Evaluation by MRI of paraparesis and tetraparesis of undiagnosed aetiology.
The clinical, neuroradiological, electrophysiological and CSF findings of seven patients with slowly progressive paraparesis or tetraparesis are presented. In all patients, the results of the tests performed, including evoked potentials, CT scanning, oligoclonal bands in the CSF and myelography, were normal or inconclusive and did not lead to the correct diagnosis of the aetiology. In contrast, magnetic resonance imaging (MRI) provided the diagnosis of the causative process: multiple sclerosis in four cases, meningioma of the craniocervical junction or upper thoracic spinal cord in two cases, and upper cervical cord low-grade astrocytoma in one case. The patients with tumour could be treated effectively. Without MRI, however, the correct diagnosis would have been delayed. T2-weighted spin-echo scans provided maximal sensitivity for the detection of MS plaques, although they lacked specificity for a special disease. Several morphological criteria during MRI were helpful in differentiating Binswanger's disease, leucodystrophy and adrenoleucodystrophy from MS. It is concluded that at present MRI is the only non-invasive test with which to screen reliably the craniocervical junction and the upper cervical level, both of which are diagnostically difficult regions. The case histories also demonstrate that MRI is essential in all patients where a full clinical evaluation of the suspected spinal segment is not possible. "Pure spinal MS" is a misleading diagnosis and should not be accepted without confirmation by MRI. MRI has to be performed early enough to permit timely treatment of spinal and brain-stem disorders.


Structural elucidation of aculeximycin. II. Structures of carbohydrate moieties.
Treatment of aculeximycin with 2% 1,8-diazabicyclo[5,4,0]undecene-7 (DBU)-methanol yielded three products, aculexitriose, pseudoaglycones I and II. The structural elucidation of aculexitriose was carried out by spectral analyses (MS, NMR (1H-1H 2D NMR spectroscopy, nuclear Overhauser effect] and chemical degradations of aculexitriose and its derivatives. The structure of aculexitriose was established to be a branched trisaccharide, O-6-deoxy-beta-D-glucopyranosyl-(1----2)-O-[3-amino-2,3,6-trideoxy-beta- D- arabino-hexopyranosyl-(1----3)]-6-deoxy-D-glucopyranose. On the other hand the pseudoaglycones I and II were stereoisomers with respect to a chiral center newly formed by the DBU reaction. The pseudoaglycones contain one neutral sugar and one amino sugar, which turned out to be D-mannose and L-vancosamine, respectively.


Facile characterization of polymer fractions from waste electrical and electronic equipment (WEEE) for mechanical recycling.
In view of the environmental problem involved in the management of WEEE, and then in the recycling of post-consumer plastic of WEEE there is a pressing need for rapid measurement technologies for simple identification of the various commercial plastic materials and of the several contaminants, to improve the recycling of such wastes. This research is focused on the characterization and recycling of two types of plastics, namely plastic from personal computer (grey plastic) and plastic from television (black plastic). Various analytical techniques were used to monitor the compositions of WEEE. Initially, the chemical structure of each plastic material was identified by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). Polymeric contaminants of these plastics, in particular brominated flame retardants (BFRs) were detected in grey plastics only using different techniques. These techniques are useful for a rapid, correct and economics identification of a large volumes of WEEE plastics.


Circulating concentrations of glucagon-like peptide 1, glucose-dependent insulinotropic peptide, peptide YY, and insulin in client-owned lean, overweight, and diabetic cats.
Our objectives were to measure plasma concentrations of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) in client-owned newly diagnosed diabetic cats and nondiabetic lean or overweight cats and to determine whether circulating concentrations of these hormones differed between study groups and if they increased postprandially as seen in other species. A total of 31 cats were recruited and placed into 1 of 3 study groups: lean (body condition score 4-5 on a scale of 1-9; n = 10), overweight (body condition score 6-8; n = 11), or diabetic (n = 10). Diabetics were newly diagnosed and had not had prior insulin therapy. Preprandial (fasting) and postprandial (60 min after meal) plasma hormone and glucose concentrations were measured at baseline and 2 and 4 wk. All cats were exclusively fed a commercially available high-protein and low-carbohydrate diet commonly prescribed to feline diabetic patients for 2 wk before the 2-wk assessment and continued through the 4-wk assessment. Results showed that plasma concentrations of GLP-1, GIP, PYY, and insulin increased in general after a meal in all study groups. Plasma PYY concentrations did not differ (P > 0.10) between study groups. Diabetics had greater plasma concentrations of GLP-1 and GIP compared with the other study groups at baseline (P < 0.05), and greater preprandial and postprandial GLP-1 concentrations than lean cats at 2 and 4 wk (P < 0.05). Preprandial plasma GIP concentrations were greater in diabetics than obese and lean (P < 0.05) cats at week 4. Postprandial plasma GIP concentrations in diabetics were greater than lean (P < 0.05) at week 2 and obese and lean cats (P < 0.05) at week 4. Together, our findings suggest that diabetic status is an important determinant of circulating concentrations of GLP-1 and GIP, but not PYY, in cats. The role of GLP-1, GIP, and PYY in the pathophysiology of feline obesity and diabetes remains to be determined.


Complement C7 deficiency: seven further molecular defects and their associated marker haplotypes.
Seven further molecular bases of C7 deficiency are described. All these new molecular defects involve single-nucleotide events, deletions and substitutions, some of which alter splice sites, and others codons. They are distributed along the C7 gene, but predominantly towards the 3' end. All were found in compound heterozygous individuals. The C6/C7 marker haplotypes associated with most C7 defects are tabulated.


Total surgical time in laparoscopic supracervical hysterectomy with laparoscopic in-bag-morcellation compared to laparoscopic supracervical hysterectomy with uncontained morcellation.
A possible solution to the problem of cell dissemination through laparoscopic uncontained morcellation during laparoscopic supracervical hysterectomy (LASH) is the use of laparoscopic in-bag morcellation. One criticism regarding the use of in-bag morcellation is the additional surgical time associated with this procedure. In this retrospective study we compared the total surgical time in LASH with laparoscopic in-bag morcellation (107 cases from 2016-2018) and LASH with uncontained morcellation (47 cases from 2015-2017). All surgeries were performed in the same department of minimally invasive gynaecological surgery by a total of three experienced surgeons for the indication of bleeding disorder and / or dysmenorrhea. We measured and compared total surgical time, surgical outcome, blood loss and complications in LASH with in-bag morcellation and with uncontained morcellation. Total surgical time in both procedures do not show a significant difference. Considering the learning curve in laparoscopic bag use, the total surgical time in LASH with laparoscopic in-bag morcellation is shorter than total surgical time in LASH with uncontained morcellation. Laparoscopic in-bag morcellation consumes time for bag use and handling, but saves time as it eliminates the need for meticulous sampling of lost tissue fragments and the complex lavage of the peritoneal cavity after morcellation. There is no difference between both groups in terms of blood loss, complications and surgical results. We conclude that LASH with in-bag morcellation is not related to additional surgical time when compared to LASH with uncontained morcellation.


Quantitative high-performance thin-layer chromatography of lipids in plasma and liver homogenates after direct application of 0.5-microliter samples to the silica-gel layer.
Lipid profiles were determined by high-performance thin-layer chromatography (HPTLC) after direct application of 0.5 microliter plasma from capillary blood to the silica-gel layer. Coefficients of variation for the fluorescence measurements were 2.1% for phosphatidylcholine. The recovery of known amounts of lipid was 96--100%. A linear relationship between peak area and amount of lipid was found in the nmole range, corresponding to the amount of lipid in 0.125--0.75 microliter Lipid-Trol, which served as the standard reference sample. The plasma lipids of healthy subjects and of patients suffering from various illnesses were analyzed using reference methods and HPTLC. Identical values were obtained for cholesterol esters, triacylglycerols and phosphatidylcholine. Free cholesterol values determined by HPTLC were slightly lower (7%). The correlation between data obtained by reference methods and HPTLC was as follows: cholesterol, r = 0.938; cholesterol esters, r = 0.964; triacylglycerols, r = 0.985; phosphatidylcholine, r = 0.938. The separaiton and quantitation of liver lipids using HPTLC after direct application of the tissue homogenate to the silical-gel layer was carried out. Comparison with reference methods revealed that HPTLC gave higher cholesterol values (24%). The triacylglycerol concentrations, however, were identical under both methods and correalted satisfactorily (r = 0.959).


Determination of organochlorine insecticide residues in fatty foodstuffs using a clean-up technique based on a single column of activated alumina.
A method is described for the extraction and clean-up of fatty foods prior to the determination of organochlorine insecticides and related compounds. Clean-up is based on the use of a single 22-g column of activity-4 alumina and the method is capable of routinely determining cyclodienes, BHC isomers and HCB at the 5-10 microgram/kg level and DDT-type compounds at 20-30 microgram/kg level.


Alpha-fetoprotein contributes to THP-1 cell invasion and chemotaxis via protein kinase and Gi-protein-dependent pathways.
Alpha-fetoprotein (AFP) for long was known as immunomodulator and tumor marker having multifaceted actions on the activity of normal and transformed cells. In present study, we have investigated the involvement of AFP in regulation of THP-1 cell line invasion and underlying mechanisms. Treatment with human recombinant AFP causes up-regulation of MMP9 expression, chemotaxis and calcium mobilization, and increases invasion through Matrigel, with no significant impact on THP-1 cell growth or viability. Using small molecule inhibitors, we have shown that the rhAFP-induced MMP9 expression depends on the activation of ERK1,2, JNK and Akt kinases, with the involvement of NFκB and likely, AP-1 transcription factors. In contrast, inhibition of p38 kinase, but not of JNK, had dramatic suppressive effect on the rhAFP-triggered chemotaxis. In addition, rhAFP-induced MMP9 expression and calcium response were completely blocked by pertussis toxin, indicating that Gi-protein-coupled receptor(s) has a mediatory role in these processes. CCR5 chemokine receptor is the only known Gi-protein binding to AFP. The action of CCR5 inhibitor Maraviroc results in partial suppression of MMP9 up-regulation and calcium response suggesting that CCR5 might be involved in these effects.


