The multidimensional prognostic index (MPI) predicts long-term mortality in old type 2 diabetes mellitus patients: a 13-year follow-up study.
The Multidimensional Prognostic Index (MPI) is a tool capable of holistically frame older patients in different settings and affected by different pathologies, establishing a risk of adverse events. Among them, type 2 diabetes mellitus (T2DM), a common metabolic disease in the elderly, is responsible for complications and deaths. Few previous works have focused specifically on MPI and DM, and none have followed up the patients for more than 3 years. The aim of the present study is to analyze MPI accuracy in predicting mortality in a cohort of T2DM patients followed-up for 13 years. The enrolled subjects were evaluated with MPI, identifying three levels of risk: MPI1 (low risk, 0.0-0.33), MPI2 (moderate risk, 0.34-0.66), and MPI3 (severe risk, 0.67-1.0), and with glycated hemoglobin, and years since T2DM diagnosis. One hundred and seven patients met the inclusion criteria. MPI3 was excluded by further analysis since it was made up of only three patients. Overall, cognitive performances, autonomies in daily living, nutritional status, risk of pressure injuries, comorbidities, and taken drugs were better (p ≤ 0.0077) in MPI1 than MPI2; moreover, the story of T2DM was shorter (p = 0.0026). Cox model showed an overall 13-year survival of 51.9%, and survival rates were significantly smaller in MPI2 (HR: 4.71, p = 0.0007). Finally, increased age (HR: 1.15), poorer cognitive abilities (HR: 1.26), vascular (HR: 2.15), and kidney (HR: 2.17) diseases were independently associated with death. Our results prove that MPI predicts short-, mid-, and even long-term mortality in T2DM patients, whose death seems to be related to age and cognitive status, and even more to vascular and kidney diseases.


Psychiatric disorders in clinical genetics I: Addressing family histories of psychiatric illness.
This is the first article of a two-part professional development series addressing genetic counseling for personal and family histories of psychiatric disorders. It is based on an Educational Breakout Session presented by the Psychiatric Special Interest Group of the National Society of Genetic Counselors at the 2006 Annual Education Conference. This article examines issues that arise in addressing family histories of psychiatric illness, while the second article in the series considers the generation and provision of individualized recurrence risks for psychiatric disorders. In this article we discuss the importance of managing uncertainty for affected individuals and their close family members who have been referred to genetics for a number of different indications. We then use four simulated cases to make recommendations about the scope and timing of discussions related to the psychiatric family history.


Substance use as a risk factor for bipolar disorder: A systematic review.
Detecting substance use as a predictor of bipolar disorder (BD) is important for clinicians to perform accurate and early diagnosis, as well as better manage the treatment of individuals with BD. The aim of this systematic review was to describe whether substance use is a predictor of BD. A literature search was conducted using the following databases: PubMed, PsycINFO, and Embase. All eligible studies published up to February 9, 2021 were included. This systematic review included 22 studies. We found that 66.7% of the studies assessing overall substance use found that overall substance use was a risk factor for BD. Regarding the specific substances assessed, cannabis use was described as a risk factor for BD in 55.6% of the studies, nonmedical use of prescription medications was a risk factor for BD in 50% of the studies, nicotine was found as a risk factor for BD in 50% of the studies, and alcohol use was described as a risk factor for BD in 42.9% of the studies assessing it. Only one study assessed whether cocaine use was a risk factor for BD and found a significant association. Interestingly, some studies suggested that the greater frequency of cannabis use was associated with greater risk to develop BD or hypomanic/manic symptoms. In conclusion, there is evidence supporting that substance use is a risk factor for BD. Importantly, when assessing the risk factors for BD related to psychoactive substance use, special attention should be given for the frequency of cannabis use.


Determination of the anticancer drug, 15-deoxyspergualin, in plasma ultrafiltrate by liquid chromatography and precolumn derivatization with naphthalene-2,3-dicarboxaldehyde/cyanide.
An alternative analytical method for the determination of 15-deoxyspergualin in plasma is described. The drug was initially separated from the plasma matrix by ultrafiltration and a precolumn derivatization step was performed with naphthalene-2,3-dicarboxaldehyde in the presence of sodium cyanide to yield the fluorescent N-substituted 1-cyanobenz[f]isoindole (CBI) derivative. The CBI derivative was separated and quantitated by reversed-phase chromatography using an ODS Hypersil column and mobile phase of KH2PO4 (0.1 M)-H3PO4-acetonitrile (48:0.8:52, v/v/v) containing dodecyl sodium sulphate (18 mM). The excitation and emission wavelengths for the fluorescence detector were 420 and 490 nm, respectively. The peak height was linearly related to drug concentration over the range from 5 ng ml-1 (10 nM) to 10 micrograms ml-1 (20 microM) in phosphate buffer (0.1 M, pH 7.0), spiked plasma ultrafiltrate and ultrafiltrate obtained from spiked plasma. Measurements could be made with a relative standard deviation of 4.5% or less in phosphate buffer (0.1 M, pH 7.0), 6.1% or less in spiked plasma ultrafiltrate and 12% or less in ultrafiltrate obtained from spiked plasma.


