect the number of dentate gyrus granule cells. Prenatal exposure to ethanol permanently reduced the number of prenatally formed hippocampal neurons without altering physical growth, which suggested that the developing nervous system is particularly sensitive to the toxic effects of ethanol.


The relative roles of charge and a recognition peptide in luminal targeting of colorectal cancer by fluorescent polyacrylamide.
Real time detection of biomarkers at the mucosal level is imperative for the prevention and efficient treatment of colorectal cancer. Cationized polyacrylamide (CPAA) with increasing charge densities was prepared by radical polymerization of acrylamide and different mol% ratios of N-acryloyl, N'-(tert-butyl-carbonyl) diaminoethane. The NIR fluorophore derivative of IR-783, IR-783-S-Ph-COOH, was attached to the CPAA to give CPAA-783. After selecting the optimal IR-783-S-Ph-COOH ratio that avoids quenching, the preferential binding of the polymer was tested in SW-620, SW-480, HT-29, and LS-174T cancer cells. The optimal polymeric product was tested in situ in gut sac preparations of the dimethylhydrazine induced rat model. To increase the detection capabilities of CPAA-783, the FITC-labeled peptide EPPT1, that targets the cell transmembrane underglycosylated MUC-1 (uMUC-1), was conjugated to the polymer to obtain CPAA-783-EPPT1. The dually labeled modified polymer was tested in HT-29 and LS-174T cells (over expressing uMUC-1), followed by an examination in an orthotopic mouse model. CPAA-783 preferentially bound to the cancer cells, depending on CRC staging. The best binding occurred when the fraction of the cationic monomer was 100 mol%, labeled with 0.75 mol% of IR-783-S-Ph-COOH. An increase in the recognition of the dually labeled polymeric product, CPAA-783-EPPT1, towards HT-29 and LS-174T cells occurred in the lowest EPPT1molar ratio (0.63 mol%) only, probably due to quenching phenomena and steric hindrance. Similar observation was obtained in the orthotopic mice. It is concluded that fluorescently tagged CPAA can be used for the detection of malignant tissues in colorectal cancer after luminal instillation. Dually targeted CPAA with EPPT1is feasible, but requires further optimization.


Sector expansion and elliptical modeling of blue-gray ovoids for basal cell carcinoma discrimination in dermoscopy images.
Blue-gray ovoids (B-GOs), a critical dermoscopic structure for basal cell carcinoma (BCC), offer an opportunity for automatic detection of BCC. Due to variation in size and color, B-GOs can be easily mistaken for similar structures in benign lesions. Analysis of these structures could afford accurate characterization and automatic recognition of B-GOs, furthering the goal of automatic BCC detection. This study utilizes a novel segmentation method to discriminate B-GOs from their benign mimics. Contact dermoscopy images of 68 confirmed BCCs with B-GOs were obtained. Another set of 131 contact dermoscopic images of benign lesions possessing B-GO mimics provided a benign competitive set. A total of 22 B-GO features were analyzed for all structures: 21 color features and one size feature. Regarding segmentation, this study utilized a novel sector-based, non-recursive segmentation method to expand the masks applied to the B-GOs and mimicking structures. Logistic regression analysis determined that blue chromaticity was the best feature for discriminating true B-GOs in BCC from benign, mimicking structures. Discrimination of malignant structures was optimal when the final B-GO border was approximated by a best-fit ellipse. Using this optimal configuration, logistic regression analysis discriminated the expanded and fitted malignant structures from similar benign structures with a classification rate as high as 96.5%. Experimental results show that color features allow accurate expansion and localization of structures from seed areas. Modeling these structures as ellipses allows high discrimination of B-GOs in BCCs from similar structures in benign images.


A low-cost open-architecture taste delivery system for gustatory fMRI and BCI experiments.
Tasting is a complex process involving chemosensory perception and cognitive evaluation. Different experimental designs and solution delivery approaches may in part explain the variability reported in literature. These technical aspects certainly limit the development of taste-related brain computer interface devices. We propose a novel modular, scalable and low-cost device for rapid injection of small volumes of taste solutions during fMRI experiments that gathers the possibility to flexibly increase the number of channels, allowing complex multi-dimensional taste experiments. We provide the full description of the hardware and software architecture and illustrate the application of the working prototype in single-subject event-related fMRI experiments by showing the BOLD responses to basic taste qualities and to five intensities of tastes during the course of perception. The device is shown to be effective in activating multiple clusters within the gustatory pathway and a precise time-resolved event-related analysis is shown to be possible by the impulsive nature of the induced perception. This gustometer represents the first implementation of a low-cost, easily replicable and portable device that is suitable for all kinds of fMRI taste experiments. Its scalability will boost the experimental design of more complex multi-dimensional fMRI studies of the human taste pathway. The gustometer represents a valid open-architecture alternative to other available devices and its spread and development may contribute to an increased standardization of experimental designs in human fMRI studies of taste perception and pave the way to the development of novel taste-related BCIs.


When the treatment goal is not cure: are patients informed adequately?
We determined the extent to which Australian patients with incurable cancer are informed of their prognosis and treatment options by their oncologists and are encouraged to participate in treatment decisions. To this end, 118 patients with incurable cancer presenting for an initial consultation with one of nine oncologists in two Sydney teaching hospitals were enrolled in the study. Consultations were audio-taped. We developed a coding system to assess the disclosure of information considered necessary to equip patients to make informed decisions and to evaluate doctor encouragement of patient participation in treatment decision-making. Patient recall, satisfaction, and anxiety and their perceptions of the decision-making process were assessed. Most patients were informed about the aim of cancer treatment (84.7%), that their disease was incurable (74.6%) and about life expectancy (57.6%); 44.1% were presented with an alternative to cancer treatments, such as supportive care, 36.3% were informed how anticancer treatment would affect quality of life, and 29.7% were offered a management choice. Patient understanding was checked in only 10% of consultations. While greater information disclosure did not appear to elevate anxiety levels, greater patient participation in the decision making process was associated with increased anxiety levels ( P=0.0005), which persisted over a 2-week time span. Most patients were well informed, but important gaps remain, especially concerning information about prognosis and alternatives to cancer treatment.


Relationship between the nutritional status and safety and efficacy outcomes in atrial fibrillation patients aged 80 years and over receiving oral anticoagulants.
Malnutrition has been reported to be associated with worse clinical outcomes in various cardiovascular diseases. We aimed to investigate the clinical significance of the nutritional status in atrial fibrillation (AF) patients aged 80 years and over receiving oral anticoagulants (OACs), focusing on the difference between direct OACs (DOACs) and warfarin treatment. This was a retrospective and observational study. We enrolled 332 consecutive AF patients aged 80 years and over who were treated with OACs: DOACs (n = 256) and warfarin (n = 76). A controlling nutritional status (CONUT) score was used to evaluate the nutritional status. The enrolled patients were divided into two groups based on the CONUT score: CONUT score <5 (n = 239) and CONUT score ≥5 (n = 93) groups. We investigated the relationship between the nutritional status and clinical outcomes. The CONUT score ≥5 group had significantly higher incidence of major bleeding (MB) compared to the CONUT score <5 group (4.6/100 person-years vs. 0.7/100 person-years, p < 0.01). On Cox hazard analysis, CONUT score ≥5 group was significantly associated with increased MB compared with the CONUT score <5 group (hazard ratio: 5.80, 95% confidence interval: 1.44-23.33, p = 0.013). In the DOAC group, the incidence of MB did not differ between the CONUT score ≥5 and CONUT score <5 groups (p = 0.54). In the warfarin group, MB occurred more frequently in the CONUT score ≥5 group than CONUT score <5 group (p < 0.01). There was no significant difference in the incidence of thromboembolic events between the CONUT score ≥5 and CONUT score <5 groups in both the DOAC and warfarin groups. The prognostic values of the nutritional status based on the CONUT score for MB differed between AF patients aged 80 years and over receiving DOACs and those receiving warfarin. It may be favorable to use DOACs to avoid bleeding events in those with malnutrition.