Degradation of thyrotropin-releasing hormone and luteinising hormone-releasing hormone by enzymes of brain tissue.
In this article, the enzymes of brain and associated tissues that can degrade thyrotropin-releasing hormone (TRH) and luteinising hormone-releasing hormone (LH-RH) are reviewed. As both TRH and LH-RH are considered to act as neurotransmitters or neuromodulators in the CNS, attention is paid to the subcellular location of the enzymes described and how their topographies and substrate specificities fit them to playing roles as inactivating agents for TRH and LH-RH or as regulators of intracellular concentrations of TRH and LH-RH. Consideration is also given to enzymes involved in biotransformation of TRH to secondary metabolites that exhibit biological activity and to enzymes involved in the metabolism of secondary metabolites.


The prevalence of moderate-severe premenstrual syndrome and premenstrual dysphoric disorder and the related factors in high school students: A cross-sectional study.
Premenstrual syndrome (PMS) is a clinical condition with physical and psychological symptoms affecting female students' quality of life, social activity, and school performance. Since most studies have focused on adult women, this study aimed to evaluate the prevalence of moderate-severe PMS, premenstrual dysphoric disorder (PMDD), and their related factors in high school students. The participants of this cross-sectional study, conducted in 2019, were 900 high school students in Sari, north of Iran. They were selected by census method from six high schools. Data were collected using Premenstrual Syndrome Screening Tool and General Health Questionnaire. The prevalence of moderate-severe PMS and PMDD were 33.9% and 12.3%, respectively. According to the logistic regression model, dysmenorrhea was significantly associated with a higher prevalence of moderate-severe PMS [adjusted odds ratio (AOR) 2.356, confidence interval (CI): 1.706-3.254, p < 0.0001] and PMDD (AOR: 1.924, CI: 1.186-3.120, p = 0.0008). Moreover, optimal general health was associated with a lower prevalence of moderate-severe PMS (AOR: 0.326, CI: 0.221-0.480, p < 0.0001) and PMDD (AOR: 0.309, CI: 0.161-0.593, p < 0.0001). The findings revealed that a family history of PMS and adding excess salt to the food were associated with a higher prevalence of PMDD (p < 0.05). Although many high school students do not meet the criteria for PMDD, many experience PMS, which could be diminished with proper diet and improved general health.


Abscess after cardiac pacemaker implantation: A case report.
This is a report of one of the most serious complications of the cardiac pacemaker implantation - infection of the implanted system. We present the case, which was misdiagnosed at the beginning and after cardiological consultation it was decided to immediately remove the peacemaker and transfer the patient to the Cardiological Department.


Superb water splitting activity of the electrocatalyst Fe3Co(PO4)4 designed with computation aid.
For efficient water splitting, it is essential to develop inexpensive and super-efficient electrocatalysts for the oxygen evolution reaction (OER). Herein, we report a phosphate-based electrocatalyst [Fe3Co(PO4)4@reduced-graphene-oxide(rGO)] showing outstanding OER performance (much higher than state-of-the-art Ir/C catalysts), the design of which was aided by first-principles calculations. This electrocatalyst displays low overpotential (237 mV at high current density 100 mA cm-2 in 1 M KOH), high turnover frequency (TOF: 0.54 s-1), high Faradaic efficiency (98%), and long-term durability. Its remarkable performance is ascribed to the optimal free energy for OER at Fe sites and efficient mass/charge transfer. When a Fe3Co(PO4)4@rGO anodic electrode is integrated with a Pt/C cathodic electrode, the electrolyzer requires only 1.45 V to achieve 10 mA cm-2 for whole water splitting in 1 M KOH (1.39 V in 6 M KOH), which is much smaller than commercial Ir-C//Pt-C electrocatalysts. This cost-effective powerful oxygen production material with carbon-supporting substrates offers great promise for water splitting.


Statewide availability of acute stroke treatment, services, and programs: A survey of North Carolina Hospitals.
We conducted a statewide assessment of the availability of stroke treatment, services, and programs in North Carolina (NC) hospitals. We also examined differences in stroke care capabilities between urban, suburban, and rural hospitals and trends over the past 2 decades. An electronic survey was distributed to all 111 licensed hospitals in NC. Survey questions asked about stroke center certification status (i.e., standardized levels of stroke care capabilities), diagnostic testing, acute treatments and protocols, and post-acute management. Responses were collected from October 2020-April 2021. Select characteristics were compared to those from prior NC surveys in 1998, 2003, and 2008. All 111 hospitals responded to the survey (100% response rate). Among 108 hospitals providing acute stroke care, 12 (11%) were Comprehensive Stroke Centers or Thrombectomy-Capable Stroke Centers, which were all located in urban or suburban areas. While 38% of urban/suburban hospitals were non-certified, 48% of rural hospitals were non-certified. Non-contrast computed tomography (CT), CT angiography, and alteplase treatment were widely available (100%, 95%, and 99%, respectively). Endovascular thrombectomy was solely available in urban/suburban hospitals (29%). Of non-tertiary hospitals, 81% were using telestroke for treatment and transfer decisions. Compared to prior survey results, the availability of CT angiography (76% in 2008 to 95% in 2020-2021), alteplase treatment (69% in 2008 to 99% in 2020-2021), and acute stroke clinical pathways (47% in 2008 to 90% in 2020-2021) increased. However, having an in-house neurologist on staff dropped from approximately 55% in prior surveys to 21% in the current survey. Rural NC hospitals were less likely to have advanced diagnostic imaging and treatment capabilities for acute stroke. Temporal trends in staffing with an in-house neurologist and use of telestroke services should be further examined.


Presence of NGAL/MMP-9 complexes in human abdominal aortic aneurysms.
It has been suggested that the intraluminal thrombus of abdominal aortic aneurysms (AAAs) predisposes for AAA enlargement and rupture. The growth of the AAA is dependent on proteolytic degradation of elastin. Here, we analysed whether the neutrophil gelatinase-associated lipocalin (NGAL) is expressed within the thrombus and the aneurysm wall. NGAL can bind to metalloproteinase-9 (MMP-9) and inhibit its degradation, thereby preserving enzymatic activity. Biopsies were obtained from thrombus-free and thrombus-covered aneurysm wall and the intraluminal thrombus from patients undergoing elective surgery for AAA. Immunohistochemistry and real-time PCR were used to study NGAL and MMP-9 expression. Immunoprecipitation, gel zymography, Western blot and ELISA were used to detect and quantify NGAL/MMP-9 complexes. NGAL was detected in the thrombus, the interface between the thrombus and the underlying wall and in the wall itself. Double staining showed that neutrophils are the major source of NGAL expression. Immunoprecipitation of MMP-9 with antibody against NGAL showed that complexes of NGAL and active MMP-9 were present in thrombus, the interface fluid and the aneurysm wall. Western blot analyses using non-reducing conditions and gel zymography demonstrated that high-molecular-weight complexes of NGAL/MMP-9 were present within the different regions. The concentration of the NGAL/MMP-9 complex was highest in the luminal part of the thrombus. In conclusion, NGAL in complex with activated MMP-9 is present in AAA wall and thrombus. Neutrophil-derived NGAL could enhance the proteolytic activity associated with AAA, but the importance of this mechanism for aneurysm growth remains to be shown.


Valproic Acid Enhances iPSC Induction From Human Bone Marrow-Derived Cells Through the Suppression of Reprogramming-Induced Senescence.
Reprogramming of human somatic cells into pluripotent cells (iPSCs) by defined transcription factors is an extremely inefficient process. Treatment with the histone deacetylase inhibitor valproic acid (VPA) during reprogramming can improve the induction of iPSCs. To examine the specific mechanism underlying the role of VPA in reprogramming, we transfected human bone marrow-derived cells (HSC-J2 and HSC-L1) with lentiviruses carrying defined factors (OCT4, SOX2, KLF4, and c-MYC, OSKM) in the presence of VPA. We found that, OSKM lentiviruses caused significant senescence in transfected cells. Administration of VPA, however, significantly suppressed this reprogramming-induced stress. Notably, VPA treatment improved cell proliferation in the early stages of reprogramming, and this was related to the down-regulation of the activated p16/p21 pathway. In addition, VPA also released the G2/M phase blockade in lentivirus-transfected cells. This study demonstrates a new mechanistic role of the histone deacetylase inhibitor in enhancing the induction of pluripotency. J. Cell. Physiol. 231: 1719-1727, 2016. © 2015 Wiley Periodicals, Inc.


Pharmacological treatments of COVID-19.
The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and sub-clinical studies are currently undertaken to find a gold-standard therapeutic regimen with high efficacy and low side effect. Based on the published scientific evidence published to date, we summarized herein the effects of different potential therapies and up-to-date clinical trials. The review is intended to help readers aware of potentially effective COVID-19 treatment and provide useful references for future studies.


Multiple granular-cell tumors of the ascending colon: microscopic study.
Light and electron microscopic study of a case of multiple granular-cell tumor of the ascending colon is presented, and the relevant medical literature is reviewed. It seems that the biologic behavior of this tumor in the colon does not differ from that in other locations. Histologically, a few granular cells are seen in neural tissue in the vicinity of the tumor, suggesting a close relation of the tumor to the neural tissue. Electron-microscopically, the granular cells resemble Schwann cells more closely than neural cells and axons. Histochemically, the granules of the tumor cells show autofluorescence and high activity of acid phosphatase, which was located electron-microscopically in the limiting membranes and matrices of the granules. It is suggested that the granular-cell tumor is a neoplasm of Schwann-cell origin with a unique metabolism that causes acceleration of autophagocytosis and accumulation of ceroidlipofuscin.


Polarographic determination of extraction constants.
The extraction constant of three organic compounds containing nitrogen as a picrate ion pair in a water-chloroform system were determined by following polarographically the picrate concentration in the aqueous phase as a function of the added amount of reagent. The extraction constants were also determined spectrophotometrically (via batch extraction). The obtained results are in good agreement. The proposed method is applicable for extraction constants with values between 10(3) and 10(9).


The operation of the century: total hip replacement.
In the 1960s, total hip replacement revolutionised management of elderly patients crippled with arthritis, with very good long-term results. Today, young patients present for hip-replacement surgery hoping to restore their quality of life, which typically includes physically demanding activities. Advances in bioengineering technology have driven development of hip prostheses. Both cemented and uncemented hips can provide durable fixation. Better materials and design have allowed use of large-bore bearings, which provide an increased range of motion with enhanced stability and very low wear. Minimally invasive surgery limits soft-tissue damage and facilitates accelerated discharge and rehabilitation. Short-term objectives must not compromise long-term performance. Computer-assisted surgery will contribute to reproducible and accurate placement of implants. Universal economic constraints in healthcare services dictate that further developments in total hip replacement will be governed by their cost-effectiveness.