Fluoride inhibition of inorganic pyrophosphatase. IV. Evidence for metal participation in the active center and a four-site model of metal effect on catalysis.
Atomic spectroscopy of native yeast inorganic pyrophosphatase (pyrophosphate phosphohydrolase, EC 184.108.40.206) after gel filtration showed that it only binds activating Mg2% in an easily dissociable manner. Formation of a covalent intermediate between the enzyme and an entire substrate molecular in the presence of fluoride, however, dramatically strengthened the binding of two Mg2+ per subunit and eliminated at neutral pH the effect of added metals on protein fluorescence but not on the absorption spectrum, suggesting that different mental binding sites influence the two spectra. This conclusion was confirmed by spectra studied on native enzyme. A third, low-affinity site for Mg2+ was found on the enzyme pH greater than 8. A model of enzyme-substrate-metal interactions was proposed, according to which the fluorescence-controlling site belongs to the active center and substrate can only be bound to it as a 1 : 1 complex with metals.


Evolution of regional oxygen saturation in the peri-operative of thoracic surgery and its relationship with central venous saturation.
To study the relationship between the values of SvcO2 and SrcO2 in lung resection with one lung ventilation (OLV) and changes in these variables and mean arterial pressure (MAP) and arterial oxygen saturation (SpO2) during the perioperative period. Prospective, observational study of 25 patients in whom pulmonary resection was performed with OLV. The values of MAP, SpO2, SvO2, and SrcO2 were recorded at 6 different times: 1)baseline; 2)double-lung ventilation before the OLV (VBP1); 3)during OLV; 4)after double-lung ventilation (VBP2); 5)30minutes after surgery, and 6)6hours after surgery. The SrcO2 showed a significant increase from baseline to starting ventilation (65.72±9.05% vs 70.44±7.24%; P<.01). There were no significant changes in their values at the different intraoperative times. Post-operatively, as in the case of the SvcO2, a significant decrease (P<.001) of its value compared with the previous value was observed. SrcO2 showed a significant increase after induction of anaesthesia and initiation of mechanical ventilation compared to baseline, and a significant decrease at the end of surgery after extubation in the immediate postoperative period. Being a tissue monitoring, non-invasive technique and with continuous values it can alert the clinician of changes in the ratio of oxygen consumption (VO2) to oxygen delivery (DO2) at times of greatest risk, such as OLV, extubation, and the early postoperative period.


Comparable outcomes among unmanipulated haploidentical, matched unrelated, and matched sibling donors in BU-based myeloablative hematopoietic stem cell transplantation for intermediate and adverse risk acute myeloid leukemia in complete remission: a single-center study.
There are a limited number of studies comparing outcomes of busulfan (BU)-based myeloablative hematopoietic stem cell transplantation using unmanipulated haploidentical donors (HIDs), HLA-matched unrelated donors (MUDs), and HLA-matched sibling related donors (MSDs) in acute myeloid leukemia (AML) patients with complete remission (CR) status. With this background, we compared outcomes among 377 cases of CR following consecutive HID-HSCT for AML (CR) to 86 MUD and 92 MSD-HSCT cases. All patients received BU-based myeloablative conditioning and an unmanipulated graft within the same period. The median patient age was 23 years (range 1.1 to 65 years), and 230 patients (41.4%) were under age18. Among the 555 patients, 432 (77.8%) were of intermediate cytogenetic risk and 123 (22.2%) were of adverse risk. A total of 113 patients (20.5%) had FLT3-ITD+ AML, 425 patients (76.6%) were in first complete remission (CR1) post-transplant, and 130 (23.4%) patients were in second CR (CR2). GVHD prophylaxis included mycophenolate mofetil (MMF), cyclosporine-A (CSA) with short-term methotrexate (MTX) for HID, and MUD-HSCT. MMF is not used for MSD-HSCT. The median survival follow-up time was 42 months (range 18-91 months). The 3-year leukemia-free survival (LFS) among the HID, MUD, and MSD cohorts was 73.8% ± 4.8%, 66.4% ± 8.5%, 74.5% ± 2.4%, respectively (P = 0.637). Three-year overall survival (OS) was 74.9% ± 2.4%, 81.8% ± 4.3%, and 77.5% ± 4.5% among the HID, MUD, and MSD cohorts, respectively (P = 0.322). There were no difference among the relapse rate among the HID, MUD, and MSD donor cohorts (14.3% ± 4.0% vs 20.3% ± 6.4% vs 14.5% ± 2.2, respectively; P = 0.851) or the non-relapse mortality (NRM) (12.3% ± 3.5% vs 9.5% ± 3.2% vs 14.0% ± 1.8%, respectively; P = 0.441). Multivariate analyses showed that MRD-positive pre-HSCT was the only risk factor associated with a lower OS and LFS and higher risk of relapse among all 555 patients. Compared with the use of a MUD or MSD, an HID for HSCT had similar outcomes among AML patients with CR states who underwent an allo-HSCT with BU-based myeloablative conditioning. MFC-MRD-positive pre-HSCT was an independent negative factor impact on outcomes for AML patients in CR. We conclude that for AML patients who do not have a MSD or if an urgent transplant is required, HSCT from an HID is a valid option.


