Chimney Grafts in Aortic Stent Grafting: Hazardous or Useful Technique? Systematic Review of Current Data.
The chimney graft (CG) technique was introduced to rescue accidentally covered aortic branches during aortic endovascular repair. It extends the sealing zone. There is concern about "gutter" type I endoleak (EL-I) and about the durability of CGs. The aim of the present report was to analyze the rapidly increasing existing data. A search was performed (PRISMA criteria) for all studies of visceral and thoracic/arch chimney grafts. Technical and clinical details and outcome were assessed. The present review includes 831 patients who underwent EVAR/TEVAR (endovascular aneurysm repair/thoracic endovascular aneurysm repair) with one or more chimney, periscope, or sandwich grafts. For aortic visceral vessels 517 patients received 911 visceral CGs and 314 patients received 364 arch CGs. Most procedures (81% visceral and 69% arch CGs) were elective. Thirty day mortality was 4% for both groups. The rate of early EL-I was 13% (visceral CGs) and 11% (arch CGs). Most EL-I were handled conservatively (observation: 70% for visceral CG and 45% for arch CG). Early CG patency was high (97-99%) and remained high during follow up (median 17 months). Late (after 30 days) EL-I was reported in nine visceral (2%) and 12 arch (4%) CG cases. Few other late complications were reported, but those losing a kidney at the initial repair seemed to have a high risk of requiring permanent hemodialysis. Increasing amounts of data support the benefit of visceral and arch chimney graft techniques. In particular, the low early mortality and complication rates and high long-term patency seem advantageous; however, the majority of cases have been treated electively, and there is a high risk of bias in all studies. Mid- to long-term data suggest few late complications, except in cases where one renal artery was sacrificed. The CG technique is valuable for complex urgent patients and needs further documentation for other patient groups.


Changes in mean airway pressure during HFOV influences cardiac output in neonates and infants.
Changes in mean airway pressure affect cardiac output during conventional positive pressure ventilation. The effect of high-frequency oscillation ventilation (HFOV) on cardiac output is less studied. A prospective study in a university hospital pediatric intensive care unit. Fourteen patients aged <1 year and weighing <10 kg who were on HFOV were included. All patients had been on HFOV for >12 h and were considered to be in a stable condition. In the study group (n = 9) the mean proximal airway pressure (Paw) was increased and decreased by +5 and -3 cmH2O, respectively, from baseline in each patient. Measurements were made at each level including baseline settings between each change. In a control group (n = 5) no changes in ventilatory parameters were made. Cardiac output was assessed with echocardiography and the Doppler technique at each level of Paw and at similar intervals in the control group. Cardiac output changed significantly when Paw was changed in the study group (P = 0.02), with the greatest change at the highest Paw at -11% (range: -19 to -9) compared with baseline. We found no significant changes over time in the control group. This study shows that CO is affected by changes in mean airway pressure during HFOV in concordance with the known effects of mean airway pressure during conventional positive pressure ventilation. The mean changes are smaller than expected compared with earlier studies of conventional mechanical ventilation. Further studies are needed to better understand these relationships.


A new, highly sensitive and specific assay for chymotrypsin.
1. A simple, highly sensitive, specific fluorometric method for the determination of chymotrypsin is described. 2. The new substrate utilized in this assay, N-glutaryl-glycyl-glycyl-l-phenylalanine beta-naphthylamide (GGPNA), is readily soluble in water, stable and highly specific for chymotrypsin. It is not degraded by a large excess of carboxypeptidase B, elastase, thrombin or plasmin and is virtually resistant to trypsin. 3. GGPNA is extremely sensitive to the action of chymotrypsin and permits detection of enzyme concentrations as low as 1 ng/ml. Linearity between enzyme concentration and fluorescence produced is maintained up to at least 3000 ng/ml. 4. alpha2-Macroglobulin-bound chymotrypsin hydrolyzes GGPNA at a rate about 2/3 of that exhibited by the free enzyme. 5. Bile pigments in amounts normally found in duodenal juice or traces of blood do not interfere with the assay. 6. GG PNA which releases beta-naphthylamine upon hydrolysis is suitable also for colorimetric and histological determination of chymotrypsin.


Modulators of cellular protein phosphorylation alter the trans-activation function of human progesterone receptor and the biological activity of progesterone antagonists.
Addition of progesterone to breast cancer cells in vivo increases phosphorylation of human progesterone receptor (PR), suggesting that phosphorylation has a regulatory role in producing the activated form of receptor. Kinetic analysis indicates that hormone-dependent phosphorylation is sequential and that early stages of phosphorylation(s) are closely associated with enhancement of PR-DNA binding while later stages are associated with a trans-activation function. Various agents that stimulate cellular protein phosphorylation (8-Br cAMP, okadaic acid, TPA) functionally synergize with progesterone to enhance progesterone-dependent PR trans-activation in intact cells. These results suggest that protein phosphorylation does have a role in modulating the trans-activation function of PR in vivo. They also demonstrate cross-talk between second messenger signal transduction pathways and nuclear steroid receptors. Whether the phosphorylated target that provides the link between these two signal transduction pathways is PR itself or another protein involved in PR-mediated gene transcription is not known. Positive cooperative interactions were also observed between cAMP signaling pathways and the progesterone antagonist RU486, that resulted in RU486 exerting substantial agonist activities. This ability of cross-talk between second messenger and steroid receptor signal transduction pathways to override the antagonistic effects of RU486 suggests a novel mechanism to explain the problem of resistance to clinically important steroid antagonists.


Substantial risk of recurrence even after 5 recurrence-free years in early-stage hepatocellular carcinoma patients.
Although hepatocellular carcinoma (HCC) is notorious for its high recurrence rate, some patients do not experience recurrence for more than 5 years after resection or radiofrequency ablation for early-stage HCC. For those with five recurrence-free period, the risk of HCC recurrence within the next 5 years remains unknown. A total of 1,451 consecutive patients (median, 55 years old; males, 79.0%; hepatitis B virus-related, 79.3%) with good liver function (Child-Pugh class A) diagnosed with early-stage HCC by Barcelona Clinic Liver Cancer Staging and received radiofrequency ablation or resection as an initial treatment between 2005 and 2010 were analyzed. During a median follow-up period of 8.1 years, 961 patients (66.2%) experienced HCC recurrence. The cumulative recurrence rates increased to 39.7%, 60.3%, and 71.0% at 2, 5, and 10 years, respectively, and did not reach a plateau. Five years after HCC diagnosis, 487 patients were alive without experiencing a recurrence. Among them, during a median of 3.9 additional years of follow-up (range, 0.1-9.0 years), 127 patients (26.1%) experienced recurrence. The next 5-year cumulative recurrence rate (5-10 years from initial diagnosis) was 27.0%. Male sex, higher fibrosis-4 scores, and alpha-fetoprotein levels at 5 years were associated with later HCC recurrence among patients who did not experience recurrence for more than 5 years. The HCC recurrence rate following 5 recurrence-free years after HCC treatment was high, indicating that HCC patients warrant continued HCC surveillance, even after 5 recurrence-free years.


Varying constants.
We review properties of theories for the variation of gravitation and fine structure 'constants'. We highlight some general features of the cosmological models that exist in these theories with reference to recent quasar data that are consistent with time variation in the fine structure constant since a redshift of 3.5. The behaviour of a simple class of varying-alpha cosmologies is outlined in the light of all the observational constraints.


The use of surgical rating scales for the evaluation of surgical working conditions during laparoscopic surgery: a scoping review.
Surgical rating scales (SRSs) enable the surgeon to uniformly quantify surgical working conditions. They are increasingly used as a primary outcome in studies evaluating the effect of anaesthesia or surgery-related interventions on the quality of the surgical work field. SRSs are especially used in laparoscopic surgery due to a renewed interest in deep neuromuscular block. There are however no guidelines regarding the uniform use of SRS and the uniform reporting of results. A systematic search was conducted in the databases of PubMed, Web of Science and Embase for studies that reported the use of an SRS to evaluate surgical conditions in laparoscopic surgery. Only original human research in English language with full text availability through the Leiden university library was considered for this review. The full texts of eligible abstracts were independently reviewed by the first and second author. The quality of SRSs and methodology of rating were systematically reviewed. The search yielded 2830 reports, of which 17 were identified using a surgical rating scale (SRS) in laparoscopic surgery. Ten of these reports used a unique SRS, these were systematically appraised for their quality. The overall quality of the SRSs was low: the majority of the scales were poorly described and lacked assessment of inter- and intra-rater reliability. In addition, considerable differences exist in the methodology of rating and the reporting of results. There is substantial inconsistency in SRS quality, methodology, and results reporting. The uniform use of high-quality surgical rating scales is needed to improve the quality and reproducibility of future research.


Changes of water-relation characteristics and levels of organic cytoplasmic solutes during salinity induced transition of Mesembryanthemum crystallinum from C3-photosynthesis to crassulacean acid metabolism.
NaCl was added to the nutrient solution of 4-6-week old Mesembryanthemum crystallinum plants so that the concentration rose by 50 mM per day. Ten to fifteen days after a concentration of 400 mM was reached, pronounced diurnal oscillations of malate levels indicated that plants had changed from C3-photosynthesis to crassulacean acid metabolism (CAM). Due to the NaCl-treatment the solute potential (Ψs) decreased from about -6 bar to -25 bar, and the water potential (Ψ) changed from about -5 bar to -23 bar on average. Ψ showed small diurnal oscillations both in controls and NaCl-treated plants, with an amplitude of 1 to 3 bar, the value at the end of the dark phase being less negative than that at the end of the light phase. Changes of ion levels due to the NaCl-treatment were average increases in Na+ and Cl- from 10-20 to 370-470 mmol kg-1 FW and from below 10 to 280-325 mmol kg-1 FW, respectively, and a decrease in K+ from 70-80 to 25 mmol kg-1 FW. These changes of ion levels corresponded very closely to an increase of dry weight in per cent of fresh weight observed during the NaCl-treatment (e.g. a change of 2% in one experiment), and osmotically they matched the measured change in Ψs (e.g. about 18-20 bar in one experiment).Most of the organic solutes analysed did not show any significant changes as a result of the NaCl-treatment. The following compounds were identified within the respective ranges of concentrations: mannitol (0.2 to 0.5 mmol kg-1 FW), sum of quaternary ammonium compounds (60 to 140 mg kg-1 FW), choline (0.1 to 0.4 mmol kg-1 FW), betaine (0.3 to 0.7 mmol kg-1 FW), hexoses (2-9 mmol kg-1 FW), pentoses (1-5 mmol kg-1 FW) and sucrose (2-4 mmol kg-1 FW). The levels of proline and of total amino acids minus proline rose during the NaCl-treatment from 0.1-1 mmol kg-1 FW to 2.5-5 mmol kg-1 FW and from 2.5-4 mmol kg-1 FW to 6-8 mmol kg-1 FW, respectively.The changes of Ψs and Ψ, and of Na+- and Cl--levels were complete, and new steady levels were attained by the time 400 mM NaCl was reached in the nutrient solution, i.e. many days before pronounced diurnal malate oscillations indicated that the change from C3-photosynthesis to CAM had occurred. The attainment of new steady levels of proline and K+, however, was much slower and coincided with the onset of CAM.


