The natural history of pancreatic pseudocysts: a unified concept of management.
Between 1971 and 1976, ninety-three patients with a clinical diagnosis of pseudocyst confirmed by ultrasonography were identified from a group of 923 patients admitted for pancreatic disease. Uncertainties in diagnosis and/or rapid progression of underlying pancreatitis led to urgent laparotomy and drainage in eleven of the ninety-three patients. Another twenty-eight patients underwent elective drainage of the pseudocyst. The remaining fifty-four constituted the study group and were followed with serial clinical and sonographic examinations until either spontaneous resolution occurred, complications developed, or the patients did not return. Complications arising during the period of observation in the untreated patients (rupture, abscess, jaundice, and hemorrhage) occurred more than twice as commonly as spontaneous resolution (41 per cent versus 20 per cent), and led directly to death in seven cases (14 per cent). No deaths occurred in the group of patients undergoing elective surgical drainage (p less than 0.05). The interval between presumed formation of the pseudocyst and the development of a complication averaged 13.5 +/- 6 weeks. Prolonged observation of pancreatic pseudocysts in the expectation of spontaneous resolution exposed the patient to an unwarranted risk, which, after seven weeks, greatly exceeded the mortality of elective surgery.


Effects of halothane on arrhythmias induced by myocardial ischaemia.
The effect of halothane on arrhythmias induced by ischaemia was investigated in rats, isolated perfused rat hearts, and pigs. Responses to the occlusion of the left anterior descending coronary artery were determined in groups (n = 9) of chronically prepared rats treated with no halothane, 0.5, or 1.0 per cent halothane immediately after occlusion; in isolated rat hearts (n = 10) treated with no halothane, 0.5, 1.0, 2.0, or 4.0 per cent halothane for 15 min before and after occlusion; and 20-25 kg pigs (n = 11) anaesthetised with halothane or pentobarbital. The ECG, arrhythmias, blood pressure (BP), heart rate (HR) and extent of infarction were determined in each model. In pigs, left ventricular pressure, dp/dtmax and cardiac output were also measured. In chronically prepared rats, halothane anaesthesia started after occlusion was antiarrhythmic and decreased the incidence of ventricular fibrillation and resulting mortality. In isolated rat hearts, 0.5 or 1.0 per cent halothane had little effect on occlusion-induced arrhythmias. The highest concentration of halothane increased the incidence of ventricular fibrillation both before and after occlusion. Halothane decreased developed ventricular pressure in a dose-dependent manner. In acutely prepared pigs, halothane pre-treatment had no appreciable effect upon occlusion-induced arrhythmias when compared with pentobarbital anaesthesia. Thus, halothane is antiarrhythmic when treatment is initiated after occlusion in the rat but this action is not seen in isolated hearts or intact pigs. The antiarrhythmic action of halothane is, therefore, species and model dependent.


Optimal sampling times for OIH-clearance calculations using a two-compartment/two-sample method.
Orthoiodohippurate (OIH) clearance data obtained with the two-compartment/two-sample method of Lear which uses varying sampling time combinations, were compared with those of the reference two-compartment/multi-sample method of Sapirstein. A total of 35 studies were performed in 33 adult patients. The OIH clearance values determined by the reference method ranged from 107 to 883 ml/min/1.73 m2, with a median of 406 ml/min/1.73 m2. It was ascertained that the precision of the Lear method is partially dependent upon the sampling time combination. The most reliable results with the Lear method in this patient population were obtained by taking a first sample at approximately 8 min p.i., and a second sample at 32 min p.i. or later.


Analysis of caprine IgG1 and IgG2 subclass responses to Chlamydia psittaci infection and vaccination.
Enzyme-linked immunosorbent assays (ELISAs) specific for caprine IgG(H+L), IgG1 and IgG2 were developed and evaluated for serodiagnosis of Chlamydia psittaci infections in a Tunisian goat flock with currently occurring chlamydial abortions and a clinically inapparent goat flock of an animal research facility. Additionally, ELISAs were applied to record the IgG1 and IgG2 dynamics of four goats vaccinated with inactivated Chlamydia psittaci and Coxiella burnetii. For screening purposes, the IgG(H+L) ELISA proved to be superior to the complement fixation test because it detected a larger number of chlamydial abortions and was easier to perform and to interpret. Analysis of Chlamydia psittaci-specific IgG1 and IgG2 responses to naturally occurring infections by ELISA revealed high IgG1 levels associated with IgG2 in goats with current abortions, whereas clinically inapparent, but seropositive goats were characterized by significantly lower IgG1 levels only (P less than 0.001). Similarly, the four vaccinated goats responded initially with Chlamydia psittaci-specific IgG1, whereas second and third vaccinations induced (as in goats with chlamydial abortions) predominantly IgG1, but also IgG2. The results indicated that clinically inapparent chlamydial infection may be distinguished from overt disease by analysing specific IgG1 and IgG2 responses. Applying Coxiella burnetii- specific ELISAs on field samples, IgG1 alone could be detected in eight, IgG2 alone in one and IgG1 combined with IgG2 in nine goats. The coxiella-specific antibody response of the four vaccinated goats was--in contrast to the chlamydia-specific response--characterized by IgG2 dominance.


Phase Angle Is a Useful indicator for Muscle Function in Older Adults.
Phase angle (PhA) can be determined through bioelectrical impedance analysis and is a unique variable for skeletal muscle. The objective of this study was to evaluate the relationship between PhA and muscle mass/quality in older adults. In addition, we attempted to determine the cutoff value of PhA for poor muscle function. Community-dwelling Japanese older men (n=285, 81.1±7.1 years) and women (n=724, 80.4±6.8 years) participated in this study and were classified into four groups based on the Asian Working Group for Sarcopenia (normal, presarcopenia, dynapenia, and sarcopenia). We measured PhA using bioelectrical impedance analysis, muscle quantity and quality indicators using ultrasonography, muscle strength, and physical performance and compared them in four groups. We also tried to determine the cutoff value of PhA for poor muscle function. We found a significant difference in PhA among the four groups in men (P<0.05), and the dynapenia (3.61±0.75°) and sarcopenia groups (3.40±0.74°) showed significantly lower values than the normal group (4.50±0.86°) (P<0.05), but not the presarcopenia group (4.12±0.85°). In women, a significant difference was also observed among the four groups (P<0.05), and the dynapenia (3.41±0.65°) and sarcopenia groups (3.31±0.66°) showed significantly lower measures than the normal group (4.14±0.71°) (P<0.05), but not the presarcopenia group (4.07±0.51°). The receiver-operating characteristic curve analysis indicated the best cutoff value of PhA (men: 4.05°, women: 3.55°) to discriminate sarcopenia and dynapenia from normal and presarcopenia. These findings suggest that PhA is a useful indicator for muscle function.


Proteinuria in a child with sialidosis: case report and histological studies.
A 9-year-old body with sialidosis had nephrotic-range proteinuria. Histological studies demonstrated massive distension of renal cells, particularly glomerular visceral epithelial cells, by cytoplasmic vesicles which contained material reactive with concanavalin A and wheat-germ agglutinin. In addition, some glomeruli exhibited segmental mesangial thickening or glomerulosclerosis. Ultrastructurally, focal detachment of visceral epithelial cells from the underlying glomerular basement membrane was observed. We postulate that glomerular visceral epithelial cell dysfunction may underlie the proteinuria and focal glomerulosclerosis exhibited by this patient. Hyperfiltration, as suggested by the child's elevated creatinine clearances, may be a contributing factor.


[Proposals for economic regulatory mechanisms].
Economic mechanisms are needed to guarantee that longterm needs are not forgotten over short term benefits and desires. In traffic, variable costs (cost per mile) should be increased relative to fixed costs, traffic education should be supported and--where needed--fines for undesirable behavior should be introduced. Toxic substances should be taxed. As far as tobacco and alcohol consumption is concerned, abstinence or temperance should be rewarded. In medical care and medical education, prevention should be promoted by increased financial support.


Seasonal fluctuation in heavy metal pollution in Iran's Siahroud River. A preliminary study.
The management of its available water resources has become a key issue for Iran. During the last few decades, the water quality of Siahroud River in the coastal plain of the Caspian Sea in Gilan Province in Northern Iran has significantly degraded. The scarcity of water has been compounded by rapid population growth and increasing pollution from fertilizers, pesticides, and municipal and industrial wastes. One of the sources of this degradation is the movement of heavy metals from the river's watershed into the various water systems supported by the river, including the water system for Rasht City. To study the magnitude of heavy metal pollution in the Siahroud River, seven heavy metals including Zn, Cu, Pb, Cd, Mn, Fe, and Ni were measured in duplicate from replicated water samples collected over five consecutive seasons and analyzed by Atomic Absorption Spectrometry. In situ measurements of pH were taken with the samples and total organic carbon (TOC) was analyzed by IR gas measurement. The results demonstrated that four of the seven heavy metals including Pb, Fe, Cd, and Mn exceeded permissible safe levels as established by the United States Environmental Protection Agency. Multivariate factor analysis suggested that industrial land-use was the main contributing factor for the high levels of Fe and Mn in the Siahroud River, whereas, Cd was principly from agricultural activities in the watershed. The data also suggested that pH and TOC had an important role in the behaviour of Pb and Mn, and that the elevated levels of these two heavy metals in Siahroud River was the consequence of other anthropogenic sources. Only negligible levels of Zn, Cu and Ni were detected. Finally, all the sampling stations were subjected to cluster analysis. The results indicated that three different zones could be distinguished according to the levels of pollution. In addition, it was shown that the urban areas did not have a significant impact on the heavy metal pollution in the river. This observation stems from the fact that the data from the sampling stations before and after Rasht City were not significantly different. Preventive measures need to be undertaken in the land-use systems and watersheds of the Siahroud River to reduce the pollution levels of Pb, Cd, Mn and Fe.Cd, Mn and Fe.