Unique properties of Plasmodium falciparum porphobilinogen deaminase.
The hybrid pathway for heme biosynthesis in the malarial parasite proposes the involvement of parasite genome-coded enzymes of the pathway localized in different compartments such as apicoplast, mitochondria, and cytosol. However, knowledge on the functionality and localization of many of these enzymes is not available. In this study, we demonstrate that porphobilinogen deaminase encoded by the Plasmodium falciparum genome (PfPBGD) has several unique biochemical properties. Studies carried out with PfPBGD partially purified from parasite membrane fraction, as well as recombinant PfPBGD lacking N-terminal 64 amino acids expressed and purified from Escherichia coli cells (DeltaPfPBGD), indicate that both the proteins are catalytically active. Surprisingly, PfPBGD catalyzes the conversion of porphobilinogen to uroporphyrinogen III (UROGEN III), indicating that it also possesses uroporphyrinogen III synthase (UROS) activity, catalyzing the next step. This obviates the necessity to have a separate gene for UROS that has not been so far annotated in the parasite genome. Interestingly, DeltaPfP-BGD gives rise to UROGEN III even after heat treatment, although UROS from other sources is known to be heat-sensitive. Based on the analysis of active site residues, a DeltaPfPBGDL116K mutant enzyme was created and the specific activity of this recombinant mutant enzyme is 5-fold higher than DeltaPfPBGD. More interestingly, DeltaPfPBGDL116K catalyzes the formation of uroporphyrinogen I (UROGEN I) in addition to UROGEN III, indicating that with increased PBGD activity the UROS activity of PBGD may perhaps become rate-limiting, thus leading to non-enzymatic cyclization of preuroporphyrinogen to UROGEN I. PfPBGD is localized to the apicoplast and is catalytically very inefficient compared with the host red cell enzyme.


Hemostatic abnormalities in nephrotic syndrome.
Nephrotic syndrome is often associated with a hypercoagulable state and thrombotic complications. Thrombosis may be due to a number of abnormalities in blood, including AT III deficiency, increased concentrations of fibrinogen, factors V and VIII, and platelet hyperaggregability. The therapeutic approach to thrombosis in nephrotic syndrome is the use of anticoagulants as a preventive measure or an attempt at thrombolysis with streptokinase, urokinase, or stanozolol.


Case report: benefits of quantitative polymerase chain reaction in the clinical management of herpes simplex virus 1 infection with prominent hepatitis and unusual secondary progression.
Herpes simplex virus (HSV) infection is rarely considered in the differential diagnosis of severe acute hepatitis and disseminated infection in immunocompetent adults. A case of disseminated HSV-1 infection in an 82-year-old woman initially presenting with neurological problems, signs of meningitis and prominent hepatitis was investigated. Initial diagnosis, monitoring, and follow-up were based on the application of molecular methods to cerebrospinal fluid, serum, and liver tissue samples from this patient. Following an initial full recovery, the patient presented delayed intracerebral haemorrhage and diffuse arthralgia. This atypical case, with delayed secondary progression, highlights the wide range of clinical features of HSV infection and the benefits of monitoring viral load by quantitative real-time polymerase chain reaction (PCR) during patient management.


Intracellular recordings from Deiters' neurons in response to saccular and oculomotor nucleus stimulations.
2 populations of cells were found in the Deiters' nucleus responsive to direct electrical stimulation of the ipsilateral saccule. Only those Deiters' neurons activated monosynaptically from the saccule could be driven antidromically from the oculomotor nucleus. Such an intracellular study provides strong evidence for a tri-neuronal arc in the sacculo-ocular reflex for vertical eye movements.