Analysis of 6 VNTR loci by 'multiplex' PCR and automated fluorescent detection.
The polymerase chain reaction was used to amplify six small variable number of tandem repeat loci in two reactions (D19S20 co-amplifying with D17S5 and D1S80; D17S766 co-amplifying with D16S83 and D17S24). When coupled with fluorescent detection of the products, this provides a rapid, highly discriminating automated test. Preferential amplification of small alleles, leading to 'allelic dropout' was found to occur in D19S20 and D16S83. Population databases are presented for Caucasians and Afro-Caribbeans at loci D19S20, D16S83 and D17S24, and for Asians at D19S20.


How to Measure Moral Realism.
In recent years an increasing number of psychologists have begun to explore the prevalence, causes and effects of ordinary people's intuitions about moral realism. Many of these studies have lacked in construct validity, i.e., they have failed to (fully or exclusively) measure moral realism. My aim in this paper accordingly is to motivate and guide methodological improvements. In analysis of prominent existing measures, I develop general recommendations for overcoming ten prima facie serious worries about research on folk moral realism. G1 and G2 require studies' answer choices to be as metaethically comprehensive as methodologically feasible. G3 and G4 prevent fallacious inferences from intuitions about related debates. G5 and G6 limit first-order moral and epistemic influences. G7 address studies' instructions. And G8 and G9 suggest tests of important psychological presuppositions.


Taxonomic revision of Ustilago, Sporisorium and Macalpinomyces.
Morphological characters within the Ustilago-Sporisorium-Macalpinomyces complex are defined explicitly. The genera Sporisorium and Anthracocystis are emended to reflect morphological synapomorphies. Three new genera, Langdonia, Stollia and Triodiomyces are described based on soral synapomorphies and host classification. The new classification of the Ustilago-Sporisorium-Macalpinomyces complex incorporates 142 new taxonomic combinations.


Mycotic aortocaval fistula: efficient evaluation by bolus-chase MR angiography.
Aortocaval fistula (ACF) is a rare but life-threatening condition. This case report describes the use of bolus-chase gadolinium-enhanced 3D magnetic resonance angiography (MRA) to provide an efficient evaluation of a patient with ACF associated with a mycotic abdominal aortic aneurysm. This case highlights the ability of bolus-chase MRA to provide both the specific diagnosis of ACF as well as the information necessary for extra-anatomic arterial bypass. Bolus-chase MRA is a promising method for the evaluation of patients with this disease entity.


Recurrence patterns and postrecurrence survival after curative intent resection for pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma has a high rate of recurrence after resection. We aimed to investigate patterns of recurrence of pancreatic ductal adenocarcinoma to identify opportunities for targeted intervention toward improving survival. This was a retrospective analysis of consecutive patients that underwent curative-intent resection for pancreatic ductal adenocarcinoma between 2007 and 2015. Recurrence and survival were analyzed based on site of recurrence. Multiple clinicopathologic factors were calculated for likelihood of site-specific recurrence. The study included 221 patients with median follow-up of 83 months. Median overall and recurrence-free survival was 19 and 13 months, respectively. Recurrence was observed in 71.9% patients. Local recurrence occurred in 16.4%, distant recurrence in 67.3%, and combined in 15.9%. The most common site of distant recurrence was the liver (49.7%) followed by lung (31.8%) and peritoneum (16.6%). Median time to liver recurrence was shortest (5 months, 95% confidence interval 1.7-8.3) and post recurrence survival was poor (4 months, 95% confidence interval 1.9-6.1). Patients with poorly differentiated tumors on pathology were 4.8 times more likely to recur in the liver (odds ratio 4.83, 95% confidence interval 1.7-13.9). Liver metastasis after resection of pancreatic ductal adenocarcinoma occurs most frequently, earliest after surgery, and is rapidly fatal. Liver-directed therapies represent a target for future study.


Instrumental and transcriptome analysis reveals the chemotherapeutic effects of doxorubicin-loaded black phosphate nanosheets on abiraterone-resistant prostate cancer.
Prostate cancer is the second most common cause of cancer-related deaths in men and is common in most developed countries. Androgen deprivation therapy (ADT) that uses abiraterone acetate (AA) is an effective second-line treatment for prostate cancer. However, approximately 20-40% of patients develop primary resistance to abiraterone post-treatment. In this study, we aimed to understand the molecular mechanisms underlying the development of abiraterone resistance in prostate cancer cells and the potential use of black phosphorus nanosheets (BPNS) for treating abiraterone-resistant prostate cancer. We first established abiraterone-resistant prostate cancer PC-3 cells and found that these cells have higher migration ability than normal prostate cancer cells. Using comparative transcriptomic and bioinformatics analyses between abiraterone-sensitive PC-3 and abiraterone-resistant PC-3 cells, we highlighted the differentially expressed genes (DEGs) involved in the biological processes related to prostate gland morphogenesis, drug response, immune response, angiogenesis. We further studied the therapeutic effects of BPNS. Our results show that BPNS reduced the proliferation and migration of abiraterone-resistant PC-3 cells. Bioinformatics analysis, including gene ontology, Kyoto encyclopedia of genes and genomes enrichment analysis, and ingenuity pathway analysis (IPA) of the DEGs, suggested that BPNS treatment controlled cancer cell proliferation, metastasis, and oncogenic signaling pathways. Furthermore, the IPA gene network highlighted the involvement of the MMP family, ATF, and notch families in the anti-prostate cancer function of BPNS. Our findings suggest that BPNS may have a chemotherapeutic function in treating abiraterone-resistant prostate cancer.


Influence of L-methioninase targeted to the urokinase receptor on the proliferation and motility of lung and prostate cancer cells.
Previously, we reported that a novel fusion protein consisting of an amino-terminal fragment of urokinase linked to the amino terminus of the enzyme L-methioninase inhibited MCF-7 breast cancer cells in vitro to a greater extent than treatment with L-methioninase. The fusion protein, L-methioninase and a mutated fusion protein without L-methioninase activity were produced by recombinant methods. The effects of fusion protein, L-methioninase, and mutated fusion protein treatment on the proliferation and motility of SK-LU-i lung and PC-3 prostate and cancer cells were measured in vitro using a culture wounding assay. The fusion protein produced a dose-dependent inhibition of the proliferation and motility of both cancer cell lines. In addition, the fusion protein was found to be significantly more effective than L-methioninase alone or mutated fusion protein. Our results suggest that this fusion protein has potential as a selective therapeutic agent for the treatment of various methionine-dependent cancers.


Identification of the full set of Listeria monocytogenes penicillin-binding proteins and characterization of PBPD2 (Lmo2812).
Bacterial penicillin-binding proteins (PBPs) can be visualized by their ability to bind radiolabeled or fluorescent β-lactam derivatives both whole cells and membrane/cell enriched fractions. Analysis of the Listeria monocytogenes genome sequence predicted ten genes coding for putative PBPs, but not all of their products have been detected in studies using radiolabeled antibiotics, thus hindering their characterization. Here we report the positive identification of the full set of L. monocytogenes PBPs and the characteristics of the hitherto undescribed PBPD2 (Lmo2812). Eight L. monocytogenes PBPs were identified by the binding of fluorescent β-lactam antibiotic derivatives Boc-FL, Boc-650 and Amp-Alexa430 to proteins in whole cells or membrane/cell wall extracts. The gene encoding a ninth PBP (Lmo2812) was cloned and expressed in Escherichia coli as a His-tagged protein. The affinity purified recombinant protein had DD-carboxypeptidase activity and preferentially degraded low-molecular-weight substrates. L. monocytogenes mutants lacking the functional Lmo2812 enzyme were constructed and, compared to the wild-type, the cells were longer and slightly curved with bent ends.Protein Lmo1855, previously designated PBPD3, did not bind any of the antibiotic derivatives tested, similarly to the homologous enterococcal protein VanY. Nine out of the ten putative L. monocytogenes PBP genes were shown to encode proteins that bind derivatives of β-lactam antibiotics, thus enabling their positive identification. PBPD2 (Lmo2812) was not visualized in whole cell extracts, most probably due to its low abundance, but it was shown to bind Boc-FL after recombinant overexpression and purification. Mutants lacking Lmo2812 and another low molecular mass (LMM) PBP, PBP5 (PBPD1)--both with DD-carboxypeptidase activity--displayed only slight morphological alterations, demonstrating that they are dispensable for cell survival and probably participate in the latter stages of peptidoglycan synthesis. Since Lmo2812 preferentially degrades low-molecular- mass substrates, this may indicate a role in cell wall turnover.


Desmin regulates airway smooth muscle hypertrophy through early growth-responsive protein-1 and microRNA-26a.
Bronchial biopsies of asthmatic patients show a negative correlation desmin expression in airway smooth muscle cell (ASMC) and airway hyperresponsiveness. We previously showed that desmin is an intracellular load-bearing protein, which influences airway compliance, lung recoil, and airway contractile responsiveness (Shardonofsky, F. R., Capetanaki, Y., and Boriek, A. M. (2006) Am. J. Physiol. Lung Cell. Mol. Physiol. 290, L890-L896). These results suggest that desmin may play an important role in ASMC homeostasis. Here, we report that ASMCs of desmin null mice (ASMCs(Des-/-)) show hypertrophy and up-regulation microRNA-26a (miR-26a). Knockdown of miR-26a in ASMCs(Des-/-) inhibits hypertrophy, whereas enforced expression of miR-26a in ASMCs(Des+/+) induces hypertrophy. We identify that Egr1 (early growth responsive protein-1) activates miR-26a promoter via enhanced phosphorylation of Erk1/2 in ASMCs(Des-/-). We show glycogen synthase kinase-3β (GSK-3β) as a target gene of miR-26a. Moreover, induction of ASMCs(Des-/-) hypertrophy by the Erk-1/2/Egr-1/miR-26a/GSK-3β pathway is consistent in human recombinant ASMCs, which stably suppresses 90% endogenous desmin expression. Overall, our data demonstrate a novel role for desmin as an anti-hypertrophic protein necessary for ASMC homeostasis and identifies desmin as a novel regulator of microRNA.


