Validation of the AMPFlSTR SGM plus system for use in forensic casework.
The AMPFlSTR((R)) SGM Plus system is a commercially available STR multiplex produced by Applied Biosystems, a division of Perkin Elmer, Foster City, California, USA that supersedes SGM. The multiplex contains the six SGM loci, amelogenin and four additional loci. These additional loci are D3S1358, D19S433, D16S539 and D2S1338. Consequently, the match probability is significantly improved (conservatively quoted as 1 in 10(9) for reporting a full profile match). The system was subjected to validation. For example, ageing and degradation studies demonstrated semen stains to be the most stable evidence type, whereas buccal scrapes were the least stable. An apparent rise in the sensitivity increases the chance of obtaining successful results from the more difficult samples submitted for analysis. Two of the new loci (D3S1358 and D19S433) are low molecular weight (between 100 and 150 base pairs); this improved the success rates of the degraded samples where high molecular weight loci may drop out. Of 26 non-primates tested, four gave results that appeared as single peaks and were unlikely to cause interpretation problems. None of the 19 micro-organisms tested gave discernible results. Extensive casework and simulated casework studies demonstrated that SGM and SGM plus results were comparable. There was one example of a null allele (primer binding site mutation) recorded at the HUMFIBRA locus (in both systems). However, a concordance study of 1000 samples using both SGM and SGM plus did not demonstrate any differences in typing.


Mechanism of enhanced bioavailability and diuretic effect of azosemide by ascorbic acid in rats.
To increase the extent of comparative oral bioavailability (F) value and the diuretic and natriuretic effects of orally administered azosemide, ascorbic acid was coadministered to rats. The rationales for this study are that ascorbic acid might inhibit intestinal first-pass effect of azosemide and might increase the unionized fraction of azosemide at the receptor sites. After oral administration of azosemide (20 mg/kg) with 100 mg of ascorbic acid, the F value (138% vs. 100%), 8-h urinary excretion of azosemide (5.18% vs. 1.32% of oral dose), 8-h urine output (41.3 vs. 23.0 ml), and 8-h urinary excretion of sodium (24.6 vs. 15.3 mmol/kg) were greater than controls (without ascorbic acid). The amount of spiked azosemide remaining after 30 min incubation of 50 mug of azosemide with the 9000 g supernatant fraction of rat small intestine was significantly greater by 100 microg of ascorbic acid (45.3 vs. 40.9 microg) than controls (without ascorbic acid). After oral administration of azosemide with NH4Cl, the urine pH decreased by 0.5 U, and 8-h urine output (25.8 vs. 11.0 ml) and 8-h urinary excretion of sodium (13.3 vs. 6.89 mmol/kg) were significantly greater than controls (without NH4Cl). The increase in F value and diuretic and natriuretic effects of azosemide with coadministration of ascorbic acid seemed to be due to reduced intestinal first-pass metabolism of azosemide, increased urinary excretion of azosemide, and increased unionized fraction of azosemide at the renal tubular receptor sites.


Ceratonia siliqua pods (Carob) methanol extract alleviates doxorubicin-induced nephrotoxicity via antioxidant, anti-inflammatory and anti-apoptotic pathways in rats.
Doxorubicin (DOX) is an anti-neoplastic therapy, but its use is limited by its deleterious toxic effects including nephrotoxicity and cardiotoxicity. This work aimed at assessing the potential protective effect of Ceratonia siliqua methanol extract (CME) on DOX-induced nephrotoxicity in 5 groups of Wistar rats. Nephrotoxicity was induced experimentally by intraperitoneal (IP) injection of DOX (15 mg/kg). DOX increased serum creatinine, urea, sodium, and potassium levels. It elevated MDA levels in the renal tissue but decreased the concentration of GSH and the activity of GST, CAT, and SOD. Meanwhile, it decreased the level of immunomodulatory anti-inflammatory mediators: IL-10 and TGF-β, as well as the activity of MPO but increased the level of IL-6, TNF-α, and caspase-3 in the renal tissue. DOX has upregulated COX-2, caspase-9, and Bax gene expression and downregulated the Bcl-2 gene expression. Immunolabeling of renal tubular epithelium in DOX-intoxicated rats was moderate to strong against Bax, COX-2, and NF-kβ and weak against Bcl-2. Treatment with CME significantly restored the levels of kidney function parameters and the levels of oxidative stress markers. It stimulated the production of IL-10 and TGF-β and decreased the level of IL-6 and TNF-α. CME reverted the gene expression of COX-2, caspase-9, and Bax. Microscopically, CME alleviated the DOX-induced renal damage. Phytochemical analysis revealed the presence of 26 compounds in the CME. No signs of acute toxicity were recorded by CME up to 4000 mg/kg b. wt. orally into mice. Finally, CME could effectively alleviate the deleterious effects of DOX on the kidney. The safety of carob extract encourages its use in the preparation of valuable therapeutic agents.


The Zavanelli maneuver extended: progression of a revolutionary concept.
Since description of the Zavanelli maneuver in 1984, 15 additional cases have come to light in which partially born but vaginally undeliverable fetuses have been returned to the vagina and subsequently extracted by cesarean section. Ten presentations were vertex, five breech. Half or more of each fetus had been delivered before vaginal reinsertion in eight of the 15. With one exception, all fetuses survived. There were no instances of fetal or maternal trauma. These cases represent a natural and progressive extension of the revolutionary concept behind the Zavanelli maneuver. Contrary to the age-old dicta, the process of vaginal birth, once initiated, does not have to proceed inexorably to completion with either life or death for the fetus in the balance. These cases demonstrate that delivery can be reversed at essentially any moment with excellent potential for fetal survival and relatively insignificant maternal risk.


Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility.
Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3 years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of this pathway and MTHFR C677T polymorphism reported as risk factor for autism in several case control studies. However, controversial reports were also published. Hence the present meta-analysis was designed to investigate the relationship of the MTHFR C677T polymorphism with the risk of autism. Electronic databases were searched for case control studies with following search terms - 'MTHFR', 'C677T', in combination with 'Autism'. Pooled OR with its corresponding 95 % CI was calculated and used as association measure to investigate the association between MTHFR C677T polymorphism and risk of autism. Total of thirteen studies were found suitable for the inclusion in the present meta-analysis, which comprises 1978 cases and 7257 controls. Meta-analysis using all four genetic models showed significant association between C677T polymorphism and autism (ORTvs.C = 1.48; 95 % CI: 1.18-1.86; P = 0.0007; ORTT + CT vs. CC = 1.70, 95 % CI = 0.96-2.9, p = 0.05; ORTT vs. CC = 1.84, 95 % CI = 1.12-3.02, p = 0.02; ORCT vs.CC = 1.60, 95 % CI = 1.2-2.1, p = 0.003; ORTT vs.CT+CC = 1.5, 95 % CI = 1.02-2.2, p = 0.03). In total 13 studies, 9 studies were from Caucasian population and 4 studies were from Asian population. The association between C677T polymorphism and autism was significant in Caucasian (ORTvs.C = 1.43; 95 % CI = 1.1-1.87; p = 0.009) and Asian population (ORTvs.C = 1.68; 95 % CI = 1.02-2.77; p = 0.04) using allele contrast model. In conclusion, present meta-analysis strongly suggested a significant association of the MTHFR C677T polymorphism with autism.


Anti-reflux mucosectomy (ARMS) results in improved recovery and similar reflux quality of life outcomes compared to laparoscopic Nissen fundoplication.
Anti-reflux mucosectomy (ARMS) is a new endoscopic procedure involving a hemi-circumferential endoscopic mucosal resection (EMR) around the gastroesophageal junction. We aim to compare perioperative and quality of life outcomes of patients with reflux who underwent ARMS to a comparable group who underwent laparoscopic Nissen fundoplication (NF). A retrospective review of a prospectively maintained quality database was performed. All patients who underwent ARMS (n = 33) were matched with patients who underwent NF (n = 67). Clinical and quality of life (QOL) outcomes were collected preoperatively and up to two years postoperatively, measured by the Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL), and Dysphagia Score. Outcomes were compared using the Wilcoxon rank-sum and Fisher's exact test. While 10 patients (30.3%) who underwent ARMS required additional laparoscopic anti-reflux operations, the ARMS group had shorter OR time (p<0.001), less estimated blood loss (p<0.001), shorter hospital stay (p<0.001), less pain at discharge (p = 0.007), earlier narcotic discontinuation (p<0.001), and earlier return to activities of daily living (p<0.001) compared to the NF group. There was no difference in 30-day complication rates, emergency room visits, or readmission rates between the groups. There was no difference between ARMS and NF groups in terms of GERD-HRQL, RSI, or Dysphagia scores at 3 weeks, 6 months, 1 year, or 2 years postoperatively. However, the ARMS group reported less symptoms of gas and bloating postoperatively at all time points (all p<0.05). Both groups reported increased dysphagia at 3 weeks postoperatively (p<0.01) but this did not persist at 6 months, 1 year, or 2 years. While ARMS had better perioperative outcomes compared to NF, reflux quality of life outcomes were comparable. ARMS can be an effective endoscopic intervention for GERD when performed on appropriately selected patients without limiting future laparoscopic anti-reflux interventions.


Differential rates of relapse in subgroups of male and female smokers.
Subjects for this study were 265 participants of stop-smoking clinics (mean age = 42.6 years; average number of cigarettes smoked daily = 26.0) who were examined before and immediately after cessation and then followed for 1 year. The objective of this study was to identify subgroups of smokers with different rates of relapse using tree-structured survival analysis, a multivariate approach to classification. Five distinct subgroups that differed with respect to the rate of relapse were identified: (I) subjects (n = 15) with very low precessation cotinine levels (< or = 129 ng/ml), who had an exceptionally low rate of relapse (mean abstinence time = 270 days); (II) women 32 years old and younger (n = 24), who had a very high rate of relapse (mean abstinence time = 30.5 days); (III) women over 32 years old (n = 121), with the next highest rate of relapse (mean abstinence time = 98.9 days); (IV) men 36 years old and younger (n = 31), who had a mean abstinence time of 196.7 days; and (V) men over 36 years old (n = 74), who abstained an average of 130.2 days before relapsing. Relapse curves for all groups (except III vs V) differed significantly from each other, p < 0.05. Results indicate that this approach can identify interactions among individual differences that are variably associated with relapse rates. Identification of relapse subgroups may have important implications for both theories and treatment of smoking relapse.