Parental Autonomy Support in the Context of Parent-Child Negotiation for Children's Independent Mobility: 'I Always Feel Safer With My Parents' to 'Boom! Bust Down Those Walls!'
Autonomy - acting volitionally with a sense of choice - is a crucial right for children. Given parents' pivotal position in their child's autonomy development, we examined how parental autonomy support and children's need for autonomy were negotiated and manifested in the context of children's independent mobility - children's ability to play, walk or cycle unsupervised. We interviewed 105 Canadian children between 10 and 13-years-old and their parents (n = 135) to examine child-parents' negotiation patterns as to children's independent mobility. Four patterns emerged, varying on parental autonomy support and children's need/motivation for independent mobility: (1) child/parent dyad wants to increase independent mobility; (2) child only wants to increase independent mobility while parents do not; (3) child does not want to increase independent mobility while parents do; and (4) child/parent dyad does not want to increase independent mobility. Findings illuminate the importance of recognizing children as active and capable agents of change.


Detection of Crimean-Congo hemorrhagic fever virus in ticks collected from South Russia.
Crimean-Congo hemorrhagic fever (CCHF) has a central role among tick-borne infections in southern Russia. Multiple cases of disease are recorded annually in most regions with the СCHF foci; moreover, an expansion of the geographic range of the disease has been noted. Since 1999, more than 2300 people have fallen ill in Russia. Ticks are the main vectors and reservoirs of the Crimean-Congo hemorrhagic fever virus (CCHFV). As it is currently known, CCHFV has been detected in ticks of 33 species. In the period 2012-2019 in the south of the European part of Russia, more than 38,000 ticks of 14 species of the genera Hyalomma, Rhipicephalus, Dermacentor, Haemaphysalis and Ixodes were tested for the presence of CCHFV. Among 4,188 tick pools studied, the virus was detected in 252 (6%). The main vector, as expected, is H. marginatum (81% of positive pools). The same species is the most numerous among the studied ticks (66%). Apart from H. marginatum, the virus was detected in the following species: H. scupense, R. rossicus, R. turanicus, R. bursa, R. annulatus, D. marginatus, Haem. punctata and Ixodes ricinus. Most of the positive results were obtained from ticks collected from vertebrate hosts. As for H. marginatum, R. rossicus, D. marginatus, and Haem. punctata, the virus was detected in questing unfed specimens collected from vegetation and soil surface, which indicates the participation of these ticks in the circulation of the virus.


Neutrophil myeloperoxidase: a simple, reproducible technique to determine activity.
Neutrophil MPO deficiency has been rarely documented. This is because of the low incidence of infections in these individuals and the lack of use of various screening techniques which would detect them. Using the Hemalog D, we have identified one completely deficient and 18 partially deficient subjects. These subjects were studied by staining their peripheral blood smears for MPO and grading the intensity of the stain on 100 consecutive neutrophils (MPO score) as well as by chemically quantifying the MPO activity. There is an excellent correlation between MPO score and quantitated MPO activity. The MPO score is a simple semiquantitative method to estimate MPO activity.


Diffuse granulomatous mesenteric disease caused by intravesical bacillus Calmette-Guérin instillation masquerading as peritoneal carcinomatosis.
Intravesical instillation with bacillus Calmette-Guérin is the most common therapy used for nonmuscle invasive bladder cancer in North America. Although local side effects are common, systemic side effects are rare when it is administered correctly. We present a case of diffuse mesenteric granulomatous disease resulting from inappropriate instillation of this agent. This patient was thought to have peritoneal carcinomatosis. One must be cognizant of the possibility when evaluating patients with similar findings and images after bacillus Calmette-Guérin therapy.


Strength: a relevant link to functional performance in the neurodegenerative disease of adrenomyeloneuropathy.
With progressive abnormalities in leg strength, tone, and sensation, adrenomyeloneuropathy (AMN) is a differential diagnosis for multiple sclerosis and hereditary spastic paraparesis. AMN pathology has been linked to weakness, making it a relevant model to evaluate the relationship between neurodegeneration and disability. Quantifying symptom severity in AMN is essential for treatment development in rehabilitative management. To identify deficits in body functions, activity, and participation of people with AMN and provide a practical framework for evaluating the severity of disability. Cohort analysis of 142 participants with AMN. of body functions (leg strength, vibration sensation, range of motion, and spasticity), activity (walk velocity, standing balance, Timed Up and Go, and Sit-to-Stand Time), and participation (6-Minute Walk) are evaluated. Regression analyses identify relationships between the measures. A staging framework (mild, moderate, and severe) reflects the continuum of disability. Finally, an analysis of variance/Kruskal-Wallis was used for between-stage and sex differences among the variables. Strength is the strongest correlate for the 5 measures of activity and participation. Staging based on weakness distinguishes 3 levels of severity along a continuum of disability. Differences between the sexes are more prevalent earlier in the continuum but show equally severe deficits in the last stage. In AMN, staging based on degrees of weakness provides a practical means to characterize the severity of common deficits in body functions as well as activity and participation at each stage, to direct the evaluation. Such information could help clinicians develop more effective rehabilitative techniques.


