Novel Monoterpene Lactones from Cinnamomum inunctum.
Four new monoterpene lactones, 5-(2,3-dihydroxy-3-methylbutyl)-4-hydroxy-4-methyldihydrofuran-2(3H)-one (1), 5-(2,3-dihydroxy-3-methylbutyl)-4-methylfuran-2(5H)-one (2), 8-hydroxy-4,7,7-trimethyl-1,6-dioxaspiro[4.4]non-3-en-2-one (3) and 8-hydroxy-4,7,7-trimethyl-1,6-dioxaspiro[4.4]non-3-en-2-one (4), were isolated from the methanolic extract of the fruit of Cinnamomum inunctum, a folk medicine in Myanmar, together with a known compound, 3-hydroxy-4,4-dimethyl-4-butyrolactone (5). Their chemical structures were determined by spectral methods. Among these, 3 and 4 possessed unique spirolactone moieties.


Use of beta-lactamase as a secreted reporter of promoter function in yeast.
K1 preprotoxin is the 316 residue precursor of the K1 killer toxin secreted by the yeast Saccharomyces cerevisiae. The SP beta la reporter consists of the mature, secreted form of beta-lactamase (beta la) fused to S and P, two fragments of preprotoxin. S is the N-terminal 34 residues, including the secretion signal. P, a 67 residue 'processing' segment with three sites for N-glycosylation, terminates in a Lys Arg site for cleavage by the Kex2 protease. Expression of SP beta 1a in yeast results in efficient secretion, processing by signal peptidase and glycosylation in the endoplasmic reticulum, producing pro beta la. Kex2 cleavage of pro beta la in the lumen of a late Golgi compartment releases beta la, which accumulates stably in culture media buffered at pH 5.8-7. The half-life of secretion is 11 min at 30 degrees C; 10-12% of the total activity in exponential-phase cells is intracellular, mostly in the form of pro beta la, indicating that transit from the endoplasmic reticulum to the Golgi is rate limiting. We have used SP beta la expression in single- and multi-copy vectors to compare the PGK, GAL1, GAL10, PHO5 and CUP1 promoters under varying nutritional conditions. In exponential-phase cells, secretion of beta la over a 40-fold range and up to several micrograms/ml was proportional to transcript level, demonstrating that SP beta la can be employed as a convenient secreted reporter of promoter function in yeast.


Pulmonary arteriovenous malformation in a child with multiple brain abscesses: A case report.
Pulmonary arteriovenous malformations (PAVMs) are caused by abnormal connections between arteries and veins, which lead to right-to-left shunting of deoxygenated blood. Here, we report an 11-year-old male who presented with signs suggestive of intracranial pathology. The patient displayed signs of a chronic illness, possibly congenital malformation that was complicated by PAVM and multiple brain abscesses. This case illustrates the importance of doing a detailed examination and investigations, especially if the history alone is not helpful in making a diagnosis.


Pyramidal and Taurodont Molars and Their Association With Other Tooth Anomalies.
Determine the prevalence of pyramidal molars (PMs), associated tooth anomalies, and medical conditions (MC). Pantomograms from 10,168 subjects were searched for PMs. A total of 148 individuals (75.7 percent females), aged 9.7 to 18.9 years old, had PMs. Subjects with MCs (53.4 percent) had on average 17 percent more PMs (P=.0476) and 2.8 times greater odds of palatally displaced canines (P=.0309). The mean number of pyramidal and taurodont molars per subject was 2.9±1.4 (SD) and 3.1±1.7 (SD), respectively. In both sexes, 63.5 percent of all observed PMs were located in the maxilla and 78.5 percent of all PMs were second molars. Taurodont molars increased by 9.4 percent as other tooth anomalies increased by one, but decreased by 8.2 percent for each additional PM. Tooth anomalies associated with PMs were palatally displaced canines (17.6 percent) and short root anomaly of maxillary central incisors (6.1 percent). Delayed eruption was noted in 9.5 percent, tooth agenesis in 6.1 percent, and supernumerary teeth in 3.4 percent. The prevalence of pyramidal molars was 1.4 percent, and the female-to-male ratio was 3.1 to one. Pyramidal molars are often associated with medical conditions and other tooth anomalies.


Effects of exercise therapy on the balance and gait after total hip arthroplasty: a systematic review and meta-analysis.
The situation is such that there is a lack of research analyzing the effect of exercise therapy during the rehabilitation period of patients after total hip arthroplasty (THA). Therefore, the purpose of this systematic review and meta-analysis is to analyze the effects of exercise therapy on the balance and gait of patients after THA. The studies selected for this study were based on the PICO as follows: P (Patient)-patients after THA, I (Intervention)-exercise therapy, C (Comparison)-control and other therapy groups, O (Outcome)-balance and gait. Additional criteria for this study were study design (randomized controlled study), language (English), publication status (journal), and the year of publication were not limited. Eleven studies were included. The effects of exercise therapy on balance and gait in patients after THA were significantly different. Balance: standardized mean difference (SMD), 0.51; 95% confidence intervals (CI), 0.24-0.78; I2=22%. Gait: SMD, 0.39; 95% CI, 0.01-0.76; I2=66%. Rehabilitation specialists recommend that exercise therapy be included in rehabilitation programs to improve balance and gait in patients after THA. Further research is needed in the future, including more studies and a network meta-analysis that analyzes the effect size of each exercise therapy.


The consequences of missing appendicitis during pregnancy.
A 23-year-old second para was admitted for severe anaemia with abdominal distension in the immediate puerperal period following a preterm delivery. She suffered from acute abdominal pain 3 days back (at 32 weeks of gestation) and was evaluated in the emergency medical department for appendicitis/cholecystitis. Abdominal ultrasound was found to be normal and she received antacids for her pain abdomen. Clinical examination the day after delivery revealed abdominal distension, guarding and rigidity. Ultrasonography revealed a normal puerperal uterus with free fluid in the abdomen which on diagnostic aspiration was pus. Emergency laparotomy showed acute suppurative appendicitis with perforation. Appendecectomy with peritoneal lavage was done. Her postoperative period was stormy with high febrile spikes and evaluation confirmed septicaemia. The organism grown on postoperative blood culture and cervical swab culture was Enterococcus fecalis sensitive to vancomycin and she received the same for 10 days and recovered.


Insights into the role of sulfated glycans in cancer cell adhesion and migration through use of branched peptide probe.
The tetra-branched peptide NT4 selectively binds to different human cancer cells and tissues. NT4 specifically binds to sulfated glycosaminoglycans on cancer cell membranes. Since sulfated glycosaminoglycans are involved in cancer cell interaction with the extracellular matrix, we evaluated the effect of NT4 on cancer cell adhesion and migration. We demonstrated here that the branched peptide NT4 binds sulfated glycosaminoglycans with high affinity and with preferential binding to heparan sulfate. NT4 inhibits cancer cell adhesion and migration on different proteins, without modifying cancer cell morphology or their ability to produce protrusions, but dramatically affecting the directionality and polarity of cell movement. Results obtained by taking advantage of the selective targeting of glycosaminoglycans chains by NT4, provide insights into the role of heparan sulfate proteoglycans in cancer cell adhesion and migration and suggest a determinant role of sulfated glycosaminoglycans in the control of cancer cell directional migration.


Resolving biofilm infections: current therapy and drug discovery strategies.
Biofilms formed by pathogenic bacteria present a serious threat to human health as the efficacy of standard antibiotic therapeutic regimens is compromised by reduced microbial susceptibility within the biofilm environment. The discovery of improved therapies for biofilm elimination requires an understanding of biofilm formation and dispersal, and the development of assays to specifically analyze these dynamic processes. This review will discuss biofilm screening strategies suitable for drug discovery efforts, especially chemical and biological approaches that specifically target biofilm destruction.


Staphylococcal exanthematous disease in a newborn due to a virulent methicillin-resistant Staphylococcus aureus strain containing the TSST-1 gene in Europe: an alert for neonatologists.
We report a case of staphylococcal exanthematous disease in a newborn due to a toxic shock syndrome toxin 1- and SEC-producing methicillin-resistant Staphylococcus aureus strain and alert neonatologists to the probable emergence in France of the neonatal toxic shock syndrome-like exanthematous disease in newborns previously described in Japan. We advise neonatologists to pay careful attention to clinical parameters and to prescribe appropriate tests: platelet count, serum C-reactive protein concentration, and Vbeta2-positive T-cell counts.


The Effect of Lowering the Legal Drink-Drive Limit on the Toxicological Findings in Driver Fatalities: A Comparison of Two Jurisdictions.
In December 2014, the legal blood alcohol limit for drivers in both Scotland and New Zealand was reduced from 80 to 50 mg/100 mL. This paper reports a retrospective study comparing changes in the toxicological findings in deceased drivers and motorcyclists before and after the limit change in both jurisdictions. A year of fatal motor vehicle crashes prior to and following the limit change is examined for both countries. In Scotland, there was an increase in drug prevalence among fatally injured drivers and motorcyclists, with the use of all drug groups increasing after the limit change, with the exception of cannabinoids. In New Zealand, there was a reduction in cases involving drugs only, but increases in the numbers of deceased drivers and motorcyclists positive for alcohol only and co-using alcohol and drugs.


Tuning the Selectivity of Catalytic Carbon Dioxide Hydrogenation over Iridium/Cerium Oxide Catalysts with a Strong Metal-Support Interaction.
A one-step ligand-free method based on an adsorption-precipitation process was developed to fabricate iridium/cerium oxide (Ir/CeO2 ) nanocatalysts. Ir species demonstrated a strong metal-support interaction (SMSI) with the CeO2 substrate. The chemical state of Ir could be finely tuned by altering the loading of the metal. In the carbon dioxide (CO2 ) hydrogenation reaction it was shown that the chemical state of Ir species-induced by a SMSI-has a major impact on the reaction selectivity. Direct evidence is provided indicating that a single-site catalyst is not a prerequisite for inhibition of methanation and sole production of carbon monoxide (CO) in CO2 hydrogenation. Instead, modulation of the chemical state of metal species by a strong metal-support interaction is more important for regulation of the observed selectivity (metallic Ir particles select for methane while partially oxidized Ir species select for CO production). The study provides insight into heterogeneous catalysts at nano, sub-nano, and atomic scales.