Disseminated intravascular coagulation: a review.
Disseminated intravascular coagulation (DIC) results from activation of the blood coagulation cascade by various disease processes. DIC may occur with blunt head trauma and, with severe head trauma, may reflect brain parenchymal injury. Oral and maxillofacial surgeons who treat traumatized patients should be aware of the implications of DIC with regard to patient management, diagnosis, and surgical considerations.


Emphasis on the clinical relationship between alpha-fetoprotein and hepatoid adenocarcinoma of the stomach: a retrospective study.
Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant and rare extrahepatic tumor. The prognosis is controversial because of its rarity and the lack of multi-center cohort studies, especially on the influence of serum Alpha-fetoprotein (AFP) level on prognosis. We aimed to analyze the clinicopathological characteristics and prognosis of HAS, particularly the effect of serum AFP on the prognosis of HAS. We retrospectively reviewed clinical data of one HAS patient treated at our institution in 2019 and of 252 patients reported between 1984 and 2020 in research databases. Among these patients, 60.1% were > 60 years, 51% had lesions in the gastric antrum, and 51.0% (73/143) had the ulcerative lesion type. The preoperative elevated levels of serum alpha-fetoprotein (AFP) were detected in most patients (76.7%). Lymph-node (84.6%) and preoperative liver metastasis (39.1%) were often found. The high-AFP group was characterized by a higher rate of stage IV (P = 0.000682) and liver metastasis (P = 0.000068). The 1-, 3-and 5-year progression-free survival(PFS) rates were 41%, 18%, and 0%, and the 1-, 3-, and 5-year overall survival (OS) rates were 64%, 26%, and 21%, respectively. The survival analysis showed that OS was significantly shorter for HAS with high-AFP (> 300 ng/ml) than with low-AFP (≤ 300 ng/ml) (P = 0.023). The univariate analysis indicated that the OS of HAS was associated with tumor location, pTNM stage, lymph-node metastasis, surgical resection, and serum AFP > 300 ng/ml. However,the prognostic factors for PFS was only pTNM stage and surgical resection. The multivariate analysis confirmed that the independent prognostic factor affecting OS of HAS included pTNM stage and surgical resection. Liver metastasis was increasingly more likely with increasingly higher serum AFP, but the prognosis of HAS is not necessarily poor. Serum AFP level is an important prognostic indicator in HAS and should be monitored.


Production and characterization of antibodies against fumigaclavine A.
Polyclonal antibodies against fumigaclavine A (FuA) were obtained from rabbits after immunization with a FuA-keyhole limpet hemocyanine conjugate prepared by formaldehyde condensation. Using these antibodies and a FuA-bovine serum albumine conjugate, a competitive indirect enzyme immunoassay (EIA) was established. The antiserum obtained from one rabbit enabled highly sensitive detection of FuA, with an IC50 level and detection limit of the standard curve of 3.3 ng/ml and approx. 1 ng/ml, respectively. The EIA was very specific for FuA, with 1.3% cross-reactivity with FuB. Several other lysergic acid derivatives (ergonovine, ergotamine, alpha-ergocryptine) were tested but did not cross-react in the FuA EIA. This is the first description of antibodies against FuA and the first development of an EIA for FuA.


Autophagy inhibits endothelial progenitor cells migration via the regulation of MMP2, MMP9 and uPA under normoxia condition.
The aim of this study was to explore the role of autophagy on the regulation of endothelial progenitor cells (EPCs) migration under normoxic condition. After EPCs were isolated and characterized in vitro, we employed Atg5 knocking down and rapamycin to monitor the autophagy, and performed wound healing and transwell assay to assess the cell migration. On the mechanism, the expression of matrix metalloproteinases (MMPs) and urokinase type plasminogen activator (uPA) was evaluated. Atg5 knocking down and rapamycin could respectively inhibit and enhance autophagy, which could result in significantly increased and decreased cell migration in wound healing and transwell assay under normoxic condition. Moreover, Atg5 knocking down could significantly increase the expression of MMP2, MMP9 and uPA in EPCs while rapamycin could decrease the expression of uPA and MMP9. In addition, the mTOR-P70 S6K pathway was also involved in EPCs migration regulation. These results demonstrated that autophagy could regulate the EPCs migration through mTOR-P70 S6K pathway, and MMP2, MMP9 and uPA may also involve in the regulation mechanism.


Polygenic risk scores for late smoking initiation associated with the risk of schizophrenia.
Patients with schizophrenia display characteristic smoking-related behaviors and genetic correlations between smoking behaviors and schizophrenia have been identified in European individuals. However, the genetic etiology of the association remains to be clarified. The present study investigated transethnic genetic overlaps between European-based smoking behaviors and the risk of Japanese schizophrenia by conducting polygenic risk score (PRS) analyses. Large-scale European genome-wide association study (GWAS) datasets (n = 24,114-74,035) related to four smoking-related intermediate phenotypes [(i) smoking initiation, (ii) age at smoking initiation, (iii) smoking quantity, and (iv) smoking cessation] were utilized as discovery samples. PRSs derived from these discovery GWASs were calculated for 332 Japanese subjects [schizophrenia patients, their unaffected first-degree relatives (FRs), and healthy controls (HCs)] as a target sample. Based on GWASs of European smoking phenotypes, we investigated the effects of PRSs on smoking phenotypes and the risk of schizophrenia in the Japanese population. Of the four smoking-related behaviors, the PRSs for age at smoking initiation in Europeans significantly predicted the age at smoking initiation (R2 = 0.049, p = 0.026) and the PRSs for smoking cessation significantly predicted the smoking cessation (R2 = 0.092, p = 0.027) in Japanese ever-smokers. Furthermore, the PRSs related to age at smoking initiation in Europeans were higher in Japanese schizophrenia patients than in the HCs and those of the FRs were intermediate between those of patients with schizophrenia and those of the HCs (R2 = 0.015, p = 0.015). In our target subjects, patients with schizophrenia had a higher mean age at smoking initiation (p = 0.018) and rate of daily smoking initiation after age 20 years (p = 0.023) compared with the HCs. A total of 60.6% of the patients started to smoke before the onset of schizophrenia. These findings suggest that genetic factors affecting late smoking initiation are associated with the risk of schizophrenia.


Postmortem MRI Evaluation of Maceration Degree of Deceased Fetus.
We studied the possibilities of postmortem MRI for assessing the degree of maceration and determining the duration of intrauterine fetal death. Postmortem radiological and pathoanatomic study of the bodies of 38 stillbirths who died antenatally (main group, n=31) and intranatally (control group, n=5), who were born at gestational periods of 22-40 weeks was performed. Before the autopsy, MRI was performed in standard T1 and T2 modes. The tissue of the liver, kidney, brain, femoral muscle, lung, and skin in the hip, abdomen, and skull were studied on T1- and T2-weighted images (WI), followed by calculation of the of MR signal intensity ratio in T2- and T1-WI (SIR). The duration of intrauterine fetal death was determined based on the results of autopsy and analysis of histological preparations. It was found that the calculated values of SIR depended on the evaluated organ and the duration of intrauterine fetal death. Unfortunately, the revealed dynamics of changes in SIR does not allow unambiguous assessment of the severity of maceration processes and, accordingly, the time of fetal death due to its non-linear nature. Nevertheless, the use of SIR indicators of several organs and areas of the body makes it easier to determine the duration of intrauterine fetal death and, hence, to clarify the links of thanatogenesis of the stillborn. The advantages of post-mortem MRI compared to autopsy include non-invasive nature of the study, the possibility of archiving and subsequent multiple delayed analysis of tomograms, as well as the speed of MRI analysis, in contrast to microscopic stage of pathological examination associated with the need to prepare histological preparations.


Multi-technique comparison of atherogenic and MCD NASH models highlights changes in sphingolipid metabolism.
Lipotoxicity is a key player in the pathogenesis of nonalcoholic steatohepatitis (NASH), a progressive subtype of nonalcoholic fatty liver disease (NAFLD). In the present study, we combine histological, transcriptional and lipidomic approaches to dissociate common and specific alterations induced by two classical dietary NASH models (atherogenic (ATH) and methionine/choline deficient (MCD) diet) in C57BL/6J male mice. Despite a similar degree of steatosis, MCD-fed mice showed more pronounced liver damage and a worsened pro-inflammatory and pro-fibrogenic environment than ATH-fed mice. Regarding lipid metabolism, the ATH diet triggered hepatic counter regulatory mechanisms, while the MCD diet worsened liver lipid accumulation by a concomitant increase in lipid import and reduction in lipid export. Liver lipidomics revealed sphingolipid enrichment in both NASH models that was accompanied by an upregulation of the ceramide biosynthesis pathway and a significant rise in dihydroceramide levels. In contrast, the phospholipid composition was not substantially altered by the ATH diet, whereas the livers of MCD-fed mice presented a reduced phosphatidylcholine to phosphatidylethanolamine (PC/PE) ratio and a strong depletion in phospholipids containing the sum of 34-36 carbons in their fatty acid chains. Therefore, the assessment of liver damage at the histological and transcriptional level combined with a lipidomic analysis reveals sphingolipids as shared mediators in liver lipotoxicity and pathogenesis of NASH.


Influence of fatty fish intake during pregnancy in the polyunsaturated fatty acids of erythrocyte phospholipids in the mother at labor and newborn infant.
Assessing the relationship between fatty fish intake, the main source of N-3 polyunsaturated fatty acids and maternal and fetal levels in erythrocytes at labor. The fatty acid composition was studied in 64 mother-newborn infant pairs by means of capillar gas chromatography. Following a nutritional inquiry our population was classified as follows: superior intake group (SIG) (> 4 times fatty fish per month; 54.4 +/- 20.5 g/day), medium intake group (MIG) (2-4 per month; 16.5 +/- 4 g/day) and inferior intake group (IIG) (< 2 times per month; 4.3 +/- 4 g/day). In erythrocyte phospholipids higher levels were observed in SIG in relation to IIG in mothers regarding eicosapentaenoic (0.56 +/- 0.3% and 0.39 +/- 0.2%; p = 0.02) and docosahexaenoic acids (6.14 +/- 1.16% and 5.4 +/- 0.98%; p = 0.02) and in newborn infants regarding eicosapentaenoic acid (0.32 +/- 0.24% and 0.17 +/- 0.09%; p < 0.01). On the other hand, SIG had lower values of arachidonic acid than IIG in mother (11.15 +/- 1.61% vs 12.83 +/- 1.86%; p < 0.01) and newborn infants (16.08 +/- 3.42% vs 17.89 +/- 2.57%; p = 0.05). From a biochemical point of view, and taking into account the pre-existing literature, it is suggested that a minimum fatty fish intake of twice per month should be recommended (edible portion 85 g.) in order to reach the N-6/N-3 quotient usually proposed.