Fumonisin B1: Isolation from corn culture, and purification by high performance liquid chromatography.
A method is described to isolate fumonisin B1 (FB1) from corn cultured for 18 days at 25°C withFusarium moniliforme. Cultured corn was extracted with aqueous methanol and purified with XAD-2 column chromatography and high performance liquid chromatography (HPLC). About 450 mg of FB1 were obtained from 800g cultured corn. Its identity was established by fast-atom bombardment (FAB) mass spectrometry, and infrared spectrum and nuclear magnetic spectrum. Its purity was estimated to be 95% by gas chromatography/mass spectrometry (GC/MS).References.


Association of interleukin-13 SNP rs20541 (Arg>Gln) to allergic rhinitis in an Asian population of ethnic Chinese in Singapore.
In this study, we report our findings as we evaluated the association of IL-13 SNP rs20541 to AR as reported in the meta-analysis (Ying, X-J et al., April, Gene 2013) in an Asian population of 1322 ethnic Chinese recruited in Singapore well defined and characterized for allergic rhinitis. The SNP was significantly associated with AR at an odds ratio of 1.57 for the homozygous genotype comparisons indicating a strong risk for AR. This highlights the importance of this mutation in Asian populations for risk towards allergic phenotypes and also warrants further functional work to characterize the mechanism behind this genetic predisposition.


The use of inhaled antibiotic therapy in the treatment of ventilator-associated pneumonia and tracheobronchitis: a systematic review.
Ventilator-associated respiratory infections (tracheobronchitis, pneumonia) contribute significant morbidity and mortality to adults receiving care in intensive care units (ICU). Administration of broad-spectrum intravenous antibiotics, the current standard of care, may have systemic adverse effects. The efficacy of aerosolized antibiotics for treatment of ventilator-associated respiratory infections remains unclear. Our objective was to conduct a systematic review of the efficacy of aerosolized antibiotics in the treatment of ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT), using the Cochrane Collaboration guidelines. We conducted a search of three databases (PubMed, Web of Knowledge and the Cochrane Collaboration) for randomized, controlled trials studying the use of nebulized antibiotics in VAP and VAT that measured clinical cure (e.g., change in Clinical Pulmonary Infection Score) as an outcome measurement. We augmented the electronic searches with hand searches of the references for any narrative review articles as well as any article included in the systematic review. Included studies were examined for risk of bias using the Cochrane Handbook's "Risk of Bias" assessment tool. Six studies met full inclusion criteria. For the systemic review's primary outcome (clinical cure), two studies found clinically and statistically significant improvements in measures of VAP cure while four found no statistically significant difference in measurements of cure. No studies found inferiority of aerosolized antibiotics. The included studies had various degrees of biases, particularly in the performance and detection bias domains. Given that outcome measures of clinical cure were not uniform, we were unable to conduct a meta-analysis. There is insufficient evidence for the use of inhaled antibiotic therapy as primary or adjuvant treatment of VAP or VAT. Additional, better-powered randomized-controlled trials are needed to assess the efficacy of inhaled antibiotic therapy for VAP and VAT.


Pleural effusion coinciding with acute exacerbations in a patient with chronic hepatitis B.
A 28-yr-old man had pleural effusions coinciding with two separate episodes of acute exacerbation of chronic type B hepatitis. In both episodes, the pleural effusion was exudative with lymphocyte predominance, and there was no ascites. Hypocomplementemia was evident in the second episode when the complement level was determined, but immune complexes were not detected in the serum. The hepatitis itself was thought to be directly responsible for the pleural effusions because of meticulous exclusion of other causes and the fact that, without specific treatment, the effusions resolved completely as the hepatitis subsided.