Neuropeptides in insect sensory neurones: tachykinin-, FMRFamide- and allatotropin-related peptides in terminals of locust thoracic sensory afferents.
Sensory afferents in the thoracic ganglia of the locust Locusta migratoria were labelled with antisera to different neuropeptides: locustatachykinins, FMRFamide and allatotropin. The locustatachykinin-immunoreactive (LTKIR) sensory fibres were derived from the legs and entered the ventral sensory neuropil of each of the thoracic ganglia via nerve 5. In the thoracic neuropil, the LTKIR sensory fibres formed a distinct plexus of terminations ventrally in the ipsilateral hemisphere. The peripheral cell bodies of the sensory neurones could not be revealed, but lesion experiments indicated that origin of the LTKIR fibres was the tarsus of each leg. Possibly the thin fibres are from tarsal chemoreceptors. Double labelling immunocytochemistry revealed that all the LTKIR sensory fibres contained colocalized FMRFamide immunoreactivity. A larger population of sensory fibres reacted with antiserum to moth (Manduca sexta) allatotropin. By means of double labelling immunocytochemistry, we could show that the LTKIR fibres constituted a subpopulation of the larger set of allatotropin-like immunoreactive fibres. Thus some sensory fibres may contain colocalized peptides related to locustatachykinins, FMRFamide-related peptide(s) and allatotropin-like peptide. A separate non-overlapping small set of sensory fibres in nerve 5 reacted with an antiserum to serotonin. Sensory fibres of the other nerves of the ventral nerve cord, including the abdominal ganglia, did not react with the peptide antisera. Since acetylcholine is the likely primary neurotransmitter of insect sensory fibres, it is possible that the peptides and serotonin are colocalized with this transmitter and serve modulatory functions in a subset of the leg afferents.


Circadian plasticity: from structure to behavior.
Over the years it has become clear that the biological clock acts at different levels, ranging from the control of gene expression, protein stability, or subcellular localization of key proteins, to the fine tuning of network properties and modulation of input signals, ultimately ensuring that the organism will be best synchronized to a changing environment at the physiological and behavioral levels. The purpose of this chapter is to discuss the circadian control of clock outputs, spanning the most immediate ones within pacemaker neurons (i.e., membrane excitability, release of neurotransmitters, structural changes) to the circadian modulation of different behaviors (locomotor activity, learning and memory, social interaction), with a focus on the examples that shed light on the surprising degree of plasticity that characterizes the underlying circuits.


Behavioural state differentially engages septohippocampal cholinergic and GABAergic neurons in R6/1 Huntington's disease mice.
Huntington's disease (HD) is a neurodegenerative condition characterised by progressive motor, psychological and cognitive decline. R6/1 HD transgenic mice model the clinical hippocampal-dependent cognitive deficits observed in patients. Cholinergic and GABAergic septohippocampal projections play important roles in hippocampal-dependent cognition. The current study examined neuronal activity of cholinergic and GABAergic septohippocampal projections in response to arousal elicited during differing behavioural states. The different behavioural states examined were; home cage (controls), acute exploration of a novel enriched environment and either spontaneous wakefulness (dark phase) or spontaneous sleep (light phase). We employed triple-label immunohistochemistry using c-Fos as an indirect marker of neuron activation and parvalbumin and choline acetyltransferase (ChAT) to label GABAergic and cholinergic neurons in the basal forebrain, respectively. The Y-maze was used to assess short-term hippocampal-dependent memory independently during either the dark or light phase and revealed a memory deficit in R6/1 HD mice compared to wild types that was particularly prominent during the dark phase. Three-way ANOVA of basal forebrain cholinergic and GABAergic activity through co-expression of c-Fos revealed overt responses to differing behavioural states. Both genotypes increased cholinergic neuron activity in response to exploring a novel enriched environment and also an increase during the dark phase compared to the light phase. Novel enriched environment exploration caused a larger response of GABAergic neuron activity in R6/1 HD mice, which also failed to increase the activity of GABAergic neurons during the dark phase compared to the light phase as observed for wildtype mice. Basal levels of c-Fos-positive cells were greatly increased in the hippocampal granule cell layer of R6/1 HD mice during both circadian phases. The differential activation of septohippocampal cholinergic and GABAergic neurons in R6/1 HD mice in response to differing behavioural states may be associated with impaired hippocampal-dependent short-term memory.


Synthesis of a new hydrophobic coating film from stearic acid of buffalo fat.
This experiment involved the chemical conversion of pure stearic acid from buffalo adipose tissue to a waxy stearyl stearate, which was subsequently applied as a coating film to extend the shelf life of recently harvested fruits. Fat was extracted from minced adipose tissue using the dry rendering procedure, and it was then characterized. The extracted fat was hydrolyzed into a mixture of free fatty acids and glycerol. The supercritical CO2 extractor was used for stearic acid individual extraction in pure form from the free fatty acid mixture, and it was confirmed according to its melting point (69.2-70.0 °C), elemental analysis, GC-MS for esterified fatty acids. The isolated stearic acid was used for the synthesis of a new hydrophobic wax named stearyl stearate. The chemical structure of the prepared compound was established according to its elemental analysis and spectral data. The new hydrophobic wax was used as a coating film to enhance the shelf life of freshly harvested tomato fruits. Therefore, stearyl stearate solution (2.00% w/v diethyl ether) was used for tomato coating and compared to chitosan-coated tomatoes, where weight loss, pH, fruit firmness, ascorbic acid concentration, and total soluble solids were studied for a period of 15 days at 23 ± 1.0 °C and 65 ± 2.0% relative humidity. The results revealed that coating with stearyl stearate solution (2.00% w/v diethyl ether) could delay tomatoes' ripening during the experiment condition. A sensory evaluation of the coated tomatoes was carried out and showed acceptable taste for the tomatoes that were coated with stearyl stearate. On the other hand, the acute oral toxicity of stearyl stearate using albino mice showed complete safety up to 25 g/kg mice weight.


Spatio-temporal analysis and simulation of urban ecological resilience in Guangzhou City based on the FLUS model.
Prediction of urban ecological risk, which is increasing with the rapid development of China's economy, has become more complex and difficult, resulting in great damage to the safety of people's lives and property and the quality of the ecological environment. Elucidation of the change mechanism of the urban ecological resilience level from the perspective of the resilience characteristics and exploration of the spatiotemporal differences of the urban ability are necessary to prevent and resolve ecological risks. To this end, here, a model for the evaluation of urban ecological resilience was constructed by considering three aspects: resistance, adaptability, and resilience. The spatiotemporal change pattern of urban ecological resilience in Guangzhou from 2000 to 2020 was evaluated. Furthermore, a spatial autocorrelation model was used to explore the management model of Guangzhou's ecological resilience in 2020. Finally, based on the FLUS model, the spatial pattern of urban land use under the 2035 benchmark and innovation- and entrepreneurship-oriented scenarios was simulated and the spatial distribution of the ecological resilience level under different urban development scenarios was evaluated. We found that from 2000 to 2020, areas with a low ecological resilience expanded to the northeast and southeast, whereas areas with a high ecological resilience significantly decreased; from 2000 to 2010, original high-level regions in the northeast and east of Guangzhou were transformed into medium level regions. Further, in 2020, the southwestern region of the city will show a low level of resilience and high density of pollutant discharge enterprises, indicating that the ability to prevent and resolve environmental and ecological risks in this region is relatively low. Additionally, the overall ecological resilience of Guangzhou under the innovation- and entrepreneurship-oriented "City of Innovation" urban development scenario is higher than that under the benchmark scenario in 2035. The results of this study provide a theoretical basis for the development of resilient urban ecological environment.


Quality evaluation of commercially sold table water samples in Michael Okpara University of Agriculture, Umudike, Nigeria and surrounding environments.
In Michael Okpara University of Agriculture, Umudike, Nigeria (MOUAU) and surrounding environments, table water of different brands is commercially hawked by vendors. To the best of our knowledge, there is no scientific documentation on the quality of these water samples. Hence this study which evaluated the quality of different brands of water samples commercially sold in MOUAU and surrounding environments. The physicochemical properties (pH, total dissolved solids (TDS), biochemical oxygen demand (BOD), total hardness, dissolved oxygen, Cl, NO3, ammonium nitrogen (NH3N), turbidity, total suspended solids (TSS), Ca, Mg, Na and K) of the water samples as indices of their quality were carried out using standard techniques. Results obtained from this study indicated that most of the chemical constituents of these table water samples commercially sold in Umudike environment conformed to the standards given by the Nigerian Industrial Standard (NIS), World Health Organization (WHO) and American Public Health Association (APHA), respectively, while values obtained for ammonium nitrogen in these water samples calls for serious checks on methods of their production and delivery to the end users.


Elective laparoscopic versus open colectomy for diverticulosis: an analysis of ACS-NSQIP database.
The benefits of laparoscopic (LC) versus open (OC) colectomy for symptomatic colonic diverticulosis as an elective operation remain unclear. Using the American College of Surgeons-National Surgical Quality Improvement Project (ACS-NSQIP) participant-user file, patients were identified who underwent elective colon resection for symptomatic colonic diverticulosis, between 2005 and 2008. Demographic, clinical, intraoperative variables, and 30-day morbidity and mortality were collected. Logistic regression analysis was performed to determine the association between the surgical approach (LC vs. OC) and risk-adjusted overall mortality, overall morbidity, serious morbidity, and wound complications. A total of 7,629 patients were identified who underwent colon resection for symptomatic diverticulosis. They were subdivided into two groups: OC (3,870 (50.7%)) and LC (3,759 (49.3%)). Patients who underwent OC were significantly older (59.0 vs. 55.7 years, P < 0.0001) with more comorbidities compared with those who underwent LC. After risk-adjusted analysis, it was noted that the patients treated with LC were significantly less likely to experience overall morbidity (11.9% vs. 23.2%), serious morbidity (4.6% vs. 10.9%), and wound complications (9.1% vs. 17.5%), but not mortality (0.3% vs. 0.8%). Operative duration was significantly longer with LC (176.64 vs. 166.70 min, P < 0.0001), but the length of stay was significantly shorter (4.77 vs. 7.68 days, P < 0.0001). Using logistic regression analysis, patients with history of peripheral vascular disease, percutaneous coronary interventions, current steroid use, and hypertension requiring medication were at an increased risk of morbidity and mortality at 30 days. Patients with history of chronic obstructive pulmonary disease and smoking experienced more wound complications at 30 days. In the elective setting for symptomatic diverticulosis, LC seems to be associated with lower 30-day morbidity and complication rates compared with OC.