Organ-specific chemotactic factors present in lung extracellular matrix.
The preferential colonization of a distant organ by a circulating tumor cell (organ specific metastasis) may be regulated by chemotactic factors present within the extracellular matrix of the host organ. Organ-specific extracellular matrix was prepared from murine kidney and lung by high salt extraction and DNAase/RNAase digestion. A soluble protein fraction (S2) from each of the matricies was obtained by 4 M guanidine extraction and was tested for organ-specific chemotactic activity in a modified Boyden chamber. The lung colonizing B16-F10 and B16-BL6 tumor cell lines demonstrated organ-specific motility only toward the lung extract. The low metastasizing B16 parental line and liver colonizing B16-L4b line showed no preference for either lung or kidney. The lung activity resolves into five fractions by gel filtration chromatography, with the highest activity eluting at Mr approximately 71,000. Chemotactic factors present in lung extracellular matrix may regulate the preferential colonization of an organ by stimulating the migration of tumor cells in a specific manner. These factors may be released during the degradation of the extracellular matrix.


XlnR-independent signaling pathway regulates both cellulase and xylanase genes in response to cellobiose in Aspergillus aculeatus.
The expression levels of the cellulase and xylanase genes between the host strain and an xlnR disruptant were compared by quantitative RT-PCR (qPCR) to identify the genes controlled by XlnR-independent signaling pathway. The cellulose induction of the FI-carboxymethyl cellulase (cmc1) and FIb-xylanase (xynIb) genes was controlled by XlnR; in contrast, the cellulose induction of the FIII-avicelase (cbhI), FII-carboxymethyl cellulase (cmc2), and FIa-xylanase (xynIa) genes was controlled by an XlnR-independent signaling pathway. To gain deeper insight into the XlnR-independent signaling pathway, the expression profile of cbhI was analyzed as a representative target gene. Cellobiose together with 1-deoxynojirimycin (DNJ), a glucosidase inhibitor, induced cbhI the most efficiently among disaccharides composed of β-glucosidic bonds. Furthermore, cellobiose with DNJ induced the transcription of cmc2 and xynIa, whereas cmc1 and xynIb were not induced. GUS reporter fusion analyses of truncated and mutated cbhI promoters revealed that three regions were necessary for effective cellulose-induced transcription, all of which contained the conserved sequence 5'-CCGN(2)CCN(7)G(C/A)-3' within the CeRE, which has been identified as the upstream activating element essential for expression of eglA in A. nidulans (Endo et al. 2008). The data therefore delineate a pathway in which A. aculeatus perceives the presence of cellobiose, thereby activating a signaling pathway that drives cellulase and hemicellulase gene expression under the control of the XlnR-independent regulation through CeRE.


New insights in mucopolysaccharidosis type VI: neurological perspective.
Mucopolysaccharidosis type VI is a rare autosomal recessive storage disorder, caused by deficiency of arylsulfatase B. Data on neurological involvement in mucopolysaccharidosis type VI patients under enzyme-replacement therapy are limited. This study explores the neurological and magnetic resonance imaging findings in a sample of mucopolysaccharidosis type VI patients receiving enzyme-replacement therapy. We performed a cross-sectional study including six patients with biochemical confirmation of mucopolysaccharidosis type VI and at least 105 consecutive weeks (two years) receiving intravenous enzyme-replacement therapy. The protocol included a comprehensive clinical examination, brain and spinal cord magnetic resonance imaging for all subjects. Overall, cognition was spared, while we found presence of hearing impairment, increasing in deep tendon reflexes and deep sensation reduction in three patients. In addition to the classical abnormalities related to other types of mucopolysaccharidosis, imaging studies demonstrated morphological changes in anatomy of middle cranial fossa and sella shape. Even in asymptomatic or mild compromised patients, spinal cord compression was found. In four patients we noticed atlantoaxial joint subluxation and three had cervical spinal stenosis. Degenerative processes involving vertebral column, including discal protrusion and axis abnormalities, were present in all patients. Neuroaxis involvement was a universal finding and neurological examination might not predict the severity of the disease in course. Image studies should not be performed according exclusively clinical parameters for these patients, once we have demonstrated that neurological involvement may be silent in these patients.


Ginsenoside Rg₃ regulates GABAA receptor channel activity: involvement of interaction with the γ₂ subunit.
Ginseng exhibits beneficial effects on GABAA receptor-related anxiety and sleep disorders. However, little is known regarding the cellular and molecular bases of the ginseng action on GABAA receptor. The present study was performed to elucidate the molecular mechanism of the ginseng effect on GABAA receptor. The effect of ginsenoside Rg₃ (Rg₃), one of the active ingredients of ginseng, on γ-aminobutyric acid (GABA)A receptor channel activity was examined in Xenopus oocytes using two-electrode voltage-clamp technique. Rg₃ itself evoked an inward current in Xenopus oocytes expressing GABAA receptor subunits (α₁β₁γ₂) and the Rg₃ itself-elicited inward current was only selective to γ₂ subunit expression ratio, since Rg₃ alone had no effects in oocytes expressing other subunits such as γ₁, γ₃, δ, or ε. Co-treatment of Rg₃ with GABA enhanced GABA receptor (α₁β₁γ₂)-mediated inward currents (IGABA) but Rg₃-mediated IGABA enhancement was independent on γ₂. Rg₃ itself-elicited inward current was blocked by GABAA receptor antagonist. The present results indicate that Rg₃-induced GABAA receptor activation via the γ₂ subunit and IGABA enhancement by Rg₃ might be one of the molecular bases of ginseng effects on GABAA receptor.


Survey of fatal anaphylactic reactions to imported fire ant stings. Report of the Fire Ant Subcommittee of the American Academy of Allergy and Immunology.
A physician questionnaire survey was conducted by the Fire Ant Subcommittee of the American Academy of Allergy and Immunology to document deaths caused by imported fire ant stings. From the 29,300 physicians surveyed, reports of 83 fatal and two near-fatal fire ant-sting reactions were received. Most anaphylactic deaths were reported from Florida (22) and Texas (19). After excluding duplicate reports, four confirmed deaths were documented in Alabama, 10 in Florida, two in Georgia, two in Louisiana, and 14 in Texas.


[Relationship between the local invasion and the lymph node metastasis of the supraglottic carcinoma].
To explore the histopathology characteristics of supraglottic carcinoma with cervical lymph node metastasis. Sixty-six specimens from patients with supraglottic laryngeal carcinoma were imbedded in collodion, made whole-organ serial section for HE staining, and observed under light microscope. The rate of supraglottic carcinoma with lymph node metastasis invasion to pre-epiglottic space, supraglottic space and infraparaglottic space was 100.0% (18/18), 83.3% (15/18) and 44.4% (8/18) respectively, all of which were higher than that of supraglottic carcinoma with no lymph node metastasis (P < 0.05). The rate of supraglottic carcinoma with lymph node metastasis invasion to the whole pre-epiglottic space was 55.5% (10/18), and it was 29.1% (14/48) in supraglottic carcinoma without lymph node metastasis; there were significant differences between them (P < 0.05). The width and height of supraglottic carcinoma with lymph node metastasis invasion to supraglottic space was (7.4 +/- 5.2)mm, (11.6 +/- 7.6) mm, respectively. The width and height of the supraglottic carcinoma invasion to infraparaglottic space was (2.9 +/- 3.8) mm, (2.2 +/- 3.7) mm, respectively. Both of them were larger than that in supraglottic carcinoma with no lymph node metastasis (P < 0.05). For the supraglottic carcinoma with lymph node metastasis, the rate of the vocal cord fixation was 44.4% (8/18), which was significantly higher than that of supraglottic carcinoma without lymph node metastasis (P < 0.05). The supraglottic carcinoma with lymph node metastasis has special local invasion ability, and its important characteristics is the invasion to pre-epiglottic space and paraglottic space.


Monoflanged Custom-Made Acetabular Components Promote Biomechanical Restoration of Severe Acetabular Bone Defects by Metallic Defect Reconstruction.
Custom-made acetabular components (CMAC) are one established method to address severe acetabular bone defects. Monoflanged CMAC may represent an advantageous alternative to establish triflanged CMAC as they promote better primary stability through metallic defect reconstruction and thus anatomic restoration of the center of rotation (COR). Fifty-eight consecutive (21 triflanged and 37 monoflanged) CMAC were evaluated for overall survival, reasons for revision, radiological restoration of COR, and clinical outcome parameters. There were no significant differences between both design types regarding overall survival, revision rates, Harris Hip Score, or visual analog scale (pain) score at latest follow-up (mean, 56.3 ± 28.7 months). Triflanged CMAC showed a significant lateralization (P ≤ .001) and cranialization (P = .003) of the COR compared to the contralateral side. Monoflanged CMAC restored the anatomic COR. Reasons for revision surgery and explantation were periprosthetic joint infection (n = 12) and aseptic loosening (n = 2) without significant differences between both groups. Monoflanged CMAC demonstrate similar clinical outcome parameters and survival rates as triflanged CMAC but superior biomechanical features and represent therefore a solid alternative treatment option and implant design.


Practical models for light distribution in laser-irradiated tissue.
The distribution of light in laser-irradiated biological medium is computed using four different procedures. Values computed with Beer's law of attenuation, Kubelka-Munk theory, the diffusion approximation, and a seven-flux model are compared. The proper conditions for using each model are discussed.


Placental blood flow and pregnancy outcomes in women with abnormal placental localization and absence of placental "migration".
We investigated the arcuate artery blood flow in the region of the abnormally localized placenta in women who had undergone insertion of an obstetric pessary and were receiving micronized progesterone. The study included 120 pregnant women with high perinatal risks and abnormal placental localization. The patients were randomized to receive the Arabin's pessary and vaginal micronized progesterone (Group A, n = 60) or vaginal micronized progesterone only (Group B, n = 60). Randomization was carried based on the order of hospital admission: odd patient numbers were allocated to Group A and even numbers to Group B. Patients underwent a series of ultrasound scans to evaluate the placental migration and presence of abnormal placental attachment. Depending on the results of the scan, study participants were divided into the following groups: (1) patients without placental migration: A1 (n = 23) and B1 (n = 42); and (2) patients with placental migration: A2 (n = 37) and B2 (n = 18). Women in subgroups A1 and B1 were further divided into the subgroups based on the presence of abnormal placental attachment: A1x (n = 5) and B1x (n = 12) with abnormal placental attachment; and A1O (n = 18) and B1O (n = 30) without the abnormal placental attachment. In patients with abnormal placental attachment, the resistance of blood flow in the arcuate arteries was significantly higher than in those with normal placental attachment. A significant increase in the blood flow resistance occurred between 24 and 28 weeks of gestation. The combined use of the obstetric pessary and vaginal micronized progesterone in women with abnormal placental localization helped maintain the resistivity index at low levels and reduce the rate of abnormal placental attachment by 1.3-fold (OR 0.694 (95% CI: 0.21-2.29)).