Isolation of Group A Streptococci with Reduced In Vitro β-Lactam Susceptibility Harboring Amino Acid Substitutions in Penicillin-Binding Proteins in Japan.
Streptococcus pyogenes (group A Streptococcus [GAS]) has long been regarded as being susceptible to β-lactams. However, amino acid substitutions in penicillin-binding protein 2X (PBP2X) conferring reduced in vitro β-lactam susceptibility have been indicated since 2019 in the United States and Iceland. Here, we report the first isolation of Streptococcus pyogenes possessing the PBP2X substitution conferring reduced in vitro β-lactam susceptibility in Asia; however, the MICs were below the susceptible breakpoint of the CLSI.


Metallothionein-I-II expression in young and adult bovine pineal gland.
Aging is characterized, among other features, by an increased concentration of metal ions in the brain that may contribute to a greater increase in free radicals production. The present paper reports data regarding the concentration of some relevant metal ions (Cu, Fe, Mn, Zn), as well as the immunopositivity of metallothionein-I-II and GFAP in the bovine pineal gland with respect to animal aging. The pineal gland of young bovines displays several immunoreactive metallothionein-I-II positive elements in the parenchyma, whose number decreases with age. We also report that a well defined group of neurons bordering the third ventricle and located close to the subcommissural organ shows an intense metallothionein-I-II immunopositivity. The presence of metallothionein-I-II was confirmed by means of liquid chromatography coupled to tandem mass spectrometry. In particular, it proved possible to identify the amino acid sequences of the unique tryptic peptide not containing cysteine and two pepsin fragments containing cysteines. In conclusion, our data suggest the presence of a metallothionein-I-II expressing system in the pineal gland and ventricle-adjacent areas of the bovine epithalamus might possibly be related to the anti-aging effects of melatonin.


[Juvenile nasopharyngeal angiofibroma with orbital extension].
The case is presented of a 21 year-old male with a history of left proptosis and diplopia of two weeks of onset. The MRI showed an ethmoid-orbital vascular lesion with anterior skull base invasion and orbital extension. Biopsy of the ethmoid confirmed fibrovascular tissue, which supported the diagnosis of angiofibroma. It is a benign neoplasm with local characteristics of malignancy due to its ability to invade adjacent areas. In this case, the debut presented with manifestations of orbital extension. A broad and multidisciplinary approach is needed in order to improve prognosis.


Pediatric and Adolescent Shoulder Instability.
Traumatic and atraumatic shoulder instability is common in pediatric and adolescent patients. It is well-established that young patients with anterior shoulder dislocation are at high risk of recurrent instability. This review assesses the current literature pertaining to management of both anterior instability and MDI in the pediatric and adolescent populations. Current research suggests that pediatric and adolescent patients with shoulder instability have excellent outcomes following arthroscopic Bankart repair; however, higher rates of recurrent instability requiring revision surgical management have been identified in patients with more than one dislocation episode pre-operatively, those with Hill-Sachs lesions and those under age 16. The addition of the remplissage procedure to an arthroscopic Bankart repair may be useful in preventing recurrent instability for patients with large Hill-Sachs lesions. Open procedures with bony glenoid augmentation may be indicated in patients with significant glenoid bone loss, or those who have failed primary surgical management, with promising outcomes reported following the Latarjet coracoid process transfer procedure in the adolescent population. Pediatric and adolescent patients with hyperlaxity, and those participating in swimming or gymnastics are more likely to have multidirectional instability (MDI). Non-surgical management with physical therapy is the mainstay of treatment for MDI with positive outcomes reported overall. In young patients with MDI who continue to have symptoms of instability and pain that effects daily activities or sports despite an adequate and appropriate course of rehabilitation, surgical management with capsulorrhaphy may be considered, with promising outcomes reported for both open and arthroscopic techniques. Attentive selection of timing and surgical procedure for pediatric and adolescent patients with anterior shoulder instability may help to prevent recurrent instability following shoulder stabilization. Although most pediatric and adolescent patients with MDI do well following non-surgical management alone, those that fail conservative management have good outcomes following arthroscopic or open capsulorrhaphy.


LncRNA TUG1 inhibits the proliferation and fibrosis of mesangial cells in diabetic nephropathy via inhibiting the PI3K/AKT pathway.
To elucidate the potential function of long non-coding RNA (lncRNA) TUG1 in the progression of diabetic nephropathy (DN) and the underlying mechanism. Rat diabetes mellitus (DM) model was established by streptozocin (STZ) administration. In vivo levels of TUG1 and relative genes in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in DM rats and control rats were determined by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Moreover, levels of kidney weight, 24 h-urine protein, blood urea nitrogen and serum creatinine in DM rats and controls were detected. Mesangial cells were subjected to induction of high-level glucose. Relative levels of TUG1 and relative genes in the PI3K/AKT pathway in mesangial cells were determined as well. Through Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assay, the regulatory effect of TUG1 on the proliferative ability of mesangial cells induced with high-level glucose was evaluated. Finally, expression changes in the PI3K/AKT pathway and extracellular matrix (ECM)-related genes in mesangial cells were determined. TUG1 was downregulated in DM rats and mesangial cells induced with high-level glucose. Compared with controls, DM rats presented higher levels of kidney weight, 24 h-urine protein, blood urea nitrogen and serum creatinine, which were markedly reduced after TUG1 overexpression in vivo. Moreover, overexpression of TUG1 downregulated TGF-β1, FN, and COL-IV, and inhibited the activation of the PI3K/AKT pathway. TUG1 is downregulated in DN. The overexpression of TUG1 could suppress the proliferation and ECM accumulation of mesangial cells via inhibiting the PI3K/AKT pathway.


Modeling Emergent Properties in the Brain Using Tissue Models to Investigate Neurodegenerative Disease.
Here we describe emergent properties of the brain and the key challenges associated with modelling them in vitro. Modeling emergent properties of the brain will provide insights into brain function, development, and disease.


Electrospun nanofiber scaffold for vascular tissue engineering.
Due to the prevalence of cardiovascular diseases, there is a large need for small diameter vascular grafts that cannot be fulfilled using autologous vessels. Although medium to large diameter synthetic vessels are in use, no suitable small diameter vascular graft has been developed due to the unique dynamic environment that exists in small vessels. To achieve long term patency, a successful tissue engineered vascular graft would need to closely match the mechanical properties of native tissue, be non-thrombotic and non-immunogenic, and elicit the proper healing response and undergo remodeling to incorporate into the native vasculature. Electrospinning presents a promising approach to the development of a suitable tissue engineered vascular graft. This review provides a comprehensive overview of the different polymers, techniques, and functionalization approaches that have been used to develop an electrospun tissue engineered vascular graft.


Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis.
In spite of the growing literature about adult attention-deficit hyperactivity disorder (ADHD), relatively little is known about the prevalence and correlates of this disorder. To estimate the prevalence of adult ADHD and to identify its demographic correlates using meta-regression analysis. We used the MEDLINE, PsycLit and EMBASE databases as well as hand-searching to find relevant publications. The pooled prevalence of adult ADHD was 2.5% (95% CI 2.1-3.1). Gender and mean age, interacting with each other, were significantly related to prevalence of ADHD. Meta-regression analysis indicated that the proportion of participants with ADHD decreased with age when men and women were equally represented in the sample. Prevalence of ADHD in adults declines with age in the general population. We think, however, that the unclear validity of DSM-IV diagnostic criteria for this condition can lead to reduced prevalence rates by underestimation of the prevalence of adult ADHD.


Omeprazole induces high intraglandular pressure in the rat gastric mucosa.
In a few patients receiving high doses of omeprazole for a prolonged period, cystic changes have developed in the gastric mucosa, possibly consisting of enlarged gland lumina. To investigate this question, the luminal pressure in gastric glands was studied after omeprazole treatment in Inactin-anesthetized rats. The gland luminal pressure and mucus thickness were measured with microelectrodes. For pressure measurements (servo-null technique) the microelectrode was inserted into a gland at an angle of approximately 30 degrees to the mucosal surface. Animals given omeprazole by gavage, 400 micromol/kg daily for 1 week, showed high gland luminal pressures (27.4 +/- 2.4 mm Hg). Similar values were found in animals given an intravenous omeprazole injection (40 micromol/kg). Much lower pressures were noted after vehicle or pentagastrin infusion. The thickness of the lower, firm mucus layer was not altered by omeprazole treatment. The significantly higher gland luminal pressure after treatment with omeprazole, compared with the values during pentagastrin or vehicle infusion, cannot be explained by increased mucus thickness. The results suggest accumulation of fluid in the gland lumen caused by increased resistance to outflow from the gland. This might explain the proposed enlargement of gland lumina.