No colocalization of immunoreactivities for VIP and neuronal NOS, and a differential relation to cGMP-immunoreactivity in bovine penile smooth muscle.
The distribution of immunoreactivity (IR) for the neuropeptide vasoactive intestinal polypeptide (VIP) and neuronal nitric oxide synthase (nNOS) in the bovine retractor penis muscle (RP) and penile artery (PA) was studied by using two different methods. The distribution of these immunoreactivities was also compared with that of the immunoreactivity for cyclic guanosine monophosphate (cGMP). In both tissues the nerve fibers and terminals immunoreactive for VIP had a distribution that was completely different from that of the nerve fibers and terminals immunoreactive for nNOS. This contrasts with the previous observations in penile smooth muscle of other species. In the RP, as well as in the PA, many of the VIP-IR fibers were also immunoreactive for neurofilaments (NF), whereas the nNOS-IR fibers were consistently devoid of NF-IR. Stimulation with sodium nitroprusside, a nitric oxide donor, considerably increased cGMP-IR in the smooth muscle cells in both RP and PA, and in several nerve fibers in PA. Many of these cGMP-IR nerve fibers exhibited nNOS-IR, whereas none of them was immunoreactive for VIP. Our results suggest that the degree of coexistence of VIP-IR and nNOS-IR in the nerve fibers and terminals innervating penile smooth muscle show wide species differences. They also suggest that the mechanisms by which VIP could be involved in neurogenic penile erection may vary between species.


Optimal number of image slices for reliable measurement of left ventricular volumes and ejection fraction by three-dimensional transesophageal echocardiography.
Quantification of the left ventricular (LV) volume by three-dimensional echocardiography is accurate but time-consuming. To shorten the time required, we sought to determine the minimum number of image planes necessary to measure LV volume reliably. We analyzed transesophageal three-dimensional echocardiographic LV data obtained by the rotational scanning method in 16 patients: 11 had ischemic heart disease, and 5 had dilated cardiomyopathy. LV volumes were calculated from 6, 10, and 30 short-axis images using the disk-summation method and from 2, 4, 6, 10, 20, and 30 longitudinal images using the new average rotation method. LV volume varied less with the average rotation method than with the disk-summation method. The 95% limit of agreement between the 30-image and 6-image methods was 0.3% ± 3.7% for the average rotation method, whereas it was -2.0% ± 6.9% for the disk-summation method. The time required for analysis decreased from 12.5 ± 2.8 min with the 30-image method to only 3.3 ± 0.5 min for the 6-image method. Measurement of six longitudinal images provided reliable LV volume data, even in patients with enlarged or deformed left ventricles. The short measurement time supports the use of three-dimensional echocardiographic LV volume measurement in the clinical setting.


The influence of isotretinoin upon fibrinolysis in patients with acne.
A patient with haemophilia A and acne was recently reported to have experienced increased bleeding during therapy with isotretinoin. The aim of the present study was to investigate the influence of isotretinoin upon fibrinolysis, and more specifically upon tissue plasminogen activator (tPA) and tissue plasminogen activator inhibitor (PAI) levels, in haemostatically normal individuals. Thirteen patients with severe acne received a 4-month course of isotretinoin at a dose of 1 mg/kg per day. In all cases, the acne responded to therapy, and the patients did not show any evidence of unexpected bleeding or bruising throughout the study. Although all investigations remained within the normal range, tPA measurements rose significantly (P < 0.001) after 3 months' therapy compared with pretreatment values. Retinoids have been shown to stimulate tPA production in vitro from human endothelial cells. Our results confirm that this can be demonstrated in vivo. Prior to therapy with isotretinoin, when all patients had inflammatory acne, PAI measurements were elevated in 12 of 13 individuals. The mean measurement of PAI decreased from 98.38 +/- 63.30 ng/ml prior to treatment, to 24.63 +/- 15.2 ng/ml (P < 0.01) in the eight patients who returned for blood tests 6 weeks after completing therapy. The decline in PAI levels appears to reflect the resolving cutaneous inflammation following treatment with isotretinoin, rather than a direct effect of isotretinoin on the synthesis or release of PAI. This study provides further evidence that tPA production is stimulated by isotretinoin, and that this, together with falling PAI levels, may accelerate fibrinolysis. There was no clinical evidence that haemostasis was impaired in these haematologically normal individuals.(ABSTRACT TRUNCATED AT 250 WORDS)


Radiation therapy for localized low-grade non-Hodgkin's lymphomas.
The most common low grade B-cell non-Hodgkin's lymphomas are follicular lymphomas, and extranodal marginal zone lymphomas, also known as mucosa-associated lymphoid tissue (MALT) lymphomas. Localized presentations of follicular lymphoma occur in 20-30% of cases, while for MALT lymphomas, stage I-II disease presentations occur in 70-90%. These are radiation-sensitive lymphomas. Following moderate dose local radiation treatment (30-35 Gy) for these stage I and II low grade lymphomas, the clinical results indicate long-term local control and possible cure. While local control is achieved with minimal morbidity with involved-field radiation therapy, a significant proportion of patients relapse with systemic disease outside of radiation fields. For follicular lymphoma, this occurs in approximately 50% of patients after 15 years, and for non-gastric MALT lymphoma, 30-40% after 10 years. Although patients with relapsed systemic disease are not curable with chemotherapy, the disease often behaves in an indolent fashion and prolonged survival is observed. For gastric MALT lymphomas, radiation therapy is indicated in patients whose lymphoma did not respond to Helicobacter pylori eradication therapy, or in gastric lymphoma not related to this microorganism. The subject of causative agents responsible for non-gastric MALT lymphomas is under active study and the identification of putative microorganisms will lead to improved treatment strategies for these unusual lymphomas, similar to the success in gastric lymphomas over the last decade.


An efficient way to synthesize biomass-based molybdenum carbide catalyst via pyrolysis carbonization and its application for lignin catalytic pyrolysis.
In this study, a simple and rapid method was proposed to synthesize orthorhombic α-Mo2C as catalyst for lignin catalytic pyrolysis. Biomass in-situ pyrolysis products were used as the carbon source and supporter, the carbonization of Mo precursor was realized under rapid heating. Experimental results show that Pine-Mo2C catalyst can achieve lignin pyrolysis vapor bond breaking and deoxidation under normal pressure, and the yield of monocyclic aromatic hydrocarbons is 13.26 wt%, of which aromatic hydrocarbons with side chain account for 74%. The side chain aliphatic hydrocarbons of lignin are effectively retained, and hydrogen consumption is minimized. The characterization of catalyst and experiments of guaiacol, 2-phenoxy-1-phenylethanol and 4,4'-biphenol shows that efficient deoxidation is due to targeted attack of catalyst on C-O. Therefore, Pine-Mo2C shows excellent activity in promoting direct bond breaking deoxidation of lignin.


IAEA Co-ordinated Research Project: update of X-ray and gamma-ray decay data standards for detector calibration and other applications.
A Co-ordinated Research Project (CRP) was established in 1998 by the IAEA Nuclear Data Section (Update of X-ray and gamma-ray Decay Data Standards for Detector Calibration and Other Applications), in order to improve further the recommended decay data used to undertake efficiency calibrations of gamma-ray detectors. Participants in this CRP reviewed and modified the list of radionuclides most suited for detector efficiency calibration, and also considered the decay-data needs for safeguards, waste management, dosimetry, nuclear medicine, material analysis and environmental monitoring. Overall, 62 radionuclides were selected for decay-data evaluation, along with four parent-daughter combinations and two natural decay chains. gamma-ray emissions from specific nuclear reactions were also included to extend the calibrant energy well beyond 10 MeV. A significant number of these decay-data evaluations have been completed, and an IAEA-TECDOC report and database are in the process of being assembled for planned completion by the end of 2003.


The effects of B7-dependent costimulation on T cell division and survival in vivo and in vitro are dependent on antigen concentration.
We used 5-(and 6-) carboxyfluorescein diacetate succinimidyl ester labeled TCR-transgenic CD4(+) T cells to investigate the contribution of B7 costimulation to T cell activation and clonal expansion. B7 costimulation was blocked with the fusion protein cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)-Ig, which prevents the interaction of B7 with its receptor CD28 on T cells. CTLA4-Ig had different effects depending on the density of antigen (Ag)/MHC ligands available by T cells. In the presence of CTLA4-Ig, tenfold higher concentrations of Ag were required for T cells to undergo cell division in vitro. At high Ag concentrations, T cell division occurred at comparable rates whether in the presence or absence of CTLA4-Ig; however, T cell survival and clonal expansion were strongly inhibited. Addition of IL-2 restored T cell survival but not responsiveness to low doses of Ag. In vivo, B7 costimulation was similarly required for the survival of Ag-specific T cells but not for cell division in response to high amounts of Ag. Thus, B7 costimulation regulates CD4(+) T cell responses by promoting cell division in the presence of limiting amounts of Ag, and by protecting T cells from the onset of apoptosis.


Comparative assessment of toxic responses in 3D embryoid body differentiation model and mouse early embryos treated with 5-hydroxytryptophan.
Pluripotent stem cells recapitulate in vitro the early developmental stages and are considered promising cell models for predictive developmental toxicity studies. To investigate the consistency between adverse drug effects on early development and the early stages of embryonic stem cell differentiation in three-dimensional (3D) in vitro culture, the toxic responses to 5-hydroxytryptophan (5-HTP; 0.5-2 mM) were evaluated in early mouse embryos and the embryoid body (EB) differentiation model. 3D architectures, developmental and differentiation dynamics and the cell death rates were analyzed in early mouse embryos (E2.5-E5.5) and EBs at 1 and 6 days of differentiation using a combination of confocal immunofluorescence microscopy with high content imaging analysis and quantitative gene expression analysis. Comparative analysis of toxic responses in early embryos and EBs revealed a similar dose- and stage-dependent decrease in the 5-HTP toxic effects during development and differentiation. The integral toxic responses in the early embryos and EBs were significantly dependent on their 3D architecture and cellular composition. Treatment with 5-HTP (1 mM and above) induced developmental arrest, growth inhibition, and increased cell death in the early embryos without the trophoblasts (E2.5) and those with impaired trophoblasts and in early EBs, whereas later embryos and EBs were more resistant due to the protection of the extraembryonic tissues. This study demonstrates that the EB differentiation model is a relevant 3D-model of early mammalian development and can be useful for the predictive evaluation of toxic and teratogenic effects in embryos at the preimplantation and early post-implantation developmental stages.