Spatio-temporal hydrochemistry of two selected Ramsar sites (Rara and Ghodaghodi) of west Nepal.
The present study was conducted in two Ramsar sites, Lake Rara and Lake Ghodaghodi, of the western Nepal covering pre-monsoon and post-monsoon seasons of 2019 to find out the dynamics of the hydrochemistry. A total of 11 major ions (Na+, K+, Ca2+, Mg2+, NH4 +, F-, Cl-, SO4 2-, NO3 -, NO2 -, HCO3 -) along with six on-site parameters (temperature, pH, electrical conductivity, total dissolved solids, dissolved oxygen, and turbidity) were sampled in replicates from 18 sites in Lake Rara and 13 sites in Lake Ghodaghodi. Major ions were analyzed using ion chromatography including field and procedural blanks to maintain quality standards, whereas on-site parameters were measured by using standard multi-meter probes. The most dominant cation and anions were Ca2+ and HCO3 - in both lakes indicating rock dominance through carbonate weathering as the primary source of dissolved ions in the lake waters. Further analysis indicated that Rara belongs to Ca(Mg)HCO3 and Ghodaghodi belongs to Ca-HCO3 type. The higher concentrations of Na+ and Cl- during the post-monsoon indicates a possibility of long-range marine transport through monsoon precipitation.


Satellite DNA loss and nucleolar organiser activity in an individual with a de novo chromosome 13,14 translocation.
The distribution of satellite DNA and nucleolar organiser activity have been studied in a female with a new dicentric translocation chromosome derived from the maternal chromosomes 13 and 14. More than half the satellite DNA (60.5%) was lost in the translocation, together with both the nucleolar organiser regions (NOR'S). However, at least one NOR (chromosome 21) which was inactive in the mother (by the AgI reaction) is active in the subject, and this may be an example of functional compensation. The somatic cells of the mother of the subject, which do not have the translocation, show a high frequency of acrocentric associations, but these do not include any obvious excess of associations involving chromosomes 13 and 14, indicating that the high frequency of association in somatic cells is not in itself a predisposition to Robertsonian translocation in germ line cells. The father's chromosomes 9 both have more satellite DNA in the secondary constriction than normal, but this is not reflected in any obviously larger size of the C-band in this region.


Infectious risks in patients treated with extracorporeal photopheresis for graft-versus-host disease: A retrospective cohort study.
Infections are common with significant mortality and morbidity in patients with graft-versus-host disease (GvHD). Extracorporeal photopheresis (ECP) is an advantageous treatment option for patients with GvHD because it is not immunosuppressive. The objective of this study was to assess the rate of infections and to determine risk factors in patients with GvHD. In a single-center cohort, we retrospectively collected data on infectious episodes by evaluating the clinical records of patients with GvHD treated by ECP since 2011. A total of 47 patients were included in this study. At ECP initiation, there were 10 patients with acute GvHD and 37 with chronic GvHD. At the final follow-up, 200 infectious episodes were diagnosed in 91.5% of patients with an average follow-up of 25.9 months (ie, 1.97 infections per patient per year). Most episodes had positive outcomes as there was no death related to infections, and only six infections required long-term treatment. Higher dose of corticosteroids at the initiation of ECP was significantly associated with a shorter onset of the first infection (hazard ratio [HR] = 2.05; 95% confidence interval [CI] [1.17, 3.57]; P = .013). Unrelated donor transplants were significantly associated with a lower rate of infection (HR = 0.61; 95% CI [0.39, 0.95]; P = .028). The results of our study suggest that ECP is associated with a low infection rate and an optimal clinical efficacy. Thus, ECP is still a suitable treatment for GvHD. Yet, a future study with a larger cohort will be necessary to deepen the identification of risk factors for infection.


Narcolepsy in the custodial setting.
A case of a detained person who suffered from narcolepsy is presented. The management of the condition in general and with particular reference to the custodial setting is discussed. The management of obstructive sleep apnoea, the commonest sleep disorder, is contrasted. Forensic physicians are often confronted with rare or unusual medical problems in the custodial setting, often having to make immediate medical decisions without access to specialist medical advice. Twenty-four hour access to Internet medical resources in the custodial setting may be helpful.


Characterization of cellular attachment and spreading molecules at liquid-liquid interfaces.
Cells are grown at a liquid-liquid interface (ultrafiltrate of growth medium--heptacosafluorotributylamine). Following attachment and spreading an intermediate-density, isotonic solution of metrizamide-Ficoll is introduced. Cells are detached by centrifugation at 150,000g X 45 min. Molecules deposited at the interface are removed and examined by gel electrophoresis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals 20 protein bands ranging in molecular weight from 30,000 to 200,000. Most bands have molecular weights less than 120,000. The substrate-attached material contains approximately 2.8 pg of protein per attached cell. Substrate-attached molecules can be removed without detergent denaturation for additional studies.


XMRV and prostate cancer--a 'final' perspective.
XMRV was first described in 2006, when it was identified in samples isolated from prostate cancer tissues. However, studies have since shown that XMRV arose in the laboratory and was formed by genetic recombination between two viral genomes carried in the germline DNA of mice used during serial transplantation of the CWR22 prostate cancer xenograft. These new findings strongly imply that XMRV does not circulate in humans, but is only present in the laboratory. Thus, there is no reason to believe that it has any role in the etiology of prostate cancer or other diseases.


Effects of UV-B radiation on the structural and physiological diversity of bacterioneuston and bacterioplankton.
The effects of UV radiation (UVR) on estuarine bacterioneuston and bacterioplankton were assessed in microcosm experiments. Bacterial abundance and DNA synthesis were more affected in bacterioplankton. Protein synthesis was more inhibited in bacterioneuston. Community analysis indicated that UVR has the potential to select resistant bacteria (e.g., Gammaproteobacteria), particularly abundant in bacterioneuston.


Neuroscience: Action history and the orbitofrontal cortex.
Decisions are often made in the absence of instructive cues, based instead on memories of previous actions and outcomes. A new study sheds light on how orbitofrontal cortex tracks action history to adjust actions over time.


[Clinical experience with automated percutaneous diskectomy].
Percutaneous automated aspiration discectomy (Nucleotome, Surgical Dynamics) is a new procedure for treating herniated lumbar discs. In a series of 35 patients, followed-up after 6 months, the overall success rate was 74%. 19 patients resumed work 4 weeks after surgery. In 6 patients the interventions were judged as failures and required reoperation (laminectomies). All the patients obtained complete relief. Meticulous selection of patients for percutaneous lumbar discectomy is the key to success. No intra-operative or post-operative complications occurred.


Glucose and glutamine metabolism of a murine B-lymphocyte hybridoma grown in batch culture.
The energy metabolism of a mammalian cell line grown in vitro was analyzed by substrate consumption rates and metabolic flux measurements. The data allowed the determination of the relative importance of the pathways of glucose and glutamine metabolism to the energy requirements of the cell. Changes in the substrate concentrations during culture contributed to the changing catalytic activities of key enzymes, which were determined. 1. A murine B-lymphocyte hybridoma (PQXB1/2) was grown in batch culture to a maximum cell density of 1-2 x 10(6) cells/mL in 3-4 d. The intracellular protein content showed a maximum value during the exponential growth phase of 0.55 mg/10(6) cells. Glutamine was completely depleted, but glucose only partially depleted to 50% of its original concentration when the cells reached a stationary phase following exponential growth. 2. The specific rates of glutamine and glucose utilization varied during culture and showed maximal values at the midexponential phase of 2.4 nmol/min/10(6) cells and 4.3 nmol/min/10(6) cells, respectively. 3. A high proportion of glucose (96%) was metabolized by glycolysis, but only limited amounts by the pentose phosphate pathway (3.3%) and TCA cycle (0.21%). 4. The maximum catalytic activity of hexokinase approximates to the measured flux of glycolysis and is suggested as a rate-limiting step. In the stationary phase, the hexokinase activity reduced to 11% of its original value and may explain the reduced glucose utilization at this stage. 5. The maximal activities of two TCA cycle enzymes were well above the measured metabolic flux and are unlikely to pose regulatory barriers. However, the activity of pyruvate dehydrogenase was undetectable by spectrophotometric assay and explains the low level of flux of glycolytic metabolites into the TCA cycle. 6. A significant proportion of the glutamine (36%) utilized by the cells was completely oxidized to CO2. 7. The measured rate of glutamine transport into the cells approximated to the metabolic flux and is suggested as a rate-limiting step. 8. Glutamine metabolism is likely to occur via glutaminase and amino transaminase, which have significantly higher activities than glutamate dehydrogenase. 9. The calculated potential ATP production suggests that, overall, glutamine is the major contributor of cellular energy. However, at the midexponential phase, the energy contribution from the catabolism of the two substrates was finely balanced--glutamine (55%) and glucose (45%).


Identification of high risk DISC1 protein structural variants in patients with bipolar spectrum disorder.
In a large Scottish pedigree, a balanced translocation t (1;11)(q42.1;q14.3) disrupting the DISC1 and DISC2 genes segregates with major mental illness, including schizophrenia and depression. A frame-shift carboxyl-terminal deletion was reported in DISC1 in an American family with schizophrenia, but subsequently found in two controls. Herein, we test one hypothesis utilizing a large scale case-control mutation analysis: uncommon DISC1 variants are associated with high risk for bipolar spectrum disorder. We have analyzed the regions of likely functional significance in the DISC1 gene in 504 patients with bipolar spectrum disorder and 576 ethnically similar controls. Five patients were heterozygous for ultra-rare protein structural variants not found in the 576 controls (p=0.02, one-sided Fisher's exact test) and shown to be ultra-rare by their absence in a pool of 10,000 control alleles. In our sample, ultra-rare (private) protein structural variants in DISC1 are associated with an estimated attributable risk of about 0.5% in bipolar spectrum disorder. These data are consistent with: (i) the high frequency of depression in the large Scottish family with a translocation disrupting DISC1; (ii) linkage disequilibrium analysis demonstrating haplotypes associated with relatively small increases in risk for bipolar disorder (<3-fold odds ratio). The data illustrate how low/moderate risk haplotypes that might be found by the HapMap project can be followed up by resequencing to identify protein structural variants with high risk, low frequency and of potential clinical utility.


Meta-analysis to determine effects of treatment with FSH when there is progestin-priming on in-vitro embryo production using ovum pick-up in Bos taurus cows.
Treatments with follicle stimulating hormone (FSH) to enhance ovarian follicular development before ovum pick-up (OPU) are important for improving in-vitro embryo production (IVEP) procedures in cows, however, their procedural efficacy needs to be evaluated. The objective of the present study was to use meta-analytic methods to determine the effects of FSH treatments prior to OPU when there is progestin-priming on ovarian functions and IVEP in parous Bos taurus cows (n = 243). The literature was systematically reviewed and data from eight experiments, with 23 treatment means including 448 OPU sessions, were used for analyses. All eight experiments included a group of cows in which there was no FSH treatment (CON), and treatment with FSH before OPU to conduct IVEP. Mixed models were fitted using MIXED and GLIMMIX procedures of SAS. Additionally, classical meta-analytical statistics were also fitted using METAN and METAREG procedures of STATA. Models included fixed effects of treatment (i.e., CON and FSH) and random effect of the experiment, and data were weighted using the inverse of the SEM squared to account for precision of each experiment. Number of medium sized follicles, quality of oocytes, and transferable embryos were greater (P < 0.05) in FSH-treated as compared with cows of the CON group, without indications of publication bias or heterogeneity of data. Taken together, the results from the present study lead to the recommendation for treatments with FSH prior to OPU for IVEP when there was progestin-priming imposed to obtain a large number of transferable embryos for economic sustainability of commercial embryo transfer programs in parous non-lactating Bos taurus cows.