[Identification and properties of insulin receptors in neuroblastoma C 1300 N 18 cells in various functional states].
The presence of insulin receptors in neuroblastoma C 1300 N18 cells was shown by the method of the [125I]insulin binding with cells as well as by the electron-cytochemical methods based on the analysis of the binding of colloid gold-labelled insulin and of agglutinin of wheat embryos with the surface of plasma membrane. It is established that the number and distribution of insulin receptors depend on the functional state of cells. Expression of receptors on the membrane increases after 5'-deoxyuridine-induced differentiation of cells. Due to changes in the lipid composition of cells caused by the incubation with lecithin-cholesterol liposomes (an increase in the content of cholesterol and its esters, as well as of unsaturated fatty acids and appearance of lysolecithin) the quantity of insulin receptors decreases and cell membranes are damaged. The lowering insulin regulation is not observed for insulin receptors of the neuroblastoma C 1300 N18 cells.


Chronic renal failure in Khartoum, Sudan.
A study of the clinical presentation and conceivable causes of chronic renal failure (CRF) in 61 Sudanese patients in Khartoum is presented. The clinical features involved almost all the systems, however, gastrointestinal and cardiovascular signs and symptoms predominated. The causes of chronic renal failure in Sudan and Sweden are also studied for comparison. The causes of CRF in Sudan are chronic glomerulonephritis, obstructive nephropathy (stone disease), hypertension and diabetes mellitus in that order. The main causes of CRF in Sweden are chronic glomerulonephritis, diabetes mellitus and chronic pyelonephritis. Of the 61 Sudanese patients 16 have kidney transplants, only one in Sudan, three patients are on regular hemodialysis, nine patients are on intermittent peritoneal dialysis, 16 are on conservative treatment and 17 died during the course of treatment.


The molecular pathogenesis of pituitary tumors: implications for clinical management.
Pituitary adenomas are unique in several ways, and while they are rarely malignant they may be invasive and/or recurrent. Several attempts have been made to determine the growth potential of pituitary adenomas. Pituitary tumors predominantly arise in a sporadic setting or more rarely as part of hereditary genetic syndromes. Molecular analysis of these familial pituitary adenomas has provided significant insight into pituitary tumorigenesis. Some specific genes have been identified that predispose to pituitary neoplasia, but these are rarely involved in the pathogenesis of sporadic tumors. The number of genes or molecular alterations involved in pituitary tumorigenesis is progressively increasing, providing a hope for development of new predictive and prognostic markers. The aim of this review is to focus on the molecular pathology of pituitary adenomas in the context of their implications on management and targeted therapy. We have summarized our current knowledge on the molecular biology in familial and sporadic pituitary adenomas, and we subsequently focus on prognostic factors as well as specific predictive markers for new promising targeted therapies.


A peculiar case of acute myeloid leukemia mimicking plasmacytoid dendritic precursor cell leukemia.
Differential diagnosis between plasmacytoid dendritic precursor cell leukemia (pDC leukemia) and acute myeloid leukemia (AML) with monocytic differentiation is difficult due to shared clinicopathological features ; however, such diagnosis is critical because the two leukemias are treated differently. Here we report a peculiar case of AML mimicking pDC leukemia. A 22-year-old man presented with leukocytopenia and bone marrow involvement of atypical plasmacytoid cells with a prominent nucleolus. In spite of positive cytochemical staining for NaF-sensitive naphthyl butyrate esterase, this case was diagnosed as pDC leukemia because the abnormal cells were positive for CD4, CD56, and CD123, and negative for myeloperoxidase and lysozyme. The patient achieved complete remission after 4 courses of combination chemotherapy, but relapsed four months later with leukemic manifestation and skin involvement. The morphology of the leukemia cells became myelomonoblastic, and some were immunohistochemically positive for lysozyme, suggesting AML. Although the patient received allogenic stem cell transplantation twice, he died of progressive disease. This case demonstrates the importance of cytochemical staining for naphthyl butyrate esterase in differential diagnosis between AML and pDC leukemia coexpressing CD4, CD56, and CD123.


Real-time Detection of Breast Cancer Cells Using Peptide-functionalized Microcantilever Arrays.
Ligand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch(®)) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells. The peptide-functionalized microcantilever allowed efficient capture and detection of cancer cells in MCF7 spiked human blood samples emulating CTCs in human blood. A detection limit of 50-100 cancer cells mL(-1) from blood samples was achieved with a capture yield of 80% from spiked whole blood samples. The results emphasize the potential of peptide 18-4 as a novel peptide for capturing and detecting cancer cells in conjunction with nanomechanical cantilever platform. The reported peptide-based cantilever platform represents a new analytical approach that can lead to an alternative to the various detection platforms and can be leveraged to further study CTCs.


Mechanisms underlying reduced apoptosis in neonatal neutrophils.
Apoptosis, which leads to phagocytosis by mononuclear cells, represents the primary mechanism for removing neutrophils from inflamed tissues and minimizing injury. The present studies show that membrane phosphatidylserine turnover and permeability, as well as DNA fragmentation, were reduced in neutrophils from neonates when compared with adults. The activity of caspase 3 and expression of the proapoptotic proteins Bax, Bad, and Bak were also decreased in neonatal relative to adult neutrophils. These findings are consistent with impaired apoptosis in neonatal cells, which may contribute to prolonged inflammation in infants after oxidative stress or infection. Neutrophil apoptosis is induced by endogenous ligands such as Fas (FasL), which engage death receptors of the tumor necrosis factor/nerve growth factor superfamily, including Fas receptor (FasR). We found that expression of FasR was decreased in neonatal when compared with adult cells. Moreover, neonatal neutrophils did not undergo apoptosis in response to anti-FasR antibody and exhibited impaired chemotaxis to soluble FasL. However, in both adult and neonatal cells, p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase inhibitors blocked Fas-induced activity. These data suggest that prolonged survival of neonatal neutrophils at injured sites is due, in part, to reduced responsiveness to FasL. This may be related to decreased expression of both FasR and Bcl-2-family proteins that mediate neutrophil apoptosis.


Post-ERCP pancreatitis: reduction by routine antibiotics.
Cholangitis and pancreatitis are severe complications of endoscopic retrograde cholangiopancreatography (ERCP). Antibiotics have been considered important in preventing cholangitis, especially in those with jaundice. Some have suggested that bacteria may play a role in the induction of post-ERCP pancreatitis. It is not clear, however, whether the incidence of post-ERCP pancreatitis could be reduced by antibiotic prophylaxis, as is the case with septic complications. In this prospective study, a total of 321 consecutive patients were randomized to the following two groups: (1) a prophylaxis group (n = 161) that was given 2 g of cephtazidime intravenously 30 minutes before ERCP, and (2) a control group (n = 160) that received no antibiotics. All patients admitted to the hospital for ERCP who had not taken any antibiotics during the preceding week were included. Patients who were allergic to cephalosporins, patients with immune deficiency or any other condition requiring antibiotic prophylaxis, patients with clinical jaundice, and pregnant patients were excluded. In the final analysis six patients were excluded because of a diagnosis of bile duct obstruction but with unsuccessful biliary drainage that required immediate antibiotic treatment. The diagnosis of cholangitis was based on a rising fever, an increase in the C-reactive protein (CRP) level, and increases in leukocyte count and liver function values, which were associated with bacteremia in some. The diagnosis of acute pancreatitis was based on clinical findings, and increases in the serum amylase level (>900 IU/L), CRP level, and leukocyte count with no increase in liver chemical values. The control group had significantly more patients with post-ERCP pancreatitis (15 of 160 in the prophylaxis group vs. 4 of 155 in the control group; P = 0.009) and cholangitis (7 of 160 vs. 0 of 155; P = 0.009) compared to the prophylaxis group. Nine patients in the prophylaxis group (6%) and 15 patients in the control group (9%) had remarkably increased serum amylase levels (>900 IU/L) after ERCP, but clinical signs of acute pancreatitis with leukocytosis, CRP reaction, and pain developed in four of nine patients in the prophylaxis group compared to 15 of 15 patients with hyperamylasemia in the control group (P = 0.003). In a multivariate analysis, the lack of antibiotic prophylaxis (odds ratio 6.63, P = 0.03) and sphincterotomy (odds ratio 5.60, P = 0.05) were independent risk factors for the development of post-ERCP pancreatitis. We conclude that antibiotic prophylaxis effectively decreases the risk of pancreatitis, in addition to cholangitis after ERCP, and can thus be routinely recommended prior to ERCP. These results suggest that bacteria could play a role in the pathogenesis of post-ERCP pancreatitis


Angiogenic stem cell delivery platform to augment post-infarction neovasculature and reverse ventricular remodeling.
Many cell-based therapies are challenged by the poor localization of introduced cells and the use of biomaterial scaffolds with questionable biocompatibility or bio-functionality. Endothelial progenitor cells (EPCs), a popular cell type used in cell-based therapies due to their robust angiogenic potential, are limited in their therapeutic capacity to develop into mature vasculature. Here, we demonstrate a joint delivery of human-derived endothelial progenitor cells (EPC) and smooth muscle cells (SMC) as a scaffold-free, bi-level cell sheet platform to improve ventricular remodeling and function in an athymic rat model of myocardial infarction. The transplanted bi-level cell sheet on the ischemic heart provides a biomimetic microenvironment and improved cell-cell communication, enhancing cell engraftment and angiogenesis, thereby improving ventricular remodeling. Notably, the increased density of vessel-like structures and upregulation of biological adhesion and vasculature developmental genes, such as Cxcl12 and Notch3, particularly in the ischemic border zone myocardium, were observed following cell sheet transplantation. We provide compelling evidence that this SMC-EPC bi-level cell sheet construct can be a promising therapy to repair ischemic cardiomyopathy.


Recent introduction and rapid dissemination of Chikungunya virus and Dengue virus serotype 2 associated with human and mosquito coinfections in Gabon, central Africa.
Chikungunya virus (CHIKV) and Dengue virus serotype 2 (DENV-2) were recently introduced in central Africa, along with Aedes albopictus. Simultaneous outbreaks of CHIKV and DENV-2 have subsequently occurred, in Cameroon in 2006 and Gabon in 2007. To study the spread of the 2 viruses, we conducted active surveillance of acute febrile syndromes throughout Gabon between 2007 and 2010. Diagnostic methods included quantitative real-time reverse-transcription polymerase chain reaction, and molecular characterization was based on partial envelope gene sequences. Between 2007 and 2010, 4287 acutely febrile patients were investigated for CHIKV and DENV-2 infections, of whom 1567 were CHIKV-positive, 376 DENV-2-positive, and 37 coinfected. We diagnosed 153 CHIKV and 11 DENV-2 cases in 2008, and 5 CHIKV and 9 DENV-2 cases in 2009. In 2010, CHIKV and DENV-2 caused a second large simultaneous outbreak. Among 2826 acutely febrile patients examined during this outbreak, 1112 were CHIKV-positive, 288 DENV-2-positive, and 28 coinfected. Mosquitoes were collected near the homes of coinfected patients, and 1 Aedes albopictus specimen was found to be positive for both CHIKV and DENV-2. These findings show the rapid dissemination of CHIKV and DENV-2 within a nonimmune population in a tropical African country, probably facilitated by the spread of Aedes albopictus. This has resulted in major simultaneous outbreaks with numerous coinfections in both human and mosquito.