Anticipated, experienced, and remembered subjective effort and discomfort on sustained attention versus working memory tasks.
This study examined individuals' ability to accurately anticipate how cognitively effortful and uncomfortable a task will feel based on a short sample of the task. Participants completed a sustained attention or working memory task. Post-practice, participants rated the effort and discomfort that they anticipated their task would require and engender, respectively. Participants also rated their effort and discomfort during task-administration and the effort and discomfort they recalled feeling after task-administration. Sustained attention task participants anticipated significantly less effort than working memory task participants. Sustained attention task participants felt significantly more effort during the task and remembered feeling more effort than they had anticipated. Working memory task participants felt significantly less effort during the task than they had anticipated. Sustained attention task participants anticipated, experienced, and recalled feeling more discomfort than working memory task participants. Individuals' anticipation of effort required depends on the task and is different from the effort they actually feel during the task and later recall feeling.


Effect of isoproterenol on regional myocardial segment work, O2 consumption, and oxygen balance.
We tested the hypothesis that positive inotropic stimulation by isoproterenol alters the relationship between regional segment work and regional myocardial oxygen consumption. Regional parameters were compared with external cardiac work and global LV oxygen consumption. In anesthetized open-chest dogs, regional myocardial segment length (ultrasonic dimension crystals) and force development (miniature force transducer) were measured. The integrated multiples of myocardial shortening by corresponding force during an averaged beat expressed segment work (area under the systolic portion of the length-force loop). External cardiac work was calculated from aortic blood pressure and cardiac output. Global and regional myocardial MVO2 were evaluated at baseline and during intravenous infusion of isoproterenol (0.5 and 1.0 micrograms/kg per min). Regional coronary blood flow was measured with radioactive microspheres, and microspectrophotometry of frozen myocardial biopsies was used to evaluate O2 saturation in small arteries and veins. These parameters were used to calculate regional MVO2. Arterial and coronary sinus O2 saturation was used to calculate global LV O2 consumption. Regional myocardial O2 balance was estimated by measurement of NADH redox level using surface fluorometry. It was found that 0.5 micrograms/kg per min isoproterenol increased regional segment work/minute from 4650 +/- 495 to 6750 +/- 750 mm.g/min. Corresponding regional oxygen consumption was disproportionately increased from 5.43 +/- 0.61 to 15.24 +/- 1.37 ml/min per 100 g. External cardiac work was found to decrease from 728 +/- 13 to 562 +/- 25 mmHg.1/min (due to decreased aortic blood pressure), whereas global myocardial O2 consumption increased. Regional myocardial O2 extraction and NADH fluorescence were elevated, indicating impaired tissue oxygenation. Regional MVO2 was increased by 153 +/- 56%, but regional work by only 45.3 +/- 33% (P < 0.05). These results indicate that regional contraction efficiency was markedly reduced by isoproterenol.


Brain cannabinoid CB₂ receptors modulate cocaine's actions in mice.
The presence and function of cannabinoid CB(2) receptors in the brain have been the subjects of much debate. We found that systemic, intranasal or intra-accumbens local administration of JWH133, a selective CB(2) receptor agonist, dose-dependently inhibited intravenous cocaine self-administration, cocaine-enhanced locomotion, and cocaine-enhanced accumbens extracellular dopamine in wild-type and CB(1) receptor knockout (CB(1)(-/-), also known as Cnr1(-/-)) mice, but not in CB(2)(-/-) (Cnr2(-/-)) mice. This inhibition was mimicked by GW405833, another CB(2) receptor agonist with a different chemical structure, and was blocked by AM630, a selective CB(2) receptor antagonist. Intra-accumbens administration of JWH133 alone dose-dependently decreased, whereas intra-accumbens administration of AM630 elevated, extracellular dopamine and locomotion in wild-type and CB(1)(-/-) mice, but not in CB(2)(-/-) mice. Intra-accumbens administration of AM630 also blocked the reduction in cocaine self-administration and extracellular dopamine produced by systemic administration of JWH133. These findings suggest that brain CB(2) receptors modulate cocaine's rewarding and locomotor-stimulating effects, likely by a dopamine-dependent mechanism.


Small-scale fluctuations of laser beam fluence at the large B-integral in ultra-high intensity lasers.
Analytical expressions for the spatial spectrum of fluence fluctuations of a laser pulse propagating in a medium with Kerr nonlinearity have been obtained. It is shown that inhomogeneities with a spatial scale much larger than the critical scale of self-focusing grow insignificantly even at large values of the B-integral. Experiments using BK7 glass and a KDP crystal as a nonlinear medium confirm the obtained theoretical results. This may be interesting for pulse post-compression, frequency doubling, and other experiments using transmission optical elements in ultra-high intensity lasers.


Laboratory evaluation of sugar alcohols for control of mosquitoes and other medically important flies.
Insecticide application for vector control is the most controversial component of a public health program due to concerns about environmental and human health safety. One approach to overcome this challenge is the use of environmentally benign active ingredients. Among the most promising emerging strategies are attractive toxic sugar baits. Sugar alcohols-naturally occurring molecules safe for human consumption but potentially toxic to insects when ingested, have received increased attention for use with this approach. For this study, we screened the toxicity of four different sugar alcohols on several mosquito species, a biting midge, and a filth fly. Sugar alcohol mortalities exceeded those in the sucrose (positive control) only group. However, only erythritol and highly concentrated xylitol induced mortalities exceeding those in the water only (negative control) treatment ranging from approximately 40-75%. Formulations containing erythritol and xylitol should be further investigated under field conditions for efficacy in reducing populations of biting flies and for assessing potential non-target impacts.


Comparative studies on six blood serum glycosidases from several mammalian species.
1. Peripheral blood serum alpha-D-galactosidase, beta-D-galactosidase, beta-D-glucosidase, alpha-D-mannosidase, beta-D-xylosidase and beta-D-glucuronidase have been studied with a comparative point of view from several mammalian species: Bos taurus L. (bull), Capra hircus L. (goat), Sus scropha var. domestica L. (pig) and man. 2. Fluorimetric and spectrophotometric procedures were used for determination of enzyme activities and pH optima. 3. Glycosidase activity was generally higher with fluorescent substrates than with chromogenic substrates. 4. alpha-D-mannosidase was the most active with both fluorescent and chromogenic substrates. 5. All the studied enzymes had the same pH optimum (4.0) when the chromogenic substrates were used. 6. pH optima of these glycosidases ranged from 3.0 to 5.5 when the fluorescent substrates were used.


The utility of flow cytometry in differentiating NK/T cell lymphoma from indolent and reactive NK cell proliferations.
The WHO defines three categories of NK cell malignancies; extra nodal NK/T cell lymphoma (NKTCL), aggressive NK cell leukemia, and the provisional entity chronic lymphoproliferative disorder of NK cells (CLPD-NK). Although the flow cytometric (FC) phenotype of CLPD-NK has been described, studies on FC phenotype of NKTCL are limited. To the best of our knowledge ours is the first study to compare the phenotype of NKTCL, CLPD-NK, reactive NK lymphocytosis (RNKL), and normal NK cells using eight color (8C) FC. Specimens analyzed using the Euroflow8C NK Lymphoproliferative Disorder (NKLPD) panel between 2011 and 2014 were identified from our database. All samples were analyzed on the FACSCantoII cytometer. NK cells were identified as CD45+, smCD3-, CD19-, CD56+ and normal T-cells served as internal controls. The majority of NKTCL were CD56 bright, CD16 dim, CD57-, and CD94+. CLPD-NK and RNKL were predominantly CD56+ or dim with positive expression of CD16 and CD57 and weak CD94 expression. Antigen based statistical analyses showed robust division of samples along the NKTCL/normal CD56 bright NK cell and CLPD-NK/RNKL/normal CD56 positive NK cell groups. It was concluded that FC can reliably distinguish NKTCL from CLPD-NK, normal NK cells of CD56+ phenotype, and RNKL. It was proposed that the typical phenotype for NKTCL is: CD56 bright, CD16 dim with positive CD2, CD7, CD94, HLADR, CD25, CD26, and absent CD57. This resembles the phenotype of the CD56 bright immunoregulatory subset of NK cells which we therefore hypothesize is the cell of origin of NKTCL. © 2017 International Clinical Cytometry Society.