Vertebral body morphology is associated with incident lumbar vertebral fracture in postmenopausal women. The OFELY study.
We investigate the predictive role of vertebral anterior cortical curvature and height heterogeneity in the occurrence of vertebral fractures in postmenopausal women. Women who will fracture had shorter vertebral height, greater heterogeneity of height than those who will not fracture, and their anterior vertebral body edge was less concave. Vertebral morphology has been demonstrated to be associated with further risk of fracture. The aim of this study was to analyze vertebral anterior cortical curvature (Ct.curv) and vertebral height heterogeneity in postmenopausal women before the occurrence of a vertebral fracture. This case-control study included 29 postmenopausal women who have underwent incident lumbar vertebral fractures (mean age 71 ± 9 years, mean time to fractures 9 ± 4 years), age-matched with 57 controls. From lateral X-rays of lumbar spine radiographs (T12 to L4), the following parameters were measured: (1) the posterior, middle, and anterior vertebral heights; (2) the heterogeneity of heights evaluated by the coefficient of variation of these three variables; (3) antero-posterior width, a 2D estimator of cross-sectional area; and (4) Ct.curv. Mean vertebral heights were significantly lower among women who fractured than in controls (p < 0.05). The anterior and middle heights were significantly lower at L4 and L3 levels in fracture group (p = 0.02). The heterogeneity of vertebral height was significantly greater in the fracture group (p = 0.003). In addition, fractured patients had a significantly higher Ct.curv on L3 (p = 0.04). After adjustment for bone mineral density (BMD), only the heterogeneity of vertebral height remained significant (p = 0.005). The current case-control study confirmed the association between vertebral height and occurrence of future vertebral fracture in postmenopausal women. The vertebrae with the smallest Ct.curv tended to fracture less often, and the heterogeneity of vertebral heights was associated with future fracture independently of BMD. An additional validation in a prospective study would be needed to confirm these initial results.


Change in corneal hysteresis over time in normal, glaucomatous and diabetic eyes.
Corneal hysteresis (CH) is lower in glaucomatous eyes. The aim of this study was to determine and compare the change in CH over time between normal, open angle glaucoma (POAG) and diabetic subjects. We retrospectively analysed records of patients undergoing assessment with the Ocular Response Analyzer (Reichert, Corp., New York, NY, USA). Right eyes with at least 7 measurements were included. Patients with ocular pathology other than POAG were excluded. Two-sample t-tests, chi-squared and logistic regression were used to analyse data. A total of 1418 normal and 322 POAG patients were included. Patients with POAG were significantly older (70.73 ± 11.33 vs. 61.59 ± 16.56 years; p < 0.001), had a longer follow-up (4.14 ± 1.34 vs. 2.72 ± 1.49 years; p < 0.001) and had lower CH (9.58 ± 2.17 vs. 9.95 ± 2.19 mmHg p = 0.01), but there were no gender differences between groups (61.5 vs. 57.7% female; p = 0.21). We observed a significantly greater decrease in CH among patients with POAG (-0.11 ± 0.73 vs. 0.07 ± 2.31 mm Hg/year; p = 0.02). The relation between ∆CH/year and diagnosis persisted after adjusting for age and follow-up time (OR 0.90; 95% CI 0.82, 0.99; p = 0.03). We found CH to be higher in diabetics vs. non-diabetics (10.34 ± 2.04 vs. 9.88 ± 2.19; p = 0.02), but ∆CH/year was not different (0.07 ± 1.27 vs. 0.03 ± 2.10; p = 0.77). Patients with POAG in this study had a significantly greater rate of CH decline compared to normal. There was no significant difference in rate of CH change in diabetic and non-diabetic patients.


Folds on Europa: implications for crustal cycling and accommodation of extension.
Regional-scale undulations with associated small-scale secondary structures are inferred to be folds on Jupiter's moon Europa. Formation is consistent with stresses from tidal deformation, potentially triggering compressional instability of a region of locally high thermal gradient. Folds may compensate for extension elsewhere on Europa and then relax away over time.


Leveraging affordances in an ecological stance: Reflective language teaching for professional development during COVID-19.
The COVID-19 pandemic has made a prominent impact of social contexts on teachers' professional development in remote classroom teaching. To explore how the change has altered human-environment relationships in university language classes, this qualitative case study investigated three teachers' progressive reflection on their use of affordances for teaching Chinese as a second language (L2) during COVID-19. Under the framework of human ecological language pedagogy, three themes of emergency remote teaching emerged from monthly semi-structured interviews about the three teachers' reflective practice in remote classrooms: computer-dominant teaching conditions, flexible classroom interaction, and rational social empathy in L2 education. The findings suggest the importance of a growth mindset for L2 teachers to leverage their teaching abilities and environmental resources for continuing professional development during COVID-19 and post-pandemic periods.


A virtual reality home-based training for the management of stress and anxiety among healthcare workers during the COVID-19 pandemic: study protocol for a randomized controlled trial.
Healthcare workers represent one of the most affected categories by the adverse effects of the COVID-19 pandemic on mental health. Excessive stress and anxiety are critical factors that could compromise work performance. Besides, high levels of stress and anxiety may have long-term physical and psychological consequences. Recent studies investigated virtual reality to reduce stress and anxiety among healthcare workers during the COVID-19 pandemic. However, the proposed virtual reality interventions have important limitations related to their location (i.e., research lab and hospitals) and content (i.e., virtual experiences only for relaxation). Within this context, this randomized controlled trial aims to investigate the efficacy and acceptability of a brief home-based virtual reality training for managing stress and anxiety during the COVID-19 crisis in a sample of Italian healthcare workers. The study is a randomized controlled trial. It includes two groups of 30 individuals recruited from healthcare workers: (1) the experimental group and (2) the control group. Participants in the experimental group will receive a training consisting of three home sessions performed in a week. In each session, participants will try through an immersive virtual reality standalone system (i.e., Oculus Quest 2) a virtual psychoeducation experience on stress and anxiety (i.e., MIND-VR). Subsequently, they will try the virtual relaxation content (i.e., The Secret Garden). The control group will receive no training and will be reassessed one week and one month after the initial evaluation. If the proposed brief home-based virtual reality training will result helpful and easy to use, it could become an empirically assessed viable option for protecting healthcare workers' mental health both during the COVID-19 pandemic and once it will be over. Furthermore, the intervention might be easily adapted for other categories of people who need support in managing stress and anxiety. ClinicalTrials.gov NCT04611399 .


A systematic review of tumor treating fields therapy for high-grade gliomas.
Tumor treating fields (TTF) is a unique treatment modality that utilizes alternating electric fields to deliver therapy. Treatment effects have been assessed in patients with newly diagnosed and recurrent glioblastoma in clinical trials and retrospective studies. While the results of these studies led to FDA approval for both populations, a portion of the neuro-oncology and neurosurgery community remains skeptical of TTF. Thus, this review aims to systematically summarize and evaluate prior studies investigating the efficacy and safety of TTF in patients with high-grade gliomas. A systematic review of the literature was performed according to PRISMA guidelines from database inception through February 2019. To be included, studies must have investigated the efficacy of TTF in adult high-grade glioma patients. In total, 852 studies were initially identified, 9 of which met final inclusion criteria. In total, 1191 patients were identified who received TTF. Included studies consisted of two pilot clinical trials, two randomized clinical trials, and five retrospective studies. In randomized clinical trials, TTF improved survival for newly diagnosed glioblastoma patients but not for recurrent glioblastoma patients. Adverse skin reactions were the primary adverse effect associated with TTF. While TTF has been evaluated for safety and efficacy in a number of studies, concerns remain regarding study design, quality of life, and cost of therapy. Further investigation is needed regarding the therapy, and ongoing trials are already underway to provide more data regarding therapy outcomes and interactions in combination regimens.


Paradise lost: older Cuban American exiles' ambiguous loss of leaving the homeland.
To explore the experience of leaving Cuba, 2 Cuban American émigrés interviewed 20 Cuban exiles aged 65 or older, who left Cuba between 1959 and 1971. The interviews were conducted in New York and New Jersey using a phenomenological approach (Moutsakas, 1994). Themes included feeling betrayed by the Revolution, the inevitability of leaving, the expectation of a temporary refuge, and longing for and idealizing the past. The psychological presence that participants expressed, along with an endless sense of loss, resonates with ambiguous loss theory (Boss, 2006)-themes that have yet to be explored in the literature and that have research and practice implications.


A new approach for selection of Oenococcus oeni strains in order to produce malolactic starters.
The lactic acid bacterium Oenococcus oeni, mainly responsible for malolactic fermentation (MLF), is used in new winery process as starter culture for direct inoculation. The difficulty to master MLF according to the wine led us to search a new approach to select effective O. oeni strains. Biochemical and molecular tests were performed in order to characterize three strains of O. oeni selected for malolactic starter elaboration. Malolactic and ATPase activities that appeared as a great interest in MLF were measured and the expression of a small heat shock protein Lo18 was evaluated by immunoblotting and real-time PCR. These results were correlated with the performances of strains in two red wines. Physiological and molecular characteristics of the three strains showed significant differences for the global malolactic activity on intact cell at pH 3.0 and at the level of induction of the small heat shock protein Lo18. These two parameters appeared of interest to evaluate in the ability of O. oeni strains to survive into wine after direct inoculation and to perform MLF. Indeed, a tested strain that presented the highest malolactic activity on intact cells at pH 3.0 and a high level of Lo18 induction showed a high growth rate and a high specific kinetic of malate consumption. The techniques used in this work carry out more quickly and more reliable than usual for the selection of effective strains intended for direct inoculation in wines.


Understanding Vascular Diseases: Lessons From Premature Aging Syndromes.
Early human mummies examined recently by computed tomography demonstrated a high prevalence of vascular calcification, a pathognomonic sign of atherosclerosis, which was correlated with estimated age at death. Early populations had little exposure to modern-day metabolic risk factors: these observations thus suggest that humans have an inherent age-dependent predisposition to atherosclerosis. Premature aging syndromes are extremely rare genetic disorders that exhibit clinical phenotypes resembling accelerated aging, including severe atherosclerosis, but those phenotypes are usually segmental. Controversy persists, therefore, regarding the extent to which the molecular mechanisms underlying premature aging syndromes overlap with those of physiological aging. Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome are well-characterized premature aging syndromes. HGPS is caused by gain-of-function mutations in the LMNA gene, which result in the accumulation of a mutant nuclear protein, called "progerin," at the nuclear rim. In contrast, loss-of-function mutations in Werner syndrome ATP-dependent helicase (WRN) lead to Werner syndrome. Mesenchymal stem cells (MSCs), which can differentiate into vascular cells to maintain vascular homeostasis in response to injury, are severely affected in these syndromes. Mechanistically, either aberrant expression of progerin or loss of WRN protein in MSCs alters heterochromatin structure, resulting in premature senescence and exhaustion of functional MSCs in premature aging syndromes. Surprisingly, vascular cells and MSCs in elderly healthy individuals have shown progerin expression and decreased expression levels of WRN, respectively. Studying these rare genetic disorders could thus provide valuable insights into age-related vascular diseases that occur in the general population.