Lack of association between macrophage migration inhibitory factor gene (-173 G/C) polymorphism and cutaneous vasculitis.
To assess whether polymorphism of the macrophage migration inhibitory factor (MIF) gene at position -173 was implicated in the incidence of Henoch-Schönlein purpura (HSP) and cutaneous leukocytoclastic angiitis (CLA). A further objective was to determine if any relationship existed with severe systemic complications of HSP, in particular with severe renal involvement and permanent renal dysfunction. Unselected patients from Northwest Spain with primary cutaneous vasculitis classified as HSP or hypersensitivity vasculitis (HV) according to proposed criteria were studied. Patients with HV were included in this study if they fulfilled the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis definitions for CLA. Patients and controls were genotyped for a single nucleotide polymorphism (SNP) in the 5'-flanking region at position -173 of the MIF gene, using SNapshot ddNTP primer extension, followed by capillary electrophoresis (ABI 3100). Ninety-five Caucasian patients (57 classified as having HSP and 38 who fulfilled definitions for CLA) and 122 healthy controls were studied. No allele or genotype differences between the whole group of HSP or CLA patients and controls were observed. This was also the case when HSP patients were stratified by the presence of gastrointestinal complications, nephritis, and permanent renal involvement (renal sequelae). The polymorphism in MIF gene promoter (-173 G/C) does not appear to be genetic risk factors for cutaneous vasculitis in Northwest Spain.


Across the "Sweetest" Properties of Human Breast Milk: Focus on Oligosaccharides.
Breast Milk (BM), containing nutrients and bioactive components, represents the best source for neonatal nutrition and determines short- and long- term benefits. Human milk oligosaccharides (HMOs) play an active role in these pathophysiological mechanisms. In fact, they influence the shaping of breastfed infant's gut microbiota, promote intestinal development, confer protection against intestinal or systemic infections modulating immune system; moreover, HMOs determine extra-intestinal effects on several target organs, i.e reducing necrotizing enterocolitis rate or improving brain development. In this review, we analyze the great inter- and intra-individual variability of BM HMOs, investigating maternal, genetic and environmental factors modulating their composition. Moreover, we provide an update regarding HMOs' unique properties, underlining their complex interaction with intestinal microbiota and host-derived metabolites. The possible HMOs' influence on extraintestinal bacterial communities, potentially influencing newborns' and even lactating mothers' health, have been hypothesized. Finally, recognized HMOs' crucial role, we underline the promising opportunities showed by their addition in formula milk, to make it more similar to maternal milk itself.


Relationship between selected perinatal paratuberculosis management interventions and passive transfer of immunity in dairy calves.
The objective of this cohort study was to assess the relationship between perinatal calf management practices relevant to the control of paratuberculosis and passive transfer of immunoglobulin in calves born in an endemically infected Irish dairy herd. Data from 176 calves were used to assess the effect of time spent in the calving area, individual versus non-designated calving and colostrum pasteurisation on serum total protein, zinc sulphate turbidity, globulin and γ-glutamyltransferase. In addition, the effects of colostrum quality, volume of colostrum fed, method of colostrum administration and calving season on passive transfer were quantified. Serum samples were collected as part of routine herd health monitoring from calves aged between one and seven days. Multivariate linear and logistic regression models were used to assess the effect of each variable on the test result and failure of passive transfer as determined using a cut-off point for each diagnostic test. Colostrum pasteurisation and calving area were not significantly associated with passive transfer, whereas increased time spent in the calving pen was consistently associated with a detrimental effect. In addition, a strong seasonal effect was apparent, which appeared to be unrelated to colostrum quality and calf management. The authors are unaware of published studies documenting such a significant seasonal effect on passive transfer.


[Progress in understanding genetics of allergy and asthma].
Progress in genetics of allergic diseases is based upon the basic science development. Some problems in genetic predisposition to disease and prognosis of clinical course have been discussed and presented in relation to allergic diseases. Moreover, pharmacogenetics of asthma and allergy have been pointed in relation to beta 2-adrenoreceptor.


Investigation of Kingella kingae Invasive Infection Outbreaks in Day Care Facilities: Assessment of a Rapid Genotyping Tool Targeting the DNA Uptake Sequence.
Outbreaks of Kingella kingae invasive infections have recently been reported in day care centers. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) revealed that although the invasive strains had widespread dissemination in the day care population, less virulent strains were also circulating in the facilities. However, these typing tools are costly, time-consuming, and labor-intensive and provide delayed results. A study was conducted to assess the performance of a rapid and cost-effective genotyping tool targeting the DNA uptake sequence (DUS) in the investigation of outbreaks of K. kingae disease. DUS typing (DUST) patterns of each strain from 7 different clusters were compared to distinguish genotypically linked strains from others. PFGE and, when available, MLST results were used as gold standards. DUST was assessed on 80 K. kingae isolates from Nir-Itzhak (n = 14), Tel-Nof (n = 14), Palmahim (n = 5), Umm-al-Fahm (n = 7), Eilat (n = 8), Nevatim (n = 15) in Israel and Paris, France (n = 17). A unique DUST pattern was involved in the Nir-Itzhak, Palmahim, Umm-al-Fahm, and Paris episodes. Two DUST patterns were found in Eilat, whereas at least 3 were identified in the Tel-Nof and Nevatim episodes. In total, 11 (13.8%) children carried a K. kingae isolate that differed from the outbreak strain. These results were concordant with those obtained with the traditional PFGE and MLST methods. DUST appears to be sensitive and specific in distinguishing the invasive outbreak strain from others in asymptomatic carriers and could be useful to limit unnecessary exposure of the entire day care population to selective antibiotic pressure.


Centrosome amplification induced by hydroxyurea leads to aneuploidy in pRB deficient human and mouse fibroblasts.
Alterations in the number and/or morphology of centrosomes are frequently observed in human tumours. However, it is still debated if a direct link between supernumerary centrosomes and tumorigenesis exists and if centrosome amplification could directly cause aneuploidy. Here, we report that hydroxyurea treatment induced centrosome amplification in both human fibroblasts expressing the HPV16 -E6-E7 oncoproteins, which act principally by targeting p53 and pRB, respectively, and in conditional pRB deficient mouse fibroblasts. Following hydroxyurea removal both normal and p53 deficient human fibroblasts arrested. On the contrary pRB deficient fibroblasts entered the cell cycle generating aneuploid cells. Also the majority of conditional Rb deficient MEFs showed supernumerary centrosomes and aneuploid cells which increased over time. Finally, our results suggest that pRB dysfunction both in human and murine fibroblasts transiently arrested in G1/S by hydroxyurea allows centrosomes amplification, in the absence of DNA synthesis, that in turn could drive aneuploidy.


[Animal experiment and in vitro studies with inhaled environmental pollutants].
Risk assessment of inhaled toxicants is a critical treatise in inhalation toxicology. In particular, the extent of extrapolation from animal experiments to the human situation is frequently influenced by such factors as the method of application (Implantation, instillation or inhalation) and species-specific differences. This difficulty becomes especially conspicuous when the carcinogenicity is to be determined after the inhalation of, for example, diesel engine exhaust, coal oven flue gas, or cadmium compounds. Nowadays, in-vitro techniques are also available for successfully investigating the metabolism of hazardous compounds and thereby-induced DNA damage in animal and human airway epithelial cells; results gained through the employment of these techniques will, at all events, bear increasing weight in terms of the valuation and assessment of risks to humans.


The benzodiazepine agonist clonazepam potentiates the effects of gamma-aminobutyric acid on alpha-MSH release from neurointermediate lobes in vitro.
The action of the central-type benzodiazepine-receptor agonist clonazepam on alpha-MSH release has been studied in vitro using perifused frog neurointermediate lobes. High concentrations of clonazepam (3.16 X 10(-5) and 10(-4) M) caused an inhibition of alpha-MSH release and this effect was reversed by the central-type benzodiazepine-receptor antagonist Ro 15-1788. High doses of GABA (10(-5) and 10(-4) M) induced a biphasic effect on pars intermedia cells: a brief stimulation followed by a sustained inhibition of alpha-MSH secretion. Administration of clonazepam (10(-5) M) in the presence of various concentrations of GABA (10(-6) to 10(-4) M) led to a potentiation of both stimulatory and inhibitory phases of alpha-MSH secretion induced by GABA. Ro 15-1788 completely abolished the potentiating effect of clonazepam. Thus our results indicate that endogenous benzodiazepine receptors may modulate the effects of GABA on alpha-MSH secretion.


Meta-analysis To Define a Core Microbiota in the Swine Gut.
The swine gut microbiota encompasses a large and diverse population of bacteria that play a significant role in pig health. As such, a number of recent studies have utilized high-throughput sequencing of the 16S rRNA gene to characterize the composition and structure of the swine gut microbiota, often in response to dietary feed additives. It is important to determine which factors shape the composition of the gut microbiota among multiple studies and if certain bacteria are always present in the gut microbiota of swine, independently of study variables such as country of origin and experimental design. Therefore, we performed a meta-analysis using 20 publically available data sets from high-throughput 16S rRNA gene sequence studies of the swine gut microbiota. Next to the "study" itself, the gastrointestinal (GI) tract section that was sampled had the greatest effect on the composition and structure of the swine gut microbiota (P = 0.0001). Technical variation among studies, particularly the 16S rRNA gene hypervariable region sequenced, also significantly affected the composition of the swine gut microbiota (P = 0.0001). Despite this, numerous commonalities were discovered. Among fecal samples, the genera Prevotella, Clostridium, Alloprevotella, and Ruminococcus and the RC9 gut group were found in 99% of all fecal samples. Additionally, Clostridium, Blautia, Lactobacillus, Prevotella, Ruminococcus, Roseburia, the RC9 gut group, and Subdoligranulum were shared by >90% of all GI samples, suggesting a so-called "core" microbiota for commercial swine worldwide. IMPORTANCE The results of this meta-analysis demonstrate that "study" and GI sample location are the most significant factors in shaping the swine gut microbiota. However, in comparisons of results from different studies, some biological factors may be obscured by technical variation among studies. Nonetheless, there are some bacterial taxa that appear to form a core microbiota within the swine GI tract regardless of country of origin, diet, age, or breed. Thus, these results provide the framework for future studies to manipulate the swine gut microbiota for potential health benefits.