Failure of indium-111 leukocyte scanning to detect nodal involvement with Mycobacterium avium-intracellulare infection in the acquired immunodeficiency syndrome.
An In-111 leukocyte scan was used to evaluate fever of unknown origin in a patient with the AIDS rather than Ga-67. The scan was normal despite an impressively positive Ga-67 scan performed 48 hours later. In-111 should not be used to evaluate fever in patients with AIDS where mycrobacterium avium-intracellular infection is a diagnostic possibility.


A general health promotion approach to helping smokers with non-communicable diseases quit smoking: A pilot randomized controlled trial.
Despite evidence showing that continued smoking in patients with non-communicable diseases can reduce treatment efficacy and increase the risk of disease progression and multimorbidity, many smoker patients either have no intention to quit or have had failed attempts at quitting. To examine the feasibility of a general health promotion approach that uses instant messaging to deliver brief motivational interviewing to help smokers with non-communicable diseases quit smoking. In total, 60 participants who had medical follow-up in a special out-patient clinic were randomized into two groups, 30 in the intervention group received brief motivational interviewing to assist them with their chosen behavioral changes, and 30 in the control group received only a smoking cessation booklet. The outcome measures included self-reported 7-day point prevalence of smoking abstinence and any behavioral change reported by the participants at 6 and 12 months. Biochemical validation was performed for those who verbally reported a 7-day point prevalence of smoking abstinence at 12 months. The majority (95%) of smokers who attended the out-patient clinic owned a smartphone. The response rate was 73.2%. Retention rates at 6-month and 12-month follow-up were 83.3 and 71.7%, respectively. The process evaluation indicated that participants were satisfied with the content of the brief MI messages and appreciated the use of instant messaging as a way to provide them with professional advice and support for managing their health-related lifestyles. The intervention group had a higher biochemically validated abstinence rate than the control group at 12 months (16.7 vs. 6.7 P = 0.23) although the difference was not statistically significant (Adjusted odd ratio 2.4, 95% confidence interval, 0.43-13.75; P = 0.32.), In addition, the proportion of participants reporting a behavioral change was higher in the intervention group at 6 and 12 months. This study suggested the potential efficacy and feasibility of a general health promotion approach that uses instant messaging to deliver brief motivational interviewing to help smokers with non-communicable diseases quit smoking. The findings can be used to create a new smoking cessation service model that implements a flexible, proactive and personalized approach to help smokers quit smoking. ClinicalTrials.gov, identifier: NCT03983330.


A microassay for the determination of iodide and its application to the measurement of the iodination of proteins and the catalytic activities of iodo compounds.
A microassay system based on the effect of the catalytic Sandell-Kolthoff reaction of iodide on the oxidation of arsenic(III) by cerium(IV) was developed to measure iodine-containing compounds. This rapid assay uses small quantities of reagents, is suitable for use with a photometric microplate reader, can test many samples simultaneously, and eliminates problems associated with the use of radiolabeled compounds to measure iodination. It can detect picogram quantities of iodide. We report the use of this assay to measure the conjugation of an iodine-containing hapten (iodinated Bolton-Hunter reagent, IBHR) to ovalbumin and human serum albumin. It has proven to be excellent for studying the relative molar catalytic activity of the iodine-containing compounds IBHR, thyroxine, 4-iodophenol, and lithium 3,4-diiodosalicylate. The interference by azide on the assay was investigated.


The Trojan Horse Tale Revisited: An Eye on Metastatic Spread of Carcinoma Cells.
The metastatic spread of carcinoma cells is not fully understood. Here, we compare the peripheral blood mononuclear cells (PBMC) and intraocular metastatic cells in parotid gland carcinoma with the PBMCs of healthy donors by immunohistochemistry and flow cytometry. We found Ber-EP4 tumor marker-positive carcinoma cells in the aqueous humor of the patient's right eye and a CD45 and Ber-EP4-expressing PBMC population in his blood. These Ber-EP4-expressing cells exhibited a monocytic-myeloid phenotype with coexpression of CD11b, CD115, and the macrophage marker CD172a (SIRP-α). Uptake of pHrodogreen revealed their phagocytic activity. Our findings suggest that the tumor cells in the anterior chamber originally derived from cell fusions between tumor cells and myeloid cells in the peripheral blood. Thus, metastases of a solid malignancy could use monocytes-macrophages as the Trojan horse to enter the eye.


Severe complication after termination of a second trimester cervical pregnancy.
To report a supracervical hysterectomy performed after a life-threatening hemorrhage due to an attempted surgical termination at a gestational age of 18 weeks, which appeared to be a cervical pregnancy. Case report. Teaching hospital. A 36-year-old pregnant woman, with two previous cesarean sections. Supracervical hysterectomy. Not applicable. A stable patient. By missing a cervical pregnancy in the second trimester, a life-threatening hemorrhage occurred after an attempted surgical termination. In case of failure of the conservative therapy this rare diagnosis should be considered. A supracervical hysterectomy at this gestational age is the only therapeutic option.


Correction: Inhibition of IRE1α-driven pro-survival pathways is a promising therapeutic application in acute myeloid leukemia.
[This corrects the article DOI: 10.18632/oncotarget.7702.].


Effects of aldehydes and organic solvents on concanavalin A binding sites in cerebellar tissue sections.
Fresh frozen cerebellar sections of adult mice treated with aldehydes and organic solvents reveal differences in detectability of Concanavalin A (Con A) binding sites. While fluorescein coupled Con A shows intense labeling of synaptic glomeruli and granule cell bodies under all conditions, the molecular layer labels intensely after treatment with paraformaldehyde, glutaraldehyde, acetone, ethanol and butanol. Complete loss of staining in molecular and granular layers and substantial increase in white matter labeling occurs after chloroform-methanol treatment. Except for glutaraldehyde treated sections, all labeling is specifically inhibited by methyl-alpha-D-mannoside, but not by galactose.


Strain analysis using feature tracking cardiac magnetic resonance (FT-CMR) in the assessment of myocardial viability in chronic ischemic patients.
The purpose of this study is to test the capability of a commercially available feature tracking-cardiac magnetic resonance (FT-CMR) strain analysis software module in differentiating between viable and non-viable myocardium in chronic ischemic patients. Thirty chronic ischemic patients and 10 healthy volunteers were enrolled. Cine images were used for peak circumferential and radial strains quantification using dedicated FT-CMR software. Global strain was compared between patients and controls. In patients, segmental strain was compared in viable and non-viable myocardium determined by late gadolinium enhancement (LGE); and in segments with wall abnormalities. Among 480 myocardial segments analyzed in patients, 76 segments were non-viable on LGE. The mean left ventricular ejection fraction (LVEF) of the patients (87% males, mean age 55 ± 12 years) was 40 ± 12% vs. 61 ± 5% for the controls (80% males, mean age 39 ± 11 years). Peak global circumferential strain (GCS) and global radial strain (GRS) were significantly impaired in patients compared to controls (-13.89 ± 4.12% vs. -19.84 ± 1.47%), p < 0.001 and (23.11 ± 6.59% vs. 31.72 ± 5.52%), p = 0.001. Segmental circumferential strain (SCS) and segmental radial strain (SRS) were significantly impaired in non-viable compared to viable segments (-9.47 ± 7.26% vs. -14.72 ± 7.5%), p < 0.001 and (15.67 ± 12.11% vs. 24.51 ± 16.22%), p < 0.001. Cut-off points of -9.36% for the SCS (AUC = 0.7, 95% CI = 0.63-0.77) and 19.5% for the SRS (AUC = 0.67, 95%CI = 0.61-0.73) were attained above which the segment is considered viable.SCS was able to discriminate between normokinetic, hypokinetic and akinetic segments (mean = 27.6 ± 17.13%, 18.66 ± 12.88% and 15.24 ± 10.70% respectively, p < 0.001). Circumferential and radial segmental strain analysis by FT-CMR was able to discriminate between viable and non-viable segments of the myocardium defined by LGE and between normokinetic, hypokinetic and akinetic segments, using routinely acquired cine images, and thus can provide a more objective metric for risk stratification in chronic ischemic patients.


Do men consult less than women? An analysis of routinely collected UK general practice data.
To examine whether gender differences in primary care consultation rates (1) vary by age and deprivation status and (2) diminish when consultation for reproductive reasons or common underlying morbidities are accounted for. Cross-sectional study of a cohort of patients registered with general practice. UK primary care. Patients (1 869 149 men and 1 916 898 women) registered with 446 eligible practices in 2010. Primary care consultation rate. This study analyses routinely collected primary care consultation data. The crude consultation rate was 32% lower in men than women. The magnitude of gender difference varied across the life course, and there was no 'excess' female consulting in early and later life. The greatest gender gap in primary care consultations was seen among those aged between 16 and 60 years. Gender differences in consulting were higher in people from more deprived areas than among those from more affluent areas. Accounting for reproductive-related consultations diminished but did not eradicate the gender gap. However, consultation rates in men and women who had comparable underlying morbidities (as assessed by receipt of medication) were similar; men in receipt of antidepressant medication were only 8% less likely to consult than women in receipt of antidepressant medication (relative risk (RR) 0.916, 95% CI 0.913 to 0.918), and men in receipt of medication to treat cardiovascular disease were just 5% less likely to consult (RR=0.950, 95% CI 0.948 to 0.952) than women receiving similar medication. These small gender differences diminished further, particularly for depression (RR=0.950, 95% CI 0.947 to 0.953), after also taking account of reproductive consultations. Overall gender differences in consulting are most marked between the ages of 16 and 60 years; these differences are only partially accounted for by consultations for reproductive reasons. Differences in consultation rates between men and women were largely eradicated when comparing men and women in receipt of medication for similar underlying morbidities.