Lessons learned about virtual cancer care and distress screening in the time of COVID-19.
Cancer-related biopsychosocial distress is highly prevalent across the cancer care continuum. The implementation of screening patients for biopsychosocial distress has become a standard of practice in cancer care. With the presence of COVID-19, clinical care has shifted from in-person care to virtual care in many instances. One of the realities of COVID-19 is the significant decrease in screening patients for biopsychosocial symptom burden. Given that screening for distress has become an accreditation standard in many cancer programs, in the province of Alberta, Canada, all patients are screened for distress with every visit to the cancer centre. Given the presence of COVID-19, much of cancer care has shifted to being delivered virtually (through mediums such as Zoom). In this paper, we present pre- and post-COVID data on the frequency of distress screening and its impact on patient care. A review of pre- and post-COVID-19 screening for distress questionnaires revealed that patients who received virtual care were less satisfied in the areas of emotional support and received less resources and referrals to supportive care. The rapid integration of virtual care without the inclusion of a standardized distress screening tool was akin to a natural experiment, as two groups (virtual and in-person clinic patients) received different levels of care and interventions. Without the inclusion of distress screening, the clinical conversation around symptoms is less likely to occur and results in fewer referrals to best practices in supportive care services. Lessons learned about virtual cancer care without distress screening in the time of COVID-19 demonstrates significantly fewer patients being screened for distress and subsequently has resulted in less supportive care referrals. Going forward, we must find ways to ensure that virtual cancer care continues to support distress screening and best patient-centric care.


Molecular bases of the crosstalk between bone and muscle.
Exercise is an evolutionary conserved survival function that nowadays has beneficial health effects. The increased metabolic activity of contracting skeletal muscle affects the biology of many organs involved in regulating muscle functions. The discovery of hormones and cytokines secreted by bone and skeletal muscle during exercise, has recently added experimental credence to the notion that a crosstalk exists between these organs. Bone through the hormone osteocalcin, promotes exercise capacity in the mouse. After binding to a G-coupled protein receptor, Gprc6a, osteocalcin increases nutrients uptake and catabolism in myofibers during exercise. The catabolic aspect of osteocalcin distinguishes it from insulin signaling. In addition, osteocalcin regulates the endocrine function of skeletal muscle because it enhances the expression of interleukin-6 (IL-6). IL-6 is produced and secreted by contracting skeletal muscle and exerts autocrine, paracrine and systemic effects. One of the systemic functions of IL-6 is to drive the generation of bioactive osteocalcin. Altogether, these studies have revealed a feed-forward loop between bone and skeletal muscle that are necessary and sufficient for optimum exercise capacity. This endocrine regulation of exercise biology, suggest novel and adapted strategies for the prevention or treatment of age related muscle loss.


Chromosome analyses of two recently established human tumour cell lines derived from a carcinoma of the oesophagus and a primary liver tumour.
An oesophageal carcinoma cell line was karyotyped at passages 8,48,64 and 88. It showed a persistent loss of D group chromosomes and subtelocentric, acrocentric, dicentric and other markers were frequently present. During 80 passages the modal number declined from 60,5 to 54,09. The chromosome pattern of a hepatoma cell line was studied at passages 15/17 and 28. It showed a loss of D and G group chromosomes and the presence of various markers including a D/G fusion.


Access to high-volume surgeons and the opportunity cost of performing radical prostatectomy by low-volume providers.
Evidence suggests that redirecting surgeries to high-volume providers may be associated with better outcomes and significant societal savings. Whether such referrals are feasible remains unanswered. Medicare Provider Utilization and Payment Data, SEER 18, and US Incidence data were used to determine the geographic distribution and radical prostatectomy volume for providers. Access was defined as availability of a high-volume provider within driving distance of 100 miles. The opportunity cost was defined as the value of benefits achievable by performing the surgery by a high-volume provider that was forgone by not making a referral. The savings per referral were derived from a published Markov model for radical prostatectomy. A total of 14% of providers performed>27% of the radical prostatectomies with>30 cases per year and were designated high-volume providers. Providers with below-median volume (≤16 prostatectomies per year) performed>32% of radical prostatectomies. At least 47% of these were within a 100-mile driving distance (median = 22 miles), and therefore had access to a high-volume provider (>30 prostatectomies per year). This translated into a discounted savings of more than $24 million per year, representing the opportunity cost of not making a referral. The average volume for high- and low-volume providers was 55 and 13, respectively, resulting in an annual experience gap of 43 and a cumulative gap of 125 surgeries over 3 years. In 2014, the number of surgeons performing radical prostatectomy decreased by 5% while the number of high- and low-volume providers decreased by 25% and 11% showing a faster decline in the number of high-volume providers compared with low-volume surgeons. About half of prostatectomies performed by surgeons with below-median annual volume were within a 100-mile driving distance (median of 22 miles) of a high-volume surgeon. Such a referral may result in minimal additional costs and substantially improved outcomes.


Prevalence of pathogenic bee viruses in Hungarian apiaries: situation before joining the European Union.
A survey on the occurrence of six honeybee-pathogenic viruses was carried out using one-step RT-PCR assays. Samples were collected between 1999 and 2004 in 52 Hungarian apiaries located in different regions of the country. The results of the assays on samples of adult honeybees and Varroa destructor mites were compared to similar surveys from France and Austria. The study demonstrates geographical differences in the prevalence of honeybee viruses between Hungary and the older EU member states. The results could serve as a basis for monitoring further changes in the distribution of honeybee viruses in Europe.


Etiological spectrum, clinico-radiological profile and treatment outcomes of longitudinally extensive transverse myelitis - A prospective study from Northwest India.
To study etiological, clinical and radiological profile and treatment outcomes in patients of longitudinally extensive transverse myelitis (LETM). This was a prospective study conducted at Dr. S.N. medical college, Jodhpur, India, of patients presenting with LETM between March 2018 to March 2020. Our study included 32 patients (median age 32 years, female to male ratio of 2.5: 1). Neuromyelitis optica spectrum disorders (NMOsd) was the most common diagnosis affecting 14 patients followed by 5 patients of idiopathic myelitis, 4 patients of para-infectious myelitis, 3 patients of multiple sclerosis (MS), 3 patients of acute demyelinating encephalomyelitis (ADEM) and 1 patient each of myelin oligodendrocyte glycoprotein (MOG) antibody disease, sarcoidosis and mixed connective tissue disorder (MCTD). All the patients of NMOsd were positive for aquaporin 4 (AQP4) antibody. Spinal MRI showed central pattern of involvement in NMOsd and eccentric pattern of involvement in MS. All the patients of para-infectious myelitis were varicella myelitis. Twenty-eight (87.5%) patients had good clinical recovery at 6 months. Although, LETM is classically associated with NMOsd, it can have multiple etiologies. Identifying the etiology is important for long term treatment and prognosis which varies according to the disease. Patients in our study presented with relapses and severe disease but had good clinical recovery with treatment.


Sometimes You Do Get a Second Chance: Emergency Contraception for Adolescents.
Unplanned or unintended pregnancy remains a significant challenge for adolescents; many teens who plan ahead but opt not to choose long-acting reversible contraceptive methods have high failure rates with condom usage, oral contraceptives, and other less long-acting methods. Emergency contraception (EC) remains a necessity for those adolescents seeking a second chance to prevent the unintended consequences of unplanned sexual activity. At present, 5 postcoital methods remain available as EC globally: intrauterine devices, ulipristal acetate, a selective progesterone modulator, mifepristone; levonorgestrel, and ethinyl estradiol plus levonorgestrel or norgestrel (rarely used now that progestin only methods are more readily available).