Treatment of glaucoma with high intensity focused ultrasound.
Glaucoma is a common disease mainly due to an increase in pressure inside the eye, leading to a progressive destruction of the optic nerve, potentially to blindness. Intraocular pressure (IOP) is the result of a balance between production of liquid that fills the eye--aqueous humour--and its resorption. All treatments for glaucoma aim to reduce IOP and can therefore have two mechanisms of action: reducing aqueous humour production by the partial destruction or medical inhibition of the ciliary body--the anatomical structure responsible for production of aqueous humour--or facilitating the evacuation of aqueous humour from the eye. Several physical methods can be used to destroy the ciliary body, e.g. laser, cryotherapy, microwave. All these methods have two major drawbacks: they are non-selective for the organ to be treated and they have an unpredictable dose–effect relationship. High intensity focused ultrasound (HIFU) can be used to coagulate the ciliary body and avoid these drawbacks. A commercially available device was marketed in the 1980s, but later abandoned, essentially for technical reasons. A smaller circular device using miniaturised transducers was recently developed and proposed for clinical practice. Experimental studies have shown selective coagulation necrosis of the treated ciliary body. The first three clinical trials in humans have shown that this device was well tolerated and allowed a significant, predictable and sustained reduction of IOP. The aim of this contribution is to present a summary of the work concerning the use of HIFU to treat glaucoma.


Viral burden, inflammatory milieu and CD8+ T-cell responses to influenza virus in a second-generation thiazolide (RM-5061) and oseltamivir combination therapy study.
Influenza viruses cause significant morbidity and mortality, especially in young children, elderly, pregnant women and individuals with co-morbidities. Patients with severe influenza disease are typically treated with one neuraminidase inhibitor, oseltamivir or zanamivir. These antivirals need to be taken early to be most effective and often lead to the emergence of drug resistance and/or decreased drug susceptibility. Combining oseltamivir with another antiviral with an alternative mode of action has the potential to improve clinical effectiveness and reduce drug resistance. In this study, we utilized a host-targeting molecule RM-5061, a second-generation thiazolide, in combination with oseltamivir to determine whether these compounds could reduce viral burden and understand their effects on the immune response to influenza virus infection in mice, compared with either monotherapy or placebo. The combination of RM-5061 and OST administered for 5 days after influenza infection reduced viral burden at day 5 post-infection, when compared to placebo and RM-5061 monotherapy, but was not significantly different from oseltamivir monotherapy. The inflammatory cytokine milieu was also reduced in animals which received a combination therapy when compared to RM-5061 and placebo-treated animals. Antiviral treatment in all groups led to a reduction in CD8+ T-cell responses in the BAL when compared to placebo. To our knowledge, this is the first time a combination of a host-targeting compound, RM-5061, and neuraminidase inhibitor, OST, has been tested in vivo. This antiviral combination was safe in mice and led to reduced inflammatory responses following viral infection when compared to untreated animals.


Hypodontia: etiology, clinical features, and management.
Patients who are congenitally missing one tooth or more are frequently encountered in routine practice. The etiology, classification, and clinical features of hypodontia are reviewed, and treatment modalities are discussed. One case of mild-to-moderate hypodontia and one case of severe hypodontia are described. Osseointegrated implants have provided encouraging results, especially in patients who are missing anterior teeth or who have severe hypodontia.


Initiation and processing of signals from the B cell antigen receptor.
Current models of signal transduction from the antigen receptors on B and T cells still resemble equations with several unknown elements. Data from recent knockout experiments in cell lines and mice contradict the assumption that Src-family kinase and tyrosine kinases of the Syk/Zap-70 family are the transducer elements that set signaling from these receptors in motion. Using a functional definition of signaling elements, we discuss the current knowledge of signaling events from the BCR and suggest the existence of an as-yet-unknown BCR transducer complex.


Recent developments in software tools for high-throughput in vitro ADME support with high-resolution MS.
The last several years have seen the rapid adoption of the high-resolution MS (HRMS) for bioanalytical support of high throughput in vitro ADME profiling. Many capable software tools have been developed and refined to process quantitative HRMS bioanalysis data for ADME samples with excellent performance. Additionally, new software applications specifically designed for quan/qual soft spot identification workflows using HRMS have greatly enhanced the quality and efficiency of the structure elucidation process for high throughput metabolite ID in early in vitro ADME profiling. Finally, novel approaches in data acquisition and compression, as well as tools for transferring, archiving and retrieving HRMS data, are being continuously refined to tackle the issue of large data file size typical for HRMS analyses.


What role does adolescent neighborhood play for adult health? A cross-classified multilevel analysis of life course models in Northern Sweden.
This study examined whether, and by which life course models, adolescent neighborhood environment relate to health in mid-adulthood. Data came from the Northern Swedish Cohort (n=1001), surveyed at age 16, 21, 30 and 42 years including functional somatic symptoms at age 42, and individual disadvantage neighborhood disadvantage at all four ages. Results from cross-classified multilevel models showed that 12.7% of age 42 health variance was explained by an interaction of age 16 and age 42 neighborhood of residence. Our study thus suggests that health variation by neighborhood in mid-adulthood may partly depend on neighborhood of residence in adolescence.


Interdisciplinary rehabilitation after whiplash injury: An observational prospective 5 years outcome study.
Whiplash injury associated disorders (WAD) cause high costs for public health care. Neck pain is number 16 on the global prevalence lists for the 50 most common sequelae. It is of importance to obtain long-term data on disability and working capacity outcomes after rehabilitation. Long-term prospective data of the outcome course of whiplash are sparse. The aim of this study was to quantify improvements of pain, function/role performance, vitality, and working capacity 5 years after whiplash injury and to compare the state of health to normative values at 5 years after rehabilitation.In this naturalistic, observational, prospective cohort study, 115 patients were assessed 5 years (60 months) after a multidisciplinary rehabilitation program. The assessment set consisted of the Short Form 36 (SF-36), parts of the North American Spine Society's cervical spine assessment questionnaire (NASS) and the coping strategies questionnaire (CSQ). The effects were quantified by effect size (ES) and standardized response mean (SRM). Score differences over the course were tested by the Wilcoxon-Mann-Whitney U test for significance.Comparing data between entry and 60 months after rehabilitation 8 of 15 parameters improved with large ES/SRM. Outcome between 6 and 60 months showed small to moderate ES/SRM. Working capacity increased from 0 at entry to rehabilitation to 21 h/wk at 6 months and to 30 h/wk at 60 months follow-up.After large improvements in health and working capacity in the mid-term, further important improvements were observed in the long-term course. It can be hypothesized that part of those can be attributed to the interventions during inpatient rehabilitation, for example, due to better coping strategies.


Sigmoid colon endometriosis treated with laparoscopy-assisted sigmoidectomy: significance of preoperative diagnosis.
We present a female patient with sigmoid colon endome-triosis who was diagnosed correctly preoperatively and underwent minimally invasive surgery. She was admitted to our hospital with rectal bleeding and constipation. We performed several workups. Colonoscopy and endoscopic ultrasonography showed sigmoid colon stenosis caused by submucosal tumor, and magnetic resonance imaging revealed a sigmoid colon tumor displaying signal hy-pointensity on both T1- and T2-weighted imaging. However, colonoscopic ultrasonography-assisted needle aspiration biopsy could not specify tumor characteristics. From these examinations, the lesion was diagnosed as sigmoid colon endometriosis and laparoscopy-assisted sigmoidectomy was performed. Pathological diagnosis from the resected specimen was identical to preoperative diagnosis, i.e., colonic endometriosis. Since differential diagnosis of intestinal endometriosis seems difficult, a cautious preoperative diagnosis is required to select treatments including minimally invasive surgery.


From the RSNA refresher courses: MR imaging of aortic and peripheral vascular disease.
Acquired diseases of the aorta and peripheral arteries are common. Owing to technical advances, magnetic resonance (MR) angiography has become the primary imaging modality for assessment of aortic and peripheral arterial disease. Contrast material-enhanced MR angiography is a rapid and robust technique that has emerged as the principal MR angiographic technique for evaluation of vascular disease. Two-dimensional time-of-flight MR angiography still has some well-validated applications, especially in distal peripheral vascular disease. Phase-contrast flow imaging is an important technique for quantification of blood flow. Black-blood imaging is a valuable tool for evaluation of the vessel wall. Understanding the principles of the main MR angiographic techniques is essential for consistent acquisition of diagnostic images. In addition, tailoring the acquisition parameters and the imaging protocol to the vessel being imaged and the clinical question is mandatory for optimal results. Future technical developments that will lead to faster image acquisition and better contrast agents promise to further improve image quality.


Molecular cloning and expression of the rat beta 1-adrenergic receptor gene.
Using the sequence homology approach for cloning related genes within the G-protein-coupled receptor gene family, we have cloned the gene for the rat beta 1-adrenergic receptor (beta 1-AR). The rat beta 1-adrenergic receptor gene was isolated from a lambda EMBL3 rat genomic DNA library using the hamster beta 2-adrenergic receptor (beta 2-AR) coding sequence as a probe under low stringency hybridization conditions. The rat beta 1-AR gene encodes a protein of 466 amino acids that contains one consensus site for N-linked glycosylation (Asn-15) and three consensus sites for cAMP-dependent protein kinase phosphorylation (Ser-296, Ser-301, and Ser-401). The encoded rat beta 1-AR is 98 and 91% similar at the amino acid level with the human beta 1-AR in the transmembrane domains and in the overall sequence, respectively. Genomic Southern blot and gene dosage analyses indicate that the rat beta 1-AR gene is a single copy gene. The tissue distribution of the rat beta 1-AR mRNA was highest in the pineal gland with other brain regions and peripheral tissues, including the heart, expressing the mRNA at moderate levels. The bacteriophage clone containing the rat beta 1-AR gene with its natural promoter was co-transfected with the selectable marker (pRSVneo) conferring neomycin resistance into beta 1-AR-deficient mouse L cells. Analyses of the selected transfectant demonstrates efficient expression of the beta 1-AR gene and functional receptor. 125I-Labeled iodocyanopindolol bound transfectant membranes with an affinity of KD = 24 pm; the beta 1-AR-selective antagonist ICI 89,406 displaced iodocyanopindolol binding with a Ki approximately 140 times lower than that for the beta 2-AR-selective antagonist ICI 118,551. In addition, in the transfectant cell line, adenylylcyclase was stimulated by beta-adrenergic receptor agonists with the rank order of potency of isoproterenol greater than norepinephrine = epinephrine, consistent with properties expected of the beta 1-AR subtype.