Traumatic fascicular neuroma.
A 72-year-old man had developed amiodarone neuropathy. He was found, at biopsy, to have a fascicular neuroma of his right sural nerve, unassociated with his underlying neuropathy, apparently due to blunt trauma, as electroneurographic needling of this nerve could safely be ruled out by the patient and his physicians. Such fascicular neuromas, which may remain without sensory deficits, may develop at an unknown frequency, and may only be uncovered by biopsy--or autopsy--in a coincidental neuropathic process.


Carnosine has antinociceptive properties in the inflammation-induced nociceptive response in mice.
Carnosine is a biologically active dipeptide that is found in fish and chicken muscle. Recent studies have revealed that carnosine has neuroprotective activity in zinc-induced neural cell apoptosis and ischemic stroke. In the present study, we examined the expression of carnosine in the spinal cord, and the antinociceptive potency of carnosine in a mouse model of inflammation-induced nociceptive pain. Immunohistochemical studies with antiserum against carnosine showed an abundance of carnosine-immunoreactivity in the dorsal horn of the mouse spinal cord. Double-immunostaining techniques revealed that carnosine was expressed in the neurons and astrocytes in the spinal cord. Oral administration of carnosine attenuated the number of writhing behaviors induced by the intraperitoneal administration of 0.6% acetic acid. Treatment with carnosine also attenuated the second phase, but not the first phase, of the nociceptive response to formalin. Moreover, intrathecal, but not intraplanter, administration of carnosine attenuated the second phase of the nociceptive response to formalin. Our immunohistochemical and behavioral data suggest that carnosine has antinociceptive effects toward inflammatory pain, which may be mediated by the attenuation of nociceptive sensitization in the spinal cord.


Enrichment of Yersinia pestis from blood cultures enables rapid antimicrobial susceptibility determination by flow cytometry.
Mortality from plague is high if not treated with the proper antibiotics within 18-24 hours after onset of symptoms. The process of antibiotic susceptibility determination of Yersinia pestis isolated from blood samples may extend from 4 to more than 7 days, since the in vitro growth is very slow. To accelerate this process, we developed an enrichment protocol as well as a non-standard yet reliable method for rapid antibiotic susceptibility analysis of Y. pestis from blood cultures using flow cytometry technology. This rapid method is applicable to blood cultures containing low levels of Y. pestis.


Identification of miRNAs from stem cell derived microparticles in umbilical cord blood.
Umbilical cord blood CD34+ (UCB-CD34+) stem cells are clinically used in hematopoietic cell transplantation. However, there are limitations in the use of umbilical cord blood transplants because of the small number of cells and delayed engraftment. To gain a better understanding of functional components of UCB, we have detected and characterized CD34+ microparticles (CD34+MPs) from cord blood units. We collected cord blood units and assessed the numbers of CD34+MPs before and after red blood cell and plasma depletion by SEPAX processing using flow cytometry analysis. In parallel we identified MPs by electron microscopy. CD34+MPs and cells were isolated by MACs sorting. MicroRNAs (miR-106, miR-221, miR-517, miR-519, and miR-221) exhibited a characteristic microRNA profile that was further validated in isolated CD34+MPs. We found that in cord blood, there are CD34+MPs that carry microRNAs.


Suppression of pineal melatonin in Peromyscus leucopus by different monochromatic wavelengths of visible and near-ultraviolet light (UV-A).
The purpose of this study was to examine the effects of monochromatic visible and near-ultraviolet radiation (UV-A) on pineal melatonin suppression in the white-footed mouse, Peromyscus leucopus. To this end, mice were entrained to a daily cycle of 8 h of light and 16 h of darkness. During the night when pineal melatonin contents were high, mice were individually exposed for 5 min to specific wavelengths of monochromatic light (10 nm half-peak bandwidths). Control animals received the same handling conditions but no experimental exposure. Pineal glands were collected from animals 18 min after the 5 min experimental exposure and were later assayed for melatonin content. In groups of animals exposed to equal photon densities (2.64 X 10(15) photons/cm2) of either 320, 340, 360, 500, or 560 nm, mean pineal melatonin content was significantly suppressed as compared to the unexposed control animals. The 640 nm wavelength (red) at the same photon density did not suppress pineal melatonin. These experiments are the first to demonstrate light-induced suppression of pineal melatonin in Peromyscus leucopus. In addition, these data reveal a novel finding: the suppression of pineal melatonin content by ultraviolet wavelengths as low as 320 and 340 nm.


Oral immunization with a shiga toxin B subunit: rotavirus NSP4(90) fusion protein protects mice against gastroenteritis.
A fusion protein containing the shiga toxin-1 B subunit (STB) linked to a 90 amino acid peptide (aa residues 86--175) from simian rotavirus (SA--11) nonstructural protein NSP4 was synthesized in Escherichia coli. Mice orally inoculated with 60 microg of STB::NSP4(90) fusion protein per dose generated higher humoral and intestinal antibody titers than mice inoculated with 30 microg of NSP4 alone. Serum anti-NSP4 IgG2a isotype titers were substantially greater than IgG1 titers, suggesting a dominant Th1 immune response. ELISA measurement of cytokines secreted from splenocytes isolated from immunized mice confirmed the STB::NSP4(90) fusion protein stimulation of a strong Th1 cell mediated immune response. Diarrhea in SA-11 rotavirus challenged neonates suckling from STB::NSP4 immunized dams was significantly reduced in severity and duration in comparison with virus challenged neonates from unimmunized mice. Together, our experiments demonstrate for the first time that the shiga toxin B subunit provides ligand mediated delivery of virus antigens to the gut-associated lymphoid tissues for enhanced stimulation of humoral and cellular responses against rotavirus gastroenteritis.


Summary of the Experiences and Results of Transesophageal Ultrasound-Guided Ventricular Septal Defect and Atrial Septal Defect Closure Operation.
Ventricular septal defect (VSD) and atrial septal defect (ASD) are congenital heart diseases. The techniques of transthoracic closure (TC) and percutaneous closure (PC) for the treatment of VSD and ASD have continuously improved and matured. This study aimed to retrospectively analyze the therapeutic effects of TC and PC on VSD and ASD patients. We retrospectively reviewed 928 patients (552 VSD and 376 ASD) who had undergone TC or PC guided by transesophageal ultrasound at the Department of Cardiac Macrovascular Surgery of the First Affiliated Hospital of Nanchang University between August 2010 and August 2020. We collected and evaluated the clinical data of the patients, including age, gender, weight, inlet and outlet diameters of defect, and the operation results of TC and PC. Descriptive statistics were used to analyze means and standard deviations (SD), and the Chi-square test was used to evaluate the difference between groups. Among the 928 patients who were treated with the closure operation, there were no casualties, with 907 patients (97.7%) showing successful closure. Among the 552 VSD patients who were treated with TC, 540 showed successful close, while 12 cases required extracorporeal circulation after the failure of TC. Among the 376 patients with ASD, 256 patients were treated with TC, of which 251 were successful, and five were failures, including three shedding cases. In addition, among the 120 patients who were treated with PC, 116 were successful, and four were failures, including two shedding cases. Postoperative follow up for patients with successful closure operations demonstrated that the complications of aortic and tricuspid regurgitation, hydro-pericardium, III° atrioventricular block, shedding of closure umbrella, hemolysis, and thrombosis had not occurred. Closure operation of VSD and ASD by esophageal ultrasound has the advantages of lower trauma and blood loss, shorter hospital stay, simple operation, fewer postoperative complications, and significant therapeutic efficacy.


Risk factors for severe bacterial infections after valve replacement and aortocoronary bypass operations: analysis of 246 cases by logistic regression.
Risk factors for severe bacterial infections, that is, deep sternal wound infection, pneumonia, septicemia, and prosthetic valve endocarditis, were evaluated in 246 consecutive patients undergoing valve replacement (N = 84) or aortocoronary bypass operation (N = 162). Multiple logistic regression analysis was applied to determine the ability of putative risk factors to predict infection. The risk factors considered were age, sex, diabetes mellitus, duration of cardiopulmonary bypass (CPB), duration of operation, amount of blood restored on the day of operation, repeat thoracotomy for bleeding, intraaortic balloon pumping, reoperation, emergency operation, and the professional status of the surgeon. Severe infections occurred in similar frequency after valve replacement (8/84; 9.5%) and aortocoronary bypass (11/162; 6.8%). For patients who had a bypass procedure, repeat thoracotomy was the only factor significantly associated with infection (p = 0.0004). However, the classification analysis revealed that this variable alone is too unspecific for a reliable prediction. Univariate analysis indicated that restoration of more than 2,500 ml of blood (p = 0.0001), reoperation (p = 0.0821), duration of operation (p = 0.0061), duration of CPB (p = 0.0318), and intraaortic balloon pumping (p = 0.0281) were associated with infection following valve replacement. A model with three variables emerged from the multiple logistic regression: after correction for blood restoration, reoperation, and duration of CPB, no other variable was of additional predictive value. For patients who underwent valve replacement, the model performed well in predicting complications. The classification analysis revealed a high correspondence between observed and predicted instances of infection: it correctly predicted 75% of the patients with infection and 96% of those without infection.(ABSTRACT TRUNCATED AT 250 WORDS)


Detecting single-target changes in multiple object tracking: The case of peripheral vision.
In the present study, we investigated whether peripheral vision can be used to monitor multiple moving objects and to detect single-target changes. For this purpose, in Experiment 1, a modified multiple object tracking (MOT) setup with a large projection screen and a constant-position centroid phase had to be checked first. Classical findings regarding the use of a virtual centroid to track multiple objects and the dependency of tracking accuracy on target speed could be successfully replicated. Thereafter, the main experimental variations regarding the manipulation of to-be-detected target changes could be introduced in Experiment 2. In addition to a button press used for the detection task, gaze behavior was assessed using an integrated eyetracking system. The analysis of saccadic reaction times in relation to the motor response showed that peripheral vision is naturally used to detect motion and form changes in MOT, because saccades to the target often occurred after target-change offset. Furthermore, for changes of comparable task difficulties, motion changes are detected better by peripheral vision than are form changes. These findings indicate that the capabilities of the visual system (e.g., visual acuity) affect change detection rates and that covert-attention processes may be affected by vision-related aspects such as spatial uncertainty. Moreover, we argue that a centroid-MOT strategy might reduce saccade-related costs and that eyetracking seems to be generally valuable to test the predictions derived from theories of MOT. Finally, we propose implications for testing covert attention in applied settings.