Audiological characteristics and effect of endoscopic surgery for simple congenital malformation of ossicular chain.
To analyze the audiological characteristics and surgical results in patients undergoing surgery for simple congenital ossicular chain malformation, and the effect of endoscopic surgery. A retrospective review was performed on 86 patients who underwent surgery for the congenital malformation of the ossicular chain. Clinical characteristics and audiometric data were analyzed. Fifty-eight patients had detailed postoperative data, and the preoperative and postoperative audiometric results were compared. The subjects were further divided into endoscopic and microscopic groups, and their surgical effects were examined. The preoperative audiometry results in the low-frequency group were worse than those in the high-frequency group (P < 0.05). A postoperative air-bone gap closure to 20 dB or less was achieved in 73.33% of the 60 ears of patients postoperatively. The postoperative air conduction and air-bone gap were significantly better than the preoperative ones (P < 0.05), and the improvement effect was the best in class III patients (P < 0.05). Postoperative hearing had no significant differences between the endoscopic and microscopic groups. However, endoscopic surgery also was more advantageous in terms of operating time (P < 0.05). Preoperative pure tone audiometric results showed moderate or moderate-severe hearing loss, especially in the low-frequency area. The reconstruction of the auditory ossicle chain can achieve satisfactory results, especially in class III patients. Endoscopic and microscopic surgery in the treatment of simple congenital ossicular chain malformations can effectively improve postoperative hearing.


The association between ambient fine particulate air pollution and physical activity: a cohort study of university students living in Beijing.
Air pollution has become a substantial environmental issue affecting human health and health-related behavior in China. Physical activity is widely accepted as a method to promote health and well-being and is potentially influenced by air pollution. Previous population-based studies have focused on the impact of air pollution on physical activity in the U.S. using a cross-sectional survey method; however, few have examined the impact on middle income countries such as China using follow-up data. The purpose of this study is to examine the impact of ambient fine particulate matter (PM2.5) air pollution on physical activity among freshmen students living in Beijing by use of follow-up data. We conducted 4 follow-up health surveys on 3445 freshmen students from Tsinghua University from 2012 to 2013 and 2480 freshmen completed all 4 surveys. Linear individual fixed-effect regressions were performed based on repeated-measure physical activity-related health behaviors and ambient PM2.5 concentrations among the follow-up participants. An increase in ambient PM2.5 concentration by one standard deviation (44.72 μg/m3) was associated with a reduction in 22.32 weekly minutes of vigorous physical activity (95% confidence interval [CI] = 24.88-19.77), a reduction in 10.63 weekly minutes of moderate physical activity (95% CI = 14.61-6.64), a reduction in 32.45 weekly minutes of moderate to vigorous physical activity (MVPA) (95% CI = 37.63-27.28), and a reduction in 226.14 weekly physical activity MET-minute scores (95% CI = 256.06-196.21). The impact of ambient PM2.5 concentration on weekly total minutes of moderate physical activity tended to be greater among males than among females. Ambient PM2.5 air pollution significantly discouraged physical activity among Chinese freshmen students living in Beijing. Future studies are warranted to replicate study findings in other Chinese cities and universities, and policy interventions are urgently needed to reduce air pollution levels in China.


Cerebellar role in smooth pursuit movement.
It is generally believed that pursuit eye movements are unaffected by cerebellar cortical atrophy or cerebellectomy. The present study was performed on patients who underwent partial vermis and hemisphere ablations as a result of severe cranial injury or cerebellar tumors. Eye movements were measured by DC electro-oculography. A clear disparity of the slow phase of the optokinetic nystagmus was observed. When eye movements were contralateral to the ablated side the slow phase of optokinetic nystagmus was statistically slower than drum or visual field velocity. It is suggested that the cerebellum network is involved in the mechanisms of the smooth pursuit movement.


[Possible role of high molecular weight polyphosphates in ATP synthesis from exogenous adenine by the culture of Corynebacterium sp., strain VSTI-301].
An addition of exogenous adenine to an autolysing 72-hour culture of Corynebacterium sp., strain BSTI-301 results in accumulation of as much as 0,6--1,0 mp of ATP per 1 ml of medium. Extracellular ATP accumulation under such conditions is coupled with a considerable decrease of the intracellular content of 5'-phosphoribosyl-1-pyrophosphate, orthophosphate, pyrophosphate and two fractions of high-polymeric polyphosphates PPh3 and PPh4, as compared to the control. The activity of pyrophosphate phosphohydrolase (EC 126.96.36.199) and polyphosphate phosphohydrolase (EC 18.104.22.168) is thereby considerably decreased in the cells growing on exogenous adenine, while the activity of ADP-phosphotransferase (EC 220.127.116.11) is increased 2-fold. It was found that in experiments with 14C-adenine the intracellular content of both ATP and ADP remains unchanged despite a considerable accumulation of extracellular ATP in Corynebacterium sp., strain BSTI-301 cells.