A systems biology approach for understanding the collagen regulatory network in alcoholic liver disease.
Among the pathogenesis and risk factors of alcoholic liver disease (ALD) are the source of dietary fat, obesity, insulin resistance, adipokines and acetaldehyde. Translocation of Gram-negative bacteria from the gut, the subsequent effects mediated by endotoxin, and the increased production of matricellular proteins, cytokines, chemokines and growth factors, actively participate in the progression of liver injury. In addition, generation of reactive oxygen and nitrogen species and the activation of non-parenchymal cells also contribute to the pathophysiology of ALD. A key event leading to liver damage is the transition of quiescent hepatic stellate cells into activated myofibroblasts, with the consequent deposition of fibrillar collagen I resulting in significant scarring. Thus, it is becoming clearer that matricellular proteins are critical players in the pathophysiology of liver disease; however, additional mechanistic insight is needed to understand the signalling pathways involved in the up-regulation of collagen I protein. At present, systems biology approaches are helping to answer the many unresolved questions in this field and are allowing to more comprehensively identify protein networks regulating pathological collagen I deposition in hopes of determining how to prevent the onset of liver fibrosis and/or to slow disease progression. Thus, this review article provides a snapshot on current efforts for identifying pathological protein regulatory networks in the liver using systems biology tools. These approaches hold great promise for future research in liver disease.


Economic and employment potential in textile waste management of Faisalabad.
The aim of this study is to characterize the waste from the textile industry, to identify the sources and types of waste generation and to find out the economic and employment potential in this sector. Textile waste, its management, and the economic and employment potential in this sector are unrevealed facts in developing countries such as Pakistan. The textile industry is ranked first in export earning in Pakistan. Textile export of yarn and cloth from Faisalabad is US$3 billion per year. On average 161 325 people are employed in the textile sector in Faisalabad, of which 11 860 are involved in solid waste handling and management. The textile industries generate solid wastes such as fibre, metal, plastic and paper waste. A total of 794 209 kg day(-1) (289 886 285 kg year(-1)) solid waste is produced from this sector and purchased by cotton waste junkshop owners at US$125 027 day(-1) (US$45 634 855 year(-1)). Only pre-consumer textile waste is considered. Interestingly no waste is sent to landfill. The waste is first segregated into different categories/ types by hand and then weighed. Cotton waste is sold to brick kilns where it is used as an alternative fuel as it is cheaper than wood/coal. Iron scrap is sold in the junk market from where it is resold to recycling industries. Paper waste is recycled, minimizing the virgin material used for producing new paper products. Iron and plastic drums are returned to the chemical industries for refilling, thus decreasing the cost of dyes and decreasing the demand for new drums. Cutting rags are used for making different things such as ropes and underlay, it is also shredded and used as fillings for pillows and mattresses, thus improving waste management, reducing cost and minimizing the need for virgin material. As no system of quality control and no monitoring of subsequent products exist there is a need to carry out quality control and monitoring.


Preparation of Sustained Release Tablet with Minimized Usage of Glyceryl Behenate Using Post-Heating Method.
The purpose of this study was to prepare sustained release (SR) matrix tablets using a direct compression incorporated with a post-heating process. Allopurinol was selected due to the water-soluble property and Compritol 888 ATO® (also known as glyceryl behenate) was used as an SR matrix-forming agent. The API, SR material, microcrystalline cellulose, and magnesium stearate (lubricant) were mixed and prepared into a tablet by a direct compression method. The compressed tablets were stored in a dry oven at four temperatures (60, 70, 80, and 90°C) and for three time periods (15, 30, 45 min). The DSC and PXRD data indicated that the crystallinity of the API was not altered by the post-heating method. However, SEM images demonstrated that Compritol 888 ATO® was melted by the post-heating method, and that the melted Compritol 888 ATO® could form a strong matrix. This strong matrix led to the significant sustained release behavior of hydrophilic APIs. As little as 3 mg of Compritol 888 ATO® (0.65% of total tablet weight), when heated at 80°C for 15 min, showed sustained release over 10 h. The post-heating method exerted a significant influence on lipid-based matrix tablets and allowed a reduction in the amount of material required for a water-soluble drug. This will also provide a valuable insight into lipid-based SR tablets and will allow their application to higher quality products and easier processing procedures.


[Studies on Lyme disease incidence rates in selected groups of forestry workers in West Pomerania, 2005-2014].
The data collected by sanitary-epidemiological stations in 2005-2014 were analyzed to determine the incidence rates of borreliosis Lyme disease in the West Pomerania group of workers exposed to tick bites. It was assumed that an adequate comparison of official epidemiological data with the data concerning the number of exposed people, is an indispensable condition for assessing properly the trend in Lyme disease incidence rates, concerning at the same time a real scale of occupational exposure. The study covered a selected group of forestry workers, i.e., white-collar staff employed in different units of the State Forests National Forest Holding with their seats in West Pomerania. The aim of the research was to process and analyze the data on workers employed in the forest sector and their positions, requested from district sanitary-epidemiological stations. In the years concerned 282 cases of the occupational disease were recorded mainly in the groups of forest rangers, junior foresters and forest service inspectors. The values of the incidence factor exhibit high variability with the major share of cases recorded in the years 2008-2010 that accounted for 61.8% of the total occurrences concerned. The incidence in the years 2008, 2009 and 2010 amounted to 2418, 2828 and 2646 cases per 100 000 employees, respectively. The results show that previously published information about the incidence of Lyme disease in the agriculture, forestry and hunting sector, did not fully illustrate a real scale of occupational risk. Med Pr 2017;68(2):211-220.


Differential synchronization in default and task-specific networks of the human brain.
On a regional scale the brain is organized into dynamic functional networks. The activity within one of these, the default network, can be dissociated from that in other task-specific networks. All brain networks are connected structurally but evidently are only transiently connected functionally. One hypothesis as to how such transient functional coupling occurs is that network formation and dissolution is mediated by increases and decreases in oscillatory synchronization between constituent brain regions. If so, then we should be able to find transient differences in intra-network synchronization between the default network and a task-specific network. In order to investigate this hypothesis we conducted two experiments in which subjects engaged in a Sustained Attention to Response Task while having brain activity recorded via high-density electroencephalography (EEG). We found that during periods when attention was focused internally (mind wandering) there was significantly more neural phase synchronization between brain regions associated with the default network, whereas during periods when subjects were focused on performing the visual task there was significantly more neural phase synchrony within a task-specific brain network that shared some of the same brain regions. These differences in network synchrony occurred in each of theta, alpha, and gamma frequency bands. A similar pattern of differential oscillatory power changes, indicating modulation of local synchronization by attention state, was also found. These results provide further evidence that the human brain is intrinsically organized into default and task-specific brain networks, and confirm that oscillatory synchronization is a potential mechanism for functional coupling within these networks.


What do color vision defectives say about everyday tasks?
A lengthy questionnaire was administered to 102 people with defective color vision and to an equal number of people with normal color vision. The questionnaire asked about the subjects' awareness of their defect and their knowledge of defective color vision as well as exploring the difficulties they experience with color at work and in pursuing leisure activities. The questionnaire was administered in the consulting room under conditions that might be expected to elicit frank replies. Nearly 90% of dichromats and up to two-thirds of anomalous trichomats reported difficulties with everyday tasks that involve color, nearly one-half of the dichromats and one in five anomalous trichromats reported difficulty with traffic lights, and similar proportions reported color difficulties in their present jobs. Substantial numbers reported that their color vision defect had affected their choice of career and many had been excluded from a chosen occupation. The screening of color vision in schools and provision of appropriate career counselling is urged.


Outcomes of 25-gauge pars plana vitrectomy for cytomegalovirus retinitis-related retinal detachment.
The purpose of this study is to evaluate the anatomical and functional outcomes of 25-gauge (G) pars plana vitrectomy (PPV) in patients with cytomegalovirus retinitis (CMVR)-related rhegmatogenous retinal detachment (RRD). Single-center retrospective consecutive case series of patients who underwent 25-G PPV for CMVR-related RRD repair with a minimum follow-up of 3 months. Complete anatomic success was defined as the complete attachment of retina including the periphery. Best-corrected visual acuity (BCVA) of ≥20/400 was defined as functional success. Sixteen eyes of 15 patients were included in the study. Eleven patients were human immunodeficiency virus positive, three patients had hematological malignancies, and one patient suffered from dyskeratosis congenita. The mean follow-up was 20.5 ± 17.4 months (range 3-60 months). Complete anatomical success was seen in 15 eyes (93.75%). One eye had a residual inferior detachment with attached macula. Silicone oil was used as tamponade in 15 eyes and C3F8 gas in one eye. The mean change in BCVA was statistically significant, preoperative LogMAR BCVA was 2.05 ± 0.94 while the final follow-up postoperative LogMAR BCVA was 1.03 ± 0.61 (P < 0.001). Thirteen eyes (81.25%) had final BCVA ≥20/400. Microincision vitrectomy surgery can achieve excellent retinal reattachment rates in post-CMVR RRDs without significant intraoperative and postoperative complications. The visual outcome varies depending on the status of the optic disc and macula. Majority of the patients maintained functional vision.


The Top 100 Spine Surgery Articles on Social Media: An Altmetric Study.
Literature review. To discern which social media outlets contribute most to spine surgery literature dissemination and to investigate how popular articles compare to articles with most citations. Scientific literature is increasingly disseminated through social media. The Altmetric Attention Score (AAS) is defined as an automated, weighted score calculation from counts of all online attention received by various research outputs. Increasing AAS values indicate more online attention. For example, the overall top 100 Altmetric spine surgery peer-reviewed articles since 2010 had an AAS range from 78 to 1537. Among all spine surgery literature reviewed since 2010, the mean AAS was 5.3 with a median of 1.0. We performed an Altmetric database search of nine spine surgery journals from January 2010 to October 2019. Mean AAS was summarized alongside metrics including citation count and impact factor. We assessed correlations between AAS and online sources, readers, and citations. Journals were grouped by impact factor, and analysis-of-variance compared mean AAS. The 100 highest AAS articles were compared to the most cited. 13,601 articles were included. The mean AAS was 5.3, with Twitter contributing the most. The three highest associations were news (P < 0.001), Twitter (P < 0.001), and Facebook (P < 0.001). There was no significant association between impact factor and AAS. Compared with the most cited articles, the top 100 AAS articles had significantly more article types, more prospective studies, fewer retrospective studies, fewer reviews, and fewer systematic reviews (P < 0.001 for all). Spine contributed the most articles in both top 100 sets. Our evaluation revealed Twitter, newsfeeds, and Facebook were the most significant social media outlets. Compared to articles with the most citations, the most popular articles are prospective and encompass broader study designs. Social media plays an integral role in dissemination, both within spine literature and the public sphere. 3.