Stability and degradation patterns of chemically modified analogs of apelin-13 in plasma and cerebrospinal fluid.
Apelin is the endogenous ligand of APJ, which belongs to the superfamily of G protein-coupled receptors. In recent years, the apelin/APJ system has been detected in many tissues and emerges as a promising target for the treatment of various pathophysiological conditions. Pyr1-apelin-13 is the major isoform of apelin in human plasma; however its stability and proteolytic degradation pattern remain poorly understood. The aim of the present study was first to identify the cleavage sites of Pyr1-apelin-13 in mouse, rat and human plasma and rat cerebrospinal fluid, then to determine its stability to proteolytic degradation following intravenous administration in rats. Secondly, key residues were substituted by natural and unnatural amino acids in order to examine the impact on in vitro stability and degradation pattern. The kinetics of degradation revealed that the Leu5-Ser6 peptide bond of Pyr1-apelin-13 is the first cleavage observed in plasma, independently of the species. Replacement of Phe13 by unnatural amino acids showed a 10-fold increase in plasma stability although the hydrolysis of Pro12-Phe13 bond, previously described as a site of cleavage by ACE-2, was not observed. In vivo, this Pro12-Phe13 bond was cleaved yet appears as a minor product compared to hydrolysis of the Pro10-Met11 bond. This study pinpoints the most critical amino acids targeted by proteases and will be instrumental for the design of Pyr1-apelin-13 analogs possessing increased stability.


Drosophila proboscis extension response and GCaMP imaging for assaying food appeal based on grittiness.
Fruit flies sense the features of food that are driven by particle size, including smoothness versus grittiness, by deflection of sensilla decorating the labellum, and md-L neurons. We describe adaptation of the Drosophila proboscis extension response assay, including steps to perform the taste tests and score behavioral responses, to determine preferences to foods with different sized particles. We also describe calcium imaging in GCaMP-expressing flies to assess the responses of md-L neurons to different levels of taste sensilla deflection. For complete details on the use and execution of this protocol, please refer to Li and Montell. (2021).


Ghrelin gene variants and eating disorders.
Genetic factors have been implicated in playing a significant role in susceptibility to eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Genetic variants of ghrelin, an endogenous acylated peptide that stimulates growth hormone secretion, enhances appetite, and increases body weight, have been investigated in association with eating disorders, as changes in the ghrelin/growth hormone secretagogue receptor (GHSR)/ghrelin O-acyltransferase (GOAT) system have been implicated in its pathology. Although most candidate-gene association studies have not been able to identify ghrelin gene variants as being significantly associated with either AN or BN, some ghrelin variants may be associated with BN in Japanese. Furthermore, a significant association of a GHSR gene variant with BN and that of a GOAT gene variant with AN have been found. However, there have been relatively few studies, tested variants are restricted, and sample sizes are often modest. Therefore, further studies are needed to elucidate the role of ghrelin-related gene variants in the predisposition and pathology of eating disorders.


Intracerebroventricular arginine vasopressin causes intracranial pressure to rise in conscious goats.
The effects of intracerebroventricular (i.c.v.) infusion of arginine vasopressin (AVP) on intracranial pressure (ICP), blood pressure (BP) and plasma AVP were investigated in conscious goats. The animals were implanted with ventricular (V) and cisternal (C) cannulae under halothane anaesthesia and allowed to recover prior to experimentation. After 30 min infusion of 20 microliter/min artificial cerebrospinal fluid (CSF) alone, to allow the animals to settle, ICP (estimated at both C and V cannulae), BP and plasma AVP were measured. Then the animals were infused with either artificial CSF alone or 1 or 10 pmol/min AVP for a further 150 min. One pmol/min AVP i.c.v. resulted in significant ICP increases of +2.2 cm CSF (C) and +3.1 cm CSF (V) when compared with artificial CSF alone. Ten pmol/min AVP also led to significant ICP rises of +3.2 cm CSF (C) and +4.2 cm CSF (V). There were no significant changes of BP or plasma AVP during the infusions. We conclude that central infusion of AVP leads to elevated ICP in conscious goats by a mechanism that does not involve BP alteration or changes in plasma AVP.


Catalytic acitivity of Ntau-carboxymethylhistidine-12 ribonuclease.
Ntau-Carboxymethylhistidine-12 RNase is active with both RNA and uridine cyclic 2':3'-monophosphate as substrates. Experimental evidence is presented to show that the activity cannot be due to contaminating RNase A, or other RNase-type protein, to the presence of a mixed dimer between 12- and 119-substituted RNases, or to the presence of trace amounts of Ntau-carboxymethylhistidine-12 RNase. The carboxymethyl derivative has approximately 1 and 13 per cent the specific activity of native enzyme against cyclic 2',3'-UMP at pH 5.0 and 8.5, respectively.


Psychometric Validation of the Sexual Function Questionnaire in Poland.
Questionnaires diagnosing sexual dysfunctions in women are important tools which can facilitate the diagnosis and therapy of individual female patients. The study is aimed at the adaptation of the Sexual Function Questionnaire, which was designed by Frances H. Quirk and associates for the American population, to Polish conditions (Quirk et al. in J Sex Med 4:469-77, 1). The study group consisted of 143 women aged 20-68 who were receiving gynaecological care and displayed various types of sexual dysfunction (e.g. female sexual arousal disorder, female orgasmic disorder, dyspareunia), or none of those. The good psychometric quality of the Sexual Function Questionnaire has been confirmed with the following results: convergent validity r(s)=0.62, p<0.01, construct validity was estimated by Principal Component Analysis with the promax rotation method. The 7 factors together explained 80.7% of total variance, and a reliability of 0.97 for the whole test, with that for particular domains ranging from 0.62 to 0.96 (estimated with Cronbach's alpha). The obtained results are mostly consistent with results from studies conducted by the authors of the Questionnaire in the United States, and with the adaptation study carried out in Iran. There are, however, some differences in the assignment of questions to particular domains, as well as in the names of the domains.


[Biological trials of chemical compounds: the strategy of the initial search].
Some aspects of the strategy of initial search of biologically active compounds at mass tests of chemical compounds have been discussed. Different approaches to pre-experimental estimation of biological activity using mathematical statistics and computer analysis have been analysed.


Relative contribution of trunk muscles to the stability of the lumbar spine during isometric exertions.
To compare the relative contribution of various trunk muscles to the stability of the lumbar spine. Quantification of spine stability with a biomechanical model. Modern low back rehabilitation techniques focus on muscles that stabilize the lumbar spine. However, the relative contribution of various trunk muscles to spine stability is currently unknown. Eight male subjects performed isometric exertions in trunk flexion, extension, lateral bending, and axial rotation, and isometric exertions under vertical trunk loading and in a lifting hold. Each isometric trial was repeated three times at 20%, 40%, and 60% of the maximum trunk flexion force or with a load of 0%, 20%, 40%, and 60% of body weight for the latter two exertions. Surface EMG data from 12 major trunk muscles were used in the biomechanical model to estimate stability of the lumbar spine. A simulation of each trial was performed repeatedly with one of the 10 major trunk muscle groups removed from the model. Relative contribution of each muscle to spine stability was significantly affected by the combination of loading magnitude and direction (3-way interaction). None of the removed muscles reduced spine stability by more than 30%. A single muscle cannot be identified as the most important for the stability of the lumbar spine. Rather, spine stability depends on the relative activation of all trunk muscles and other loading variables. This study will improve our understanding of individual trunk muscles' contribution to overall stability of the lumbar spine.


Consistent effects of canopy vs. understory nitrogen addition on the soil exchangeable cations and microbial community in two contrasting forests.
Anthropogenic N deposition has been well documented to cause substantial impacts on the chemical and biological properties of forest soils. In most studies, however, atmospheric N deposition has been simulated by directly adding N to the forest floor. Such studies thus ignored the potentially significant effect of some key processes occurring in forest canopy (i.e., nitrogen retention) and may therefore have incorrectly assessed the effects of N deposition on soils. Here, we conducted an experiment that included both understory addition of N (UAN) and canopy addition of N (CAN) in two contrasting forests (temperate deciduous forest vs. subtropical evergreen forest). The goal was to determine whether the effects on soil exchangeable cations and microbial biomass differed between CAN and UAN. We found that N addition reduced pH, BS (base saturation) and exchangeable Ca and increased exchangeable Al significantly only at the temperate JGS site, and reduced the biomass of most soil microbial groups only at the subtropical SMT site. Except for soil exchangeable Mn, however, effects on soil chemical properties and soil microbial community did not significantly differ between CAN and UAN. Although biotic and abiotic soil characteristics differ significantly and the responses of both soil exchangeable cations and microbial biomass were different between the two study sites, we found no significant interactive effects between study site and N treatment approach on almost all soil properties involved in this study. In addition, N addition rate (25 vs. 50 kg N ha(-1) yr(-1)) did not show different effects on soil properties under both N addition approaches. These findings did not support previous prediction which expected that, by bypassing canopy effects (i.e., canopy retention and foliage fertilization), understory addition of N would overestimate the effects of N deposition on forest soil properties, at least for short time scale.


Ecosystem services supply and demand mismatches and effect mechanisms in the mixed landscapes context.
Clarifying multiple relationships between ecosystem services (ES) supplies and socio-economical demands is the prerequisite of spatial sustainability. Ecotones are specific mixed landscapes where the characteristics of ES supply-demand mismatches are critical to explore ES effect mechanisms. This study structured the relationships that occurred during the ecosystem processes of ES into a framework and identified ecotones in Northeast China (NEC). Multi-step analysis was conducted to analyze the mismatches between 8 pairs of ES supplies and demands and the effects of landscapes on ES mismatches. The results show that the correlations between landscapes and ES mismatches could reflect the effectiveness of landscape management strategies more comprehensively. High demand for food security led to more serious regulating and cultural ES mismatches in NEC. While forest and forest-grassland ecotones were robust to alleviate ES mismatches and landscapes mixed with ecotones performed more balanced in ES supplies. Our study suggests that the comprehensive effects of landscapes on ES mismatches should be given priority in landscape management strategies. Afforestation should be strengthened in NEC, while wetland and ecotones should be protected from boundary shifts and shrinkage caused by agricultural production activities.


'Extended deep inferior epigastric artery flaps' for reconstruction after excision of chondrosarcoma sternum.
We describe a case of chondrosarcoma of the sternum requiring wide full thickness chest wall excision thereby creating a difficult defect for reconstruction. A mesh was used for support and two extended deep inferior epigastric artery fasciocutaneous flaps were mobilised medially into the defect.