Transition metals anchored on two-dimensional p-BN support with center-coordination scaling relationship descriptor for spontaneous visible-light-driven photocatalytic nitrogen reduction.
Solar energy has the potential to revolutionize the production of ammonia, as it could provide a reliable and uninterrupted source of energy for the chemical reaction involved. However, improving the catalytic performance of catalysts often leads to a reduction in their band gaps, which results in insufficient photogenerated electron potential to realize the nitrogen reduction reaction (NRR), and thus the development of NRR efficient photocatalysts remains a great challenge. Herein, based on the density functional theory (DFT), a series of single-atom photocatalysts with transition metals (TMs) doped on porous boron nitride (p-BN) nanosheet are proposed for NRR. Among them, Re-B3@p-BN could effectively catalyze gas-phase N2 through the corresponding pathways with limiting potentials of 0.31 V. Meanwhile, it exhibits excellent light absorption efficiency under illumination and could spontaneously catalyse nitrogen fixation reactions due to the suitable forbidden band and high photogenerated electron potential. Moreover, a linear relationship descriptor based on the intrinsic properties has been established, using a machine learning approach by considering the combined effects of the central metal atom and the coordination atoms. This descriptor could help accelerate the development of rational and improved 2D NRR photocatalysts with high catalytic activity and high selectivity.


Association of the vertical and horizontal force-velocity profile and acceleration with change of direction ability in various sports.
This study aimed to assess the association of the mechanical variables derived from the force-velocity (FV) profile (i.e. theoretical maximal force [F0], velocity [V0] and maximal power output [Pmax]) with change of direction (COD) performance in soccer, basketball and tennis players. Fifty-four male athletes (soccer n = 23; tennis n = 16; basketball n = 15) were assessed for the vertical (Vrt) and horizontal (Hzt) FV profiles, COD with the dominant (D) and nondominant (ND) legs, using the modified 505 test, and sprint. Hzt FV profile parameters showed stronger associations with performance than Vrt FV profile in the three sports. Specifically, the Hzt parameter most strongly associated with COD performance was F0 in tennis (r = -0.83; p<0.001) and Pmax in soccer and basketball (r = -0.79; p<0.001). Associations between sprint times and COD test ranged from (r = 0.73-0.82) in soccer players, (r = 0.74-0.87) in tennis players and (r = 0.62-0.85) in basketball players, respectively (p<0.05). Considering the whole sample and the random effect of the type of sports, an improvement in sprint acceleration (i.e. one N/kg increase in F0 and one W/kg in Pmax) was associated with -0.15 s and -0.04 s to complete the 505 test, respectively. In conclusion, our results suggest the potential usefulness of assessing the Hzt FV profile to maximize acceleration capabilities through training interventions which, in turn, may translate into improved COD performance. However, further longitudinal and experimental research is needed to confirm this hypothesis.


Randomized trial of cognitive behaviour group therapy and a mindfulness-based intervention for social anxiety disorder: Preliminary findings.
Recent studies have evaluated the possible efficacy of mindfulness-based interventions (MBIs) for social anxiety disorder (SAD). However, few trials have compared MBIs with a first-line treatment. This study evaluated the relative efficacy of an MBI adapted for SAD (MBI-SAD) to cognitive behaviour group therapy (CBGT) for SAD. Participants were randomized to 12 weekly group sessions of the MBI-SAD (n = 52) or CBGT (n = 45). Results revealed that CBGT fared better than the MBI-SAD in reducing clinician- and self-rated social anxiety severity. The difference between the MBI-SAD and CBGT exceeded the prespecified noninferiority margin for our primary outcome the Liebowitz Social Anxiety Scale, but findings are inconclusive as the width of the confidence interval extended in both directions surrounding the noninferiority margin. The MBI-SAD compared favourably with CBGT in improving other indices of well-being (depression, self-esteem, satisfaction with life, social adjustment). Contrary to expectation, the MBI-SAD did not produce greater changes in mindfulness and self-compassion than CBGT. Overall, results confirm that CBGT is robust treatment for SAD and should be considered as first-line treatment.


Emodin accelerates diabetic wound healing by promoting anti-inflammatory macrophage polarization.
Diabetic wound healing, characterized by chronic inflammation, remains a medical challenge. The failure of prompt conversion from pro-inflammatory M1-like macrophage to pro-healing M2-like macrophage is the main obstacle to diabetic wounds. Emodin, an anthraquinone derivative, has multiple bioactivities, including antibacterial, anticancer, and anti-inflammatory. Recently, emodin has shown potential in promoting wound healing. However, the underlying molecular mechanism remains unclear. In this study, we examined the effects of emodin on wound healing in db/db diabetic mice using a full-thickness excision model. Our results showed that emodin can remarkably accelerate healing by enhancing extracellular matrix (ECM) synthesis and granulation tissue formation. We identified 32 potential targets of emodin by network pharmacology analysis, and our transcriptome analysis highlighted the down-regulation of the NF-κB signaling pathway mediated by emodin. Mechanistically, emodin was shown to inhibit the p65-NF-κB complex and promote the proportion of M2 (anti-inflammatory)-like phenotype macrophages both in vitro and vivo. Then, bone-marrow-derived macrophages were co-cultured with fibroblasts (mouse dermal fibroblasts cells). Treatment of emodin significantly increased the proportion of M2-polarized macrophages and the expression level of TGF-β, a typical ECM formation-related cytokine secreted by the M2 macrophages in the co-cultured supernatant. We further revealed that emodin improved the proliferation of mouse dermal fibroblasts (MDFs) cells and upregulated the expression levels of collagen III, fibronectin and α-SMA in MDFs cells in emodin-treated co-culture systems. 1D11, a neutralizing antibody for all three major TGF-β isoforms, diminished the biological effects of emodin on proliferation and ECM formation in MDFs cells. Taken together, our study suggests emodin may serve as an effective therapeutic agent for diabetic wounds.


National trends in buprenorphine prescribing before and during the COVID-19 pandemic.
Recent studies have shown that early in the COVID-19 pandemic, rates of buprenorphine prescription dispensing for opioid use disorder (OUD) were relatively stable. However, whether that pattern continued later in the pandemic is unclear. This study examines the monthly rate of dispensed buprenorphine prescriptions during the early period and the later period of the pandemic. The study uses interrupted time series analysis to examine buprenorphine prescription dispensed, average day's supply, payment source, and the number of patients with a dispensed buprenorphine prescription. The study utilized January 2019-April 2021 data from IQVIA National Prescription Audit, PayerTrack and Total Patient Tracker databases. After an initial increase in the number of patients prescribed buprenorphine in the early period of the pandemic, the monthly rate of patients prescribed buprenorphine increased at a lower rate compared to the pre-pandemic period (6100 vs 4600/month). The study observed a decline in the number of buprenorphine prescriptions dispensed both in levels and growth rate during the pandemic, but an increase occurred in the average day's supply of buprenorphine prescriptions (17 days pre-pandemic vs 18.6 day during the pandemic). Medicaid became the primary payer of buprenorphine prescriptions as the pandemic continued, while buprenorphine prescriptions paid for by private insurance declined. Expanding and maintaining access to treatment for OUD were key priorities in federal and state responses to the COVID-19 pandemic. The results of our study underscore the importance of policy efforts to help increase buprenorphine prescribing for OUD.


Controlled decompression attenuates brain damage in a rat model of epidural extreme intracranial hypertension: Partially via inhibiting necroptosis and inflammatory response.
Intracranial hypertension (IH) remains a common symptom of neurological diseases, and requires stepwise treatments to release intracranial pressure (ICP). In the present study, we built a rat model of epidural extreme intracranial hypertension (EEIH) and verified the effectiveness of a surgery method called controlled decompression on attenuating brain injury induced by EEIH. For the model part, we determined the level of EEIH of rats via recording ICP and cerebral perfusion pressure (CPP) and the variation tendency of survival rates, mean blood artery pressure and mean velocity (Vm) of left middle cerebral artery (LMCA) as ICP ascending. SD rats were assigned into 4 groups: Sham group, Controlled decompression group (Con group), Rapid decompression group (Rap group) and Rapid decompression + Necrostatin-1 (Nec-1) group (Rap+Nec-1 group). The results suggested that controlled decompression lowered cerebral water content, improved neurological function, and attenuated EEIH-induced inflammation response and ROS generation to a greater extent than rapid decompression. Meanwhile, controlled decompression functioned to preserve more Nissl bodies, indicating alleviated neuron injury after EEIH. Additionally, the permeability of blood brain barrier (BBB) was also safeguarded in the Con group. Western blotting (WB) and Real-time Polymerase Chain Reaction (rt-PCR) assays consistently determined lower protein and mRNA levels of necroptosis-related molecules receptor interacting protein kinase 1 (RIPK1), interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) (WB only) in the Con and Rap+Nec-1 group. Double immunofluorescent staining found weaker fluorescence intensity of RIPK3 in the compressed cortex of the Con and Rap+Nec-1 group.


Incidence and risk factors for delirium development in ICU patients - a prospective observational study.
Delirium is an acute brain dysfunction and a frequent complication in critically ill patients. When present it significantly worsens the prognosis of patients. The aim of this study was to evaluate the incidence of delirium and risk factors for delirium in a mixed group of trauma, medical and surgical ICU patients. A prospective observational study was conducted in one of the six-bed Intensive Care Units of the University Hospital Ostrava in the Czech Republic during a 12-month period. We evaluated the incidence of delirium and its predisposing and precipitating risk factors. All patients were assessed daily using the Confusion Assessment Method for the ICU (CAM-ICU). Of the total of 332 patients with a median APACHE II (the Acute Physiology and Chronic Health Evaluation) score of 12, who were evaluated for delirium, 48 could not be assessed using CAM-ICU (47 due to prolonged coma, 1 due to language barriers). The incidence of delirium was 26.1%, with trauma and medical patients being more likely to develop delirium than surgical patients. Risk of delirium was significantly associated with age ≥ 65 years, and alcohol abuse in their anamnesis, with APACHE II score on admission, and with the use of sedatives and/or vasopressors. Delirious patients who remained in the ICU for a prolonged period showed a greater need for ventilator support and had a greater ICU-mortality.