Pyrolysis of scrap tyres with zeolite USY.
A zeolite catalyst of ultrastable Y-type (USY) was investigated in the research of two staged pyrolysis-catalysis of scrap tyres. Scrap tyres were pyrolysed in a fixed bed reactor and the evolved pyrolysis gases were passed through a secondary catalytic reactor. The main objective of this paper was to investigate the effect of zeolite USY on the yield of products and the composition of derived oil. The influences of several parameters such as pyrolysis temperature, catalytic temperature, catalyst/tyre ratio, heating rate, etc. on the yield of the derived oil, char and gas were investigated. It showed that the increase of catalytic temperature and catalyst/tyre ratio resulted in high yield of gas at the expense of the oil yield. For example, when the catalyst/tyre ratio increased from 0.25 to 1.0, the yield of gas increased from 30.5 to 49.9 wt.%, and the oil yield decreased nearly two-fold from 31.6 to 12.7 wt.%. The concentration of light naphtha (boiling point < 160 degrees C) was also investigated in this study. And the high catalyst/tyre ratio favored to increase the concentration of light naphtha (< 160 degrees C) in oil. In order to study the composition of derived oil, a distilled fraction (< 280 degrees C), which was 92.5 wt.% of the oil obtained from catalytic pyrolysis of scrap tyre at a pyrolysis temperature, catalytic temperature and catalyst/tyre ratio of 500, 400 degrees C and 0.5, respectively, was analyzed with gas chromatography/mass spectrometry (GC/MS). The distillate was found to contain 1.23 wt.% benzene, 9.35 wt.% toluene, 3.68 wt.% ethylbenzene, 12.64 wt.% xylenes, 1.81 wt.% limonene and 13.89 wt.% PAHs, etc., where the single ring aromatics represented a significant potential use as chemicals.


Rational evaluation of various epidemic models based on the COVID-19 data of China.
In this paper, based on the Akaike information criterion, root mean square error and robustness coefficient, a rational evaluation of various epidemic models/methods, including seven empirical functions, four statistical inference methods and five dynamical models, on their forecasting abilities is carried out. With respect to the outbreak data of COVID-19 epidemics in China, we find that before the inflection point, all models fail to make a reliable prediction. The Logistic function consistently underestimates the final epidemic size, while the Gompertz's function makes an overestimation in all cases. Towards statistical inference methods, the methods of sequential Bayesian and time-dependent reproduction number are more accurate at the late stage of an epidemic. And the transition-like behavior of exponential growth method from underestimation to overestimation with respect to the inflection point might be useful for constructing a more reliable forecast. Compared to ODE-based SIR, SEIR and SEIR-AHQ models, the SEIR-QD and SEIR-PO models generally show a better performance on studying the COVID-19 epidemics, whose success we believe could be attributed to a proper trade-off between model complexity and fitting accuracy. Our findings not only are crucial for the forecast of COVID-19 epidemics, but also may apply to other infectious diseases.


Allele frequencies of single nucleotide polymorphisms of clinically important drug-metabolizing enzymes CYP2C9, CYP2C19, and CYP3A4 in a Thai population.
Prior knowledge of allele frequencies of cytochrome P450 polymorphisms in a population is crucial for the revision and optimization of existing medication choices and doses. In the current study, the frequency of the CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2C19*6, CYP2C19*17, and CYP3A4 (rs4646437) alleles in a Thai population across different regions of Thailand was examined. Tests for polymorphisms of CYP2C9 and CYP3A4 were performed using TaqMan SNP genotyping assay and CYP2C19 was performed using two different methods; TaqMan SNP genotyping assay and Luminex x Tag V3. The blood samples were collected from 1205 unrelated healthy individuals across different regions within Thailand. Polymorphisms of CYP2C9 and CYP2C19 were transformed into phenotypes, which included normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM), and rapid metabolizers (RM). The CYP2C9 allele frequencies among the Thai population were 0.08% and 5.27% for the CYP2C9*2 and CYP2C9*3 alleles, respectively. The CYP2C19 allele frequencies among the Thai population were 25.60%, 2.50%, 0.10%, and 1.80% for the CYP2C19*2, CYP2C19*3, CYP2C19*6, and CYP2C19*17 alleles, respectively. The allele frequency of the CYP3A4 (rs4646437) variant allele was 28.50% in the Thai population. The frequency of the CYP2C9*3 allele was significantly lower among the Northern Thai population (P < 0.001). The frequency of the CYP2C19*17 allele was significantly higher in the Southern Thai population (P < 0.001). Our results may provide an understanding of the ethnic differences in drug responses and support for the utilization of pharmacogenomics testing in clinical practice.


Transoral flexible laser surgery of the upper aerodigestive tract with blue laser.
The introduction of fiber-guided lasers was a breakthrough in laryngology practice, opening the path for treating different pathologies with minimally invasive procedures, both in the operating room and in the office. The most recent technology in the area is the blue laser, which combines photoangiolytic and cutting properties, characteristics that make this equipment suitable for its use in upper aerodigestive tract surgery. However, there is not enough experience in this area. The authors present a case series of patients with different pharyngeal, laryngeal, and tracheal pathologies who were treated by means of transoral procedures using fiber-guided blue laser. The surgical records of patients with different upper aerodigestive tract pathologies who were treated with fiber-guided blue laser in the operating room, under general anesthesia with jet ventilation or supraglottic ventilation using suspension laryngotracheoscopy techniques between February 2018 and March 2022 were reviewed. A total of 80 surgical interventions in a group of 38 patients were performed. A wide variety of procedures was executed, either using the laser alone or in combination with other techniques to treat different pathologies of the aero-digestive tract safely and effectively, with adequate functional results. Following all necessary precautions, blue laser is a reliable tool to perform minimally invasive surgeries in the operating room using TOFLS techniques. It can be used alone or in combination with other devices to achieve the desired goals.


Failure of 2'-deoxycoformycin to protect against transient forebrain ischemia in rat.
We determined whether 2'-deoxycoformycin (DCF), a potent highly specific inhibitor of adenosine deaminase (ADA), protected against transient forebrain ischemic neuronal injury in rat. Anesthetized male Sprague-Dawley rats received i.p. injections of either saline, 0.5 mg/kg or 5 mg/kg DCF 2 h before undergoing a 10-min forebrain ischemic insult induced by bilateral carotid artery occlusion with concomitant hypotension. Rat brain sections taken 7 days post-ischemia showed damage mostly in the CA1 region of the hippocampus. Quantification of neuronal injury showed no significant differences between saline- or DCF-treated rats. These results indicate that, contrary to previous reports, DCF does not protect against the neuronal damage that follows forebrain ischemia in rat.


IBI Score to Improve Clinical Practice in Newborns and Infants ≤ 60 Days with Fever in the Emergency Department.
Fever is the most common problem of children admitted to emergency department (ED). The management of febrile patients ≤ 60 d old admitted to the Pediatric Emergency Department in the last 5 y was evaluated, applying the invasive bacterial infection (IBI) score proposed to evaluate the reliability and safety of this score in the authors' setting.Medical records of 280 patients with fever reported and/or detected in ED were retrospectively analyzed. A total of 166 patients were enrolled, whose average IBI score was 2.98 IBI score < 2 showed a sensitivity of 100.00% [95% CI (71.5-100.0)] and a specificity of 28.39% [95% CI (21.4-36.2)] compared to blood culture. IBI score can be a valid support to identify patients with low risk of invasive infection.


Ion mobility-mass spectrometry reveals the role of peripheral myelin protein dimers in peripheral neuropathy.
Peripheral myelin protein (PMP22) is an integral membrane protein that traffics inefficiently even in wild-type (WT) form, with only 20% of the WT protein reaching its final plasma membrane destination in myelinating Schwann cells. Misfolding of PMP22 has been identified as a key factor in multiple peripheral neuropathies, including Charcot-Marie-Tooth disease and Dejerine-Sottas syndrome. While biophysical analyses of disease-associated PMP22 mutants show altered protein stabilities, leading to reduced surface trafficking and loss of PMP22 function, it remains unclear how destabilization of PMP22 mutations causes mistrafficking. Here, native ion mobility-mass spectrometry (IM-MS) is used to compare the gas phase stabilities and abundances for an array of mutant PM22 complexes. We find key differences in the PMP22 mutant stabilities and propensities to form homodimeric complexes. Of particular note, we observe that severely destabilized forms of PMP22 exhibit a higher propensity to dimerize than WT PMP22. Furthermore, we employ lipid raft-mimicking SCOR bicelles to study PMP22 mutants, and find that the differences in dimer abundances are amplified in this medium when compared to micelle-based data, with disease mutants exhibiting up to 4 times more dimer than WT when liberated from SCOR bicelles. We combine our findings with previous cellular data to propose that the formation of PMP22 dimers from destabilized monomers is a key element of PMP22 mistrafficking.