A case of dengue fever presenting with acute urticaria.
Acute urticaria (AU) is characterized by the occurrence of spontaneous wheals, angioedema, or both for less than 6 weeks. Viral infection is considered to be one of the common causes of AU, however AU has never been reported in association with dengue infection. To describe the first case of AU in dengue virus infection. Case report. A 17-year-old healthy male presented with first episode of AU which associated with confirmed dengue virus infection. He responded well with antihistamine treatment and without recurrence at 2-month follow up. Patients with dengue virus infections can present with AU, possibly from viral-infected mast cell. Future research will have to clarify this association.


Clinical outcomes associated with Mu variant infection during the third epidemic peak of COVID-19 in Colombia.
The higher number of cases and deaths caused by COVID-19 in Colombia occurred during the third epidemic peak, where the Mu variant was associated with 50% of the cases. To evaluate the association between the clinical outcome of COVID-19 with health conditions and SARS-CoV-2 lineages. In this study, clinical metadata and SARS-CoV-2 lineages from 535 patients with different degrees of COVID-19 severity were obtained after the SARS-CoV-2 genomic surveillance in Colombia. Then, the associations between these variables were determined using a multidimensional unfolding analysis. Asymptomatic, symptomatic, severe, and deceased outcomes represented 15.2%, 29.7%, 7.3%, and 47.8% of the cases, respectively. Males tend to develop more serious COVID-19, and severe or fatal outcomes were typically observed in patients aged >60 years with comorbidities, including chronic obstructive pulmonary disease, heart disease, kidney disease, obesity, asthma, and smoking history. The SARS-CoV-2 Mu and Gamma variants dominated the third epidemic peak and accounted for most fatal cases with odd ratio values of 128.2 (CI 53.0-310.1) and 18.6 (CI 8.294-41.917). This study shows the high impact of SARS-CoV-2 lineages with higher prevalence on public health and the importance of monitoring COVID-19 risk factors to control the associated mortality.


Development of self-perceived risk behaviour and psychosomatic symptoms in adolescents: a longitudinal approach.
A cohort study on a sample of 327 high school students was carried out between 1983 and 1985. Health and behaviour problems were investigated. During adolescence psychosomatic, depressive and behavioural problems appear to be common. The majority of young people suffer at least one problem at 18 years of age. The type of problems are closely related to gender: among boys behavioural problems (BP), such as alcohol or drug consumption, tobacco smoking and violence, are important; among girls sleep disorders, headaches and depressive symptoms (PDS) are frequent. During adolescence sex differences become clearly established. Between 16 and 18 years of age the average number of behavioural problems rises from 0.5 to 1.5 for boys and remains stable (around 0.5) for girls. During the same period the PDS average rises from 1.6 to 2.0 for girls and remains stable (around 0.7) for boys. Even if there exists a correlation between BP and PDS (this correlation is higher in the early age than later on), one type of problem is always predominant, according to sex. BP as well as PDS are related to the intolerance of frustration. Authors conclude that these problems must be considered as the expression of the inability to metabolize or cope with the conflict.


Assessing Relationships Between Muslim Physicians' Religiosity and End-of-Life Health-Care Attitudes and Treatment Recommendations: An Exploratory National Survey.
Research demonstrates that the attitudes of religious physicians toward end-of-life care treatment can differ substantially from their nonreligious colleagues. While there are various religious perspectives regarding treatment near the end of life, the attitudes of Muslim physicians in this area are largely unknown. This article attempts to fill in this gap by presenting American Muslim physician attitudes toward end-of-life care decision-making and by examining associations between physician religiosity and these attitudes. A randomized national sample of 626 Muslim physicians completed a mailed questionnaire assessing religiosity and end-of-life care attitudes. Religiosity, religious practice, and bioethics resource utilization were analyzed as predictors of quality-of-life considerations, attitudes regarding withholding and withdrawing life-sustaining treatment, and end-of-life treatment recommendations at the bivariate and multivariable level. Two-hundred fifty-five (41% response rate) respondents completed surveys. Most physicians reported that religion was either very or the most important part of their life (89%). Physicians who reported consulting Islamic bioethics literature more often had higher odds of recommending active treatment over hospice care in an end-of-life case vignette. Physicians who were more religious had higher odds of viewing withdrawal of life-sustaining treatment more ethically and psychologically challenging than withholding it and had lower odds of agreeing that one should always comply with a competent patient's request to withdraw life-sustaining treatment. Religiosity appears to impact Muslim physician attitudes toward various aspects of end-of-life health-care decision-making. Greater research is needed to evaluate how this relationship manifests itself in patient care conversations and shared clinical decision-making in the hospital.


Correlation between anthrax lethal toxin neutralizing antibody levels and survival in guinea pigs and nonhuman primates vaccinated with the AV7909 anthrax vaccine candidate.
The anthrax vaccine candidate AV7909 is being developed as a next generation vaccine for a post-exposure prophylaxis (PEP) indication against anthrax. AV7909 consists of the Anthrax Vaccine Adsorbed (AVA, BioThrax®) bulk drug substance adjuvanted with the immunostimulatory oligodeoxynucleotide (ODN) compound, CPG 7909. The addition of CPG 7909 to AVA enhances both the magnitude and the kinetics of antibody responses in animals and human subjects, making AV7909 a suitable next-generation vaccine for use in a PEP setting. The studies described here provide initial information on AV7909-induced toxin-neutralizing antibody (TNA) levels associated with the protection of animals from lethal Bacillus anthracis challenge. Guinea pigs or nonhuman primates (NHPs) were immunized on Days 0 and 28 with various dilutions of AV7909, AVA or a saline or Alhydrogel+CPG 7909 control. Animals were challenged via the inhalational route with a lethal dose of aerosolized B. anthracis (Ames strain) spores and observed for clinical signs of disease and mortality. The relationship between pre-challenge serum TNA levels and survival following challenge was determined in order to calculate a threshold TNA level associated with protection. Immunisation with AV7909 induced a rapid, highly protective TNA response in guinea pigs and NHPs. Surprisingly, the TNA threshold associated with a 70% probability of survival for AV7909 immunized animals was substantially lower than the threshold which has been established for the licensed AVA vaccine. The results of this study suggest that the TNA threshold of protection against anthrax could be modified by the addition of an immune stimulant such as CPG 7909 and that the TNA levels associated with protection may be vaccine-specific.


Advances in radiotherapy and immunity in hepatocellular carcinoma.
Primary liver cancer is one of the most common malignant tumours worldwide; it caused approximately 830,000 deaths in 2020. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for over 80% of all cases. Various methods, including surgery, chemotherapy, radiotherapy, and radiofrequency ablation, have been widely used in the treatment of HCC. With the advancement of technology, radiotherapy has become increasingly important in the comprehensive treatment of HCC. However, due to the insufficient sensitivity of tumour cells to radiation, there are still multiple limitation in clinical application of radiotherapy. In recent years, the role of immunotherapy in cancer has been increasingly revealed, and more researchers have turned their attention to the combined application of immunotherapy and radiotherapy in the hope of achieving better treatment outcomes. This article reviews the progress on radiation therapy in HCC and the current status of its combined application with immunotherapy, and discusses the prospects and value of radioimmunotherapy in HCC.


The clinical significance of a small focus of well-differentiated carcinoma at prostate biopsy.
To compare a series of 121 sextant needle biopsy sets with their corresponding radical prostatectomy specimens in screened participants in the European Randomized study of Screening for Prostate Cancer (ERSPC), investigating the effect of screening for prostate cancer on disease-specific mortality and quality of life, as the clinical significance of a small focus of well-differentiated prostate cancer on biopsy is unclear. The expected clinical significance of the discovered tumours was estimated using an arbitrary model combining volume, grade, and stage characteristics. Of 34 patients who had a small focus (< 3 mm on a single biopsy core) of well-differentiated carcinoma on biopsy, only 18 (53%) were found to have minimal carcinoma (a small focus of well-differentiated carcinoma) at radical prostatectomy, while 16 (47%) had moderately advanced or advanced carcinoma at radical prostatectomy. The preoperative prediction of minimal carcinoma improved when the amount of cancer in the sextant biopsy set was combined with the preoperative serum prostate specific antigen (PSA) level. Of 12 patients with a small focus of well-differentiated carcinoma on biopsy and a serum PSA of < 4 ng/mL, 11 had minimal carcinoma at radical prostatectomy, while there was minimal carcinoma in only seven of 22 (32%) patients with a small focus of well-differentiated carcinoma on biopsy and a serum PSA of > or = 4 ng/mL. The predictive value of a small focus of well-differentiated cancer on systematic sextant biopsy for a small well-differentiated tumour in the prostate is limited. The predictive value improves when serum PSA levels are considered concurrently, but is still considered insufficient to support a base for selecting therapy for the individual patient.


(μ-2,2',2'',2'''-{[Pyrazine-2,3,5,6-tetra-yltetra-kis(methyl-ene)]tetra-kis(sulfanedi-yl)}tetra-acetato)bis-[aqua-nickel(II)] hepta-hydrate.
Reaction of the ligand 2,2',2'',2'''-{[pyrazine-2,3,5,6-tetra-yltetra-kis-(methyl-ene)]tetra-kis-(sulfanedi-yl)}tetra-acetic acid (H4L1), with NiCl2 leads to the formation of a binuclear complex, (μ-2,2',2'',2'''-{[pyrazine-2,3,5,6-tetra-yltetra-kis-(methyl-ene)]tetra-kis-(sulfanedi-yl)}tetra-acetato-κ5 O,S,N 1,S',O':κ5 O'',S'',N 4,S''',O''')bis[aqua-nickel(II)] hepta-hydrate, {[Ni2(C16H16N2O8S4)(H2O)2]·7H2O} (I). It crystallizes with two half mol-ecules in the asymmetric unit. The complete mol-ecules are generated by inversion symmetry, with the center of the pyrazine rings being located at crystallographic centres of inversion. The ligand coordinates two NiII ions in a bis-penta-dentate manner and the sixfold coordination sphere of each nickel(II) atom (NiS2O3N) is completed by a water mol-ecule. The complex crystallized as a hepta-hydrate. The binuclear complexes are linked by Owater-H⋯Ocarbon-yl hydrogen bonds, forming layers parallel to the (101) plane. This layered structure is additionally stabilized by weak C-H⋯O hydrogen bonds. Further O-H⋯O hydrogen bonds involving binuclear complexes and solvent water mol-ecules, together with weak C-H⋯S hydrogen bonds, link the layers to form a supra-molecular framework.