Phase stabilization and optical response in the ultraviolet range, due to terbium concentration in hafnium oxide nanoparticles.
This work reports the influence of terbium trivalent ions on growing kinetics and the phase in hafnium oxide nanoparticles, as well as response to radiation in the range from 256 to 286. The nanoparticles were obtained by the hydrothermal route maintaining the temperature constant and varying the reaction time and the terbium concentration. The results show a gradual change in the phase with the concentration of terbium trivalent ions, going from the monoclinic phase, present at low concentrations, to the tetragonal phase, which appears from dopant concentrations greater than 5% at., increasing in amount with concentration of dopant. These phases appear as two perfectly defined morphologies. Furthermore, there is a significant change in radiative lifetimes when the tetragonal phase appears.


Immunosurgery.
After being leaders in the field of transplantation, plastic surgeons became inactive in this field. Interest is reviving with the advent of the new immunosuppressant drug cyclosporine, as well as new knowledge of the immune mechanism. New generations of immunosuppressive drugs may allow allografting in patients with massive burns, limb transplants, and possibly even allografts of facial structures.


On the Catalytic Activity of Pt Supported by Graphyne in the Oxidation of Ethanol.
The adsorption of Pt clusters on β- and γ-graphyne (β-GY, γ-GY), graphdiyne (GDY), and graphene (GP) was extensively investigated with density functional theory. Ethanol adsorption and its partial oxidation on the Pt supported by the GY and GP were then explored to address the influence of the supporting materials on the activity of Pt nanoclusters to ethanol oxidation. Among the examined adsorption sites such as the hollow, Csp-Csp, and Csp-Csp2 bonds, the hollow site consisting of multiple triple bonds is the most attractive one to adsorb Pt and Pt4 regardless of β-GY, γ-GY, and GDY. The binding of Pt4 to the GDY is slightly stronger than those of β-GY and γ-GY (binding energy: -3.64, -3.73, and -4.08eV). It is remarkable that the adsorption of Pt4 on GY is 2-3 times stronger than that on GP (-3.6-4.1 vs -1.3 eV), showing that the GY and GDY are better substracts than the GP for the stability of Pt clusters. Furthermore, the potential energy profiles for the oxidation of ethanol show that in spite of the higher energy barrier for the adsorbed ethanol on Pt4 supported by γ-GY than by GP (1.54 vs 1.19eV), the dehydrogenation product and of ethanol on Pt-graphyne is much stabler than that on Pt-graphene, suggesting that graphyne is thermodynamically more favorable than graphene as a subtract for the Pt catalyst.


An estimate of the monthly cost of two major mental disorders in an Indian metropolis.
THE COMPONENTS OF HIGH COST OF TREATING A CHRONIC PSYCHIATRIC ILLNESS ARE: long-term continuous treatment consisting of consultation and medication costs, traveling to the treatment centre and taking time off from work for both patient and caregiver. Apart from direct treatment costs, expenditure of time in care-giving results in indirect costs. All these costs are borne by families as the sufferer may be unable to work. To estimate the cost of treatment of chronically ill patients at home, in terms of the above parameters. The sample consisted of 117 subjects of either sex in the age range of 18 to 60 years, ill for at least one year, diagnosed as schizophrenia (n=95) or bipolar disorder (n=22, a comparison group) who agreed to participate in the study along with at least one caregiver. The tools used were the Diagnostic Interview of Genetic Studies and Economic Burden Questionnaire administered to both the subject and the caregiver. The costs of treatment were found to be high but with wide variations in the range. Costs for bipolar disorder were somewhat higher than those for schizophrenia at least for the period of study. Demographic differences between subjects and caregivers were present.


Impact of polystyrene nanoplastics (PSNPs) on seed germination and seedling growth of wheat (Triticum aestivum L.).
Microplastics and nanoplastics are emerging pollutants of global concern. However, the understanding of their ecological effects on terrestrial plants is still limited. We conducted the systematic research to reveal the impact of polystyrene nanoplastics (PSNPs) (0.01-10 mg/L) on seed germination and seedling growth of wheat (Triticum aestivum L.). The results showed that PSNPs had no discernible effect on seed germination rate whereas significantly (p < 0.01) increased root elongation by 88.6 %-122.6 % when compared with the control. Similarly, remarkable increases in carbon, nitrogen contents, and plant biomass were also observed after exposure to PSNPs. Moreover, PSNPs could reduce the shoot to root biomass ratio (S:R ratio) of wheat seedlings. Furthermore, the imagings of a 3D laser confocal scanning microscopy (LCSM) and scanning electron microscopy (SEM) indicated that PSNPs were taken up and subsequently down-top transported to shoot. The absorption and accumulation of four micronutrients (Fe, Mn, Cu and Zn) in wheat were generally reduced in varying degrees. Notably, metabolomics analysis revealed that all PSNPs treatments altered the leaf metabolic profiles mainly by regulating energy metabolisms and amino acid metabolisms. These findings are expected to provide new insights into the effects of PSNPs on crop plants.


PIWI-interacting RNA-23210 protects against acetaminophen-induced liver injury by targeting HNF1A and HNF4A.
Acetaminophen (APAP) overdose is one of the leading causes of acute liver failure in the US and other developed countries, the molecular mechanisms of APAP-induced hepatotoxicity remain speculative. PIWI-interacting RNAs (piRNAs), a novel class of small non-coding RNAs, have been identified as epigenetic regulators of transposon silencing, mRNA deadenylation, and elimination. However, the functional role of piRNAs in APAP-induced liver injury remains unclear. In the current study, the piRNA profiles were constructed in HepaRG cells after APAP exposure, and the roles of piR-23210 in regulating nuclear receptors (NRs) expression, metabolizing enzymes expression, and consequently APAP-induced liver injury were systematically investigated. As a result, 57 upregulated piRNAs were identified after APAP exposure, indicating the stress-response characteristic of piRNA molecules. Subsequent in vitro and in vivo experiments proved that piR-23210 is a novel self-protective molecule that targets HNF1A and HNF4A transcripts by interacting with RNA binding protein Nucleolin (NCL), suppresses downstream CYPs (CYP2E1, CYP3A4, and CYP1A2) expression, and protects against APAP-induced liver injury. In conclusion, our findings provided new mechanistic clues revealing potential protective role of a piRNA against the hepatoxicity of APAP.


Focal Adhesion Isolation Assay Using ECM-Coated Magnetic Beads.
Focal adhesions are force sensitive structures that dynamically alter their composition, protein-protein interactions, and signaling in response to external mechanical stimuli. These dynamic changes are critical for focal adhesion function and are required for cellular mechanosensing. Here, we describe a simple protocol that allows for isolation of the focal adhesion complex from adherent cells in culture in response to different mechanical stimuli applied at adhesion sites. By combining this assay with approaches such as proteomics or western blot analysis, one can study the force-dependent changes in focal adhesion composition, protein-protein interactions and signaling.


Kinetics of the West Nile virus induced transcripts of selected cytokines and Toll-like receptors in equine peripheral blood mononuclear cells.
West Nile virus (WNV) is one of the most common causes of epidemic viral encephalitis in horses worldwide. Peripheral blood mononuclear cells (PBMCs) are amongst the first to encounter the virus following a mosquito bite. This study aimed to elucidate the transcription kinetics of cytokine, Toll-like receptor (TLRs) and TLRs-associated genes following WNV challenge of equine PBMCs. PBMCs were challenged with an Australian strain of WNV (WNVNSW2011) and transcriptomes were quantified at 2, 6, 12 and 24 h post-infection (pi) using qRT-PCR. Type I and II interferons (IFNα, β and γ) mRNA transcription increased following WNV exposure, as did the transcripts for IL1α, IL1β, IL6, IL8, and IL22, but with slightly varying kinetics. TLR1, 3, 5, 7-9 transcripts were also upregulated in equine PBMCsin response to WNV challenge, as were those for MyD88, NF-κB, TRAF3, STAT1 and 2, IRF3 and 7, ISG15, as well as SOCS1 and 3 compared to the control cells. Expression of selected genes in the draining lymph node, spleen and brain (medulla oblongata) of experimentally infected horses was also assessed and transcription of most of these genes was also upregulated here. Although qRT-PCR detected higher viral RNA at 24 h pi compared to 6 h pi, the virus did not replicate productively in equine PBMCs. The up-regulation of gene-transcription for selected cytokines, IFNs, TLRs and TLRs-associated molecules suggests their involvement in virus recognition and control of WNV infection in the horse.


Factors influencing social distancing to prevent the community spread of COVID-19 among Chinese adults.
The global outbreak of the coronavirus disease 2019 (COVID-19) in 2020 has been an international public health threat. Early strong social distancing efforts is needed to stop transmission of the virus. The purpose of the present study is to identify individual and environmental factors related to individuals' compliance with the recommended social distancing, as well as the moderating role of social media in influencing individuals' implementation of social distancing. A total of 2130 Chinese adults were surveyed in March 2020 during the COVID-19 pandemic. Logistic regression analyses were performed to ascertain the predictors of social distancing. Overall, the majority of respondents (95.6%) reported compliance with social distancing. Women were more likely to practice social distancing compared to men (odds ratio [OR] = 3.12, 95% confidence interval [CI] = 1.93-5.02). Psychological distress, depressive symptoms, and social media were significant predictors of social distancing after controlling for other individual and environmental factors. Social media moderated the effects of psychological distress on social distancing (OR = 0.96, 95% CI = 0.94-0.99). Findings from the study indicates that mental health status and social media are influential factors of social distancing, which have significant implications in enhancing the effectiveness of prevention strategies to contain the spread of COVID-19.


Anxiolytic- and antidepressant-like effects of the methadone metabolite 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP).
The enhancement of GABAergic and monoaminergic neurotransmission has been the mainstay of pharmacotherapy and the focus of drug-discovery for anxiety and depressive disorders for several decades. However, the significant limitations of drugs used for these disorders underscores the need for novel therapeutic targets. Neuronal nicotinic acetylcholine receptors (nAChRs) may represent one such target. For example, mecamylamine, a non-competitive antagonist of nAChRs, displays positive effects in preclinical tests for anxiolytic and antidepressant activity in rodents. In addition, nicotine elicits similar effects in rodent models, possibly by receptor desensitization. Previous studies (Xiao et al., 2001) have identified two metabolites of methadone, EMDP (2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline) and EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine), which are considered to be inactive at opiate receptors, as relatively potent noncompetitive channel blockers of rat α3β4 nAChRs. Here, we show that these compounds are likewise highly effective blockers of human α3β4 and α4β2 nAChRs. Moreover, we show that they display relatively low affinity for opiate binding sites labeled by [(3)H]-naloxone. We then evaluated these compounds in rats and mice in preclinical behavioral models predictive of potential anxiolytic and antidepressant efficacy. We found that EMDP, but not EDDP, displayed robust effects predictive of anxiolytic and antidepressant efficacy without significant effects on locomotor activity. Moreover, EMDP at behaviorally active doses, unlike mecamylamine, did not produce eyelid ptosis, suggesting it may produce fewer autonomic side effects than mecamylamine. Thus, the methadone metabolite EMDP may represent a novel therapeutic avenue for the treatment of some affective disorders.