Platelet responses in health and disease.
This article summarizes recent ultrastructure findings from our laboratory and documents some of the information accumulated primarily since 1975 from many laboratories. Special attention is given to documentation by scanning electron microscopy which affords insight into platelet activation (adhesion, aggregation, release/secretion) and especially platelet-vessel wall interactions. Structural physiology of platelets is considered in some detail as a basis for understanding platelet disorders contributing to clinical problems of thrombosis and hemorrhage. The impaired ability of von Willebrand platelets to adhere to injured vessel wall is reported using the human umbilical vein perfusion model. Relationships between platelets and blood coagulation factors focus on the exquisite sensitivity of platelets to minute amounts of thrombin. Unmasking of platelet factor 3 sites is identified on activated platelets, after glutaraldehyde fixation, by their reaction ot latex bearing anti-platelet factor 3 markers. The basis for platelet-collagen interactions is reviewed. Conditions for and possible mechanisms behind platelet interaction with vessel wall are discussed. Ex vivo flowing blood-vessel wall models offer opportunities for improved understanding of the platelets role(s) in vascular diseases.


Dipeptidyl peptidase-4 inhibitor, anagliptin, alters hepatic insulin clearance in relation to the glycemic status in Japanese individuals with type 2 diabetes.
This study investigated the impact of the dipeptidyl peptidase-4 inhibitor, anagliptin, on hepatic insulin clearance (HIC) in Japanese type 2 diabetes patients and explored its relationship to glycemic status. Data on 765 participants in anagliptin phase 2 and 3 studies were analyzed. Adjusted changes in variables during 12 weeks of anagliptin therapy were compared with a placebo. HIC was calculated as the ratio, C-peptide area under the curve 0-120 min to insulin area under the curve 0-120 min, after a meal tolerance test. To explore the effects of baseline HIC levels on variables, participants receiving anagliptin were divided according to quartiles of baseline HIC. Furthermore, multivariate analysis investigated the association between baseline HIC levels and glycemic status. Anagliptin significantly reduced glycosylated hemoglobin levels (P < 0.001 vs placebo) and HIC levels (P < 0.01). Longer duration of diabetes, lower body mass index, higher glycosylated hemoglobin and lower insulin secretion capacity were observed with increases in baseline HIC levels. Improvements in glycosylated hemoglobin, glycoalbumin and 1,5-anhydroglucitol levels were greater in the relatively higher HIC group (baseline HIC levels ≥median) than in the lower HIC group (<median). Anagliptin affected HIC levels according to HIC baseline levels. Higher baseline HIC values might result in improved hyperglycemia through reduced HIC.


A 10-Year Evaluation of Short-Term Outcomes After Synchronous Colorectal Cancer Surgery: a Dutch Population-Based Study.
Synchronous colorectal cancer (CRC) has been associated with higher postoperative morbidity and mortality rates compared to solitary CRC. The influence of improved CRC care and introduction of screening on these outcomes remains unknown. This study aimed to evaluate time trends in incidence, population characteristics, and short-term outcomes of synchronous CRC patients at the population level over a 10-year time period. Data of all patients that underwent resection for primary CRC were extracted from the Dutch ColoRectal Audit (2010-2019). Analyses were stratified for solitary and synchronous colon and rectal cancer. Multilevel logistic regression analyses were used to determine factors associated with pathological and surgical outcomes. Among 100,474 patients, 3.1% underwent surgery for synchronous CRC. A screening-related decrease for surgically treated left-sided solitary and synchronous colon cancer and a temporary increase for exclusively right-sided colon cancer were observed. Synchronous CRC patients had higher rates of complicated postoperative course, failure to rescue, and mortality. Bilateral synchronous colon cancer was more often treated with subtotal colectomy (25.4%) and demonstrated higher rates of surgical complications, reinterventions, prolonged hospital stay, and mortality than other synchronous tumor locations. National bowel screening resulted in contradictory effects on surgical resections for synchronous CRCs depending on sidedness. Bilateral synchronous colon cancer required more often extended resection resulting in significantly worse outcomes than other synchronous tumor locations. Identification of low volume, high complex CRC subpopulations is relevant for individualized care and has implications for case-mix correction and benchmarking in clinical auditing.


Impact of serum levels of IL-18 and soluble IL-2 receptor on the clinical outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP regimen.
To assess the impact of pretreatment serum levels of IL-18 and soluble IL-2 receptor (sIL-2R) on the clinical outcome of patients with diffuse large B-cell lymphoma treated with an R-CHOP protocol. Total 73 patients were included. Elevated serum IL-18 (using mean as cutoff) was associated with numerically lower complete remission, and 3-year disease-free survival rates; however, the difference was not statistically significant. Nevertheless, the 3-year overall survival rates were significantly more favorable for the lower serum level group. Correspondingly, the complete remission, 3-year disease-free survival and overall survival rates for patients with low pretreatment sIL-2R levels were significantly better than individuals with higher levels. There is a growing body of evidence supporting the utility of pretreatment serum levels of sIL-2R and IL-18 as prognostic factors in diffuse large B-cell lymphoma patients.


Microcalorimetric studies on metabolism of hepatic tissue. II. Measurements of ischemic tissue.
Biopsies of ischemic livers demonstrated a significantly higher rate of heat production when incubated in Leibowitz L-15 medium compared to incubation in modified Eagle's solution (P less than 0.01). A maximal reduction of 25% in the rate of heat production was observed after 60 min of induced ischemia. Liver tissue undergoing reperfusion showed complete and partial recovery after 60 and 90 min, respectively. We conclude that the viability of liver tissue begins to deteriorate after 1-1.5 h of ischemia. Using the level of adenosine triphosphate (ATP) as a parameter for viability, others had found this critical time period to be 1.5-2 h. Furthermore, we conclude that monitoring heat production of tissue provides a useful measure of viability for both clinical application and in connection with experimental liver surgery.


Recent advances in quantitative structure-activity relationship models of antimalarial drugs.
Due to emerging resistance to the first-line artemisinin-based antimalarials and lack of efficient vaccines and limited chemotherapeutic alternatives, there is an urgent need to develop new antimalarial compounds. In this regard, quantitative structure-activity relationship (QSAR) modeling can provide essential information about required physicochemical properties and structural parameters of antimalarial drug candidates. The authors provide an overview of recent advances of QSAR models covering different classes of antimalarial compounds as well as molecular docking studies of compounds acting on different antimalarial targets reported in the last 5 years (2015-2019) to explore the mode of interactions between the molecules and the receptors. We have tried to cover most of the QSAR models of antimalarials (along with results from some other related computational methods) reported during 2015-2019. Many QSAR reports for antimalarial compounds are based on small number of data points. This review infers that most of the present work deals with analog-based QSAR approach with a limited applicability domain (a very few cases with wide domain) whereas novel target-based computational approach is reported in very few cases, which leads to huge voids of computational work based on novel antimalarial targets.


Nanodrop on a nanorough hydrophilic solid surface: contact angle dependence on the size, arrangement, and composition of the pillars.
A two-dimensional nanodrop on a hydrophilic solid surface decorated with nanopillars is examined using a nonlocal density functional theory. It is shown that, in contrast to the commonly used Wenzel formula, even an extremely small roughness can considerably increase the contact angle. The contact angle depends on the distance between pillars, their height and width, as well as their composition. It was found that for all selected pillar heights and compositions, the largest contact angle is obtained when the distance between pillars acquires a size at which the liquid molecules can no longer penetrate between them. The further decrease in the interpillar distance decreases the contact angle, in qualitative agreement with the Cassie-Baxter formula. Considering pillars of various compositions, the role of the gradient of the fluid-solid interaction potential is examined. The presence of such a gradient does not allow the formation of a stable nanodrop on the surface. However, asymmetrical metastable nanodrops can be formed.