Effect of evodiamine on the proliferation and apoptosis of A549 human lung cancer cells.
Evodia rutaecarpa is a plant, which has antitumor activity. Evodiamine is an alkaloid with antitumor activity present in E. rutaecarpa and has potential to be developed into a therapeutic antitumor agent. The present study investigated the effect of evodiamine on the proliferation of A549 human lung cancer cells and the mechanism underlying these effects. The results indicated that evodiamine significantly inhibited proliferation, induced apoptosis and the expression of reactive oxygen species, arrested the cell cycle, regulated the expression of Survivin, Bcl-2 and Cyclin B1, regulated the activity of caspase-3/8 and glutathione in tumor cells, and decreased the activity of AKT/nuclear factor‑κB (NF‑κB) and Sonic hedgehog/GLI family zinc finger 1 (SHH/GLI1) signaling pathways in A549 cells. In conclusion, the evodiamine-induced inhibition of the proliferation of A549 lung cancer cells may be attributable to its ability to promote oxidative injury in the cells, induce apoptosis, arrest the cell cycle and regulate the AKT/NF‑κB and SHH/GLI1 signaling pathways, subsequently controlling the expression of tumor‑associated genes.


Long-term spatiotemporal stability and dynamic changes in helminth infracommunities of bank voles (Myodes glareolus) in NE Poland.
Parasites are considered to be an important selective force in host evolution but ecological studies of host-parasite systems are usually short-term providing only snap-shots of what may be dynamic systems. We have conducted four surveys of helminths of bank voles at three ecologically similar woodland sites in NE Poland, spaced over a period of 11 years, to assess the relative importance of temporal and spatial effects on helminth infracommunities. Some measures of infracommunity structure maintained relative stability: the rank order of prevalence and abundance of Heligmosomum mixtum, Heligmosomoides glareoli and Mastophorus muris changed little between the four surveys. Other measures changed markedly: dynamic changes were evident in Syphacia petrusewiczi which declined to local extinction, while the capillariid Aonchotheca annulosa first appeared in 2002 and then increased in prevalence and abundance over the remaining three surveys. Some species are therefore dynamic and both introductions and extinctions can be expected in ecological time. At higher taxonomic levels and for derived measures, year and host-age effects and their interactions with site are important. Our surveys emphasize that the site of capture is the major determinant of the species contributing to helminth community structure, providing some predictability in these systems.


Antibiotic dispensing during first year of COVID-19 pandemic in Brazilian public hospitals.
Aim: To evaluate the impact of the first year of the COVID-19 pandemic on antibiotic dispensation in three Brazilian hospitals. Methods: Stock movement was accessed from pharmacy databases and microbiological reports from 2018 to 2021. Results: Reduced antibiotic dispensation occurred during 2020 in all hospitals. The most significant reduction was in April at Hospital Doutor Jayme dos Santos Neves (∼58%), and in May at Hospital Doutor Roberto Arnizaut Silvares (∼66%) and Hospital Doutor Dório Silva (∼29%). However, azithromycin dispensation increased in all hospitals in 2020. Macrolide-resistant bacterial isolates rose from 66.6% in 2019 to 77.1% in 2020 and 88.3% in 2021. Conclusion: Despite reduced antibiotic dispensation, the increase in azithromycin consumption in 2020 highlights the urgency to monitor macrolide resistance after the pandemic and improve stewardship activities.


The human cytomegalovirus tegument protein pp65 (pUL83): a key player in innate immune evasion.
The germline encoded proteins serving as "pattern recognition receptors" (PRRs) constitute the earliest step in the innate immune response by recognizing the "pathogen-associated molecular patterns" (PAMPs) that comprise microbe nucleic acids and proteins usually absent from healthy hosts. Upon detection of exogenous nucleic acid two different innate immunity signaling cascades are activated. The first culminates in the production of chemokines, cytokines, and type I interferons (IFN-I), while the second leads to inflammasome complex formation. Human cytomegalovirus (HCMV), a member of the b-herpesvirus subfamily, is a widespread pathogen that infects the vast majority of the world's population. The virion has an icosahedral capsid that contains a linear dsDNA genome of approximately 240 kb, surrounded by an outer lipid envelope and a proteinaceous tegument containing several viral proteins. Despite the numerous and multifaceted antiviral effects of IFNs and cytokines, HCMV is able to invade, multiply, and establish persistent infection in healthy human hosts. To achieve this goal the virus has developed different strategies to block the IFN-I response and to alter the physiological outcomes of the IFN-inducible genes. This article focuses on HCMV tegument pp65 by reviewing its mechanisms of action in favoring virus evasion from the host innate immune response.


Isolation of Jamestown Canyon and snowshoe hare viruses (California serogroup) from Aedes mosquitoes in western Massachusetts.
Three isolates of Jamestown Canyon virus and one isolate of snowshoe hare virus (California serogroup) were obtained from adult Aedes females collected in western Massachusetts in 1982. Jamestown Canyon virus was isolated from Aedes abserratus/punctor once, and from Aedes intrudens twice. Snowshoe hare virus was isolated from Aedes stimulans group mosquitoes. La Crosse encephalitis (LAC) virus was not isolated from 1,552 adult Aedes triseriatus, nor from 22,557 Aedes triseriatus larvae. However, sera from 1/178 eastern chipmunks, 5/31 gray squirrels, and 8/144 white-tailed deer had neutralizing antibody to LAC virus. No sentinel rabbits placed at sites yielding virus isolates seroconverted to CAL viruses in either year.


Acute hand burns in children: management and long-term outcome based on a 10-year experience with 698 injured hands.
To document long-term results associated with an coordinated plan of care for acutely burned hands in children. Optimal hand function is a crucial component of a high-quality survival after burn injury. This can be achieved only with a coordinated approach to the injuries. Long-term outcomes associated with such a plan of care have not been previously reported. Over a 10-year period, 495 children with 698 acutely burned hands were managed at a regional pediatric burn facility; 219 children with 395 injured hands were followed in the authors' outpatient clinic for at least 1 year and an average of >5 years. The authors' approach to the acutely burned hand emphasizes ranging and splinting throughout the hospital stay, prompt sheet autograft wound closure as soon as practical, and the selective use of axial pin fixation and flaps. Long-term follow-up, hand therapy, and reconstructive surgery are emphasized. Normal functional results were seen in 97% of second-degree and 85% of third-degree injuries; in children with burns involving underlying tendon and bone, 70% could perform activities of daily living and 20% had normal function. Reconstructive hand surgery was required in 4.4% of second-degree burns, 32% of third-degree burns, and 65% of those with injuries involving underlying bone and tendon. When managed in a coordinated long-term program, the large majority of children with serious hand burns can be expected to have excellent functional results.


What are the policy implications of the evidence on cannabis and psychosis?
To explore the implications for mental health services, for health education about the risks of cannabis use, and for public policy toward cannabis use of observational evidence that cannabis use is a contributory cause of psychosis. Using comparative analyses of similar evidence for the harmful effects of alcohol, tobacco, and amphetamine use, we considered the relation between observational evidence and action on cannabis. We examined arguments on the grounds of public health prudence for discouraging cannabis use by young individuals. With the assumption that the relation may be causal, we considered recommendations for policy in mental health services, health education, and public policy toward cannabis. The observational evidence and biological plausibility of the hypothesis that cannabis is a contributory cause of psychosis is at least as strong as evidence for causal relations between heavy alcohol and amphetamine use and psychosis. On public health grounds, there is a good case for discouraging cannabis use among adolescents and young adults. It remains uncertain how best to discourage use and at whom campaigns to reduce cannabis use should be targeted. We should discourage young adults seeking treatment in mental health services from using cannabis and inform them of the probable mental health risks of cannabis use, especially of early and frequent use. We must exercise caution in liberalizing cannabis laws in ways that may increase young individuals' access to cannabis, decrease their age of first use, or increase their frequency of cannabis use. We should consider the feasibility of reducing the availability of high-potency cannabis products.


Do anti-platelet drugs improve duration of continuous renal replacement therapy? A retrospective cohort study in cardiac ICU patients.
The objective of this study was to investigate the impact of anti-platelet drug/s on duration of continuous renal replacement therapy (CRRT) in those patients where anti-coagulants were not used due to certain contraindications and in cases where patients were on anti-platelet drugs and were given anti-coagulant during CRRT. This single-center, retrospective cohort study was conducted using the medical records patients treated with CRRT in the cardiac ICU of the inpatient urban facility, located in North India. Data was collected from only those patients who received CRRT for the duration of at least 12 h. Patient's in NAC group were not on any anti-platelet/s and did not receive anti-coagulant during CRRT. AC and AP group patients received anti-coagulant alone or were already on anti-platelet/s and did not receive anti-coagulant respectively while ACAP group patients were on anti-platelet drug/s and also received anti-coagulant during CRRT. Patients in AC, AP, or ACAP group showed significantly (p < 0.001) higher CRRT filter life compared to NAC group. The median CRRT filter life was significantly higher in the ACAP group compared to AC (p < 0.05) and AP (p < 0.001) groups. This study indicates that systemic anti-platelet therapy can provide additional support in critical patients undergoing CRRT even with or without anti-coagulant therapy. However, the increase in CRRT filter life was more profound in patients who were on anti-platelet/s and also received anti-coagulant drug/s during CRRT.