Isolated axial volvulus of a Meckel's diverticulum.
A 3.5-year-old boy presented twice within 36 hours to an emergency department with worsening abdominal distress. At surgery, an isolated axial volvulus of a Meckel's diverticulum was found. This finding has been reported three times in the last 20 years and has involved only adult patients. Meckel's diverticulum, although uncommon, can be extremely serious. Its presentation and pathophysiology are reviewed.


Is there a Link between Non Melanoma Skin Cancer and Hydrochlorothiazide?
Here in we evaluated the association between the use of Hydrochlorothiazide (HCTZ) and the risk of NMSC both, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Even though the use of HCTZ is not linked with the development of serious adverse drug reactions, non-melanoma skin cancer (NMSC) has been reported in patients treated with the drug in recent years, most likely due to its photosensitizing ability. To evaluate the statistically significant difference (P<0.05) in the development of NMSC between HCTZ users and non-users and the correlation (P<0.05) between HCTZ use and NMSC. We performed a retrospective study on patients referred to general practitioners who developed skin cancer or NMSC whether or not they were treated with antihypertensive drugs. Controls were matched with the test by age and sex. We calculated odds ratios (ORs) for skin cancer and NMSC associated with hydrochlorothiazide using conditional logistic regression. We enrolled 19,320 patients in the present study, out of a total of 10,110 (52.3%) who were treated with antihypertensive drugs. Of 10,110 patients, 3,870 were treated with HCTZ (38.3%). During the study, we failed to report an increased risk of NMSC in HCTZ-treated vs. untreated patients. Gender stratification revealed an OR for NMSC of 1.36 for men and 0.56 for women. We did not find a dose-response relationship between HCTZ use and NMSC. In the present study, we failed to report an association between the use of HCTZ and the development of NMSC.


Physiological evidence for central modulation of voice tremor.
The present report presents an attempt to define the physiological parameter used to describe "voice tremor" in psychological stress evaluating machines, and to find its sources. This parameter was found to be a low frequency (5-20 Hz) random process which frequency modulates the vocal cord waveform and (independently) affects the frequency range of the third speech formant. The frequency variations in unstressed speakers were found to be the result of forced muscular undulations driven by central nervous signals and not of a passive resonant phenomenon. In this paper various physiological and clinical experiments which lead to the above conclusions are discussed. a) It is shown that induced muscular activity in the vocal tract and vocal cord regions can generate tremor in the voice. b) It is shown that relaxed subjects exhibit significant tremor correlation between spontaneously generated speech and EMG, with the EMG leading the speech tremor. c) Tremor in the electrical activity recorded from muscles overlapping vocal tract area was correlated with third formant demodulated signal and vocal cord demodulated pitch tremor was correlated with first formant demodulated tremor. d) Enhanced tremor was found in Parkinson patients and diminished tremor in patients with some traumatic brain injuries.


Cognitive content in bulimic disorders: core beliefs and eating attitudes.
Recent clinical and research reports have demonstrated that cognitive work with bulimia nervosa might benefit from addressing core beliefs (unconditional negative representations of the self), rather than simply focusing on the impact of beliefs and assumptions regarding food, shape, and weight. However, while links have been established between core beliefs and bulimic psychopathology, it remains to be established how these beliefs have their specific impact on different aspects of eating disturbance. This study investigates the links between core beliefs and "ego-dysfunction" characteristics (e.g., perfectionism, self-esteem), since those characteristics are potential mediators of that link. In a group of 75 bulimics, core beliefs were related to both eating psychopathology and ego-dysfunction characteristics. It is proposed that many of the ego-dysfunction characteristics might serve as mediators of the already-established link between core beliefs and eating pathology, although testing this model fully would require larger-scale prospective research. Clinical work with bulimics is likely to be more effective if it addresses a range of cognitive structures, as well as behaviours.


Growth following single fraction and fractionated total body irradiation for bone marrow transplantation.
Total body irradiation (TBI) is used as preparative regimen prior to bone marrow transplantation (BMT). Since there are more long-term survivors, follow up studies are important. We have performed a retrospective analysis of growth for 49 children, who had undergone treatment with cyclophosphamide and TBI before BMT. Of these patients 26 received single fraction (SF) TBI as a dose of 900-1000 cGy, whereas 23 received fractionated (FF) TBI as a total dose of either 1200 cGy divided in six fractions or 1440 cGy divided in eight fractions over 3 days. Half of the patients in the SF-TBI group, and 9 in the FF-TBI group had received low-dose cranial irradiation prior to TBI. In all groups a decrease in height SDS was observed. By evaluating the major factors leading to growth impairment the influence of cranial irradiation, which was demonstrable in the 1st year after TBI, could not be shown after 3 years. At this time growth was significantly more impaired in the SF group with a mean height SDS of -0.9 (+/- SD 0.9) compared to a mean height SDS -0.22 (1.02) in the FF group (P < 0.05). Measurement of segmental proportions showed a significant difference in SDS for sitting height in comparison to SDS for subischial leg length, irrespective of the TBI regimen. This was already evident 1 year after TBI and decreased during the following years. Twenty four of the patients (17 in the single fraction and 7 in the fractionated TBI group) were treated with growth hormone, but demonstrated an inappropriate response with absent catch-up growth in their legs.(ABSTRACT TRUNCATED AT 250 WORDS)


The spectrum of closed-head injuries in facial trauma victims: incidence and impact.
Little is known of the incidence of closed-head injury (CHI) associated with facial trauma. To study this problem, we conducted a retrospective review of 200 consecutive admissions to the University of Michigan Medical Center Emergency Department from 1980 to 1985 for treatment of acute facial fractures. All patients were admitted within 48 hours of injury (93% within 24 hours). Medical records were reviewed for age, sex, description, and circumstances of facial injury; assessment of loss of consciousness and anterograde amnesia; and associated intracranial or extracranial injuries. Seventy-three percent of the patients were men (mean age, 27.8 years). Etiologies, in descending order, were road traffic accidents (52%), assaults (22%), sports (14%), falls (7%), other injuries (3%), and gunshot wounds (2%). The incidence rate of CHI in our study was 55%. More than 90% of the head injuries were associated with the loss of consciousness of less than one hour. Risk factor analysis failed to demonstrate that an increased risk of CHI is associated with age, sex, or number of facial fractures. However, there was a one and one-halffold increased risk associated with patients involved in automobile accidents.


Traumatic Brain Injury-Mediated Neuroinflammation and Neurological Deficits are Improved by 8-Methoxypsoralen Through Modulating PPARγ/NF-κB Pathway.
8-Methoxypsoralen (8-MOP) has anti-inflammatory, antioxidant and tissue-repairing abilities. Here, we probed the function and mechanism of 8-MOP in traumatic brain injury (TBI). The in-vivo TBI model was constructed in Sprague-Dawley (SD) rats using controlled cortical impact (CCI) surgery. In parallel, BV2 microglia and HT22 neurons were activated by lipopolysaccharide (LPS) to establish an in-vitro model. The modified neurological score (mNSS) and the Morris water maze experiment were employed to evaluate the rats' neurological functions. The rats' brain edema was assessed by the dry and wet method, and neuronal apoptosis in damaged brain tissues was monitored by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Nissl's staining. Immunohistochemistry (IHC) was applied to verify Iba1-microglial activation in brain lesions of rats. The expression of inflammatory cytokines in BV2 microglia and HT22 neurons in the injured lesion of TBI rats was examined by the enzyme-linked immunosorbent assay (ELISA). The levels of iNOS, COX2, TLR4, PPARγ, STAT3, and NF-κB in brain lesions, BV2 microglia and HT22 neurons were compared by Western blot. As a result, 8-MOP administration reduced inflammation and LPS-induced neuronal damage in BV2 microglia. In vivo, 8-MOP treatment relieved neurological deficits in TBI rats, improved cognitive, learning and motor functions and mitigated brain edema and neuroinflammation induced by TBI. Furthermore, LPS or TBI activated the NF-κB and STAT3 pathways and repressed the PPARγ expression. However, 8-MOP treatment attenuated NF-κB and STAT3 phosphorylation and elevated PPARγ levels. Hence, 8-MOP exerts neuroprotective and anti-inflammatory effects in TBI rats by modulating the PPARγ/NF-κB pathway.


Stepwise Differentiation of Mesenchymal Stem Cells Augments Tendon-Like Tissue Formation and Defect Repair In Vivo.
: Tendon injuries are common and present a clinical challenge, as they often respond poorly to treatment and result in long-term functional impairment. Inferior tendon healing responses are mainly attributed to insufficient or failed tenogenesis. The main objective of this study was to establish an efficient approach to induce tenogenesis of bone marrow-derived mesenchymal stem cells (BMSCs), which are the most common seed cells in tendon tissue engineering. First, representative reported tenogenic growth factors were used as media supplementation to induce BMSC differentiation, and the expression of teno-lineage transcription factors and matrix proteins was compared. We found that transforming growth factor (TGF)-β1 significantly induced teno-lineage-specific gene scleraxis expression and collagen production. TGF-β1 combined with connective tissue growth factor (CTGF) elevated tenomodulin and Egr1 expression at day 7. Hence, a stepwise tenogenic differentiation approach was established by first using TGF-β1 stimulation, followed by combination with CTGF for another 7 days. Gene expression analysis showed that this stepwise protocol initiated and maintained highly efficient tenogenesis of BMSCs. Finally, regarding in situ rat patellar tendon repair, tendons treated with induced tenogenic BMSCs had better structural and mechanical properties than those of the control group, as evidenced by histological scoring, collagen I and tenomodulin immunohistochemical staining, and tendon mechanical testing. Collectively, these findings demonstrate a reliable and practical strategy of inducing tenogenesis of BMSCs for tendon regeneration and may enhance the effectiveness of cell therapy in treating tendon disorders. The present study investigated the efficiency of representative tenogenic factors on mesenchymal stem cells' tenogenic differentiation and established an optimized stepwise tenogenic differentiation approach to commit tendon lineage differentiation for functional tissue regeneration. The reliable tenogenic differentiation approach for stem cells not only serves as a platform for further studies of underlying molecular mechanisms but also can be used to enhance cell therapy outcome in treating tendon disorders and develop novel therapeutics for tendon injury.