On the Behavior of Different PCMs in a Hot Water Storage Tank against Thermal Demands.
Advantages, such as thermal storage improvement, are found when using PCMs (Phase Change Materials) in storage tanks. The inclusion of three different types of materials in a 60 l test tank is studied. Two test methodologies were developed, and four tests were performed following each methodology. A thermal analysis is performed to check the thermal properties of each PCM. The distributions of the water temperatures inside the test tanks are evaluated by installing four Pt-100 sensors at different heights. A temperature recovery is observed after exposing the test tank to an energy demand. An energetic analysis that takes into account the energy due to the water temperature, the energy due to the PCM and the thermal loss to the ambient environment is also presented. The percentage of each PCM that remains in the liquid state after the energy demand is obtained.


Conversion of atrial fibrillation to sinus rhythm by acute intravenous procainamide infusion.
We evaluated the efficacy of an intravenous infusion of procainamide in 26 consecutive candidates for cardioversion of atrial fibrillation. Procainamide was administered at a rate of 15 to 20 mg/min up to a maximum of 1000 mg. The treatment was considered effective only if cardioversion occurred during the procainamide infusion. Conversion to sinus rhythm occurred in 15 patients. Converters had a significantly shorter mean duration of atrial fibrillation (6 +/- 7 days, mean +/- S.D.) compared to nonconverters (79 +/- 88 days) (p less than 0.01). The mean left atrial size of converters (4.3 +/- 0.6 cm) did not differ significantly from that of nonconverters (4.7 +/- 0.9 cm). The dose of procainamide required for cardioversion ranged from 3.6 to 16.4 mg/kg. Two patients developed nonsustained ventricular tachycardia, and there was one episode of bifascicular block during the infusion. Intravenous procainamide is an effective form of therapy for conversion of atrial fibrillation of new onset.


Diabetic retinopathy and microalbuminuria can predict macroalbuminuria and renal function decline in Japanese type 2 diabetic patients: Japan Diabetes Complications Study.
To examine the interactive relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in type 2 diabetic patients and to elucidate the role of DR and microalbuminuria on the onset of macroalbuminuria and renal function decline. We explored the effects of DR and microalbuminuria on the progression of DN from normoalbuminuria and low microalbuminuria (<150 mg/gCr) to macroalbuminuria or renal function decline in the Japan Diabetes Complications Study (JDCS), which is a nationwide randomized controlled study of type 2 diabetic patients focusing on lifestyle modification. Patients were divided into four groups according to presence or absence of DR and MA: normoalbuminuria without DR [NA(DR-)] (n = 773), normoalbuminuria with DR [NA(DR+)] (n = 279), microalbuminuria without DR [MA(DR-)] (n = 277), and microalbuminuria with DR [MA(DR+)] (n = 146). Basal urinary albumin-to-creatinine ratio and DR status were determined at baseline and followed for a median of 8.0 years. Annual incidence rates of macroalbuminuria were 1.6/1,000 person-years (9 incidences), 3.9/1,000 person-years (8 incidences), 18.4/1,000 person-years (34 incidences), and 22.1/1,000 person-years (22 incidences) in the four groups, respectively. Multivariate-adjusted hazard ratios of the progression to macroalbuminuria were 2.48 (95% CI 0.94-6.50; P = 0.07), 10.40 (4.91-22.03; P < 0.01), and 11.55 (5.24-25.45; P < 0.01) in NA(DR+), MA(DR-), and MA(DR+), respectively, in comparison with NA(DR-). Decline in estimated glomerular filtration rate (GFR) per year was two to three times faster in MA(DR+) (-1.92 mL/min/1.73 m(2)/year) than in the other groups. In normo- and low microalbuminuric Japanese type 2 diabetic patients, presence of microalbuminuria at baseline was associated with higher risk of macroalbuminuria in 8 years. Patients with microalbuminuria and DR showed the fastest GFR decline. Albuminuria and DR should be considered as risk factors of renal prognosis in type 2 diabetic patients. An open sharing of information will benefit both ophthalmologists and diabetologists.


Fracture of an uncemented tantalum patellar component.
A 62-year-old man presented with the acute, atraumatic onset of pain 3 years after uncemented right total knee arthroplasty. He complained of new mechanical locking with the knee held in extension on examination and unable to flex the knee. On the plain radiographs, the patellar component peg was fractured and the plate was dislocated. The knee was immobilized, and revision to a cemented 3-peg component was performed. Fracture of a single-peg, tantalum-backed uncemented patellar component has not been described. Clinical suspicion for this should be given in the setting of acute locking. We recommend revision with a cemented polyethylene component.


Codon optimization and expression of irisin in Pichia pastoris GS115.
Irisin is a novel hormone which is related to many metabolic diseases. In order to illuminate the function and therapeutic effect of irisin, gaining active irisin is necessary. In this work, a codon-optimized irisin gene was designed according to Pichia pastoris synonymous codon usage bias and cloned into the pPIC9K expression vector. Sequencing result indicating that the sequence of irisin was consistent with the modified irisin and the irisin was in frame with α-factor secretion signal ATG. The plasmid pPIC9K-irisin was transformed into GS115 P. pastoris cells through electroporation. The positive transformants were screened on MD medium and analyzed by PCR. Five recombinant GS115/pPIC9K-irisin strains were obtained, but only one strain expressed irisin successfully. SDS-PAGE and Western blot were used to assess the expression level and purity of irisin. The irisin was also simply purified and the effect of pH value, methanol concentration and induction time on the production of irisin was investigated. The results showed that the best conditions of irisin expression were as follows: pH 6.0, 2.0% methanol and induction for 96 h. This work laid the basis for further investigation into the therapeutic and pharmacological effects of irisin, as well as development of irisin-based therapy.


GranatumX: A Community-engaging, Modularized, and Flexible Webtool for Single-cell Data Analysis.
We present GranatumX, a next-generation software environment for single-cell RNA sequencing (scRNA-seq) data analysis. GranatumX is inspired by the interactive webtool Granatum. GranatumX enables biologists to access the latest scRNA-seq bioinformatics methods in a web-based graphical environment. It also offers software developers the opportunity to rapidly promote their own tools with others in customizable pipelines. The architecture of GranatumX allows for easy inclusion of plugin modules, named Gboxes, which wrap around bioinformatics tools written in various programming languages and on various platforms. GranatumX can be run on the cloud or private servers and generate reproducible results. It is a community-engaging, flexible, and evolving software ecosystem for scRNA-seq analysis, connecting developers with bench scientists. GranatumX is freely accessible at http://garmiregroup.org/granatumx/app.


The intracellular trafficking pathway of transferrin.
Transferrin (Tf) is an iron-binding protein that facilitates iron-uptake in cells. Iron-loaded Tf first binds to the Tf receptor (TfR) and enters the cell through clathrin-mediated endocytosis. Inside the cell, Tf is trafficked to early endosomes, delivers iron, and then is subsequently directed to recycling endosomes to be taken back to the cell surface. We aim to review the various methods and techniques that researchers have employed for elucidating the Tf trafficking pathway and the cell-machinery components involved. These experimental methods can be categorized as microscopy, radioactivity, and surface plasmon resonance (SPR). Qualitative experiments, such as total internal reflectance fluorescence (TIRF), electron, laser-scanning confocal, and spinning-disk confocal microscopy, have been utilized to determine the roles of key components in the Tf trafficking pathway. These techniques allow temporal resolution and are useful for imaging Tf endocytosis and recycling, which occur on the order of seconds to minutes. Additionally, radiolabeling and SPR methods, when combined with mathematical modeling, have enabled researchers to estimate quantitative kinetic parameters and equilibrium constants associated with Tf binding and trafficking. Both qualitative and quantitative data can be used to analyze the Tf trafficking pathway. The valuable information that is obtained about the Tf trafficking pathway can then be combined with mathematical models to identify design criteria to improve the ability of Tf to deliver anticancer drugs. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders.


Re-induction with modified CLAG regimen in relapsed or refractory acute myeloid leukemia in children bridging to allogeneic hematopoietic stem cell transplantation.
The prognosis for relapsed or refractory acute myeloid leukemia (RR-AML) in children is poor, and the preferred salvage chemotherapy is unclear. One regimen is cladribine, cytarabine, and granulocyte-colony stimulating factor (CLAG), but little is known about its efficacy and safety in children with RR-AML. We enrolled RR-AML patients aged 0-18 years who received modified CLAG regimen for re-induction between July 1, 2015 and April 1, 2018, or conventional induction between August 1, 2011 and April 1, 2018. Patients were followed up to March 31, 2019. Patients underwent allogeneic stem cell transplantation (allo-SCT) or chemotherapy after the induction of complete remission (CR). The CR rate, survival, and side effects were analyzed. The CR rate for induction was 66.7% after one cycle and 75.0% after two cycles of the CLAG regimen in 12 children. The nine children who received conventional chemotherapy had a CR rate of 22.2% after one cycle and 33.3% after two cycles (P = 0.087 vs. CLAG). The 3-year event-free survival (EFS) of the CLAG group and the conventional treatment group were 44.4 ± 15.7% and 22.2 ± 13.8% (P = 0.112). The 3-year overall survival of the two groups were 59.5 ± 16.2% and 22.2% ± 13.8% (P = 0.057). The 3-year EFS for allo-SCT and chemotherapy after CLAG regimen was 66.7 ± 19.2% and 25.0 ± 21.7% (P = 0.015). A single case of chemotherapy-related death was recorded. Our data suggest a promising CR rate using CLAG salvage treatment in childhood RR-AML. Allo-SCT after CR may improve the long-term outcome in these patients.


Mucoepidermoid Carcinoma of Parotid as a Second Malignancy in Acute Lymphoblastic Leukemia.
Improved survival seen in Acute Lymphoblastic Leukemia (ALL) cases has led to increased reports of second malignant neoplasms. A 12-year-old female treated for ALL using UK ALL XI protocol nine years back presented with progressively increasing pre-auricular swelling. Investigations revealed it to be a Mucoepidermoid carcinoma. Mucoepidermoid carcinoma should be a differential in any parotid swelling of treated case of pediatric ALL.