Engineering Surface Oxophilicity of Copper for Electrochemical CO2 Reduction to Ethanol.
Copper-based materials are known for converting CO2 into deep reduction products via electrochemical reduction reaction (CO2 RR). As the major multicarbon products (C2+ ), ethanol (C2 H5 OH) and ethylene (C2 H4 ) are believed to share a common oxygenic intermediate according to theoretical studies, while the key factors that bifurcate C2 H5 OH and C2 H4 pathways on Cu-based catalysts are not fully understood. Here, a surface oxophilicity regulation strategy to enhance C2 H5 OH production in CO2 RR is proposed, demonstrated by a Cu-Sn bimetallic system. Compared with bare Cu catalyst, the Cu-Sn bimetallic catalysts show improved C2 H5 OH but suppressed C2 H4 selectivity. The experimental results and theoretical calculations demonstrate that the surface oxophilicity of Cu-Sn catalysts plays an important role in steering the protonation of the key oxygenic intermediate and guides the reaction pathways to C2 H5 OH. This study provides new insights into the electrocatalyst design for enhanced production of oxygenic products from CO2 RR by engineering the surface oxophilicity of copper-based catalysts.


Mental wellbeing in the German old age population largely unaltered during COVID-19 lockdown: results of a representative survey.
Older individuals are at increased risk of a severe and lethal course of COVID-19. They have typically been advised to practice particularly restrictive social distancing ('cocooning'), which has sparked much debate on the consequences for their mental wellbeing. We aimed to provide evidence by conducting a representative survey among the German old population during COVID-19 lockdown. A computer-assisted standardized telephone interview was conducted in a randomly selected and representative sample of the German old age population (n = 1005; age ≥ 65 years) during the first lockdown in April 2020. Assessments included sociodemographic factors, aspects of the personal life situation during lockdown, attitudes towards COVID-19, and standardized screening measures on depression, anxiety, somatization, overall psychological distress (Brief Symptom Inventory/BSI-18) and loneliness (UCLA 3-item loneliness scale). Sampling-weighted descriptive statistics and multiple multivariable regression analyses were conducted. Participants were M = 75.5 (SD = 7.1) years old; 56.3% were women. At data collection, COVID-19 lockdown had been in force for M = 28.0 (SD = 4.8) days. Overall, older individuals were worried about COVID-19, but supportive of the lockdown. Mean BSI-18 scores were 1.4 for depression, 1.6 for anxiety and 2.2 for somatization as well as 5.1 for global psychological distress. These figures did not indicate worse mental wellbeing, given normative values established by studies before the pandemic (2.0, 1.6, 2.4, 6.0, respectively). The prevalence of loneliness was 13.1%, which also fell within a range of estimates reported by studies before the pandemic. There were only few significant associations of aspects of the personal life situation during lockdown and attitudes towards COVID-19 with mental wellbeing. Resilience explained a large amount of variance. In the short-term, the mental wellbeing of the German old age population was largely unaltered during COVID-19 lockdown, suggesting resilience against the challenging pandemic situation. Our results refute common ageist stereotypes of "the weak and vulnerable older adults" that were present during the pandemic. Long-term observations are needed to provide robust evidence.


Extrasynaptic GABA(A) receptors: their function in the CNS and implications for disease.
Over the past two decades, research has identified extrasynaptic GABA(A) receptor populations that enable neurons to sense the low ambient GABA concentrations present in the extracellular space in order to generate a form of tonic inhibition not previously considered in studies of neuronal excitability. The importance of this tonic inhibition in regulating states of consciousness is highlighted by the fact that extrasynaptic GABA(A) receptors (GABA(A)Rs) are believed to be key targets for anesthetics, sleep-promoting drugs, neurosteroids, and alcohol. The neurosteroid sensitivity of these extrasynaptic GABA(A)Rs may explain their importance in stress-, ovarian cycle-, and pregnancy-related mood disorders. Moreover, disruptions in network dynamics associated with schizophrenia, epilepsy, and Parkinson's disease may well involve alterations in the tonic GABA(A)R-mediated conductance. Extrasynaptic GABA(A)Rs may therefore present a therapeutic target for treatment of these diseases, with the potential to enhance cognition and aid poststroke functional recovery.


Effect of transcutaneous electrical nerve stimulation through acupoints of Pucan (BL 61) and Shenmai (BL 62) on intraocular pressure in patients with glaucoma: a randomized controlled trial.
To investigate the effects of transcutaneous electrical nerve stimulation (TENS) through acupoints on the intraocular pressure (IOP) in patients with glaucoma. A single-blinded, randomized experimental design study was conducted. Patients from the North of Taipei Ophthalmology outpatient department diagnosed with intraocular hypertension were selected and were further enrolled if they met the research subject criteria. The patients who met all criteria, and who met no exclusion criteria became the participants. Participants were randomly assigned into the treated group, wherein the TENS electrodes (Qing Ming Medical Device Co., Ltd., New Taipei City, China) were applied with direct current (DC) on the acupoints Pucan (BL 61) and Shenmai (BL 62) for 20 min. The control group received no TENS electrode treatments. Measurements of IOP were taken four times using a pneumotonometer (Clinico Co., Ltd., New Taipei City, China), before, immediately after, 30 min after, and 60 min after TENS electrode treatments. Eighty-two participants completed the experiment. IOP decreased more in the group treated with DC (P < 0.01) than in the control group. The IOPs were not affected by the age of the patients and their usage of medications. TENS of acupoints of Pucan (BL 61) and Shenmai (BL 62) could significantly reduce the IOP in patients with glaucoma.


Potential of patulin production by Penicillium expansum strains on various fruits.
In this study, we investigated the pathogenicity and patulin production by ten strains of Penicillium expansum on various fruits (apples, apricots, kiwis, plums and peaches) at two (4°C and 25°C) different temperature regimes. All strains caused the infectious rots on all fruits at 4 and 25°C except one strain (PEX 09) at 4°C. Two strains (PEX 20 and PEX 12) out of ten produced the highest amounts of patulin on all fruits tested. The patulin production by P. expansum is high at 25°C compared to 4°C. All strains of P. expansum accumulated patulin ranging from 100-13,200 μg/kg and nine strains ranging from 100-12,100 μg/kg in all fruits at 25°C and 4°C, respectively. Among ten strains of P. expansum, strain PEX 20 produced the greatest amount of patulin on apricots (13,200 μg/kg of rotten fruit) and on apples (12,500 μg/kg) at 25°C after 9 days of incubation. At 4°C, this strain produced 12,100, 12,000, 2,100 and 1,200 μg/kg of patulin on apricots, apples, plums and peaches, respectively, after 45 days of incubation. Strain PEX 12 produced the highest amount of patulin on kiwis (10,700 μg/kg) at 25°C and 10,300 μg/kg at 4°C. Patulin production by P. expansum on peaches and plums at both temperatures were lower than other fruits. The results of this study showed that careful removal of rotten fruits is essential to produce patulin-free fruit juice, since high patulin levels in apricots, apples and kiwis could result in a level greater than 50 μg/kg of this mycotoxin in finished fruit juices, when one contaminated fruit occurs in 264, 250 and 214 fruits, respectively. So, the fruit processors should take care in not using rotten fruits for juice production to avoid the patulin problem worldwide, since this study proved that most important fruits being used for juice production and direct human consumption are susceptible to P. expansum and subsequent patulin production even at low temperatures. This is the first comprehensive report regarding patulin production by different strains of P. expansum on various fruits from Italy at different temperature regimes.


Discovery, design and synthesis of Y-shaped peroxisome proliferator-activated receptor δ agonists as potent anti-obesity agents in vivo.
We have discovered and demonstrated the in vitro and in vivo PPARδ-selective activity of novel Y-shaped agonists. These compounds activated hPPARδ with EC(50) values between 1 and 523 nM. Surprisingly, compounds 10a, 11d, 11e and 11f were the most potent and most selective hPPARδ agonists with 10(4)-fold selectivity over the other two subtypes, namely, hPPARα and hPPARγ. The PPARδ ligands 10a, 11e and 11f showed good bioavailability and in vivo efficacy.


Influence of fungi on growth and survival of Onychiurus armatus (Collembola) in a metal polluted soil.
The influence of food quantity and quality on growth and survival of Onychiurus armatus (Tullb.) in metal polluted environments has been investigated in laboratory experiments. The Collembola was reared on five species of fungi isolated from a metal polluted soil close to a brass mill in SE Sweden.Survival of O. armatus was improved when fungal biomass was continuously added in a polluted mor (1,300 ppm Zn and 200 ppm Cu), and when specimens were fed metal polluted fungi for 1, 3 and 7 days a week, only those that were starved had increased mortality. Allometric growth, on the other hand, was significantly reduced when Collembola was given surplus of metal polluted fungi, whereas growth losses caused by metals were offset by protein rich food. Hence, sufficient food quantities alone could overcome mortality losses but not growth retardation in a metal polluted environment.Feeding preference of O. armatus was not determined by the protein content of the fungi although this was beneficial for growth. Metals changed the relative palatability of fungal species, but one of the metal tolerant species, Paecilomyces farinosus, which was also protein rich, remained reasonably attractive for O. armatus also when it was metal polluted. The mechanisms by which growth and survival of O. armatus were promoted by a combination of protein and Zn/Cu rich fungi seemed to be crucial in understanding the fate of a population of this species in a metal polluted soil.


Drainage of Tumor-Derived DNA into Sentinel Lymph Nodes in Breast Cancer Patients.
Circulating tumor DNA (ctDNA) is released from cancer cells by apoptosis or other mechanisms, and as tumor tissue contains both blood and lymphatic vessels, ctDNA can spread to local lymph nodes (LNs). We aimed to detect the tumor-derived free DNA in metastasis-free LNs in patients with breast cancers harboring the PIK3CA-H1047R mutation. One hundred twenty-three patients were evaluated and the PIK3CA-H1047R mutation was assayed in sentinel LNs (SLNs), non-SLNs without metastasis, and serum by digital PCR. The mutant DNA was more frequent in metastasis-free SLNs (21.6%) than in metastasis-free non-SLNs (8.6%; P = 0.038), and patients with mutation-positive SLNs were more likely to be positive for serum mutant DNA. Apoptosis in primary breast tumors was determined by TUNEL assay. The apoptotic index was significantly higher (P = 0.003) in patients with mutation-positive SLNs without metastasis (mean, 1.17%) than those with mutation-negative SLNs without metastasis (mean, 0.79%). It was also significantly higher (P = 0.006) in those with mutation-positive serum (mean, 1.41%) than in those with mutation-negative serum (mean, 0.86%). Furthermore, fragment size of PIK3CA-H1047R mutant DNA in metastatic-free SLN lysate used for the one-step nucleic acid amplification (OSNA) assay was short (<500 bp). These results support the theory that DNA is released from the primary tumor via apoptotic fragmentation. In conclusion, ctDNA is detectable in metastasis-free LNs and significantly more frequent in SLNs from patients with breast tumors harboring a high apoptotic index, consistent with drainage of ctDNA from apoptotic primary tumor cells into SLNs.