Assessment of lateral pterygoid muscle and temporomandibular joint disc after Le Fort I osteotomy with and without intentional pterygoid plate fracture and sagittal split ramus osteotomy in class II and class III patients.
The aim of the study was to examine lateral pterygoid muscle (LPM) and temporomandibular joint (TMJ) disc before and after Le Fort I osteotomy with and without intentional pterygoid plate fracture and sagittal split ramus osteotomy (SSRO) in class II and class III patients. Le Fort I osteotomy and SSRO were performed in class II and class III patients. LPM measurements using oblique sagittal computed tomography (CT) images and TMJ disc position using magnetic resonance imaging (MRI) were examined. Statistical comparisons were performed for the LPM and TMJ between class II and class III patients and between those with and without intentional pterygoid plate fracture in Le Fort I osteotomy. The subjects comprised 60 female patients (120 sides), with 30 diagnosed as class II and 30 as class III. Preoperatively, the width of the condylar attachment, width at eminence, length of the LPM, angle of the LPM, and square of the LPM were significantly smaller in the class II group than in the class III group (p < 0.05). After 1 year, the width of the condylar attachment, width at eminence, and angle of the LPM remained significantly smaller in the class II group than in the class III group (p < 0.0001). TMJ disc position was significantly related to the width of the condylar attachment of the LPM, both pre- and postoperatively (p < 0.0001). However, postoperative disc position did not change in all patients. Next, the class II patients (60 sides) were divided into two groups who underwent Le Fort I osteotomy with or without intentional pterygoid plate fracture. Changes in all measurements of the LPM showed no significant differences between these two groups. Our study suggested that TMJ disc position classification could be associated with the width of condylar attachment of the LPM before and after surgery, while the surgical procedure, including Le Fort I osteotomy with intentional pterygoid plate fracture, might not affect postoperative LMP or disc position in class II patients.


Roughness of enamel surfaces after different bonding and debonding procedures : An in vitro study.
Maintaining an intact enamel surface is an essential aspect of orthodontic therapy; however, various therapeutic measures can affect this surface. The aim of our study was to evaluate roughness of the enamel surface after different conditioning and polishing procedures. 42 bovine incisors were submitted to conventional abrasion (using 37% phosphoric acid), to air abrasion, and a combination of the two. Brackets were put in place and then debonded, and the remaining adhesive removed with a carbide bur or via air abrasion. The enamel surface's roughness was assessed using a confocal laser scanning microscope (CLSM). Mean roughness (R(a)) was 33.1. There were no statistically significant differences among the six groups, or in R(q) values. Under CLSM, the roughness after polishing via air abrasion appeared even. Although it was macroscopically smoother after polishing with a carbide bur, the surface showed a wave-like pattern. The method of enamel conditioning revealed no significant effect on the enamel surface after debonding. Neither polishing via air abrasion nor carbide bur resulted in differences in superficial roughness. However, the carbide bur left a wave-like pattern on the enamel surface.


Dietary ecology of the scimitar-toothed cat Homotherium serum.
The scimitar-toothed cat Homotherium was one of the most cosmopolitan cats of the Pleistocene, present throughout Eurasia, Africa, and the Americas until at least ~28 thousand years ago.1-3 Friesenhahn Cave (Bexar County, Texas) contains some of the best-preserved specimens of Homotherium serum alongside an abundance of juvenile mammoths, leading some to argue that H. serum preferentially hunted juvenile mammoths.1,4 Dietary data of Homotherium are rare, with their ecology inferred from morphological, taphonomic, and genetic data.1,3-10 Here, we use a multi-proxy approach to clarify the dietary ecology of H. serum as compared to extinct and extant cats and their relatives. Dental microwear texture analysis (DMTA) reveals that H. serum consumed soft and tough foods, similar to the extant cheetah, which actively avoids bone,11,12 but in stark contrast to extant lions and hyenas, which are observed to engage in durophagy (i.e., bone processing).11-14 DMTA data are consistent with taphonomic evidence of bone defleshing and the absence of bone-crunching behavior in H. serum. Stable carbon isotope values of H. serum indicate a clear preference for C4 grazers including juvenile mammoths, in agreement with taphonomic evidence suggestive of a "Homotherium den"1,4 and morphological data indicative of a relatively cursorial lifestyle.6-8 Notably, the inferred diet of H. serum contrasts with the extinct dirk-tooth sabertooth cat Smilodon fatalis, which preferred forest/woodland prey and engaged in bone processing.15-19Homotherium serum exhibited a novel combination of morphological adaptations for acquiring open-country prey, consuming their soft and tough flesh-including the tough flesh of juvenile mammoths. VIDEO ABSTRACT.


Use of a laryngeal mask airway to stop a supraglottic air leak which prevented adequate ventilation via a tracheostomy in a patient with cerebral palsy and pneumonia.
We report an adolescent developing ventilation failure due to supraglottic air leakage with the use of an uncuffed hand-made tracheal tube fit to her tracheobronchial deformity. To eliminate the supraglottic air leakage, a size 2.5 laryngeal mask airway (LMA) was inserted into the oral pharynx. Most of air leakage arose from the LMA. Supraglottic air leakage was not detected under mandatory mechanical ventilation following sealing of the 15-mm connector of the LMA with a piece of tape, and the respiratory condition of the patient gradually improved. The combination of a hand-made Y-shaped tube and the LMA was useful in restoring adequate ventilation. In conditions where air leaks through the glottis during mechanical ventilation interfere with adequate ventilation or the maintenance of airway pressure, the use of an LMA may be adequate to stop or significantly decrease the leak.


THE RELATIONSHIP BETWEEN CROSS SUCCESS AND SPATIAL PROXIMITY OF EUCALYPTUS GLOBULUS SSP. GLOBULUS PARENTS.
The genetic structure of Eucalyptus globulus forest was examined using progeny vigor as an indirect measure of parental relatedness. Seven trees were crossed with pollen from trees: 0 m (seifing); 21 m (nearest flowering neighbors), 250 m, 500 m, 1 km, 10 km, and 100 km away from the female. Only selfing depressed seed set. Growth of the 21 m progenies was intermediate to selfing and the longer distance pollinations, suggesting tight family clusters occur due to limited seed dispersal. Under this structure biparental inbreeding may be common, however, the cumulative impact of inbreeding seems negligible as relatedness did not appear to decline with distance between mates beyond 50 m.


Fractionation analysis of oxyanion-forming metals and metalloids in leachates of cement-based materials using ion exchange solid phase extraction.
A simple and versatile solid phase extraction (SPE) method has been developed to determine the anionic species of As, Cr, Mo, Sb, Se and V in leachates of cement mortar and concrete materials in the pH range 3-13. The anionic fractions of these elements were extracted using a strong anion exchanger (SAX) and their concentrations were determined as the difference in element concentration between the sample and the SAX effluent. Inductively coupled plasma mass spectrometry (ICP-MS) was used off-line to analyse solutions before and after passing through the SAX. The extraction method has been developed by optimizing sorbent type, sorbent conditioning and sample percolation rate. Breakthrough volumes and effect of matrix constituents were also studied. It was found that a polymer-based SAX conditioned with a buffer close to the sample pH or in some cases deionised water gave the best retention of the analytes. Optimal conditions were also determined for the quantitative elution of analytes retained on the SAX. Extraction of the cement mortar and concrete leachates showed that most of the elements had similar distribution of anions in both leachate types, and that the distribution was strongly pH dependent. Cr, Mo and V exist in anionic forms in strongly basic leachates (pH>12), and significant fractions of anionic Se were also detected in these solutions. Cr, Mo, Se and V were not determined as anions by the present method in the leachates of pH<12. Anionic As and Sb were found in small fractions in most of the leachates.


Zinc and glutamine improve brain development in suckling mice subjected to early postnatal malnutrition.
The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice. Malnutrition was induced by clustering the litter size from 6-7 pups/dam (nourished control) to 12-14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40-80 microL) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin and myelin basic protein brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal gamma-aminobutyric acid and synaptophysin levels on day 14. We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments.