One- and two-year outcomes and predictors of mortality following emergency laparotomy: a consecutive series from a United Kingdom teaching hospital.
Data on outcomes of patients who underwent emergency laparotomy (EML) are limited. This prospective observational study examined aspects of inpatient care and outcomes following EML with a view to identifying predictors of mortality. Data collected from consecutive inpatients who underwent EML in a UK teaching hospital over a 3-month period included perioperative physiology, treatment, morbidity, and mortality (30-day, in-hospital, 12-month, and 24-month). Univariate and multiple logistic regression analyses were used to identify predictors of mortality. Eighty-five patients (44 male) with a mean ± SD age of 61 ± 18 years were studied. Postoperatively, 51 % of patients were admitted to the intensive care (ICU) or the high-dependency unit (HDU). 30-day, in-hospital, 12-month, and 24-month mortality was 14, 16.5, 22.4, and 25.9 %, respectively. After adjusting for confounding variables, age ≥70 years (odds ratio [OR] = 9.2, P = 0.004) and a need for postoperative ICU/HDU (OR = 15.0, P = 0.014) were independent predictors of 30-day mortality. Independent predictors of in-hospital mortality were age ≥70 years (OR = 18.2, P = 0.016), ASA ≥III (OR = 22.1, P = 0.034), preoperative sepsis (OR = 20.6, P = 0.045), and need for postoperative ICU/HDU (OR = 21.5, P = 0.038). Independent predictors of 12-month mortality were preoperative urea >7.5 mmol/L (OR = 3.5, P = 0.038) and need for postoperative ICU/HDU (OR = 3.7, P = 0.044). Age ≥70 years was the only independent predictor of 24-month mortality (OR = 4.5, P = 0.014). Almost all deaths recorded in the 24 months following surgery resulted from disseminated malignancy. Patients who underwent EML had favourable outcomes, with 2-year survival close to 75 %. Age ≥70 years and the need for postoperative ICU/HDU care were independent predictors of mortality.


Sleepwalking associated with hyperthyroidism.
To report several cases of hyperthyroidism in patients presenting with the unusual symptom of sleepwalking and to discuss the possible pathophysiologic basis for this novel association. After encountering and reporting the first case of new-onset somnambulism in a patient presenting with thyrotoxicosis at our institution, we routinely inquired about the sleep history of patients with thyrotoxicosis, questioning both the patients and family members when applicable. Those patients who actually had sleepwalking episodes coinciding with the onset of thyrotoxicosis underwent close follow-up, and the relationship between the sleepwalking and the results of thyroid function tests was analyzed. In addition, we reviewed the literature on psychiatric disorders and sleep problems, and the pathophysiologic rationale for a cause-and-effect relationship is discussed. We collected 8 cases of patients with new-onset sleepwalking episodes that coincided with the start of thyrotoxicosis. The disappearance of the sleepwalking with successful achievement of euthyroidism supports a cause-and-effect relationship. This hypothesis is further supported by the absence of a family history, the adult onset, and the relapse of sleepwalking in 2 of the patients when their thyrotoxicosis became poorly controlled as a result of noncompliance with medications and its subsequent disappearance with reachievement of euthyroidism. Of note, such a presentation was seen only in patients with thyrotoxicosis caused by diffuse toxic goiter or Graves' disease and never in patients with other causes of thyrotoxicosis. New-onset sleepwalking could be caused by thyrotoxicosis or, more specifically, by thyrotoxicosis resulting from diffuse toxic goiter. The mechanism is hypothesized to be related to the combination of prolongation of non-rapid eye movement sleep and the associated fatigue. Specific inquiry about this unusual presentation of thyrotoxicosis is encouraged, and more studies are needed to confirm and evaluate its extent.


Simultaneous determination of aspirin and isosorbide 5-mononitrate in formulation by reversed phase high pressure liquid chromatography.
A simple, precise and rapid reversed phase HPLC method was developed for the simultaneous estimation of aspirin (AS) and isosorbide 5-mononitrate (ISM) in combined formulation. The method was carried out on a Thermo Quest C18 column using a mixture of water:methanol (water pH adjusted to 3.4 using dilute orthophosphoric acid) and detection was carried out at 215 nm using chlorzoxazone as internal standard. Both the drugs showed linearity in the range of 2-10 microg/ml and limits of quantification was found to be 4 and 40 ng/ml for AS and ISM, respectively.


[The role of herpes simplex of type 1 infection in the development of tuberculous meningoencephalitis].
Cases of tuberculous meningoencephalitis in Armenia and a role of the activation of human herpes virus-1 (HHV-1) infection have been investigated. HHV-1 can be an independent factor in the development of meningoencephalitis and a cofactor that produces cellular immunodeficiency in patients with atypical tuberculous meningoencephalitis.