Ventilation strategies based on an aerodynamic analysis during a large-scale SARS-CoV-2 outbreak in an acute-care hospital.
This study aimed to investigate ventilation strategies to prevent nosocomial transmission of coronavirus disease 2019 (COVID-19). We conducted a retrospective epidemiological investigation of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a teaching hospital (February-March 2021). The largest outbreak ward was studied, and measurements were taken to determine the pressure difference and air change per hour (ACH) of the rooms. Airflow dynamics were assessed using an oil droplet generator, indoor air quality sensor, and particle image velocimetry in the index patient's room, corridor, and opposite rooms, by varying the opening and closing of windows and doors. During the outbreak, 283 COVID-19 cases were identified. The SARS-CoV-2 spread occurred sequentially from the index room to the nearest room, especially the opposite. The aerodynamic study demonstrated that droplet-like particles in the index room diffused through the corridor and the opposite room through the opening door. The mean ACH of the rooms was 1.44; the air supply volume was 15.9% larger than the exhaust volume, forming a positive pressure. Closing the door prevented diffusion between adjacent rooms facing each other, and natural ventilation reduced the concentration of particles within the ward and minimised their spread to adjacent rooms. Spread of droplet-like particles between rooms could be attributed to the pressure difference between the rooms and corridor. To prevent spread of SARS-CoV-2 between rooms, increasing the ACH in the room by maximising ventilation and minimising the positive pressure through supply/exhaust control and closing the room door are essential.


Optimizing intervention tools to improve nutrition and physical activity for colorectal cancer survivors (Tools To Be Fit): Study protocol of a randomized factorial experiment.
Colorectal cancer (CRC) is the 2nd leading cause of cancer death in the United States. The American Cancer Society (ACS) Nutrition and Physical Activity Guidelines are associated with longer survival among CRC survivors, but few report behaviors consistent with the guidelines. The Tools To Be Fit study, based on the Multiphase Optimization Strategy (MOST) framework, is a full factorial experimental to optimize a remotely delivered 48-week diet and physical activity intervention for non-metastatic CRC survivors. The intervention includes a core component (booklet and personal report). CRC survivors (N = 400) are additionally randomly assigned to one of 16 combinations of four candidate components, each with 2 options: 1) text messaging (on/off); 2) self-monitoring modality (digital/paper); 3) health coaching (on/off); and 4) support person coaching (on/off). Our primary outcome is adherence to the ACS guidelines after 48 weeks using a score that includes physical activity from accelerometers, dietary intake from a food frequency questionnaire, and body mass index (BMI) measured by a technician. Secondary outcomes include the ACS score after 24 weeks and score components at 24 and 48 weeks. Exploratory outcomes include adherence and change in Social Cognitive Theory constructs. We will explore moderation by sociodemographic, clinical, and psychological/behavioral factors; and change in the ACS score in relation to change in levels of insulin, insulin sensitivity, inflammation, gut microbiome structure, fatigue, depression, and sleep disturbance. The proposed study aims to inform a randomized controlled trial to determine whether an optimized intervention reduces risk of recurrence among CRC survivors.


Standardized pain flowsheet: impact on patient-reported pain experiences after cardiovascular surgery.
Administration of analgesics per patient request or random pain assessments may provide inadequate pain management. To examine the impact of nurses' use of a standardized pain flowsheet to document pain assessment and pharmacologic management on patient-reported pain intensity. A pre-post intervention design was used to compare 61 patients. In the preimplementation group, traditional charting of pain presence or absence was documented in the narrative notes and pharmacologic management was recorded on the medication profile. In the postimplementation group, the intensity of pain and pharmacologic management were documented on a pain flowsheet. Within 24 hours after transfer to the step-down unit, patients were interviewed regarding pain intensity experienced in the surgical heart unit and at the time of questioning. The distribution of these pain intensity scores was compared. The postimplementation group reported significantly lower pain intensity ratings for the average amount of pain experienced while in the surgical heart unit, the least amount of pain experienced while in the surgical heart unit, and the pain experienced at the moment of questioning. Use of a standardized pain flowsheet to assess pain intensity and document pharmacologic intervention may improve pain management in postsurgical cardiovascular patients.


Quantitative three-dimensional computed tomography analysis of glenoid fracture patterns according to the AO/OTA classification.
This study measures the characteristics of glenoid fractures to determine if the AO Foundation and Orthopaedic Trauma Association (AO/OTA) classification captures the most common fracture patterns. The primary null hypothesis was that surface area and degree of fragmentation do not differ among the different fracture types. Secondarily, we tested if there was a relationship between high- vs. low-energy trauma and fracture classification. Three-dimensional models were created for a consecutive series of 53 fractures. The fracture classifications, the number of fragments, and the fragmented articular surface area were related to the type of injury. The difference of articular surface size and number of fragments among classification groups was analyzed with the Kruskal-Wallis test. There is a significant difference in fractured articular surface area among classification groups. Compared with transverse and multifragmented fractures, both anterior and posterior fractures involved significantly less of the articular surface area. High-energy trauma is associated with transverse and multifragmented fractures in 93% of the cases. It is associated with a greater number of fracture fragments and fracture of a larger percentage of the glenoid surface area, with a mean fractured surface of 60% for high-energy fractures and 25% for low-energy injuries. Quantitative 3-dimensional CT analysis confirms that the current AO/OTA classification adequately characterizes and discriminates glenoid fracture patterns. The classification groups are related to the fragmented articular surface area and the number of fragments. Also, the mechanism of injury is related to the classification group, which supports the clinical relevance of the classification.


Lack of association of extraversion and neuroticism with sibship size and birth order among Arab college students.
In a sample of 450 (220 men, 230 women) Egyptian undergraduates (M age=20.6 yr., SD=1.9), scores on extraversion and neuroticism scales were not associated with sibship size and birth order.


Efferent projections of different subpopulations of central noradrenaline neurons.
Early anatomical studies of the projections of central noradrenergic (NA) neurons led to the widely accepted view of NA cells as a class of diffusely projecting neurons. This view greatly influenced the formulation of numerous hypotheses about the functional role of these neurons in the central nervous system (CNS). With the introduction of transmitter-specific retrograde and anterograde transport methods, two powerful tools became available to rigorously re-examine whether the projections of NA neurons are diffuse or topographically organized. This article summarizes some of the results of these studies in which retrograde transport of fluorescent tracers and anterograde transport of the lectin Phaseolus vulgaris leucoagglutinin (PHA-L), respectively, were combined with immunohistochemical identification of NA neurons and their projections. The results of these studies revealed a remarkable degree of specificity in the projections of different subgroups of NA neurons. In the rat CNS, the differential distribution of NA axons of the locus coeruleus (LC) and non-coerulean NA cells is particularly striking in the spinal cord and brainstem. In these regions, NA axons of the LC are primarily distributed to sensory nuclei while NA axons of non-coerulean NA neurons are distributed to motor nuclei. The results support the proposition that NA neurons can be divided into subgroups which differ in their connections and hence represent separated anatomical entities with different functional capacities.


The J558 VH CDR3 region contributes little to antibody avidity; however, it is the recognition element for cognate T cell control of the alpha(1-->3) dextran-specific antibody response.
Analysis of the humoral immune response of BALB/c mice to alpha(1-->3) dextran (Dex) reveals novel aspects of T cell-mediated control of 'type 2 thymus-independent' responses against polysaccharide antigens. The IgM and IgG antibody response, dominated by the J558 idiotype (Id), is controlled by Id-specific T cells. These regulatory T cells, for which the T cell clone 178-4 Ts with characterized TCR alpha and beta chain sequences is the prototype, expand in all BALB/c mice upon immunization with Dex. They suppress in a cognate interaction the expansion of J558 Id-bearing B cells, committed for production of IgG antibodies. Furthermore they provide a gate which precludes variability in the VH CDR3 region of IgG antibodies appearing occasionally in the periphery. The VH CDR3 region is the recognition element of 178-4 Ts analogous T cells but contributes little to affinity for the antigen. For recognition by 178-4 Ts cells not even minimal sequence deviations of the J558 Id peptide are allowed. The tight germline programmed complementarity between J558 Id-bearing Dex-specific B and J558 Id-specific 178-4 Ts analogous T cells leaves little room on both sides for ontogenetic variability.


Association between Albumin-Globulin Ratio and Mortality in Patients with Chronic Kidney Disease.
Malnutrition and inflammation are highly prevalent and tightly regulated with each other in chronic kidney disease (CKD) patients. Inflammation can lead to malnutrition in patients with sufficient nourishment, while malnutrition may also induce an inflammatory response. This study investigated whether the albumin-globulin ratio (AGR) can predict the mortality risk in CKD patients. We enrolled 956 stage 3-5 CKD patients retrospectively at a medical center. Patients' baseline characteristics including demographics, laboratory data, pharmacotherapy, and comorbidities were collected for statistical adjustments. The study patients were stratified into three AGR groups according to similar magnitudes of hazards for mortality as follows: low AGR group, AGR ≤ 1.0; moderate AGR group, 1.1 ≤ AGR < 1.3; high AGR group, AGR ≥1.3. Multivariate Cox proportional hazard analysis was performed to evaluate the association of the AGR with the study outcomes, including overall and cardiovascular disease (CVD) mortality. During a median follow-up duration of 2.44 years, 108 (11.3%) deaths were recorded and 50 patients died from CVD. In adjusted model 1, the moderate AGR group was associated with hazard ratios (HR) of 0.57 (95% CI = 0.36-0.90, p = 0.016) and 0.52 (95% CI = 0.28-0.98, p = 0.043) for all-cause and CVD mortality compared with the low AGR group, respectively. The high AGR group was associated with HRs of 0.49 (95% CI = 0.27-0.90, p = 0.021) and 0.27 (95% CI = 0.1-0.74, p = 0.01) for all-cause and CVD mortality compared with the low AGR group, respectively. Similar results were obtained in the adjusted model 2 (inverse probability of the group weighted Cox model). In addition, the association between the AGR and mortality risk remained significant when the AGR was treated as a continuous variable. AGR is a significant biomarker predicting overall and cardiovascular mortality risk independent of various important factors amongst stage 3-5 CKD patients. We suggest that the AGR may be a simple and inexpensive measurement for detecting CKD patients at risk of mortality.