Comparing Benzodithiophene Unit with Alkylthionaphthyl and Alkylthiobiphenyl Side-Chains in Constructing High-Performance Nonfullerene Solar Cells.
Using single-bonded and fused aromatic rings are two methods for extending the π-conjugation in the vertical direction of benzo [1,2-b:4,5-b'] dithiophene (BDT) unit. To investigate which method is more efficient in nonfullerene systems, two novel polymers based on alkylthionaphthyl and alkylthiobiphenyl substituted BDT named PBDTNS-FTAZ and PBDTBPS-FTAZ are designed and synthesized. Two polymers only exhibit small differences in structure, but huge differences in photovoltaic properties. They are studied by blended with 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)indanone)-5,5,11,11-tetrakis(4-hexylphenyl)dithieno [2,3-d':2,3'-d']-s-indaceno [1,2-b:5,6-b'] dithiophene (ITIC). The device based on PBDTNS-FTAZ:ITIC showed the best power conversion efficiency (PCE) of 9.63% with the Voc of 0.87 V, a Jsc of 18.06 mA/cm2 and a fill factor of 61.21%, while the PBDTBPS-FTAZ:ITIC only exhibit a maximum PCE of 7.79% with a Voc of 0.86 V, a Jsc of 16.24 mA/cm2 and a relatively low fill factor of 55.92%. Therefore, extending π-conjugation with alkylthionaphthyl is more effective against constructing nonfullerene solar cells.


Prevalence and perinatal outcomes of non-communicable diseases in pregnancy in a regional hospital in Haiti: A prospective cohort study.
The prevalence of non-communicable diseases (NCDs) is rising in low and middle-income countries (LMIC). We aimed to report on the prevalence of NCDs in pregnancy and their associated perinatal outcomes in a regional hospital in Haiti. We conducted the "Diabète et hYpertension Artéerielle et leurs issues MAternelles et Néonatales" (DYAMAN) prospective cohort study in a regional hospital in Haiti. Pregnant women presenting to care at 24-28 weeks were screened and treated for diabetes (DM) and hypertensive disorders of pregnancy (HDP) using setting-adapted protocols. Prevalence of NCDs and associated maternal-neonatal outcomes were described. 715 women were included, of which 51 (7.1%) had DM, 90 (12.6%) had HDP, and 30 (4.2%) had both DM and HDP (DM/HDP). Of 422 (59%) women delivered in hospital, 58 (13.7%) had preeclampsia, including 5 (8.6%) with eclampsia. Preterm birth <32 weeks was more common in the HDP than the control, DM, and DM/HDP groups. More low birth weight babies (n = 20, 25.6%) were born to the HDP group than to the control (n = 20, 7.1%), DM (n = 1, 2.7%), and DM/HDP (n = 3, 12%) groups (P < 0.001). Macrosomia and hypoglycemia affected 5 (8%) neonates of women with DM. Perinatal mortality, affecting 36/1000 births, was mainly driven by maternal NCDs. NCDs in pregnancy led to adverse maternal and perinatal outcomes. This study will help to prepare future refinements aimed at optimizing the management of NCDs in pregnancy in LMIC. Research is required to understand barriers to patient attendance at antenatal follow-up, treatment escalation for hyperglycemia, and in-hospital delivery.


A large solitary fibroma of the deep compartment of the sole.
A 50-year-old lady presented with a right foot mass and pain for 1year. Magnetic resonance imaging showed a 3.9×3.2×5cm mass on plantar side of the forefoot deep to the major flexor tendons and plantar aponeurosis and inferior to 1st-4th metatarsals. The mass extended dorsally through the intermetatarsal space to the foot dorsum. Ultrasound guided biopsy was performed, which confirmed it was a fibroma. This case was further complicated by pathological fracture of the 3rd metatarsal. It was resected through a dorsal incision and surgical dislocation of the 2nd and 3rd tarsometatarsal joints. Magnetic resonance imaging was repeated 1year later and showed complete resection of the lesion without recurrence.


Automatic evaluation of the exteroceptive suppression of the temporalis muscle activity.
To set up a reliable automated method of allowing to identify the ES1 and ES2 periods of exteroceptive suppression of the temporal muscle (EST), thereby reducing their intra- and inter-individual variability. Analyses were performed in 79 healthy subjects with strict inclusion and exclusion criteria. Each individual underwent two separate examinations 1 week apart. Activity of the left and right temporal muscles was recorded in response to unilateral stimulation of the left and right labial commissures. Wave forms were successively rectified, averaged, and filtered; the intersections of the resulting curve with values corresponding to 50%, 60%, 70%, 75%, and 80% of the control period (20 ms preanalysis time) were automatically determined. All subjects reached a 80% level of attenuation for ES2. The values of ES2 durations were normally distributed. The mean ES1 and ES2 durations didn't vary between the two recording session, and there was a good individual reproducibility from one session to the other. Though relatively high, the inter-individual variability was slightly lower in the second than in the first session. Computed analysis of EST may contribute to decrease inter- and intra-individual test variability. Letting patient habituate through a first recording session could increase test sensitivity, too. The obtained values for ES2 duration are normally distributed and well-reproducible at both the population and individual level. We suggest taking into account both ES2 duration and level of attenuation.


Estimating Mixture of Gaussian Processes by Kernel Smoothing.
When the functional data are not homogeneous, e.g., there exist multiple classes of functional curves in the dataset, traditional estimation methods may fail. In this paper, we propose a new estimation procedure for the Mixture of Gaussian Processes, to incorporate both functional and inhomogeneous properties of the data. Our method can be viewed as a natural extension of high-dimensional normal mixtures. However, the key difference is that smoothed structures are imposed for both the mean and covariance functions. The model is shown to be identifiable, and can be estimated efficiently by a combination of the ideas from EM algorithm, kernel regression, and functional principal component analysis. Our methodology is empirically justified by Monte Carlo simulations and illustrated by an analysis of a supermarket dataset.


Positive autoregulation of sex-lethal by alternative splicing maintains the female determined state in Drosophila.
Sex-lethal is a binary switch gene that controls all aspects of Drosophila sexual dimorphism. It must be active in females and inactive in males. The on/off regulation reflects alternative RNA splicing in which full-length proteins are produced only in females. Here we investigate the role of Sxl in maintaining sexual pathway commitments. By ectopic expression of a female Sxl cDNA in transgenic male flies, we show that Sxl protein induces a rapid switch from male- to female-specific splicing. The ectopically expressed Sxl protein wil trans-activate an endogenous wild-type Sxl gene. This establishes a feedback loop in which Sxl proteins induce their own synthesis by directing the female-specific splicing of Sxl transcripts. We conclude that the female determined state is maintained by Sxl through positive autoregulation, while the male determined state is maintained by default.


The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis.
The platelet-to-lymphocyte ratio (PLR) is a predictive clinical biomarker for different cancers. However, the results of several studies investigating the association between the PLR and the prognosis of ovarian cancer have been inconclusive. Therefore, there is a need to conduct a meta-analysis to estimate the prognostic value of the PLR in ovarian cancer. We searched the EMBASE, Medline, PubMed, and Web of Science databases to identify clinical studies that had evaluated the association between the PLR and ovarian cancer prognosis. Outcomes evaluated included overall survival (OS) and progression-free survival (PFS). We also analyzed PLR differences between malignant ovarian masses and the controls. Twelve relevant studies that comprised 2340 patients were selected for the meta-analysis. The results revealed that elevated PLR was significantly associated with poor OS (hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.05-2.56, p < 0.01) and PFS (HR 1.61, 95% CI 1.03-2.51, p < 0.01). The PLRs in malignant cases were higher than in controls (mean difference = 63.57, 95% CI 39.47-87.66, p < 0.00001). An elevated PLR is associated with poor prognosis in patients with ovarian cancer. The PLR could be employed as a prognostic marker in patients with ovarian cancer.


Synthesis and SAR study of new phenylimidazole-pyrazolo[1,5-c]quinazolines as potent phosphodiesterase 10A inhibitors.
A series of phenylimidazole-pyrazolo[1,5-c]quinazolines 1a-q was designed, synthesized and characterised as a novel class of potent phophodiesterase 10A (PDE10A) inhibitors. In this series, 2,9-dimethyl-5-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)ethyl)pyrazolo[1,5-c]quinazoline (1q) showed the highest affinity for PDE10A enzyme (IC(50)=16nM).