Patterns of electrochemical proton gradient formation by membrane vesicles from an obligately acidophilic bacterium.
Isolated membrane vesicles from the obligately acidophilic bacterium Bacillus acidocaldarius generated an electrochemical gradient of protons (delta mu- H+) upon energization with ascorbate-phenazine methosulfate at pH 6.0 or 3.0. At pH 6.0, there was little or no transmembrane pH gradient (delta pH), but a transmembrane electrical potential (delta psi) of ca. -77 mV, positive out, was observed. At pH 3.0, a delta pH equivalent to - 100 mV, acid out, and a delta psi of -73 mV, positive out, were observed upon energization. The total magnitude of the delta mu- H+ was higher than that of whole cells at acid pH, but the very large delta pHs and the reversed delta psi s, i.e., inside positive, that are typical of acidophile cells were not observed in the vesicles. The vesicles exhibited energy-dependent accumulation of alpha-aminoisobutyric acid that was inhibited by both nigericin and valinomycin (plus K+) at pH 3.0 but was inhibited little by nigericin at pH 6.0.


Correlates of HIV-1 shedding in cervicovaginal secretions and effects of antiretroviral therapies.
To evaluate the determinants of HIV-1 RNA shedding in cervicovaginal secretions and the effects of antiretroviral therapy in a group of infected women. A total of 122 women from whom paired peripheral blood and cervicovaginal lavage samples were available were enrolled in the study. HIV-1 RNA was quantified in the plasma and cell-free fraction of cervicovaginal lavages by the nucleic acid sequence-based amplification assay (lower limit of detection 80 copies/ml). Seventy-one per cent of the women had detectable viral load in the cervicovaginal lavage and this appeared to be correlated to plasma viral load and to the degree of immunodeficiency as expressed by the absolute number of CD4 cells. Antiretroviral-treated patients had a lower risk of shedding the virus in the genital tract, but this association was limited to patients treated with highly active antiretroviral therapy (HAART). However, in 25% of women with undetectable plasma viral load, a genital shedding of the virus was demonstrated. Plasma viral load may fail as a marker of infectivity of genital secretions. HAART treatment seems to be more efficacious in suppressing viral shedding at the genital level. The female genital tract represents a distinct compartment for HIV-1 replication/evolution.


Triple oral antidiabetic therapy in type 2 diabetes mellitus.
To determine the effectiveness of triple oral antidiabetic therapy with a sulfonylurea, a biguanide, and a thiazolidinedione, we analyzed the results in 35 patients who had previously had inadequate glycemic control with a combination of glimepiride and metformin. The study cohort consisted of 27 men and 8 women (mean age, 55.8 years) who had had type 2 diabetes mellitus for a mean duration of 8.7 years. The addition of troglitazone (600 mg/day administered with the largest meal) to the glimepiride and metformin therapy yielded normal or near-normal glycemia in all 35 patients. Glycemic control was initially associated with mean weight gain; subsequently, however, mean weight was reduced to below the baseline level--perhaps attributable to the anorectic effect of metformin. Thus, for the first time, triple oral antidiabetic therapy with glimepiride, metformin, and troglitazone has been shown to be an efficacious therapeutic option for type 2 diabetes.


B-type natriuretic peptide as a predictor of outcome in a general intensive care unit.
B-type natriuretic peptide is a hormone secreted by the heart in response to ventricular wall stress. Increased B-type natriuretic peptide plasma levels are also found as a consequence of noncardiac conditions including sepsis, surgery-induced systemic inflammatory response syndrome and kidney failure. Since these conditions are common in general intensive care unit patients, we hypothesized that B-type natriuretic peptide could be a helpful marker in predicting outcome in this setting. We measured plasma B-type natriuretic peptide concentrations in 228 patients at admission to our general intensive care unit. The primary aim of the study was to investigate the relationship between B-type natriuretic peptide and hospital mortality. The secondary aim of the study was to investigate the association between B-type natriuretic peptide and severity of disease, quantified by the Simplified Acute Physiology Score II. Logistic regression revealed a positive association between B-type natriuretic peptide level and in-hospital death (OR= 1.59; 95% CI 1.30 to 1.95; p<0.0001) and a Cox proportional hazards regression model showed that B-type natriuretic peptide was significantly associated with the risk of death (HR=1.27; 95% CI 1.11 to 1.46; p=0.0005). B-type natriuretic peptide was higher in patients who died in the hospital than in those who survived (371.20 pg/ml vs. 127.10 pg/ml; p<0.0001). There was a positive correlation between B-type natriuretic peptide and Simplified Acute Physiology Score II (r=0.50; 95% CI 0.40 to 0.59; p<0.0001). B-type natriuretic peptide on admission is an independent prognostic marker of outcome in an unselected cohort of critically ill patients.


Making sense of antisense: seemingly noncoding RNAs antisense to the master regulator of Kaposi's sarcoma-associated herpesvirus lytic replication do not regulate that transcript but serve as mRNAs encoding small peptides.
The mammalian transcriptome is studded with putative noncoding RNAs, many of which are antisense to known open reading frames (ORFs). Roles in the regulation of their complementary mRNAs are often imputed to these antisense transcripts, but few have been experimentally examined, and such functions remain largely conjectural. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes two transcripts that lack obvious ORFs and are complementary to the gene (RTA) encoding the master regulator of the latent/lytic switch. Here, we show that, contrary to expectation, these RNAs do not regulate RTA expression. Rather, they are found on polysomes, and genetic analysis indicates that translational initiation occurs at several AUG codons in the RNA, leading to the presumptive synthesis of peptides of 17 to 48 amino acids. These findings underscore the need for circumspection in the computational assessment of coding potential and raise the possibility that the mammalian proteome may contain many previously unsuspected peptides generated from seemingly noncoding RNAs, some of which could have important biological functions. Irrespective of their function, such peptides could also contribute substantially to the repertoire of T cell epitopes generated in both uninfected and infected cells.


Alternative to tarsorrhaphy in peripheral facial nerve palsy with expectation of functional recovery. Technical note.
A simple technique is described for protecting the cornea in patients with peripheral facial nerve palsy while waiting for recovery of nerve function. The application of an adhesive strip to the superior eyelid permits opening and closing of the eye, and provides good protection of the cornea.


Assessing representation of remote sensing derived forest structure and land cover across a network of protected areas.
Protected areas (PA) are an effective means of conserving biodiversity and protecting suites of valuable ecosystem services. Currently, many nations and international governments use proportional area protected as a critical metric for assessing progress towards biodiversity conservation. However, the areal and other common metrics do not assess the effectiveness of PA networks, nor do they assess how representative PA are of the ecosystems they aim to protect. Topography, stand structure, and land cover are all key drivers of biodiversity within forest environments, and are well-suited as indicators to assess the representation of PA. Here, we examine the PA network in British Columbia, Canada, through drivers derived from freely-available data and remote sensing products across the provincial biogeoclimatic ecosystem classification system. We examine biases in the PA network by elevation, forest disturbances, and forest structural attributes, including height, cover, and biomass by comparing a random sample of protected and unprotected pixels. Results indicate that PA are commonly biased towards high-elevation and alpine land covers, and that forest structural attributes of the park network are often significantly different in protected versus unprotected areas (426 out of 496 forest structural attributes found to be different; p < 0.01). Analysis of forest structural attributes suggests that establishing additional PA could ensure representation of various forest structure regimes across British Columbia's ecosystems. We conclude that these approaches using free and open remote sensing data are highly transferable and can be accomplished using consistent datasets to assess PA representations globally.


Testing the vesicular morphology to destruction: birth and death of diblock copolymer vesicles prepared via polymerization-induced self-assembly.
Small angle X-ray scattering (SAXS), electrospray ionization charge detection mass spectrometry (CD-MS), dynamic light scattering (DLS), and transmission electron microscopy (TEM) are used to characterize poly(glycerol monomethacrylate)55-poly(2-hydroxypropyl methacrylate)x (G55-Hx) vesicles prepared by polymerization-induced self-assembly (PISA) using a reversible addition-fragmentation chain transfer (RAFT) aqueous dispersion polymerization formulation. A G55 chain transfer agent is utilized to prepare a series of G55-Hx diblock copolymers, where the mean degree of polymerization (DP) of the membrane-forming block (x) is varied from 200 to 2000. TEM confirms that vesicles with progressively thicker membranes are produced for x = 200-1000, while SAXS indicates a gradual reduction in mean aggregation number for higher x values, which is consistent with CD-MS studies. Both DLS and SAXS studies indicate minimal change in the overall vesicle diameter between x = 400 and 800. Fitting SAXS patterns to a vesicle model enables calculation of the membrane thickness, degree of hydration of the membrane, and the mean vesicle aggregation number. The membrane thickness increases at higher x values, hence the vesicle lumen must become smaller if the external vesicle dimensions remain constant. Geometric considerations indicate that this growth mechanism lowers the total vesicle interfacial area and hence reduces the free energy of the system. However, it also inevitably leads to gradual ingress of the encapsulated water molecules into the vesicle membrane, as confirmed by SAXS analysis. Ultimately, the highly plasticized membranes become insufficiently hydrophobic to stabilize the vesicle morphology when x exceeds 1000, thus this PISA growth mechanism ultimately leads to vesicle "death".


Cellular and molecular bases for dystocia.
In this review I have briefly outlined some of the cellular and molecular reasons for dystocia. I have described the myogenic, that may control the normal progression of labor and explain inadequate uterine contractility associated with dystocia. I have placed particular emphasis on our studies of gap junctions and their regulation. These studies show that there are specific physiologic mechanisms for regulating structural and functional coupling between myometrial cells during labor. The integration of these control mechanisms probably operates to ensure appropriate activation and maintenance of synchronous contractility of the myometrium and effective delivery.


The stress granule protein G3BP1 recruits protein kinase R to promote multiple innate immune antiviral responses.
Stress granules (SGs) are cytoplasmic storage sites containing translationally silenced mRNPs that can be released to resume translation after stress subsides. We previously showed that poliovirus 3C proteinase cleaves the SG-nucleating protein G3BP1, blocking the ability of cells to form SGs late in infection. Many other viruses also target G3BP1 and inhibit SG formation, but the reasons why these functions evolved are unclear. Previously, we also showed a link between G3BP1-induced SGs and protein kinase R (PKR)-mediated translational control, but the mechanism of PKR interplay with SG and the antiviral consequences are unknown. Here, we show that G3BP1 exhibits antiviral activity against several enteroviruses, whereas truncated G3BP1 that cannot form SGs does not. G3BP1-induced SGs are linked to activation of innate immune transcriptional responses through NF-κB and JNK. The G3BP1-induced SGs also recruit PKR and other antiviral proteins. We show that the PXXP domain within G3BP1 is essential for the recruitment of PKR to SGs, for eIF2α phosphorylation driven by PKR, and for nucleating SGs of normal composition. We also show that deletion of the PXXP domain in G3BP1 compromises its antiviral activity. These findings tie PKR activation to its recruitment to SGs by G3BP1 and indicate that G3BP1 promotes innate immune responses at both the transcriptional and translational levels and integrates cellular stress responses and innate immunity. Stress granules appear during virus infection, and their importance is not well understood. Previously, it was assumed that they were nonfunctional artifacts associated with cellular stress. PKR is a well-known antiviral protein; however, its regulation in cells is not well understood. Our work links cellular stress granules with activation of PKR and other innate immune pathways through the activity of G3BP1, a critical stress granule component. The ability of stress granules and G3BP1 to activate PKR and other innate immune transcriptional responses indicates that G3BP1 is an antiviral protein. This work helps to refine a longstanding paradigm indicating stress granules are inert structures and explains why G3BP1 is subverted by many viruses to promote a productive infection.