Rapid access to spirocylic oxindoles: application of asymmetric N-heterocyclic carbene-catalyzed [3 + 3] cycloaddition of imines to oxindole-derived enals.
A chiral N-heterocyclic carbene (NHC)-catalyzed [3 + 3] cycloaddition reaction of imines and oxindole-derived enals was developed for rapid access to spirocylic oxindoles. In most cases, the desired spirocylic oxindole products were obtained in high yields and excellent enantioselectivities with less than 1 h of reaction time.


The cariogenicity of sucrose, glucose and maize starch in gnotobiotic rats mono-infected with strains of the bacteria Streptococcus mutans, Streptococcus salivarius and Streptococcus milleri.
Twenty-one-day-old weanling gnotobiotic WAG/RIJ rats were mono-infected with Streptococcus mutans NCTC 10832, Streptococcus salivarius JMB or Streptococcus milleri NCTC 11169, and maintained on a high carbohydrate diet containing sucrose, glucose or maize starch for 21-days. Fissure caries developed with all combinations of streptococcal strain and carbohydrate except maize starch/Streptococcus salivarius JMB. Caries incidence was highest with Streptococcus mutans NCTC 10832. For all species, the ranking of carbohydrates by cariogenic potential was sucrose greater than glucose greater than maize starch.


Mixed mania associated with tricyclic antidepressant therapy in prepubertal delusional depression: three cases.
This report describes the sudden appearance of mixed mania in three children with delusional depression soon after the commencement of tricyclic antidepressant therapy. The observation is consistent with reports linking psychomotor abnormalities and psychosis in severely depressed juveniles to an increased propensity for manic switching, as well as adult studies that report a greater risk of antidepressant-induced cycling in bipolar compared with unipolar affective illness. The cases described suggest the need for caution when considering tricyclic pharmacotherapy in juveniles with severe depressive disease.


A new pattern of citrullinated peptides improves the sensitivity for diagnosing rheumatoid arthritis.
Anti-citrullinated protein antibody (ACPA) is found almost exclusively in patients with rheumatoid arthritis (RA). Commercial cyclic citrullinated peptide (CCP) assays that target ACPAs yield specificities as high as 95% for RA diagnoses, but their sensitivities only reach 50-70%. To improve the sensitivity of the CCP assay, a new pattern of citrullinated peptide was identified and named the MCSM (multiple citrulline-similar motif). The MCSM comprised a citrulline core surrounded by citrulline-similar amino acids. A series of peptides with or without the MCSM was synthesized to evaluate the function of the citrulline core and citrulline-similar amino acids. These peptides were used in the enzyme-linked immunosorbent assay to compare samples from 94 RA patients, 117 non-RA patients and 116 healthy subjects. Additionally, the MCSM assay was compared with a commercial CCP assay. When the cutoff value was set at 0.274, the sensitivity and specificity of the MCSM assay were 79.6% and 96.6%, respectively. When one citrulline was substituted in the citrulline core, the sensitivity of the assay decreased from 79.6% to 61%. If all three citrulline-similar amino acids were substituted in the backbone, the sensitivity of the MCSM assay decreased from 79.6% to 58.5%. The coincidence rate of the MCSM assay to the commercial CCP assay was 97.6%. The citrulline core and citrulline-similar amino acids are crucial components of the MCSM pattern. This new MCSM assay could be used to diagnose RA.


A novel treatment for early gastrointestinal carcinoma by ultrasonic endoscopic mucosal stripping.
The aim of this study was to clarify the indications for a new endoscopic mucosal resection (EMR) technique that employs a cavitational ultrasonic surgical aspirator (CUSA). Endoscopic mucosal resection has proved an effective technique for treating early mucosal gastrointestinal cancer. However, resecting a lesion larger than 2 cm en bloc requires special devices and a long processing time; and it engenders the risk of bleeding, perforation, and other complications. We investigated application of the CUSA for detaching the mucosa from the muscularis propria of extracted porcine stomachs and then clarified the specification of an endoscopic ultrasonic scalpel for endoscopic mucosal resection by investigating characteristics of two original, handmade prototype cavitational ultrasonic surgical aspirators. Use of a cavitational ultrasonic surgical aspirator should improve the ease and safety of detaching the mucosa. A small, high-power ultrasonic cylindrical vibrator should be developed to make possible a probe-type scalpel with a piezoelectric vibrator mounted in the tip of a catheter. An ultrasonic transmission-type scalpel could lead to the development of a new endoscopic mucosal resection device for clinical use. The CUSA should enable us to develop a safer, simpler, time-saving scalpel for endoscopic mucosal resection, although some resolvable technical problems remain. The CUSA might enable us to diagnose carcinoma invasion into the submucosa in aspirated specimens and then aspirate out the entire invading submucosal carcinoma.


MYH2 myopathy, a new case expands the clinical and pathological spectrum of the recessive form.
Hereditary myosin myopathies are a group of rare muscle disorders, caused by mutations in genes encoding for skeletal myosin heavy chains (MyHCs). MyHCIIa is encoded by MYH2 and is expressed in fast type 2A and 2B muscle fibers. MYH2 mutations are responsible for an autosomal dominant (AD) progressive myopathy, characterized by the presence of rimmed vacuoles and by a reduction in the number and size of type 2A fibers, and a recessive early onset myopathy characterized by complete loss of type 2A fibers. Recently, a patient with a homozygous mutation but presenting a dominant phenotype has been reported. The patient was examined thoroughly and two muscle biopsies were performed through the years. NGS followed by confirmation in Sanger sequencing was used to identify the genetic cause. We describe the second case presenting with late-onset ophthalmoparesis, ptosis, diffuse muscle weakness, and histopathological features typical for AD forms but with a recessive MYH2 genotype. This report contributes to expand the clinical and genetic spectrum of MYH2 myopathies and to increase the awareness of these very rare diseases.


Comparative study on the role of diagnostic hysteroscopy in evaluation of the uterine cavity prior to in vitro fertilization in a developing country.
Diagnostic hysteroscopy is a vital tool and a gold standard to evaluate the uterine cavity. The aim of this study was to estimate the prevalence of unsuspected intrauterine abnormalities. This cross-sectional study was done involving 870 asymptomatic, infertile women enrolled for IVF, who underwent a transvaginal ultrasound followed by office hysteroscopy. The presence of uterine cavity abnormalities was recorded. Transvaginal sonography revealed abnormal findings in 113 patients (12.9 %). Hysteroscopy confirmed the ultrasound findings in 76 (67.3 %) women with no obvious findings seen on hysteroscopy in 37 (32.7 %). Among the 757 women, who had a normal pelvic scan, abnormal findings were observed in 108 (14.2 %) on hysteroscopy, while the remaining 649 (85.7 %) patients had normal findings on hysteroscopy. Thus, a total of 184 (21.1 %) patients had confirmed abnormalities that required to be treated before performing IVF/ICSI. The present study highlights the relatively higher prevalence of intrauterine abnormalities in our patient population. Diagnosing and treating these abnormalities are imperative to improve the success of IVF treatment. Therefore, a routine diagnostic hysteroscopy in these patients becomes mandatory before proceeding with expensive procedures such as assisted reproduction.


Hepatitis C virus (HCV) infection & risk factors for HCV positivity in injecting & non-injecting drug users attending a de-addiction centre in northern India.
Injecting drug use is a major route of hepatitis C virus (HCV) infection in India, but there may be other risk factors also. This study was carried out to determine the seroprevalence of anti-HCV antibody in injecting drug users (IDUs) vs. non-IDUs (NIDUs), and to study the risk estimates for HCV seropositivity in the total sample of substance users with regard to various demographic, clinical, behavioural and personality factors. The IDUs (n = 201) and NIDUs (n = 219) were assessed for demographic, clinical and behavioural information, and were rated on instruments for severity of dependence, risk behaviour and personality profiles. Anti-HCV antibody was tested by ELISA and confirmed by recombinant immunoblot assay (RIBA) test. Almost one-third of the IDUs (64 of 201; 31.8%) were positive for anti-HCV antibody, as opposed to only seven (3.2%) of the NIDUs. The four risk factors strongly associated with HCV positivity in multivariate analysis were sharing syringe [Exp(B) 75.04; 95%CI 18.28-307.96; P<0.001], reuse of injection accessories (16.39; 3.51-76.92; P<0.001), blood transfusion (5.88; 1.63-21.23; P=0.007) and IDU status (3.60; 1.26-10.31; P=0.017). Other variables less strongly but significantly associated with HCV positivity were multiple sex partners, opioid dependence, risk behaviour scores, impulsivity, and lower age of onset of drug use. Our study showed a high seroprevalence of anti-HCV antibody in IDUs. In the substance users, HCV positivity was significantly and independently associated with several clinical, behavioural, and personality risk factors.


Successful Liver Transplantation from a Deceased Donor After Ethylene Glycol Ingestion: A Case Report and Review of the Literature of Organ Donation from Poisoned Donors.
Despite the increase in deceased organ donation over the past ten years, the gap between patients awaiting transplant and available organs continues to widen. Deceased donors secondary to acute fatal poisonings represent less than 1% of all organ donors. Organs from poisoned donors have largely been discarded due to concerns of toxin transmission and poor organ function as well as the paucity of data that exists regarding this donor population. Here, we report a case of a 40-year-old male who underwent successful liver re-transplantation from a donor who died following ethylene glycol ingestion. To our knowledge this case report is the first to describe successful re-transplantation from an ethylene glycol-poisoned donor. We also provide a comprehensive review of the literature describing organ donation from poisoned donors.


A study evaluating liquid-based endometrial cytology test and transvaginal ultrasonography as a screening tool for endometrial cancer in 570 postmenopausal women.
To evaluate the combination of transvaginal ultrasonography (TVS) and endometrial cytology test (ECT) as a potential diagnostic strategy for endometrial cancer and endometrial precancerous lesions in postmenopausal patients. 570 postmenopausal patients admitted in our hospital due to abnormal bleeding or other symptoms and/or with endometrium thickness over 5 mm on ultrasound. The endometrial thickness was evaluated by TVS. Following obtainment with written consent, all patients underwent ECT, hysteroscopy and then dilatation and curettage (D&C). Cytological sampling was conducted by scratching the uterus cavity using SAP-1 and the samples were prepared as liquid-based smear using SurePath technology. The samples were stained using Papanicolaou method. The correlation between cytological diagnosis and TVS results with the D&C histological diagnosis was analyzed. The WHO classification was used for diagnosis. Sensitivity of ECT, TVS, ECT or TVS positive, ECT and TVS positive to diagnose atypical hyperplasia or worse were estimated at 80.7%, 86.8%, 97.4%, 70.2%, specificity at 94.7%, 20.4%, 17.5%, 88.4%, positive predictive value at 58.2%, 21.1%, 22.8%, 60.2%, negative predictive value at 94.4%, 86.1%, 96.4%, 92.2%, and accuracy at 84.6%, 33.7%, 33.5%, 84.7%, respectively. Transvaginal ultrasonography and Endometrial cytology test may be regarded as a effective first-line method in endometrial pathology detection in postmenopausal women.