Nursing experiences in antimicrobial optimisation in the intensive care unit: A convergent analysis of a national survey.
Recent evidence highlights the need for an interdisciplinary approach to antimicrobial stewardship (AMS). Nursing involvement in optimising antimicrobials in the intensive care unit (ICU) remains understudied. The objective of this study was to explore nurses' perceptions and experiences of antimicrobial optimisation or stewardship in ICUs in Australia. An anonymous web-based survey was deployed nationally in early 2021 through two ICU nursing networks. Associations between survey responses were analysed descriptively and by using nonparametric tests (with statistical significance established at p ≤ 0.05). Free-text survey responses underwent qualitative thematic analysis. Interpretation and reporting of quantitative and qualitative data were integrated. A total of 226 ICU nurses completed the survey. The majority (197/226; 87%) responded that lack of education limits engagement in AMS. Only 13% (30/226) reported the presence of AMS education and training for nurses in their ICUs. Only about half (108/226; 48%) of the nurses were confident to question prescribers when they considered that the antimicrobial prescribed was unnecessary, with nurses in senior roles more likely to do so than nurses providing bedside care (p < 0.05). Gaps in education (including unfamiliarity with AMS roles), noninclusive antimicrobial discussions, moral distress, and potential workload burden were seen as potential barriers/challenges to engagement. The multifactorial barriers identified that inhibit nurses from performing AMS tasks could be addressed by strengthening interprofessional education at all levels and by applying practical AMS interventions that are inclusive for nursing participation. A purposeful culture change that fosters psychological safety and collaborative practice is paramount to supporting nurses in these roles.


Chimeric design of pyrrolysyl-tRNA synthetase/tRNA pairs and canonical synthetase/tRNA pairs for genetic code expansion.
An orthogonal aminoacyl-tRNA synthetase/tRNA pair is a crucial prerequisite for site-specific incorporation of unnatural amino acids. Due to its high codon suppression efficiency and full orthogonality, the pyrrolysyl-tRNA synthetase/pyrrolysyl-tRNA pair is currently the ideal system for genetic code expansion in both eukaryotes and prokaryotes. There is a pressing need to discover or engineer other fully orthogonal translation systems. Here, through rational chimera design by transplanting the key orthogonal components from the pyrrolysine system, we create multiple chimeric tRNA synthetase/chimeric tRNA pairs, including chimera histidine, phenylalanine, and alanine systems. We further show that these engineered chimeric systems are orthogonal and highly efficient with comparable flexibility to the pyrrolysine system. Besides, the chimera phenylalanine system can incorporate a group of phenylalanine, tyrosine, and tryptophan analogues efficiently in both E. coli and mammalian cells. These aromatic amino acids analogous exhibit unique properties and characteristics, including fluorescence, post-translation modification.


Exploration of the Mechanism Underlying the Association of Incident Microinfarct and Motor Deficit: A Preliminary Functional MRI Study.
Cerebral microinfarcts (CMIs) might cause measurable disruption to brain connections and are associated with cognitive decline, but the association between CMIs and motor impairment is still unclear. To assess the CMIs effect on motor function in vivo and explore the potential neuropathological mechanism based on graph-based network method. We identified 133 non-demented middle-aged and elderly participants who underwent MRI scanning, cognitive, and motor assessment. The short physical performance battery (SPPB) assessed motor function, including balance, walking speed, and chair stand. We grouped participants into 34 incident CMIs carriers and 99 non-CMIs carriers as controls, depending on diffusion-weighted imaging. Then we assessed the independent CMIs effects on motor function and explored neural mechanisms of CMIs on motor impairment via mapping of degree centrality (DC) and eigenvector centrality (EC). CMIs carriers had worse motor function than non-carriers. Linear regression analyses showed that CMIs independently contributed to motor function. CMIs carriers had decreased EC in the precuneus, while increased DC and EC in the middle temporal gyrus and increased DC in the inferior frontal gyrus compared to controls (p < 0.05, corrected). Correlation analyses showed that EC of precuneus was related to SPPB (r = 0.25) and balance (r = 0.27); however, DC (r = -0.25) and EC (r = -0.25) of middle temporal gyrus was related with SPPB in all participants (p < 0.05, corrected). CMIs represent an independent risk factor for motor dysfunction. The relationship between CMIs and motor function may be attributed to suppression of functional hub region and compensatory activation of motor-related regions.


Discovery of novel aminosaccharide-based sulfonamide derivatives as potential carbonic anhydrase II inhibitors.
In this paper, a new class of novel sulfonamides incorporating aminosaccharide tails were designed and synthesized based on the sugar-tail approach. Then, all the novel compounds were evaluated for their inhibitory activities against three carbonic anhydrase (CA, EC 22.214.171.124) isoenzymes (hCA I, hCA II and hCA IX). Interestingly, effective inhibition of these three CA isoforms were observed, especially the glaucoma associated isoform hCA II. It is worth noting that these glycoconjugated sulfonamide derivatives also showed better CA inhibitory effects compared to the initial segment carzenide. Among them, compound 8d was the most effective inhibitor with IC50 of 60 nM against hCA II. Subsequent physicochemical properties studies showed that all compounds have good water solubility and neutral pH values in solutions. And these important physicochemical properties make target compounds acquire obvious advantages in the preparation of topical and nonirritating antiglaucoma drugs. Moreover, the target compounds showed lower corneal cytotoxicity than acetazolamide (AAZ) and good metabolic stability in vitro. In addition, molecular docking studies confirmed the interactions between aminosaccharide fragment and hydrophilic subpocket of hCA II active site were crucial for the enhanced CA inhibitory activity. Taken together, these results suggested 8d would be a promising lead compound for the development of topical antiglaucoma CAIs.


Intestinal occlusion by gynecological cancers treated by percutaneous endoscopic gastrostomy and lanreotide: an Aviano National Cancer Institute experience.
The Commentary reports on our experience in Centro di Riferimento Oncologico IRCCS Aviano about the integrated and combined treatment with percutaneous endoscopic gastrostomy and lanreotide in patients with bowel obstructions by ovarian cancer and peritoneal carcinomatosis. We treated patients with gynecological cancers and bowel obstruction with percutaneous endoscopic gastrostomy and, when patients were partially responsive, with lanreotide. We registered a constant overall benefit for the quality of life and for the control of symptoms, which is very important especially during the home care follow-up of terminal patients.


Raman spectroscopy accurately classifies burn severity in an ex vivo model.
Accurate classification of burn severities is of vital importance for proper burn treatments. A recent article reported that using the combination of Raman spectroscopy and optical coherence tomography (OCT) classifies different degrees of burns with an overall accuracy of 85% [1]. In this study, we demonstrate the feasibility of using Raman spectroscopy alone to classify burn severities on ex vivo porcine skin tissues. To create different levels of burns, four burn conditions were designed: (i) 200°F for 10s, (ii) 200°F for 30s, (iii) 450°F for 10s and (iv) 450°F for 30s. Raman spectra from 500-2000cm-1 were collected from samples of the four burn conditions as well as the unburnt condition. Classifications were performed using kernel support vector machine (KSVM) with features extracted from the spectra by principal component analysis (PCA), and partial least-square (PLS). Both techniques yielded an average accuracy of approximately 92%, which was independently evaluated by leave-one-out cross-validation (LOOCV). By comparison, PCA+KSVM provides higher accuracy in classifying severe burns, while PLS performs better in classifying mild burns. Variable importance in the projection (VIP) scores from the PLS models reveal that proteins and lipids, amide III, and amino acids are important indicators in separating unburnt or mild burns (200°F), while amide I has a more pronounced impact in separating severe burns (450°F).


With a little help from my friends: adopting a P-E fit perspective in understanding the value of organizational learning climate for sustainable employability.
The objective of our study was to investigate how organizational learning climate (measured as developmental opportunities and team support for learning), career commitment, and age are related to employees' self-perceived employability, vitality and work ability (e.g., their sustainable employability). Our study adopted a P-E fit perspective building upon the notion that sustainable employability is a function of both the person (P) and the environment (E) and tests a three-way interaction between organizational learning climate, career commitment, and age. In total, 211 members of the support staff of a Dutch university completed a survey. Hierarchical stepwise regression analysis was used to analyze the data. Only one of the two dimensions of organizational learning climate that we measured, namely the developmental opportunities, appeared to be associated with all indicators of sustainable employability. Career commitment only had a direct positive relationship with vitality. Age was negatively related to self-perceived employability and to work ability, but not to vitality. The relationship between developmental opportunities and vitality was negatively influenced by career commitment (a negative two-way interaction effect), while a positive three-way interaction effect was found between career commitment, age, and development opportunities, and with self-perceived employability as the outcome. Our findings confirmed the relevance of adopting a P-E fit perspective on sustainable employability, and of considering the possible role of age in this. It requires more detailed analyses in future research to unravel the role of age in the shared responsibility for sustainable employability. In practice, the results of our study imply that organizations should provide all employees with a working context that facilitates learning, however, with a special focus on older employees, for whom it is a particular challenge to protect their sustainable employability, possibly due to age-related stereotyping. Our study adopted a P-E fit perspective on sustainable employability and examined the association between organizational learning climate and all three components of sustainable employability: self-perceived employability, vitality and work ability. Moreover, it investigated whether and how the employee's career commitment and age influence this relationship.


Saccadic eye movements are impaired in Duchenne muscular dystrophy.
Extraocular muscles are generally considered to be spared in Duchenne Muscular Dystrophy (DMD). However, this assumption is based mainly on clinical observations, as systematic eye movement recordings have been performed in a very limited number of cases. Our goal was to analyze several saccade parameters in a higher number of cases, in order to reveal a possible ocular-motor impairment in DMD. Data were collected from a population of 9 subjects with DMD and 9 healthy male subjects of comparable age as controls. We used the electrooculographic (EOG) technique coupled with advanced digital signal processing; saccade duration, amplitude, mean velocity, peak velocity and K factor (ratio mean/peak velocity) were measured. The DMD group showed saccades with significantly longer duration and lower velocity, with respect to controls; these differences were accounted for mainly by the largest movements, whereas there were no significant differences at the smallest eccentricity tested (3 deg). Neither amplitude nor K factor were significantly different from controls for any of the eccentricities tested. To our knowledge. this is the first study to suggest significant impairment of eye movements in Duchenne muscular dystrophy.


Screening for physical stability of a Pseudomonas amylase using self-interaction chromatography.
Formulation development is an integral step in the successful commercialization of protein-based products in both the biotechnology and pharmaceutical industries. As the number of these protein formulations increases, so does the need for innovative approaches to characterize physical and chemical product stability. In this study, the osmotic second virial coefficient (B) of a commercial amylase was evaluated by self-interaction chromatography (SIC) as an innovative approach to characterize physical protein stability. B was measured as a function of pH and several common formulation additives (cosolvents), including sodium chloride, sucrose, and sorbitol. Cosolvent- and pH-induced physical stabilization of amylase is discussed in terms of positive shifts in B. Liquid chromatographic measurements of total soluble amylase and enzymatic activity measurements correlated qualitatively with trends in B except near the pI of amylase, where physical stability was minimal.