Species restriction of Herpesvirus saimiri and Herpesvirus ateles: human lymphocyte transformation correlates with distinct signaling properties of viral oncoproteins.
The potential of Herpesvirus saimiri (HVS) subgroups A, B and C and Herpesvirus ateles (HVA) to transform primary T cells to permanent growth in vitro is restricted by the primate host species and by viral variability represented by distinct viral oncoproteins. We now addressed the relation between the transforming potential of the different viruses and the signaling pathways activated by transiently expressed oncoproteins. Marmoset lymphocytes were transformed by all HVS subgroups as well as HVA, while transformation of human cells was restricted to HVS-C and, unexpectedly, HVA. NF-κB and Src-family kinase (SFK) activity was required for survival of all transformed lymphocytes. Accordingly, NF-κB was induced by oncoproteins of all viruses. In contrast, SFK-related signaling was detectable only for oncoproteins of HVS-C and HVA. Thus, the restricted transformation of human lymphocytes likely correlates with the specific SFK targeting by these oncoproteins. These results will enable further studies into novel SFK effector mechanisms relevant for T-cell proliferation.


Effects of bilateral T2-sympathectomy on static and dynamic heart rate responses to exercise in hyperhidrosis patients.
The static/dynamic changes of gas exchange, heart rate (HR) and blood pressure in terms of work rate (WR) and WR changes in ramp exercise were investigated by cardio-pulmonary exercise tests (CPETs) in hyperhidrosis patients before (W0), one week (W1) and four weeks (W4) after bilateral T2-sympathectomy. Accompanied by constant oxygen consumption and WR at peak exercise and similar oxygen debt in recovery, the HR significantly (p<0.05) decreased statically in all stages of CPET, but was not altered dynamically, i.e., similar slope but significantly diminished intercept in HR changes versus WR changes (70+/-6.0 vs. 82+/-19 beats/min, p<0.01), in W1 (n=11), compared to W0 (n=13). However, this surgical effect on static HR changes seemed to have disappeared in W4 (n=8), albeit at that time the static blood pressure decreased significantly during exercise. These findings suggest that bilateral T2-sympathectomy will reduce static HR without causing cardiovascular insufficiency in one week, and would then recover by one month in hyperhidrosis patients.


Impact of interventions to improve the quality of peer review of biomedical journals: a systematic review and meta-analysis.
The peer review process is a cornerstone of biomedical research. We aimed to evaluate the impact of interventions to improve the quality of peer review for biomedical publications. We performed a systematic review and meta-analysis. We searched CENTRAL, MEDLINE (PubMed), Embase, Cochrane Database of Systematic Reviews, and WHO ICTRP databases, for all randomized controlled trials (RCTs) evaluating the impact of interventions to improve the quality of peer review for biomedical publications. We selected 22 reports of randomized controlled trials, for 25 comparisons evaluating training interventions (n = 5), the addition of a statistical peer reviewer (n = 2), use of a checklist (n = 2), open peer review (i.e., peer reviewers informed that their identity would be revealed; n = 7), blinded peer review (i.e., peer reviewers blinded to author names and affiliation; n = 6) and other interventions to increase the speed of the peer review process (n = 3). Results from only seven RCTs were published since 2004. As compared with the standard peer review process, training did not improve the quality of the peer review report and use of a checklist did not improve the quality of the final manuscript. Adding a statistical peer review improved the quality of the final manuscript (standardized mean difference (SMD), 0.58; 95 % CI, 0.19 to 0.98). Open peer review improved the quality of the peer review report (SMD, 0.14; 95 % CI, 0.05 to 0.24), did not affect the time peer reviewers spent on the peer review (mean difference, 0.18; 95 % CI, -0.06 to 0.43), and decreased the rate of rejection (odds ratio, 0.56; 95 % CI, 0.33 to 0.94). Blinded peer review did not affect the quality of the peer review report or rejection rate. Interventions to increase the speed of the peer review process were too heterogeneous to allow for pooling the results. Despite the essential role of peer review, only a few interventions have been assessed in randomized controlled trials. Evidence-based peer review needs to be developed in biomedical journals.


Discovery of highly potent Src SH2 binders: structure-activity studies and X-ray structures.
Optimization of the hydrophobic moiety of caprolactam/thiazepinone based compounds led to the identification of potent Src SH2 binders in two different series incorporating a phosphotyrosine group (RU 81843) or a phosphobenzoic group (RU 79181). The X-ray co-structures with the Src SH2 domain revealed different binding modes for RU 81843 and RU 79181, and an excellent fit between RU81843 and the Src SH2 protein thus explaining its high potency (9 nM, 15-fold more potent than pYEEI reference peptide).


Endovascular repair of a ruptured abdominal aortic and iliac artery aneurysm with an acute iliocaval fistula secondary to lymphoma.
Abdominal aortic aneurysms (AAA) are common and generally asymptomatic unless rupture occurs. A 3 to 4-cm AAA has a 1-2% risk of rupture over 5 years. We present the case of an 85-year-old male with a history of chronic lymphocytic leukemia, a 3-cm infrarenal AAA, and a 2-cm right common iliac artery aneurysm whose AAA ruptured and who developed an acute iliac artery-to-vena cava fistula secondary to eroding adenopathy from an aggressive low-grade lymphoma. Initially, an open repair was attempted but access to the aorta was not possible because of complete encasement of the infrarenal and suprarenal aorta with tumor that was clinically invading the aortic wall. Secondary tumor invasion into the aorta is a rare complication. An endovascular repair was accomplished with successful exclusion of both the aneurysm and the iliocaval fistula. Endovascular repair provides a valuable alternative in the "hostile abdomen" when standard open repair may be hazardous or impossible.


Imaging intracranial haemangiopericytomas: study of seven cases.
Imaging features of intracranial haemangiopericytomas are similar to those of meningiomas. Preoperative identification of these tumours is important because of their aggressive nature, high rate of local recurrence and propensity for late metastasis. We reviewed the CT, MRI and angiographic findings in seven pathologically proved haemangiopericytomas, to determine if imaging characteristics might distinguish them from meningiomas. None showed hyperostosis or tumour calcification. All showed marked enhancement. Five had prominent internal signal voids, suggesting feeding arteries. On angiography, one had only pial-cortical supply but six also had meningeal supply; all showed a persistent stain. Only one had multiple "corkscrew" feeding vessels.


Palliative care in the ambulatory geriatric practice.
Geriatrics and palliative care often overlap. This article focuses on 2 areas where the disciplines may differ in their approach. The first is planning for extreme illness and death, with explicit acknowledgment that limiting therapy might be a good idea. This situation is likely to have a different impact in the course of a routine geriatrics visit than in a palliative care context. The second is pain management, especially chronic pain. In patients with sharply limited life expectancy, the risk/benefit equation tilts easily toward narcotic use. In frail elders working to remain independent, the calculus may be quite different.


Fatal cardiac tamponade in a patient with Kawasaki disease.
Kawasaki disease (KD) is usually a self-limiting condition, but cardiac complications are not uncommon and can lead to significant morbidity and mortality. This article describes the case of an 18-year-old man with rapidly progressive and ultimately fatal KD. Polyserositis syndrome and cardiac tamponade developed during a convalescent phase of the illness. Treatment with high-dose corticosteroid and intravenous immunoglobulin-G therapy was unsuccessful. The patient continued to deteriorate despite supportive care. Severe cardiac tamponade developed, and percutaneous pericardiocentesis was performed, but the patient died hours later. This is the second reported case of KD featuring a polyserositis syndrome and impending cardiac tamponade, and the first with fatal outcome.


Fiber optic CO2-laser induced emphysema of the supraglottis.
Subcutaneous emphysema is a rare but well-defined surgical complication. However, emphysema of the supraglottic mucosa has not been described in the literature. We present a case of a 2-year-old male who suffered supraglottic emphysema secondary to fiber optic CO2-laser use during laryngeal cleft repair. The patient required preemptive postoperative intubation; however, there were no long-lasting adverse effects at 6 and 12 weeks follow up. This report illustrates a rare CO2-laser complication and describes its sequela.


An enzyme-linked antiglobulin test for assessing anti-D immunoglobulin preparations.
Two enzyme-linked antiglobulin tests (ELAT) for assessing anti-D IgG preparations are described; one is performed in tubes and the other in microtitre plates. An anti-human IgG alkaline phosphatase conjugate and the substrate p-nitrophenyl phosphate are used. Both methods were sensitive and reproducible, with variations coefficients of 7.8 and 8.6% for enzyme immunoassay in tubes and microplates, respectively. The linear relationship between the amount of red cell-bound anti-D and the optical density shows that the method is suitable for quantitative studies. Results obtained by the two methods show a very good correlation (r = 0.99) in 12 of the 14 samples assayed, and both give good agreement with results obtained in automated haemagglutination. Since microtitre plate ELAT has numerous advantages over the tube method, it could provide an alternative method for assessing anti-D activity of specific IgG preparations in control laboratories.


Socio-economic factors affecting the distribution of marine litter: The Portuguese case study.
Marine litter is a growing global problem with serious environmental, economic, social, and health threats. Understanding the socio-economic factors that influence the types and amounts of litter is of utmost importance. In this study, an integrative analysis of the socio-economic factors that characterize the beach litter distribution in continental Portugal and the Azores archipelago was conducted via a cluster analysis, implementing a novel technique to support the difficult task of marine litter characterization. The results highlighted that the most abundant beach litter material is plastic (92.9 %), followed by paper (2.2 %), wood (1.5 %), and metal (1.3 %). The majority of the items could not be attributed to a specific source (46.5 %). The remaining were attributed to public litter (34.5 % of total aggregated items), fishing (9.8 %), sewage-related debris (6.4 %) and shipping (2.2 %). The top-three beach litter categories were small plastic pieces (0-2.5 cm, 43.5 %), cigarette butts (30.1 %), and medium plastic pieces (2.5-50 cm, 26.4 %). A positive relation between both municipality environment expenditures and population density and the quantity and typology of litter was found. Beach litter quantity and categories were also associated with specific economic sectors, as well as with geographical/hydrodynamic conditions, demonstrating the utility of the technique and its applicability to other regions.


Diagnosis of carcinoma of the colon by barium enema.
Double-contrast barium enemas can detect 96% of colonic carcinomas. This is similar to the detection rate for colonoscopy. Single-contrast enemas compare badly. Small sigmoid tumours are most likely to be missed. Inadequate bowel preparation, single-contrast examinations and observer error account for most barium enema failures.


"I bet they aren't that perfect in reality:" Appearance ideals viewed from the perspective of adolescents with a positive body image.
In this qualitative study, we examined the topic of appearance ideals from the perspective of 14-year-old adolescents (N=29) with a positive body image. A thematic analysis revealed that the adolescents with a positive body image were very critical against current ideals, describing them as unnatural and unrealistic, and criticizing media for only showing those consistent with the ideals and having underlying intentions with doing so. Instead, the adolescents defined beauty widely and flexibly, stressed the importance of looking like 'oneself', and conveyed the idea of personality as outplaying looks. The perception of beauty as subjective was also prominent. These results may be helpful when forming preventions targeting those at risk for developing negative body image, adding support for preventions based on media literacy and feminist theories. Additionally, we stress the significance of providing adolescents with alternative ways of thinking about ideals, beauty, and attractiveness.


Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 1: does the 'seatbelt sign' predict intra-abdominal injury after motor vehicle trauma in children?
A short cut review was carried out to establish whether the seat belt sign was a significant predictor of intra-abdominal injury in children involved in motor vehicle collisions. 51 papers were found using the reported searches, of which three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that seatbelt sign appears to be associated with an increased risk of intra-abdominal injuries, especially gastrointestinal and pancreatic injuries.


Pulmonary arteriovenous malformation treated by lobectomy.
Pulmonary arteriovenous malformation (PAVM) may occur primarily or in association with hereditary hemorrhagic telangiectasia. We present a case of PAVM in the central lower lobe of the left lung of a 75-year-old woman, which was successfully treated by lobectomy. Contrast echocardiography is an excellent tool for evaluation of this uncommon lesion. Advances in interventional radiology have led to the introduction of obliterative techniques for the treatment of PAVM. However, in the presence of a large solitary malformation centrally located, as in our case, and in high-risk patients, surgery is still a safe and effective first option.


Immunohistochemical localization of type V collagen in normal human skin.
Tissue distribution of type V collagen in normal human skin was studied using an indirect immunofluorescent technique to determine whether type V collagen is present in the interstitium or in the basement membrane. Type V collagen was isolated from the human placenta by pepsin digestion and was purified with fractioning salt precipitations. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that type V collagen contained alpha 1(V) and alpha 2(V) chains, but not the alpha 3(V) chain. Specificity of the rabbit antibodies to type V collagen was assessed using enzyme-linked immunosorbent assay (ELISA) and an immunoblotting method. Antibodies showed no cross-reactivity to other collagens, laminin, and fibronectin. With an indirect immunofluorescent technique, type V collagen was found to be widely distributed throughout the dermis. Intense fluorescent staining was noted in the papillary dermis and adnexal dermis surrounding hair follicles and eccrine glands. The basement membrane of the dermoepidermal junction, skin appendages, and capillaries was not stained. By indirect immunoperoxidase double staining, type V collagen was not found to be deposited on type IV collagen present in the basement membrane. Immunoelectron microscopic studies showed that type V collagen was not located in the basal lamina. These results suggest that type V collagen is distributed in the interstitium, but not in the basement membrane of normal human skin.


Mycobacterium abscessus and Mycobacterium massiliense exhibit distinct host and organ specificity: a cross-sectional study.
Precise subspeciation of Mycobacterium abscessus complex (MAB) is crucial for predicting antibiotic susceptibilities and patient outcomes. However, routine clinical microbiology laboratories have limited diagnostic tools for the differentiation of the subspecies. Thus, we investigated the predictors for MAB subspecies to actuate rapid differentiation and the optimal treatment plans. We retrospectively identified stored clinical isolates of MAB and reviewed patient medical records to compare clinical characteristics, sites of infection, and outcomes among patients infected with M. abscessus subsp. abscessus (M. abscessus) and M. abscessus subsp. massiliense (M. massiliense). MAB subspecies were characterised by multilocus sequence analysis with 3-locus sequence (hsp65, rpoB, and secA1) and pulsed-field gel electrophoresis. After outbreak and duplicated cases were excluded, 56 and 36 patients with infection caused by M. abscessus and M. massiliense, respectively, were included in the analysis. Patients with either cardiovascular disease or risk factors for cardiovascular disease (male gender and age ≥55 years) were 4.5 times more likely to harbour M. abscessus (P = 0.002), whereas M. massiliense was 4.8 times more frequently recovered from cutaneous and surgical wounds (P = 0.04). Distinct host and organ specificity were observed among patients infected with M. abscessus and those with M. massiliense. These differences may provide clinically significant clues to optimise treatment strategies.


Geometric properties of two-dimensional critical and tricritical Potts models.
We investigate geometric properties of the general q-state Potts model in two dimensions, and define geometric clusters as sets of lattice sites in the same Potts state, connected by nearest-neighbor bonds with variable probability p. We find that, besides the random-cluster fixed point, both the critical and the tricritical Potts models have another fixed point in the p direction. For the critical model, the random-cluster fixed point p(r) is unstable and the other point p(g) > or =p(r) is stable; while p(r) is stable and p(g) < or =p(r) is unstable at tricriticality. Moreover, we show that the fixed point p(g) of a critical and tricritical q-state Potts models can be regarded to correspond to p(r) of a tricritical and critical q'-state Potts models, respectively. In terms of the coupling constant of the Coulomb gas g, these two models are related as gg'=16. By means of Monte Carlo simulations, we obtain p(g)=0.6227(2) and 0.6395(2) for the tricritical Blume-Capel and the q=3 Potts model, respectively, and confirm the predicted values of the magnetic and bond-dilution exponents near p(g).


[Impact of the COVID-19 pandemic on patient-reported patient safety in Primary Care].
To evaluate the impact of the changes introduced in response to the pandemic on patient-reported patient safety in Primary Care. Prospective observational panel study (health center) based on two cross-sectional surveys. 29 Primary Health Care centers from three Spanish health regions (Mallorca, Catalunya Central and Camp de Tarragona). Random sample of patients visiting their centers before (n=2199 patients) and during the pandemic (n=1955 patients) MAIN MEASUREMENTS: We used the PREOS-PC questionnaire, a validated instrument which assesses patient-reported patient safety in Primary Care. We compared mean scores of the "experiences of errors" and "harm" scales in both periods, and built multilevel regression analyzes to study the variations in patient and center characteristics associated with worse levels of safety. A qualitative (content) analysis of patients' experiences during the pandemic was also performed. The "experiences of errors" and "harm" scales scores significantly worsened during the COVID-19 period (92.65 to 88.81 (Cohen's d=0.27); and 96.92 to 79.97 (d=0.70), respectively). Patient and center characteristics associated to worsened scores were: women, people with a lower educational level, worse health status, more years assigned to the center, and health region. During the pandemic, a perceptible worsening in patient safety perceived by patients treated in Primary Care has been observed, which has differentially affected patients according to their sociodemographic characteristics or health center profiles.


Determination of protein molecular weights in denaturing solvents using glyceryl-CPG.
Glyceryl-CPG is controlled-pore glass whose surface has been chemically modified to block its slight negative charge in aqueous solution. In contrast to normal controlled-pore glass, glyceryl-CPG can be used successfully for gel filtration of proteins in a variety of denaturing solvents, viz., 8 M urea, 6 M guanidine hydrochloride, and 0.1% sodium dodecyl sulphate. It has been found that glass with a mean pore diameter near 35 nm is suitable for the molecular weight range 17,000-100,000. Glyceryl-CPG with a smaller pore diameter is more satisfactory for molecular weights below 30,000. The stable pore size and bed dimensions of controlled-pore glass allows comparison of the conformation of a particular protein in different solvents to be made with the same column.


The behavior of PCDD/Fs, PCBs, chlorobenzenes and chlorophenols in wet scrubbing system of municipal solid waste incinerator.
Though some researchers have already reported polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) concentration in flue gas at inlet and outlet of wet scrubber (WS) in municipal solid waste incinerator (MSWI), there are few investigations about scrubbing water, suspended solid (SS) in scrubbing water and sludge. In order to understand the behavior of PCDD/Fs in WS and to make clear the effect of the residence time of scrubbing water in WS on the PCDD/Fs concentrations in scrubbing water and at the outlet gas of WS, PCDD/Fs, polychlorinated biphenyls (PCBs), chlorobenzenes (CBzs) and chlorophenols (CPs) concentrations in various media around WS were investigated at two MSWIs. PCDD/Fs concentration in flue gas at outlet of WS was higher than that at inlet of WS in both MSWIs. In WS A, it was observed that the homologue profiles changed considerably and the concentration of higher chlorinated compounds such as H7CDD/Fs and O8CDD/F increased remarkably at outlet gas of WS A. Only CPs were transferred from flue gas to scrubbing water in both WSs. As for scrubbing water, a large amount of their chlorinated aromatic compounds was detected in SS particles. According to the results, it was found that not only flue gas conditions but also operational and structural conditions in WS had great influence on minimizing the memory of chlorinated aromatic compounds in WS.


A categorical data analysis of contacts with the Family Health Clinic, Calabar, Nigeria.
The relationships of population, environmental and accessibility variables to registration and attendance by mothers of children under 6 at the Family Health Clinic in Calabar, Nigeria are investigated. The technique used to analyze the data collected is categorical data analysis which proceeds in two stages, variable selection to reduce the variable set and fitting a log-linear model to the reduced set. Details of the statistical procedures used are provided to indicate how categorical data analysis can be used as a valuable tool of analysis in medical geographical studies that employ count or frequency data. It was found that younger mothers and Ibibio women registered more often at the clinic than did their counterparts. However, if the relatively sparse data on fathers is accepted, the association between age and registration is found to be spurious and a model can be substituted which shows younger fathers and fathers who spoke a non-Efik/Ibibio language to be associated with higher clinic registration of mothers. It was further found that for registered mothers the probability of a clinic visit was decreased by mother's age, increased by distance given no travel cost, unaffected by distance given some travel cost, increased by travel cost given a short distance to the clinic and decreased by travel cost given a longer distance from the clinic. These results are discussed in relation to population characteristics such as socio-economic status, clinic procedures such as health worker activities, transportation availability in Calabar, the spatial ecology of the city and local environmental conditions.


Complete Genomic Sequence of Dengue Virus Serotype 4 Isolated from Plasma Collected from a Haitian Child in 2014.
While data are limited, there is increasing evidence that infections by dengue viruses are endemic in Haiti. In 2014, an outbreak caused by dengue virus 4 (DENV-4) followed a chikungunya fever outbreak. We present here the complete genome sequence of one isolate grouped within the genotype II South America and Caribbean DENV-4 clades.


Single injection of triamcinolone versus three repeated injections of bevacizumab for treatment of diabetic macular edema.
To compare the effect of a single intravitreal injection of triamcinolone acetonide versus three consecutive monthly intravitreal injections of bevacizumab for the treatment of diabetic macular edema (DME). Forty patients treated with a single intravitreal injection of 4 mg triamcinolone acetonide (triamcinolone group) were compared with 40 patients treated with three consecutive monthly intravitreal injections of 1.25 mg bevacizumab (bevacizumab group). The triamcinolone group showed a significant decrease in mean central retinal thickness (CRT) from 472.5 μm ± 120.35 to 374.0 μm ± 152.31 after 3 months (p < 0.001). The bevacizumab group also showed a significant reduction in CRT from 464.5 μm ± 115.3 to 370.0 μm ± 142.31 (p < 0.001). The triamcinolone group displayed an increase in best-corrected visual acuity (BCVA) following a single intravitreal triamcinolone acetonide injection from a mean of +0.70 ± 0.17 logMAR to a mean of +0.54 ± 0.38 logMAR after 3 months (p < 0.05). The bevacizumab group also showed an increase in BCVA following three injections of bevacizumab from a mean of +0.73 ± 0.28 logMAR to a mean of +0.57 ± 0.33 logMAR (p < 0.05). Statistical analysis showed no significant difference between both groups at 3 months. Our study showed that a single intravitreal injection of triamcinolone is as effective as three consecutive monthly intravitreal injections of bevacizumab for treatment of DME with regard to BCVA and CRT measured by optical coherence tomography. Despite the recent popularity of bevacizumab, three injections are no more effective than a single injection of triamcinolone for the treatment of DME.