Human herpesvirus 8 and angiosarcoma: analysis of 40 cases and review of the literature.
To prove a possible involvement of the endotheliotropic human herpesvirus 8 (HHV-8) in the pathogenesis of angiosarcoma in samples from patients in a low HHV-8 seroprevalence area. A comprehensive series of angiosarcomas (n = 40) as well as positive and negative control tissues from patients with Kaposi's sarcoma, human immunodeficiency virus (HIV)-associated multicentric Castleman's disease or juvenile haemangioma, respectively, was analysed with two sensitive methods: immunohistochemical staining for the HHV-8 latency-associated nuclear antigen 1 (LANA-1); and polymerase chain reaction (PCR) for HHV-8 VP23 DNA sequences. None of the angiosarcoma cases and none of the negative control samples (juvenile haemangiomas) revealed positive immunohistochemical staining with the LANA-1 antibody. In contrast, HHV-8 LANA-1 was clearly detected in all analysed cases of Kaposi's sarcoma and multicentric Castleman's disease. These results were confirmed by PCR assay at the DNA level. In conclusion, the great majority of angiosarcomas investigated to date, including the series of 40 angiosarcomas analysed here, does not contain HHV-8 DNA sequences or protein. This argues against a relevant role of the endotheliotropic HHV-8 in the pathogenesis of angiosarcoma and, for vascular diseases, speaks in favour of a relatively restricted pathogenic role of HHV-8 to Kaposi's sarcoma and multicentric Castleman's disease.


Delirium in Older Patients With COVID-19 Presenting to the Emergency Department.
Delirium is common among older emergency department (ED) patients, is associated with high morbidity and mortality, and frequently goes unrecognized. Anecdotal evidence has described atypical presentations of coronavirus disease 2019 (COVID-19) in older adults; however, the frequency of and outcomes associated with delirium in older ED patients with COVID-19 infection have not been well described. To determine how frequently older adults with COVID-19 present to the ED with delirium and their associated hospital outcomes. This multicenter cohort study was conducted at 7 sites in the US. Participants included consecutive older adults with COVID-19 presenting to the ED on or after March 13, 2020. COVID-19 was diagnosed by positive nasal swab for severe acute respiratory syndrome coronavirus 2 (99% of cases) or classic radiological findings (1% of cases). The primary outcome was delirium as identified from the medical record according to a validated record review approach. A total of 817 older patients with COVID-19 were included, of whom 386 (47%) were male, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean (SD) age of patients was 77.7 (8.2) years. Of included patients, 226 (28%) had delirium at presentation, and delirium was the sixth most common of all presenting symptoms and signs. Among the patients with delirium, 37 (16%) had delirium as a primary symptom and 84 (37%) had no typical COVID-19 symptoms or signs, such as fever or shortness of breath. Factors associated with delirium were age older than 75 years (adjusted relative risk [aRR], 1.51; 95% CI, 1.17-1.95), living in a nursing home or assisted living (aRR, 1.23; 95% CI, 0.98-1.55), prior use of psychoactive medication (aRR, 1.42; 95% CI, 1.11-1.81), vision impairment (aRR, 1.98; 95% CI, 1.54-2.54), hearing impairment (aRR, 1.10; 95% CI 0.78-1.55), stroke (aRR, 1.47; 95% CI, 1.15-1.88), and Parkinson disease (aRR, 1.88; 95% CI, 1.30-2.58). Delirium was associated with intensive care unit stay (aRR, 1.67; 95% CI, 1.30-2.15) and death (aRR, 1.24; 95% CI, 1.00-1.55). In this cohort study of 817 older adults with COVID-19 presenting to US emergency departments, delirium was common and often was seen without other typical symptoms or signs. In addition, delirium was associated with poor hospital outcomes and death. These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation.


Pediatric Inflammatory Bowel Disease: Special Considerations.
Pediatric inflammatory bowel disease may present differently than adult onset disease. It is important to consider a broader differential diagnosis in very early onset disease. Diagnostic and treatment decisions must consider the long term risks and benefits over a lifetime. Surgical triggers in children may include impaired growth and inability to wean from steroids in addition to standard adult indications. Effective transition of care to adult providers is a key to prevent flares and loss of follow-up.


Estimation methods for flow imaging with high frequency ultrasound.
This article proposes to estimate slow blood flow with high frequency ultrasound imaging. The proposed technique combines 2 methods. First, a statistical method, called Speckle Flow Imaging (SFI) based on the analysis of changes in the speckle pattern along time, gives an index directly related to the total velocity vector. Secondly, a block matching approach estimates the in-plane velocity components. Results on calibrated flow sequences of blood mimicking fluid have shown good agreement with the statistical model. The quantification of flow is achieved with pulsed flow and is also angle independent when the flow is perpendicular to the ultrasound beam. Speckle Tracking has been evaluated on the same data and has shown good estimation of the in-plane velocity vector when the component of velocity perpendicular to the imaging plane is inferior to 1mm/s. The results of these two methods permit the evaluation of the total 3D velocity field and the orthogonal velocity component relative to the imaging plane. This allows the quantification of blood flow (volumetric per time unit across the sequence).


[Ipsilateral frontal and contralateral cerebellar diaschisis related to unilateral pontine infarction].
A right frontal and left cerebellar diaschisis, resulting from a right pontine infarction, is reported in a patient with complete left hemiplegia. Magnetic resonance imaging and CT scan supported the existence of the pontine infarction. The SPECT-HMPAO-99mTc showed a relative hypoactivity in the right frontal lobe and left cerebellar hemisphere.


[Determination of several substrate-decomposition enzyme activities of Agrocybe cylindracea at different stages of development with spectrophotometer].
In the present paper the authors studied the activities of amylase, peroxidase, laccase, protease and cellulase at different developmental stages of agrocybe cylindracea and its mutation with the spectrophotometer. The result showed that the activity of amylase and peroxidase in hyphal stage is the highest for the two basidiomycetes. It can be concluded that these two enzymes are important in vegetative growth stage, but they may have little effect after the appearance of fruit body. The change of their protease is similar: in the hyphal growth stage it is higher than that of mature mushroom. But the activities of laccase and cellulase are very different between the two basidiomycetes. It is obvious that they are some different in physiology and biochemistry.


Murine erythroid differentiation kinetics in vivo under normal and anemic stress conditions.
Our current understanding of the kinetics and dynamics of erythroid differentiation is based almost entirely on the ex vivo expansion of cultured hematopoietic progenitor cells. In this study, we used an erythroid-specific, inducible transgenic mouse line to investigate for the first time, the in vivo erythroid differentiation kinetics under steady-state conditions. We demonstrated that bipotent premegakaroycyte/erythroid (PreMegE) progenitor cells differentiate into erythroid-committed proerythroblast/basophilic erythroblasts (ProBasoE) after 6.6 days under steady-state conditions. During this process, each differentiation phase (from PreMegE to precolony forming unit-erythroid [PreCFU-E], PreCFU-E to CFU-E, and CFU-E to ProBasoE) took ∼2 days in vivo. Upon challenge with 5-flurouracil (5-FU), which leads to the induction of stress erythropoiesis, erythroid maturation time was reduced from 6.6 to 4.7 days. Furthermore, anemia induced in 5-FU-treated mice was shown to be due not only to depleted bone marrow erythroid progenitor stores but also to a block in reticulocyte exit from the bone marrow into the circulation, which differed from the mechanism induced by acute blood loss.


[Process of retrograde axonal degeneration in amyotrophic lateral sclerosis in the light of clinical electrophysiological studies].
Correlation analysis was performed comparing the parameters of 30 electrophysiological records obtained in a group of 28 SLA patients. The obtained results suggest that in this primary neuronal disease there is evidence of retrograde degeneration of axons (dying back). Differences in the degree of progression of this pathological process at different levels of spinal innervation enable the recognition of the sequence of electrophysiological changes taking place in the peripheral parts of the axons.


Disparity tuning as simulated by a neural net.
Previous research has suggested that the processing of binocular disparity in complex cells may be described with an energy formalism. The energy formalism allows for a representation of disparity by differences in the position or in the phase of monocular receptive subfields of binocular cells, or by combination of these two types. We studied the coding of disparities with an approach complementary to previous algorithmic investigations. Since realization of these representations is probably not genetically determined but learned during ontogeny, we used backpropagation networks to study which of these three possibilities were realized within neural nets. Three types of networks were trained with noise patterns in analogy to the three types of energy models. The networks learned the task and generalized to untrained correlated noise pattern input. Outputs were broadly tuned to spatial frequency and did not respond to anti-correlated noise patterns. Although the energy model was not explicitly implemented, we could analyze the outputs of the networks using predictions of the energy formalism. After learning was completed, the model neurons preferred position shifts over phase shifts in representing disparity. We discuss the general meaning of these findings and the correspondences and deviations between the energy model, V1 neurons, and our networks.


Helium-oxygen reduces work of breathing in mechanically ventilated patients with chronic obstructive pulmonary disease.
To evaluate whether helium-oxygen mixture reduces inspiratory work of breathing (WOB) in sedated, paralyzed, and mechanically ventilated patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). Open, prospective, randomized, crossover study in the medical intensive care unit in a university hospital. 23 patients admitted for acute exacerbation of COPD and mechanically ventilated. Total WOB (WOBt), elastic WOB (WOBel), resistive WOB (WOBres), and WOB due to PEEPi (WOBPeepi) were measured. Static intrinsic positive end expiratory pressure (PEEPi), static compliance (Crs), inspiratory resistance (Rins), inspiratory (tinsp) and expiratory time constant (texp) were also measured. These variables were compared between air-oxygen and helium-oxygen mixtures. WOBt significantly decreased with helium-oxygen (2.34+/-1.04 to 1.85+/-1.01 J/l, p<0.001). This reduction was significant for WOBel (1.02+/-0.61 J/l to 0.87+/-0.47, p<0.01), WOBPeepi (0.77+/-0.38 J/l to 0.54+/-0.38, p<0.001), and WOBres (0.55+/-0.19 J/l to 0.44+/-0.24, p<0.05). PEEPi, Rins, tinsp and texp significantly decreased. Crs was unchanged. Helium-oxygen mixture decreases WOB in mechanically ventilated COPD patients. Helium-oxygen mixture could be useful to reduce the burden of ventilation.