Heterologous expression of a Rauvolfia cDNA encoding strictosidine glucosidase, a biosynthetic key to over 2000 monoterpenoid indole alkaloids.
Strictosidine glucosidase (SG) is an enzyme that catalyses the second step in the biosynthesis of various classes of monoterpenoid indole alkaloids. Based on the comparison of cDNA sequences of SG from Catharanthus roseus and raucaffricine glucosidase (RG) from Rauvolfia serpentina, primers for RT-PCR were designed and the cDNA encoding SG was cloned from R. serpentina cell suspension cultures. The active enzyme was expressed in Escherichia coli and purified to homogeneity. Analysis of its deduced amino-acid sequence assigned the SG from R. serpentina to family 1 of glycosyl hydrolases. In contrast to the SG from C. roseus, the enzyme from R. serpentina is predicted to lack an uncleavable N-terminal signal sequence, which is believed to direct proteins to the endoplasmic reticulum. The temperature and pH optimum, enzyme kinetic parameters and substrate specificity of the heterologously expressed SG were studied and compared to those of the C. roseus enzyme, revealing some differences between the two glucosidases. In vitro deglucosylation of strictosidine by R. serpentina SG proceeds by the same mechanism as has been shown for the C. roseus enzyme preparation. The reaction gives rise to the end product cathenamine and involves 4,21-dehydrocorynantheine aldehyde as an intermediate. The enzymatic hydrolysis of dolichantoside (Nbeta-methylstrictosidine) leads to several products. One of them was identified as a new compound, 3-isocorreantine A. From the data it can be concluded that the divergence of the biosynthetic pathways leading to different classes of indole alkaloids formed in R. serpentina and C. roseus cell suspension cultures occurs at a later stage than strictosidine deglucosylation.


Effects of warming and clipping on ecosystem carbon fluxes across two hydrologically contrasting years in an alpine meadow of the Qinghai-Tibet Plateau.
Responses of ecosystem carbon (C) fluxes to human disturbance and climatic warming will affect terrestrial ecosystem C storage and feedback to climate change. We conducted a manipulative experiment to investigate the effects of warming and clipping on soil respiration (Rs), ecosystem respiration (ER), net ecosystem exchange (NEE) and gross ecosystem production (GEP) in an alpine meadow in a permafrost region during two hydrologically contrasting years (2012, with 29.9% higher precipitation than the long-term mean, and 2013, with 18.9% lower precipitation than the long-tem mean). Our results showed that GEP was higher than ER, leading to a net C sink (measured by NEE) over the two growing seasons. Warming significantly stimulated ecosystem C fluxes in 2012 but did not significantly affect these fluxes in 2013. On average, the warming-induced increase in GEP (1.49 µ mol m(-2) s(-1)) was higher than in ER (0.80 µ mol m(-2) s(-1)), resulting in an increase in NEE (0.70 µ mol m(-2) s(-1)). Clipping and its interaction with warming had no significant effects on C fluxes, whereas clipping significantly reduced aboveground biomass (AGB) by 51.5 g m(-2) in 2013. These results suggest the response of C fluxes to warming and clipping depends on hydrological variations. In the wet year, the warming treatment caused a reduction in water, but increases in soil temperature and AGB contributed to the positive response of ecosystem C fluxes to warming. In the dry year, the reduction in soil moisture, caused by warming, and the reduction in AGB, caused by clipping, were compensated by higher soil temperatures in warmed plots. Our findings highlight the importance of changes in soil moisture in mediating the responses of ecosystem C fluxes to climate warming in an alpine meadow ecosystem.


Organic Microporous Nanofillers with Unique Alcohol Affinity for Superior Ethanol Recovery toward Sustainable Biofuels.
To minimize energy consumption and carbon footprints, pervaporation membranes are fast becoming the preferred technology for alcohol recovery. However, this approach is confined to small-scale operations, as the flux of standard rubbery polymer membranes remain insufficient to process large solvent volumes, whereas membrane separations that use glassy polymer membranes are prone to physical aging. This study concerns how the alcohol affinity and intrinsic porosity of networked, organic, microporous polymers can simultaneously reduce physical aging and drastically enhance both flux and selectivity of a super glassy polymer, poly-[1-(trimethylsilyl)propyne] (PTMSP). Slight loss in alcohol transportation channels in PTMSP is compensated by the alcohol affinity of the microporous polymers. Even after continuous exposure to aqueous solutions of alcohols, PTMSP pervaporation membranes loaded with the microporous polymers outperform the state-of-the-art and commercial pervaporation membranes.


Behavioral thermoregulation in obese and lean Zucker rats in a thermal gradient.
Genetically obese Zucker (Z) rats have been reported to display a body core temperature (Tb) that is consistently below that of their lean littermates. We asked the question whether the lower Tb was a result of deficits in thermoregulation or a downward resetting of the set point for Tb. For a period of 45 consecutive hours, lean and obese Z rats were free to move within a thermal gradient with an ambient temperature (T(a)) range of 15-35 degrees C, while subjected to a 12:12-h light-dark cycle. Tb was measured using a miniature radio transmitter implanted within the peritoneal cavity. Oxygen consumption (VO2) was measured using an open flow technique. Movements and most frequently occupied position in the gradient (preferred T(a)) were recorded using a series of infrared phototransmitters. Obese Z rats were compared with lean Z rats matched for either age (A) or body mass (M). Our results show that obese Z rats have a lower Tb [37.1 +/- 0.1 degrees C (SD) vs. 37.3 +/- 0.1 degrees C, P < 0.001] and a lower VO2 (25.3 +/- 1.9 ml x kg(-1) x h(-1)) than lean controls [33.1 +/- 3.7 (A) and 33.9 +/- 3.9 (M) ml x kg(-1) x h(-1), P < 0.001]. Also, the obese Z rats consistently chose to occupy a cooler T(a) [20.9 +/- 0.6 degrees C vs. 22.7 +/- 0.6 degrees C (A) and 22.5 +/- 0.7 degrees C (M), P < 0.001] in the thermal gradient. This suggests a lower set point for Tb in the obese Z rat, as they refused the option to select a warmer T(a) that might allow them to counteract any thermoregulatory deficiency that could lead to a low Tb. Although all rats followed a definite circadian rhythm for both Tb and VO2, there was no discernible circadian pattern for preferred T(a) in either obese or lean rats. Obese Z rats tended to show a far less definite light-dark activity cycle compared with lean rats.


The impact of CSR and green consumption on consumer satisfaction and loyalty: moderating role of ethical beliefs.
The present study introduces an innovative conceptual framework for analyzing the influence of corporate social responsibility and green consumption on customer satisfaction and loyalty. The study employed a quantitative methodology, wherein data was gathered through face-to-face surveys from a sample of 329 participants in Pakistan during the period from November 2022 to February 2023. The collected data was subsequently subjected to analysis using partial least squares structural equation modeling (PLS-SEM). The results demonstrate that corporate social responsibility (CSR) has a significant and positive impact on consumer satisfaction, which subsequently serves as a significant predictor of loyalty. The research findings indicate a significant correlation between consumers' ethical beliefs, specifically idealism and relativism, and their engagement in green consumption. Furthermore, it is observed that green consumption positively influences consumer satisfaction. Additionally, the research revealed that the variables of idealism and relativism do not exert a moderating influence on the association between corporate social responsibility (CSR) and consumer satisfaction. The results underscore the significance of managers directing their attention towards cultivating more robust customer relationships through the prioritization of satisfaction within their corporate social responsibility (CSR) initiatives. This study aimed to assess a theoretical framework that delineates the fundamental connections between corporate social responsibility (CSR), green consumption, consumer satisfaction, and loyalty. While prior research has predominantly concentrated on corporate viewpoints and employee attitudes towards CSR, this research sought to fill the gap by examining the aforementioned relationships from a consumer perspective.


Concordance of Guideline-Based Risk Stratification and Selection of Patients for Transcatheter Aortic Valve Implantation or Surgical Replacement.
The 2020 American Health Association/American College of Cardiology valve guidelines recommend surgical aortic valve replacement (SAVR) for symptomatic patients with aortic stenosis (AS) age <65 years and transcatheter aortic valve implantation (TAVI) for patients with AS age >80 years. We analyzed TAVI versus SAVR practice patterns using age-based recommendations. We compared 2016-to-2019 TAVI and isolated SAVR in northern New England at 5 centers according to guideline-recommended age groups. Multivariable logistic regression was performed to identify independent predictors of TAVI for the intermediate age group. The study was approved by each site's institutional review board in accordance with ongoing participation and quality improvement efforts in the Northern New England Cardiovascular Study Group. Among 4,161 patients with isolated severe AS, TAVI increased from 2016 to 2019: 55.8% versus 76.1%, p <0.01 for trend. SAVR for patients with AS age >80 years was uncommon and decreased over time: 13.1% versus 1.6%, p <0.01. TAVI utilization nearly doubled over time in young patients with AS age <65 years (14.3% vs 26.2%, p <0.01). Preference for SAVR decreased by 50% over time (p <0.01) in the intermediate age group (65 to 80 years). Independent predictors of TAVI among patients aged 65 to 80 years included older age, chronic obstructive pulmonary disease, previous stroke, and coronary artery bypass grafting, whereas vascular disease and clinical urgency favored SAVR. In conclusion, consistent with current American Health Association/American College of Cardiology guidelines, TAVI was the treatment of choice in >97% of severe patients with AS age >80 years by 2019. TAVI utilization in patients <65 years has doubled over time and thus may not reflect current guideline recommendations. TAVI is the preferred choice in those aged 65 to 80 years, especially among patients with previous stroke or coronary artery bypass grafting.