"Pulmonary tongue" a right ventricle phase abnormality in muga studies in patients with pulmonary hypertension.
Pulmonary hypertension (PH) produces strain followed by hypertrophy and later dilatation of the right ventricle (RV) and pulmonary artery. The signs and symptoms are nonspecific. There is a need for a noninvasive sensitive way to diagnose PH. The purpose of this study is to evaluate phase abnormalities in radionuclide MUGA studies of patients with referred diagnosis of PH. In a retrospective analysis of 44 patients who had a radionuclide multigated study (MUGA) and contrast ventriculography (CV), 19 had high mean pulmonary pressure (over 20 mmHg) and a high pulmonary vascular resistance index (over 2.0). In 15 patients, a delayed phase segment in the RV corresponding to the pulmonary infundibulum and pulmonary conus was noted "The Pulmonary Tongue" sign (PT), 12 had PH (True positive) and 3 did not (false positive) on CV. No PT was seen in the remaining 29 patients, only 7 of them had PH (False negative). The sensitivity, specificity and accuracy of the PT sign in detecting PH was 80%, 72% and 77% respectively. The number of patients was too small to calculate the correlation of the grade of PT with the severity of PH. We conclude that "The Pulmonary Tongue" sign on a MUGA study is clinically useful in detecting PH.


Characterization of stimulator cells for alloreactive cytotoxic-T-lymphocyte responses in vivo.
Mouse spleen cells were fractionated and tested for their ability to induce alloreactive cytotoxic-T-lymphocyte responses in vivo. The cells with allostimulatory potential are enriched maximally in a population of low density, Ig-negative, Thy 1-negative cells. This fraction has the cytochemical and ultrastructural characteristics of cells of the early myeloid series and not those of typical dendritic cells or macrophages. These myeloid cells represent a new subset of accessory cells which could be a potential source of allostimulation in organ grafts. They should be considered along with other accessory cell types as potential elements which induce transplantation responses.


Context-dependent transcriptional regulations of YAP/TAZ in cancer.
As the downstream effectors of Hippo pathway, YAP/TAZ are identified to participate in organ growth, regeneration and tumorigenesis. However, owing to lack of a DNA-binding domain, YAP/TAZ usually act as coactivators and cooperate with other transcription factors or partners to mediate their transcriptional outputs. In this article, we first present an overview of the core components and the upstream regulators of Hippo-YAP/TAZ signaling in mammals, and then systematically summarize the identified transcription factors or partners that are responsible for the downstream transcriptional output of YAP/TAZ in various cancers.


Effects of delta-sleep-inducing peptide on NMDA-induced convulsive activity in rats.
Acute experiments on rats showed that the ED100 of NMDA for induction of clonic convulsions was 0.53 microgram, while the ED100 of NMDA for inducing tonic extension of the forelimbs was 5.02 micrograms/animal. Determination of these parameters after administration of delta-sleep-inducing peptide (100 micrograms/kg, i.p.) revealed 2.3- and 4.46-fold increases. These results provide evidence for a neuroprotective role of delta-sleep-inducing peptide in relation to excitatory amino acid receptor agonists.


Emergency Endovascular Management of a Symptomatic Pseudoaneurysm of the Left Subclavian Artery Ostium Using a Combination of an Abdominal Aortic Stent-Graft Extension Cuff and a Periscope Stent Graft.
A pseudoaneurysm located at the subclavian artery ostium is an infrequent but life-threatening pathology that usually requires major thoracic surgery with a high risk of mortality and morbidity. Endovascular therapy applied to the aortic arch branches is a recent alternative technique, which is still in its early stages because dedicated endovascular devices for the aortic arch are lacking. In this article, we present the emergency endovascular management of a symptomatic pseudoaneurysm of the left subclavian artery ostium which was presumably secondary to an atherosclerotic plaque rupture. Endovascular exclusion required a combination of an abdominal aortic stent-graft extension cuff, which was placed via a retroperitoneal iliac access, and a subclavian artery periscope stent graft.


In vitro activity of rifampin alone and in combination with nafcillin and Vancomycin against pathogenic strains of Staphylococcus aureus.
Twenty strains of Staphylococcus aureus isolated from patients with endocarditis were examined in vitro for susceptibility to rifampin, nafcillin, and vancomycin and to combinations of rifampin with nafcillin or vancomycin. Minimum bactericidal concentrations of rifampin ranged from 0.0031 to 0.0125 mug/ml, of nafcillin ranged from 0.078 to 0.312 mug/ml, and of vancomycin ranged from 0.312 to 1.25 mug/ml. The combination of rifampin with nafcillin was synergistic for 12 strains; the combination of rifampin plus vancomycin was synergistic for 5 of the isolates.


Hepatocellular uptake of cyclosporin A by simple diffusion.
Cyclosporin A is known to be eliminated mainly via the biliary++ pathway after biotransformation. Whether liver cells take up the drug by simple diffusion across the lipid barrier or by carrier-mediated transport, as shown for some other peptides, was unknown up to the present. Experiments with [3H]cyclosporin A on isolated rat hepatocytes indicate that the uptake of cyclosporin A is neither saturable nor is driven by metabolic energy. Cholestasis caused by cyclosporin A treatment is therefore not the result of mutual competition for a carrier protein. Nevertheless, cyclosporin A interacts with the bile acid transport system by non-competitive inhibition of bile salt uptake.


Identification of newborns with Fetal Growth Restriction (FGR) in weight and/or length based on constitutional growth potential.
This study was carried out to build statistical models for defining FGR (Fetal Growth Restriction) in weight and/or length after taking growth potential of an infant into account. From a cohort of pregnant women having given birth to 47,733 infants in 141 French maternity units, two statistical models gave individualized limits of birth weight and birth length (based on the 5th centile) below which, after adjustment for its individual growth potential, a newborn must be considered as FGR in weight and/or in length. A sample of 906 infants had measures taken of cord blood growth factors (IGF1, IGFBP3). The FGR(W) definition (weight<5th centile for growth potential) permitted the identification of infants who presented rates of maternal hypertension (13.6%) and of Apgar score at 5 min<6 (2.9%) higher than in the classical group SGA(W) (weight<5th centile for sex and gestational age) (9.6% and 2.2% respectively). By combining FGR(W) and SGA(W), a subgroup of infants, not currently recognized as SGA, presented very high rates of maternal hypertension (19.9%) and of low Apgar score (3.9%). Conversely a subgroup of infants, currently recognized as SGA(W), had rates as low as in the normal infants group, and had to be considered as "constitutionally small" (that is to say 24% of the SGA(W)). Combining FGR(W) and FGR(L) (length<5th centile of growth potential), 7.6% of infants appeared growth-restricted, and 1.8% appeared constitutionally small in weight and/or in length. The FGR(W)-FGR(L) infants showed the lowest mean values of IGF1 (126.2+/-3.2) and IGFBP3 (0.86+/-0.03). These new definitions of FGR(W) and FGR(L) could help to better identify infants at birth requiring neonatal care, and monitoring of growth catch-up and neurodevelopmental outcome.


Structural analysis of repetitive sequence elements transcribed in early development of Xenopus laevis.
A cDNA library prepared from mRNA of Xenopus laevis embryos was screened with a genomic DNA fragment containing various transcribed repetitive sequence elements. Comparison of the nucleotide sequence of two isolated cDNAs and their genomic relatives allows one to define two transcribed repetitive sequence elements. One of them belongs to a highly reiterated family and consists of a tandem array of homologous subunits of 77-80 bp. The other is reiterated approximately 2200 times, has a size of 260 bp and displays a conserved region of 135 bp. The data are consistent with the presence of repetitive sequence transcripts in the 3' part of mRNA molecules.


Role of transposable elements in trypanosomatids.
Transposable elements constitute 2-5% of the genome content in trypanosomatid parasites. Some of them are involved in critical cellular functions, such as the regulation of gene expression in Leishmania spp. In this review, we highlight the remarkable role extinct transposable elements can play as the source of potential new functions.


EZH2 Contributes to 5-FU Resistance in Gastric Cancer by Epigenetically Suppressing FBXO32 Expression [Retraction].
[This retracts the article DOI: 10.2147/OTT.S180131.].


Individualized dosing regimen for prothrombin complex concentrate more effective than standard treatment in the reversal of oral anticoagulant therapy: an open, prospective randomized controlled trial.
Prothrombin Complex Concentrate (PCC) is indicated for the acute reversal of oral anticoagulation therapy. To compare the efficacy of a "standard" dosage of 20 ml PCC equivalent to about 500 IU factor IX (group A), and an "individualized" dosage based on a target-INR of 2.1 or 1.5, the initial-INR and the patient's body weight (group B), we performed an open, prospective, randomized, controlled trial. The in vivo response and in vivo recovery of factor II, VII, IX and X in these patients on oral anticoagulation was determined. Ninety three patients (group A: 47; group B: 46) with major bleedings or admitted for urgent (surgical) interventions were enrolled. PCC and Vitamin K (10 mg) were administered intravenously. We evaluated the effect of treatment by the decrease of INR and the clinical outcome. The number of patients reaching the target-INR 15 min after the dosage of PCC was significantly higher in the group treated with an "individualized" dosage, compared to the group treated with a standard dose, (89% versus 43%; p<0.001). So, we conclude that for the acute reversal of oral anticoagulant therapy, an "individualized" dosage regimen of PCC based on the target-INR, the initial-INR, and body weight of the patient, is significantly more effective in reaching the target-INR than a "standard" dosage. The in vivo response and in vivo recovery found in this study was higher then in patients with isolated factor deficiencies. This suggests that the pharmacokinetics in patients on oral anticoagulants may be different.


Parotid gland metastasis from glioblastoma multiforme: a case report and review of the literature.
We describe a rare case of glioblastoma multiforme with extracranial metastasis to the right parotid gland. A 58-year-old man presented with a parotid tumor and facial paralysis 15 months after craniotomy and partial lobectomy for glioblastoma multiforme of the right temporal lobe. Diagnosis was confirmed by ultrasound guided core-needle biopsy. By this means, a second hospitalization with open surgical biopsy of the parotid gland under general anesthesia for diagnosis only was avoided in this obviously palliative situation. The possible mechanisms of metastasic spread in this highly aggressive tumor and its diagnostic investigation are discussed and compared with the literature.