Prenatal stress produces social behavior deficits and alters the number of oxytocin and vasopressin neurons in adult rats.
The present study investigated the long-lasting effects of prenatal repeated restraint stress on social behavior and anxiety, as well as its repercussions on oxytocin (OT) and vasopressin (VP)-positive neurons of the paraventricular (PVN) and supraoptic (SON) nuclei from stressed pups in adulthood. Female Wistar rats were exposed to restraint stress in the last 7 days of pregnancy. At birth, pups were cross-fostered and assigned to the following groups: prenatally non-stressed offspring raised by prenatally non-stressed mothers (NS:NS), prenatally non-stressed offspring raised by prenatally stressed mothers (S:NS), prenatally stressed offspring raised by prenatally non-stressed mothers (NS:S), prenatally stressed offspring raised by prenatally stressed mothers (S:S). As adults, male prenatally stressed offspring raised both by stressed mothers (S:S group) and non-stressed ones (NS:S group) showed impaired social memory and interaction. In addition, when both adverse conditions coexisted (S:S group), increased anxiety-like behavior and aggressiveness was observed in association with a decrease in the number of OT-positive magnocellular neurons, VP-positive magnocellular and parvocellular neurons of the PVN. The NS:S group exhibited a reduction in the amount of VP-positive magnocellular neurons compared to the S:NS. Thus, the social behavior deficits observed in the S:S and NS:S groups may be only partially associated with these alterations to the peptidergic systems. No changes were shown in the OT and VP cellular composition of the SON nucleus. Nevertheless, it is clear that a special attention should be given to the gestational period, since stressful events during this time may be related to the emergence of behavioral impairments in adulthood.


Combining SELEX with quantitative assays to rapidly obtain accurate models of protein-DNA interactions.
Models for the specificity of DNA-binding transcription factors are often based on small amounts of qualitative data and therefore have limited accuracy. In this study we demonstrate a simple and efficient method of affinity chromatography-SELEX followed by a quantitative binding (QuMFRA) assay to rapidly collect the data necessary for more accurate models. Using the zinc finger protein EGR as an e.g. we show that many bindings sites can be obtained efficiently with affinity chromatography-SELEX, but those sequences alone provide a weight matrix model with limited accuracy. Using a QuMFRA assay to determine the quantitative relative affinity for only a subset of the sequences obtained by SELEX leads to a much more accurate model. Application of this method to variants of a transcription factor would allow us to generate a large collection of quantitative data for modeling protein-DNA interactions that could facilitate the determination of recognition codes for different transcription factor families.


Distribution of serum uric acid levels and prevalence of hyper- and hypouricemia in a Korean general population of 172,970.
We investigated the distribution of serum uric acid (SUA) levels and estimated the prevalence of hyperuricemia and hypouricemia in the Korean population. This cross-sectional study used data from the Korean Genome and Epidemiology Study and included 172,970 participants (58,981 men and 113,989 women) aged 40 to 79 years. Hypouricemia and hyperuricemia were defined as SUA level ≤ 2.0 mg/dL and > 7 mg/dL, respectively. The prevalence of hyperuricemia and hypouricemia was evaluated by age and sex. The mean SUA levels were significantly higher in men than in women (5.71 ± 1.27 mg/dL vs. 4.21 ± 0.96 mg/dL, p < 0.001). The mean SUA levels and prevalence of hyperuricemia increased with age in women but not in men. The overall prevalence of hyperuricemia and that in men and women was 50.82, 133.25, and 8.17 per 1,000 persons, respectively; the overall prevalence of hypouricemia and that in men and women was 4.16, 1.10, and 5.75 per 1,000 persons, respectively. The prevalence of hypouricemia in men was similar across all age groups; however, that in women was the highest in the age group of 40 to 49 years and the lowest in the age group of 50 to 59 years. The distribution of SUA levels and prevalence of hyperuricemia and hypouricemia differed according to age and sex. Age and sex should be considered in studies on uric acid-related diseases.


[Clinical analysis of reoperation for recurrence thyroid carcinoma in 87 cases].
To explore the cause and the methods of reoperation for recurrent thyroid carcinoma. The clinicopathologic data of 87 cases were retrospectively analyzed. The diagnosis on recurrent thyroid carcinoma were confirmed after reoperative pathology. Forty-three cases (49.4%) were confirmed as residual carcinoma by pathology. Among 87 cases, 65 cases (74.7%) had lymph node metastasis in group VI and 42 cases (48.3%) had lateral neck lymph nodes metastasis, 3 cases were in the presence of recurrent laryngeal nerve injury temporarily, 1 case was in the presence of recurrent laryngeal nerve injury permanently, 5 cases were convulsed by hypocalcemia. The nonstandard surgical procedure in the first operation is the main cause for the reoperation of thyroid carcinoma. Increased cognitive level of thyroid carcinoma and appropriate surgical technique may be the important keys to avoid reoperating. It is necessary to protect the parathyroid and recurrent laryngeal nerve in reoperation.


Medicine on the margins: learning opportunities for undergraduates within inclusion health.
Marginalised groups, including the homeless, refugees and asylum seekers, often experience extremely poor health and present unique challenges to health systems. Undergraduate medical placements with specialist primary care services for these groups can be an insightful learning opportunity within 'inclusion health', a field committed to improving health of these populations. The aim of this project was to showcase organisations for students to gain further exposure and evaluate students' elective experiences at a specialist primary care service for marginalised groups. Students created a mind map to identify organisations in Norwich that were valuable for future students to explore. Five elective students were asked to complete qualitative questionnaires about their experiences. Approximately 10 organisations accommodated participating medical students. Three of five participants responded to the questionnaire, reporting a beneficial learning experience, enabling students to understand complex needs of marginalised groups. The findings offer creative suggestions of where students can gain further exposure. Evaluation of this elective suggests there is unique value in offering placements with a diverse range of organisations that support marginalised groups. Educators should consider integrating opportunities for debriefing and a structured curriculum. Greater support and resources must be provided to include these services for regular teaching and training.


Effect of bypass fat supplementation on productive performance and blood biochemical profile in lactating Murrah (Bubalus bubalis) buffaloes.
The study investigated the effect of dietary supplementation of bypass fat on productive performance and blood biochemical profile of lactating Murrah buffaloes (Bubalus bubalis). Fifteen multiparous buffaloes (2-4 lactation) of early to mid lactation were divided in three homogenous groups T(1) (control), T(2), and T(3) of five each. The animals in T(1) were fed with a basal diet consisting of a concentrate mixture, green sorghum, and wheat straw as per requirements, while the animals in group T(2) and T(3) were fed with same ration supplemented with 0.7 % (100 g/day) and 1.4 % (200 g/day) bypass fat (on dry matter intake (DMI) basis), respectively. The feed intake, milk yield, and milk composition were not influenced by supplemental bypass fat. However, fat-corrected milk (6.5 %) yield was higher (P < 0.05) in T(3) (14.21) than that of T(1) (9.83) and similar with T(2) (11.05). Feed efficiency (milk yield/kg DMI) was higher (P < 0.05) in group T(3) (0.51) than that of T(1) (0.38) and T(2) (0.41) indicating that buffaloes fed with bypass fat which is 1.4 % (200 g/day) of the diet were economically more efficient. The serum cholesterol level was higher (P < 0.01) in bypass fat-supplemented group (T(2) and T(3)) of animals. Serum high density lipoprotein (HDL) cholesterol (good cholesterol) level was more (P < 0.05) than LDL cholesterol (bad cholesterol) level with higher dose of bypass fat in T(3) than T(2). It was concluded that bypass fat supplementation with 1.4 % of the diet (200 g/day) increased the fat-corrected milk production and feed efficiency along with serum HDL cholesterol level in lactating Murrah buffaloes.


Synthesis and photobiological properties of acetylpsoralen derivatives.
In an investigation to find monofunctional reactants for DNA which can act as new agents in the photochemotherapy of psoriasis, we have synthesized and studied some methylpsoralen derivatives which contain an acetyl group at one of the two reactive sites of the furocoumarin skeleton (at the 3 or 5' positions). The compounds do not react easily with DNA; their photobiological properties (e.g. the lack of an ability to inhibit DNA synthesis in Ehrlich ascites tumour cells, to induce T2 phage sensitization and to induce erythema in guinea-pig skin) are exactly in line with this behaviour. Some interesting features are shown by 4,8-dimethyl-5'-acetylpsoralen: it is capable of producing a very large amount of singlet oxygen--an order of magnitude higher than the other compounds and 8-methoxypsoralen (used as reference). In spite of this property, 4,8-dimethyl-5'-acetylpsoralen is non-phototoxic to the skin, and its other photobiological properties appear to be in line with its lack of interaction with DNA rather than its enhanced singlet oxygen production.


Cardiothoracic ratio in Nigerian newborn infants.
Cardiothoracic ratio was calculated from measurements made on the frontal radiographs of 172 normal (appropriate for gestational age) Nigerian newborn infants. The normal ratio was compared with those of 30, 32 and 42 neonates with respiratory distress syndrome, birth asphyxia and parenchymal lung disease respectively. The ratio for normal neonates was 49.12%. It was however significantly increased in respiratory distress syndrome (51.18%) and asphyxia (50.81%). The cardiothoracic ratio values obtained in this study are lower than those in Caucasian newborn infants.


Socio-economic and behavioral determinants of prescription and non-prescription medicine use: the case of Turkey.
Demographic and socio-economic factors determine pharmaceutical health care utilization for individuals. Prescription and non-prescription medicine use are expected to have different determinants. Even though prescription and non-prescription medicine use is being well researched for developed countries, there are only a few studies for developing countries. This paper aims to analyze the socio-economic and individual characteristics that determine the use of prescription and non-prescription medicine. We examine the issue for the specific case of Turkey since Turkey's health system has undertaken significant changes in the last two decades and especially after 2003 with the "Health Transformation Programme". Data from the nationally representative "Health Survey" are used in the analysis. The data set covers the 2008-2016 period with two-year intervals. Pooled multivariate logistic regression is employed to identify the underlying determinants of prescription and non-prescription medicine use. When compared to 2008, non-prescription medicine use decreases until 2012, however, an increasing trend appears after 2012. For prescription medicine use, a decreasing trend emerges after 2012. Findings from the marginal effects indicate that for non-prescription medicine use, the highest effect stems from the health status. For prescription medicine use, the highest marginal effects arise from age, health and employment status indicating the importance of the need and predisposing factors. Decreasing non-prescription medicine use largely depends on easier access to health care service utilization. Although having a health insurance has a positive relationship with prescription medicine use, there is still a problem for individuals living a rural area and heaving a lower income level since they are more likely to use non-prescription medicine.


8-37hCGRP, an amylin receptor antagonist, enhances the insulin response and perturbs the glucose response to infused arginine in anesthetized rats.
When 2 mmol L-arginine was infused into non-fasted, anesthetized rats at a rate slow enough to avoid hemodynamic disturbance, there was a rise in plasma glucose concentration followed by a decline to pre-infusion levels. In animals pre-infused with 8-37hCGRP, a fragment of calcitonin gene-related peptide that blocks amylin's hyperglycemic action, the normal initial rise in plasma glucose was accompanied by an enhanced rise in plasma insulin and was then followed by an enhanced fall in plasma glucose. These perturbations of the insulin and glucose response during amylin receptor blockade are difficult to explain without invoking a role for endogenous amylin; they further suggest an autocrine/paracrine role for amylin at the pancreatic islet.


Rapidly fluctuating thresholds at the onset of experimentally-induced hydrops in the guinea pig.
Pigmented guinea pigs were chronically implanted bilaterally with a platinum electrode on each round window. After recovery the endolymphatic sac was destroyed and the duct blocked on one side only; the other side was employed as a control. The round window response thresholds on both sides were recorded several times per week over a three month period. There were three main results. A sensitivity loss of up to 20 dB was observed for frequencies between 250 Hz and 6.4 kHz within two weeks post-op. At the end of three months the threshold elevation for these frequencies was as much as 50 dB. On the other hand the thresholds for frequencies between 8 and 16 kHz remained within 10 dB of their pre-operative value for at least two months. The thresholds fluctuated with a shift of as much as 25 dB within 24 h. The threshold elevation was associated with a decrease in the latency, at threshold, of the round window AP response which at frequencies between 250 Hz and 6.4 kHz was as short as that for 8 kHz. This observation suggested that it was the base, only, of the cochlea which responded. The present study has indicated that experimentally induced endolymphatic hydrops in the guinea pig mimics well the progressive and fluctuating hearing loss characteristic of Ménière's disease.


Protease-activated kinase II as the mediator of epidermal growth factor-stimulated phosphorylation of ribosomal protein S6.
Epidermal growth factor stimulates phosphorylation of ribosomal protein S6 in serum-starved Swiss 3T3 cells, leading to the formation of highly phosphorylated derivatives containing 4-5 phosphates. Two-dimensional analysis of tryptic phosphopeptides of S6 shows an identical pattern to the ones obtained previously in other cells in response to insulin and the tumor promoting phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate. This suggests a common intracellular mediator of S6 phosphorylation by different growth promoting agents. It is proposed that the potential mediator of this phosphorylation is the Ca2+-independent, cAMP-independent protein kinase, protease activated kinase II, as shown by the extent of phosphorylation and the tryptic phosphopeptide maps of S6 with highly purified enzyme [(1983) J. Biol. Chem. 258, 13998-14002].


Insight into the heterogeneity of breast cancer through next-generation sequencing.
Rapid and sophisticated improvements in molecular analysis have allowed us to sequence whole human genomes as well as cancer genomes, and the findings suggest that we may be approaching the ability to individualize the diagnosis and treatment of cancer. This paradigmatic shift in approach will require clinicians and researchers to overcome several challenges including the huge spectrum of tumor types within a given cancer, as well as the cell-to-cell variations observed within tumors. This review discusses how next-generation sequencing of breast cancer genomes already reveals insight into tumor heterogeneity and how it can contribute to future breast cancer classification and management.


Utilization for lactic acid production with a new acid hydrolysis of ram horn waste.
The use of ram horn hydrolysate (RHH) as a substrate for lactic acid production was investigated using Lactobacillus casei. For this purpose, first RHH was produced. Ram horns were hydrolyzed by treating with acids (6N-H2SO4 and 6N-HCl) and neutralizing the solutions. The amounts of protein, nitrogen, ash, some minerals, total sugars, total lipids and amino acids of the RHH were determined. The effect of different concentrations (1-10% v/v) of RHH on the production of biomass, lactic acid concentration and sugar consumption was investigated, and a concentration of 6% RHH was found to be optimal. The content of lactic acid in the culture broth containing 6% RHH (44 g x l(-1)) for 26 h was 22% higher than that of the control culture broth (36 g x l(-1)). From this result, RHH was demonstrated to be a suitable supplement for lactic acid production, a use that would resolve a local environmental problem.


A herbivore-induced plant volatile interferes with host plant and mate location in moths through suppression of olfactory signalling pathways.
Plants under herbivore attack release volatiles that attract natural enemies, and herbivores in turn avoid such plants. Whilst herbivore-induced plant volatile blends appeared to reduce the attractiveness of host plants to herbivores, the volatiles that are key in this process and particularly the way in which deterrence is coded in the olfactory system are largely unknown. Here we demonstrate that herbivore-induced cotton volatiles suppress orientation of the moth Spodoptera littoralis to host plants and mates. We found that (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), an induced volatile, is key in herbivore deterrence: DMNT suppressed plant odour- and pheromone-induced behaviours. We then dissected the neurophysiological basis of this interaction. DMNT-responding glomeruli were also activated by other plant compounds, suggesting that S. littoralis possesses no segregated olfactory circuit dedicated exclusively to DMNT. Instead, DMNT suppressed responses to the main pheromone component, (Z)-9-(E)-11-tetradecenyl acetate, and primarily to (Z)-3-hexenyl acetate, a host plant attractant. Our study shows that olfactory sensory inhibition, which has previously been reported without reference to an animal's ecology, can be at the core of coding of ecologically relevant odours. As DMNT attracts natural enemies and deters herbivores, it may be useful in the development or enhancement of push-pull strategies for sustainable agriculture.


WormBot, an open-source robotics platform for survival and behavior analysis in C. elegans.
Caenorhabditis elegans is a popular organism for aging research owing to its highly conserved molecular pathways, short lifespan, small size, and extensive genetic and reverse genetic resources. Here we describe the WormBot, an open-source robotic image capture platform capable of conducting 144 parallel C. elegans survival and behavioral phenotyping experiments. The WormBot uses standard 12-well tissue culture plates suitable for solid agar media and is built from commercially available robotics hardware. The WormBot is controlled by a web-based interface allowing control and monitoring of experiments from any internet connected device. The standard WormBot hardware features the ability to take both time-lapse bright field images and real-time video micrographs, allowing investigators to measure lifespan, as well as heathspan metrics as worms age. The open-source nature of the hardware and software will allow for users to extend the platform and implement new software and hardware features. This extensibility, coupled with the low cost and simplicity of the system, allows the automation of C. elegans survival analysis even in small laboratory settings with modest budgets.


A photogrammetric method to measure fluid movement across isolated frog retinal pigment epithelium.
Bullfrog retinal pigment epithelium (RPE)/choroid explants were mounted in an Ussing chamber modified so that the side bathing the choroid was completely sealed. Net fluid movement across the RPE and into or out of the sealed side of the chamber forced the tissue to assume a convex or concave shape. Photogrammetry was used to measure this tissue bowing by analyzing the displacement of the image produced on the RPE surface by an off-axis laser. Under baseline conditions, measured net fluid movements were always in the retina-to-choroid direction with a mean of 7.6 microliter cm-2 h-1. Potential artifacts from a variety of sources have been examined and shown to be insignificant.


A rare case of a cardiac papillary fibroelastoma of the pulmonary valve diagnosed by echocardiography.
Primary cardiac tumors are rare. The majority of primary tumors of the heart are benign with papillary fibroelastomas being the third most common after myxomas and lipomas respectively. Papillary fibroelastomas represent the most common valvular tumor of the heart. Although benign, papillary fibroelastomas have the potential to cause turbulent flow, thrombus formation, and severe cerebral or coronary embolic disease. The majority of fibroelastomas have been described on the left side of the heart involving the aortic and mitral valves. We present a rare case of a papillary fibroelastoma occurring on the pulmonic valve.


Synthesis and evaluation of 2-substituted 8-hydroxyadenines as potent interferon inducers with improved oral bioavailabilities.
In order to create novel compounds which possess potent interferon (IFN) inducing activities with excellent oral bioavailabilities, a series of 8-hydroxyadenines, which have various alkoxy or alkylthio moieties at the adenine C(2)-position, were synthesized and evaluated. The introduction of hydrophobic groups was not considered to be effective for potentiating the IFN-inducing activity, but several compounds having hydrophilic groups were effective. Among the compounds tested, compound 13f induced IFN from the dosage of 0.03 mg/kg, which was approximately 100-fold more potent than that of Imiquimod, and showed an excellent oral bioavailability (F=40%) which was 10-fold improved over 5, a lead compound (F=4%).


Computer-assisted semen analysis: evaluation of method and assessment of the influence of sperm concentration on linear velocity determination.
Semen samples from 77 men were used to estimate the accuracy and precision of measurements of sperm density, percent motility, and motion characteristics using a new, fully automated, computer-assisted semen analyzer (CASA). Results are compared with traditional semen analysis methodology. Acceptable precision for count and percent motility was obtained using three to nine random fields of observation when there were more than 10 cells per high-power microscopic field. A highly significant correlation (P less than 0.01) was found between the two methods in the assessment of sperm concentration and percent motility, but CASA overestimated concentration significantly (P less than 0.01) by about 30% when there were less than 60 cells per high power field. This overestimation seemed to be due to the number of nonsperm particles in semen that are confused with spermatozoa by the program. Linear velocity determination was influenced by the number of tracking points as well as by the concentration of cells present in the counting chamber. More representative linear velocity estimations in semen were obtained when sperm concentration was less than 40 x 10(6) cells/ml and 20 tracking points were used in the determination. For semen specimens containing higher cell density, sperm concentration needed to be reduced by diluting the semen with the patient's own sperm-free seminal plasma before measuring motion characteristics.