Interactions between the L1 cell adhesion molecule and ezrin support traction-force generation and can be regulated by tyrosine phosphorylation.
An Ig superfamily cell-adhesion molecule, L1, forms an adhesion complex at the cell membrane containing both signaling molecules and cytoskeletal proteins. This complex mediates the transduction of extracellular signals and generates actin-mediated traction forces, both of which support axon outgrowth. The L1 cytoplasmic region binds ezrin, an adapter protein that interacts with the actin cytoskeleton. In this study, we analyzed L1-ezrin interactions in detail, assessed their role in generating traction forces by L1, and identified potential regulatory mechanisms controlling ezrin-L1 interactions. The FERM domain of ezrin binds to the juxtamembrane region of L1, demonstrated by yeast two-hybrid interaction traps and protein binding analyses in vitro. A lysine-to-leucine substitution in this domain of L1 (K1147L) shows reduced binding to the ezrin FERM domain. Additionally, in ND7 cells, the K1147L mutation inhibits retrograde movement of L1 on the cell surface that has been linked to the generation of the traction forces necessary for axon growth. A membrane-permeable peptide consisting of the juxtamembrane region of L1 that can disrupt endogenous L1-ezrin interactions inhibits neurite extension of cerebellar cells on L1 substrates. Moreover, the L1-ezrin interactions can be modulated by tyrosine phosphorylation of the L1 cytoplasmic region, namely, Y1151, possibly through Src-family kinases. Replacement of this tyrosine together with Y1176 with either aspartate or phenylalanine changes ezrin binding and alters colocalization with ezrin in ND7 cells. Collectively, these data suggest that L1-ezrin interactions mediated by the L1 juxtamembrane region are involved in traction-force generation and can be regulated by the phosphorylation of L1.


Quantifying the ranges of relative motions of the intervertebral discs and facet joints in the normal cervical spine.
Functional neck motion is achieved by the cervical segments with each composed of an intervertebral disc (IVD) and two facet joints (FJs). Using biplane fluoroscopic imaging, we investigated the ranges of motion (ROMs) of the three joints in the cervical spines (from C3 to C7) of eighteen asymptomatic subjects. Three functional neck motions were examined, including flexion-extension (FE), lateral bending (LB) and axial twisting (AT). Our measurements showed that the translations of both IVD and FJs primarily occurred in the sagittal plane during all neck motions, and the anteroposterior translations of IVDs were significantly smaller than those of the corresponding FJs (p < 0.05) at all segments. For example, the ranges of IVD and FJ anteroposterior translations at C3/4 were 2.7 ± 0.7 mm vs. 3.5 ± 1.1 mm in FE, 0.9 ± 0.5 mm vs. 4.6 ± 1.1 mm in LB, and 1.0 ± 0.5 mm vs. 3.1 ± 1.0 mm in AT. Furthermore, we introduced an IVD-FJ translation ratio, which represents the ratio of the IVD to FJ translational ROMs. In FE neck motion, the IVD-FJ anteroposterior translation ratios decreased from 0.81 ± 0.18 at C3 to 0.52 ± 0.19 at C3, indicating gradually increasing resistances of IVDs compared to FJs from the proximal to distal levels. In LB neck motion, the smallest IVD-FJ translation ratios (0.14 ± 0.09 and 0.43 ± 0.30) occurred at C4/5 for both anteroposterior and left-right translations. In AT neck motion, the largest IVD-FJ anteroposterior translation ratio (0.42 ± 0.21) occurred at C3/4, and was significantly different from those at C4/5 and C5/6 (p < 0.05). These data could be used as references for improving motion-preserving cervical treatment methods that aimed to achieve the normal ranges of translational motions of both IVD and FJs.


The Utility of Pentraxin and Modified Prognostic Scales in Predicting Outcomes of Patients with End-Stage Heart Failure.
Risk stratification is an important element of management in patients with heart failure (HF). We aimed to determine factors associated with predicting outcomes in end-stage HF patients listed for heart transplantation (HT), with particular emphasis placed on pentraxin-3 (PXT-3). In addition, we investigated whether the combination of PTX-3 with the Heart Failure Survival Score (HFSS), the Seattle Heart Failure Model (SHFM), or the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) improved the prognostic strength of these scales in the study population. We conducted a prospective analysis of 343 outpatients with end-stage HF who accepted the HT waiting list between 2015 and 2018. HFSS, SHFM, and MAGGIC scores were calculated for all patients. PTX3 was measured by sandwich enzyme-linked immunosorbent assay with a commercially available kit. The endpoints were death, left ventricular assist device implantation, and HT during the one-year follow-up. The median age was 56 (50−60) years, and 86.6% were male. During the follow-up period, 173 patients reached the endpoint. Independent risk factors associated with outcomes were ischemic etiology of HF [HR 1.731 (1.227−2.441), p = 0.0018], mean arterial pressure (MAP) [1.026 (1.010−1.042), p = 0.0011], body mass index (BMI) [1.055 (1.014−1.098), p = 0.0083], sodium [1.056 [(1.007−1.109), p = 0.0244] PTX-3 [1.187 (1.126−1.251, p < 0.0001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) [HR 1.004 (1.000−1.008), p = 0.0259]. The HFSS-PTX-3, SHFM-PTX-3 and MAGGIC-PTX-3 scores had significantly higher predictive power [AUC = 0.951, AUC = 0.973; AUC = 0.956, respectively] than original scores [AUC for HFSS = 0.8481, AUC for SHFM = 0.7976, AUC for MAGGIC = 0.7491]. Higher PTX-3 and NT-proBNP concentrations, lower sodium concentrations, lower MAP and BMI levels, and ischemic etiology of HF are associated with worse outcomes in patients with end-stage HF. The modified SHFM-PTX-3, HFSS-PTX-3, and MAGGIC-PTX-3 scores provide effective methods of assessing the outcomes in the analyzed group.


Dairy heifers have an earlier increase in serum pregnancy-specific protein B compared with lactating dairy cows. Is this an indicator of earlier conceptus attachment?
This study was designed to use within-individual daily increases in circulating pregnancy-specific protein B (PSPB) to determine time to increase in serum PSPB in nulliparous heifers and multiparous dairy cows following artificial insemination (AI). Weekly cohorts of lactating Holstein cows (n = 56) averaging 122 ± 7 d in milk at AI and nulliparous Holstein heifers (n = 23) averaging 16 ± 0.24 mo old at AI were used in this study. Lactating cows received AI to either Ovsynch (n = 38) or at ~12 h following observed standing estrus (n = 18). All heifers were inseminated ~12 h after observed standing estrus. Blood samples for measurement of PSPB were collected daily from d 15 through d 35 postovulation. Nulliparous heifers had increases in serum PSPB earlier compared with both primiparous and multiparous cows. Day of increase in serum PSPB was defined as the day serum PSPB optical density levels initially increased ≥10% from baseline and continued to increase from baseline of ≥10% the following 2 d. Average PSPB were greater in pregnant heifers compared pregnant cows from d 23 through 29. Early lactation nonpregnant cows maintained greater average optical density of serum PSPB from 15 to 35 d postovulation compared with nonpregnant heifers (n = 38). In summary, fertility differences in heifers versus lactating cows may be due to the differences in timing of increases in serum PSPB. This appears to be one of the first publications that used daily PSPB sampling to investigate possible differences in fertility in heifers versus lactating cows.


Short-term effects of different PM2.5 ranges on daily all-cause mortality in Jinan, China.
To examine the effects of different PM2.5 concentration ranges on daily all-cause mortality, 8768 all-cause deaths were recorded in the database of the Shandong Provincial Hospital Affiliated to Shandong First Medical University. Data of air pollutants (PM2.5 and O3) concentration were provided by the Jinan Environment Monitoring Center. The relative risk of all-cause mortality was assessed using a quasi-Poisson regression model after adjusting for confounding factors. The concentrations of PM2.5 were divided into four ranges 0-35 μg/m3; 35-75 μg/m3; 75-115 μg/m3; 115-150 μg/m3. There was no significant relationship between PM2.5 exposure and all-cause deaths in individuals aged < 60 years. However, for individuals aged ≥ 60 years, there was a significant positive association between exposure concentrations and all-cause deaths within the ranges 0-35 μg/m3, 35-75 μg/m3, and 115-150 μg/m3 with a mortality increase of 1.07 (1.01, 1.13), 1.03 (1.00, 1.05), and 1.05 (1.01, 1.08), respectively. When the population aged ≥ 60 years was stratified into gender groups, exposure to PM2.5 in the range 0-35 μg/m3 increased the mortality risk in men but not women. All-cause mortality in women, but not men, increased significantly with exposure to PM2.5 in the ranges of 35-75, 75-115, and 115-150 μg/m3.


Influence of medium osmolality on the in vitro growth of Plasmodium falciparum: a morphologic and radioisotopic study.
The study of the growth rate and incorporation of [3H]hypoxanthine and [14C]isoleucine showed that in vitro variations of Plasmodium falciparum parasitemia levels and incorporation rates of the two radiolabeled molecules have been correlated. In our experimental conditions, P. falciparum blood forms in vitro tolerate osmolalities ranging from 180 to 360 mOSM. A weak hypo-osmolality (241 mOSM) favored the development of the parasite. The highest sensitivity of the parasite to osmotic variations was observed during schizogony. The merozoite stage and reinvasion process seemed less affected by hypo-osmolalities than by hyperosmolalities. The minor alterations in morphology of the parasites in hypo- and hyperosmotic media suggested that P. falciparum may have efficient osmoregulatory power.


The membrane-proximal tryptophan-rich region in the transmembrane glycoprotein ectodomain of feline immunodeficiency virus is important for cell entry.
The mechanisms whereby feline immunodeficiency virus (FIV) adsorbs and enters into susceptible cells are poorly understood. Here, we investigated the role exerted in such functions by the tryptophan (Trp)-rich motif present membrane-proximally in the ectodomain of the FIV transmembrane glycoprotein. Starting from p34TF10, which encodes the entire genome of FIV Petaluma, we produced 11 mutated clones having the Trp-rich motif scrambled or variously deleted or substituted. All mutated progenies adsorbed normally to cells, but the ones with severe disruptions of the motif failed to generate proviral DNA. In the latter mutants, proviral DNA formation was restored by providing an independent source of intact FIV envelope glycoproteins or by addition of the fusing agent polyethylene glycol, thus clearly indicating that their defect resided primarily at the level of cell entry. In addition, the replication-competent mutants exhibited a generally enhanced susceptibility to selected entry inhibitory synthetic peptides, suggestive of a reduced efficiency of the entry step.