A new methodology for estimating rainfall aggressiveness risk based on daily rainfall records for multi-decennial periods.
The temporal irregularity of rainfall, characteristic of a Mediterranean climate, corresponds to the irregularity of the environmental effects on soil. We used aggressiveness as an indicator to quantify the potential environmental impact of rainfall. However, quantifying rainfall aggressiveness is conditioned by the lack of sub-hourly frequency records on which intensity models are based. On the other hand, volume models are characterized by a lack of precision in the treatment of heavy rainfall events because they are based on monthly series. Therefore, in this study, we propose a new methodology for estimating rainfall aggressiveness risk. A new synthesis parameter based on reformulation using daily data of the Modified Fournier and Oliver's Precipitation Concentration indices is defined. The weighting of both indices for calculating the aggressiveness risk is established by multiple regression with respect to the local erosion R factor estimated in the last decades. We concluded that the proposed methodology overcomes the previously mentioned limitations of the traditional intensity and volume models and provides accurate information; therefore, it is appropriate for determining potential rainfall impact over long time periods. Specifically, we applied this methodology to the daily rainfall time series from the San Fernando Observatory (1870-2010) in southwest Europe. An interannual aggressiveness risk series was generated, which allowed analysis of its evolution and determination of the temporal variability. The results imply that environmental management can use data from long-term historical series as a reference for decision making.


Energy drink usage among university students in a Caribbean country: Patterns of use and adverse effects.
There has been little inquiry addressing whether or not concerns about adverse effects of energy drink usage are relevant in the Caribbean. This survey investigated energy drink usage and adverse consequences among tertiary level students in Trinidad and Tobago. A cross-sectional survey of 1994 students from eight institutions was conducted using a de novo questionnaire based on findings from a focus group of students. Chi-squared analyses and logistic regression were used to assess relationships between energy drink usage, adverse effects and other factors affecting energy drink use, and to verify predictors of energy drink use. Prevalence of use was 86%; 38% were current users. Males were more likely to use, used more frequently and at an earlier age. Energy drinks were used most commonly to increase energy (50%), combat sleepiness (45%) and enhance academic performance (40%), and occurred during sports (23%) and mixed with alcohol (22.2%). The majority (79.6%) consumed one energy drink per sitting; 62.2% experienced adverse effects, most commonly restlessness (22%), jolt and crash (17.1%) and tachycardia (16.6%). Awareness of adverse effects was associated with no use (p=0.004), but adverse effects were not a deterrent to continued use. Energy drink usage is prevalent among students. The use is not excessive, but associated with high rates of adverse effects and occurs in potentially dangerous situations like during exercise and with alcohol. There is a need to educate students about the potential adverse effects of energy drinks.


X-rays had little value in diagnosing children's abnormal skull shapes, and primary care clinicians should refer concerns to specialist teams.
This study examined the consensus between the primary care radiological diagnosis and specialist clinical diagnosis of abnormal skull shapes in children. We performed a retrospective review of children treated at the National Paediatric Craniofacial Centre at Children's Health Ireland, Dublin, Ireland. Group 1 were referred by primary care colleagues concerned about suspected abnormal skull shapes from 1 January 2015 to 30 May 2017. These included cases where they sought specialist confirmation that the skull shape was normal. Group 2 underwent surgery for craniosynostosis from 1 January 2011 to 25 October 2017. The primary care skull X-ray reports were examined for both groups to see whether they matched the specialist diagnosis. Group 1 comprised 300 children, and 59 (20%) had pre-referral skull X-rays. The primary care X-ray reports and specialist diagnoses agreed in 44 (75%) cases, including 19 (43%) who had a normal skull shape. Group 2 comprised 274 children, and 63 (23%) had pre-referral skull X-rays. In this group, there was agreement in 41 (65%) diagnoses; however, the primary care X-ray reports did not diagnose craniosynostosis for the remaining 22 (35%) children. X-rays were of little value in diagnosing abnormal skull shapes, especially craniosynostosis, and primary care clinicians should refer concerns to specialist teams.


Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial.
Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of adaptive CRT versus conventional CRT in patients with heart failure with intact atrioventricular conduction and left bundle branch block. This global, prospective, randomised controlled trial was done in 227 hospitals in 27 countries across Asia, Australia, Europe, and North America. Eligible patients were aged 18 years or older with class 2-4 heart failure, an ejection fraction of 35% or less, left bundle branch block with QRS duration of 140 ms or more (male patients) or 130 ms or more (female patients), and a baseline PR interval 200 ms or less. Patients were randomly assigned (1:1) via block permutation to adaptive CRT (an algorithm providing synchronised left ventricular stimulation) or conventional biventricular CRT using a device programmer. All patients received device programming but were masked until procedures were completed. Site staff were not masked to group assignment. The primary outcome was a composite of all-cause death or intervention for heart failure decompensation and was assessed in the intention-to-treat population. Safety events were collected and reported in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02205359, and is closed to accrual. Between Aug 5, 2014, and Jan 31, 2019, of 3797 patients enrolled, 3617 (95·3%) were randomly assigned (1810 to adaptive CRT and 1807 to conventional CRT). The futility boundary was crossed at the third interim analysis on June 23, 2022, when the decision was made to stop the trial early. 1568 (43·4%) of 3617 patients were female and 2049 (56·6%) were male. Median follow-up was 59·0 months (IQR 45-72). A primary outcome event occurred in 430 of 1810 patients (Kaplan-Meier occurrence rate 23·5% [95% CI 21·3-25·5] at 60 months) in the adaptive CRT group and in 470 of 1807 patients (25·7% [23·5-27·8] at 60 months) in the conventional CRT group (hazard ratio 0·89, 95% CI 0·78-1·01; p=0·077). System-related adverse events were reported in 452 (25·0%) of 1810 patients in the adaptive CRT group and 440 (24·3%) of 1807 patients in the conventional CRT group. Compared with conventional CRT, adaptive CRT did not significantly reduce the incidence of all-cause death or intervention for heart failure decompensation in the included population of patients with heart failure, left bundle branch block, and intact AV conduction. Death and heart failure decompensation rates were low with both CRT therapies, suggesting a greater response to CRT occurred in this population than in patients in previous trials. Medtronic.


Tonic and baroreflex effects on arterial pressure and ventilation of pentobarbital and nicotine on the rat ventral medullary surface.
Unilateral aortic depressor nerve stimulation caused depression of arterial pressure (baropressure reflex) and ventilation (baro-ventilatory reflex) in urethane-anesthetized, spontaneously breathing Sprague-Dawley rats. Application of sodium pentobarbital to the ventral medullary surface (VMS) depressed baseline arterial pressure and ventilation, and attenuated the baro-pressure reflex, but not the baro-ventilatory reflex. Application of nicotine on the VMS decreased baseline arterial pressure and increased ventilation, but left both baro-pressure and baro-ventilatory reflexes unaltered. The results suggest that some of the structures that affect vasomotor tone may not be involved in the baroreflex inhibition of arterial pressure. Additionally, neither the neural structures near the VMS which modulate CO2 control of ventilation, nor those that affect tonic control of vasomotor tone are likely to be significantly involved in the baro-ventilatory reflex.


Synergetic degradation of Methylene Blue through photocatalysis and Fenton reaction on two-dimensional molybdenite-Fe.
The greatest problem in conventional Fenton reaction is the slow production of ROS (reactive oxygen species) because of the inefficient Fe3+/Fe2+ conversion. Based on the extraordinary photo-response property of two-dimensional molybdenite (2DM), photogenerated electrons can be easy separated to accelerate the regeneration of Fe2+. In this work, Fe2+-anchored 2DM (2DM-Fe) was prepared and used as a heterogeneous Fenton catalyst to investigate the degradation efficiency to Methylene Blue (MB) in the presence of light. According to experimental results, 2DM-Fe exhibited extraordinary catalytic activity in MB elimination, which ascribed to the synergetic effect of photogenerated carriers and anchored Fe2+ to H2O2 activation. In addition, 2DM-Fe showed nearly 100% degradation efficiency to MB within 5 cycles with slight leaching amount of Mo and Fe ions, implying the strong stability and reusability in H2O2 system. Furthermore, the influences of H2O2 and 2DM-Fe dosages, pH values as well as the degradation efficiency to different dyes were also investigated. According to quenching experiments and EPR (electron paramagnetic resonance) test, the degradation mechanism of MB mainly ascribed to the oxidation of HO• and •O2-. This finding provides a novel strategy to design rational Fenton catalyst and has great significance to water remediation in the future.


Functional changes in the reward circuit in response to gaming-related cues after training with a commercial video game.
In the present longitudinal study, we aimed to investigate video game training associated neuronal changes in reward processing using functional magnetic resonance imaging (fMRI). We recruited 48 healthy young participants which were assigned to one of 2 groups: A group in which participants were instructed to play a commercial video game ("Super Mario 64 DS") on a portable Nintendo DS handheld console at least 30minutes a day over a period of two months (video gaming group; VG) or to a matched passive control group (CG). Before and after the training phase, in both groups, fMRI imaging was conducted during passively viewing reward and punishment-related videos sequences recorded from the trained video game. The results show that video game training may lead to reward related decrease in neuronal activation in the dorsolateral prefrontal cortex (DLPFC) and increase in the hippocampus. Additionally, the decrease in DLPFC activation was associated with gaming related parameters experienced during playing. Specifically, we found that in the VG, gaming related parameters like performance, experienced fun and frustration (assessed during the training period) were correlated to decrease in reward related DLPFC activity. Thus, neuronal changes in terms of video game training seem to be highly related to the appetitive character and reinforcement schedule of the game. Those neuronal changes may also be related to the often reported video game associated improvements in cognitive functions.


[Cyst of the broken common bile duct: literature review].
Cystic malformations of the bile ducts are rare congenital disorders, with an incidence of 1/2000000 live births. Complication including the angiocholitis, chronic pancreatitis, progressive biliary cirrhosis, portal hypertension or gallbladder lithiases can reveal severe disorder. Spontaneous perforation is one of the rare complications described for the first time in 1934 by Weber. We report the case of an 18-month old baby admitted with subocclusive syndrome with biliary peritonitis. Ultrasound was performed showing abdominal effusion with cystic formation communicating with the bile ducts associated with subcapsular effusion of the liver confirmed by a scanner. Treatment was based on peritoneal toilet with redon drain at the level of the perforation and subhepatic drain without cyst excision. The patient was re-admitted 6 months after this incident to be definitively treated.