Chromosomal localization of human genes required for G1 progression in mammalian cells.
Specific probes derived from the human genes that complement the mutations of two independent temperature-sensitive (ts) mutants of the BHK-21 hamster cell line were used to determine the chromosomal locations of the loci in the human genome. The ts11 gene, which complements a mutation that blocks progression through the G1 phase of the cell cycle and which has now been identified as the structural gene for asparagine synthetase, is a member of a small gene/pseudogene family with four members. In a rodent-human somatic cell hybrid panel, the ts11 genomic locus from which the genomic probe derives segregates with human chromosome region 7cen----7q35, proximal to the TCR beta locus. In situ hybridization maps this locus more precisely to the q21-31 region of chromosome 7. Two other members of the gene family detected by the ts11 probe segregate concordantly with chromosome region 8pter----8q24 and chromosome region 21pter----21q22. Similar experiments using the same rodent-human hybrid panel conducted with a probe identifying the tsBN51 gene, which also encodes a function necessary for G1 progression, mapped this locus to human chromosome 8, proximal to the large amplification unit encompassing the c-myc gene of Colo320 cells. Chromosomal in situ hybridization of the tsBN51 probe confirmed the localization of this gene to chromosome 8, with the most likely location of the gene being 8q21.


3.0 T magnetic resonance imaging scanning on different body regions in patients with pacemakers.
Magnetic resonance imaging (MRI) at 3.0 T is becoming more common, but there is a lack of sufficient evidence on the safety of a 3.0 T scan in patients with pacemakers. This study aimed to investigate the safety and practical concerns of 3.0 T scans for patients with MR-conditional pacemakers. Twenty consecutive patients were enrolled. A standardized protocol was developed by cardiologists, pacemaker engineers, and radiologists. Pacemaker interrogation was performed immediately before and after the scan. Scan-related adverse events were documented, and imaging quality was graded as level 1 to 4 by radiologists. Twenty-three MRI scans of different body regions (brain = 13, lumbar spine = 4, cervical spine = 2, and heart = 4) were performed, and the average time of a scan was 25 ± 11 min. No significant changes in sensing amplitude (atrial 3.1 ± 1.1 mV vs. 2.9 ± 1.2 mV, P = 0.71; ventricular 9.3 ± 3.5 mV vs. 10.2 ± 3.4 mV, P = 0.46), lead impedances (atrial 647 ± 146 Ω vs. 627 ± 151 Ω, P = 0.7; ventricular: 780 ± 247 Ω vs.711 ± 226 Ω, P = 0.36), or pacing threshold (atrial 0.6 ± 0.2 V/0.4 ms vs. 0.6 ± 0.2 V/0.4 ms, P = 0.71; ventricular 0.7 ± 0.3 V/0.4 ms vs. 0.7 ± 0.2 V/0.4 ms, P = 0.85) were observed pre- and postscan. No adverse events were detected. Image quality review showed grade 1 quality in 16 patients and grade 2 quality in 4 patients with artifacts of pulse generators and leads in cardiac MRI scan and no impact on diagnostic value. Our initial data indicated that 3.0 T scanning might be feasible under a standardized protocol with good diagnostic imaging quality irrespective of body region in patients with MR-conditional pacemakers.


Risk factors for in-hospital mortality among acute ischemic stroke patients in China: a nationwide prospective study.
Objective: We aimed to investigate factors related to in-hospital mortality (IHM) in acute ischemic stroke (AIS) patients.Methods: We prospectively investigated 827,314 patients who were admitted within 7 days of AIS between August 2015 and July 2019. Demographic characteristics, risk factors, and clinical and laboratory characteristics of patients were assessed. Univariate and multivariate logistic regression analyses were performed to identify predictors associated with IHM.Results: The IHM rate in this study was 0.5% in women and 0.3% in men. Factors associated with IHM in AIS included diabetes (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.03-1.43), female (OR 0.84, 95%CI 0.74-0.96), hypertension (OR 1.16, 95%CI 1.01-1.34), atrial fib/flutter (OR 1.51, 95%CI 1.29-1.77), other heart disease (OR1.43, 95%CI 1.23-1.67), prior myocardial infarction (OR 2.00, 95%CI 1.54-2.60), antiplatelet therapies (OR 0.71, 95%CI 0.60-0.84), gastrointestinal bleeding (OR 3.54, 95%CI 2.83-4.44), pulmonary embolism (OR 2.53, 95%CI1.41-4.53), dysphagia(OR7.32, 95%CI6.23-8.61), glycosylated hemoglobin (OR1.05, 95%CI 1.02-1.09), serum creatinine (OR 1.001, 95%CI 1.001-1.002), urea nitrogen (OR 1.10, 95%CI 1.08-1.12), National Institutes of Health Stroke Scale (NIHSS) score (4-5 vs. 0-4: OR 3.58; ≥15 vs. 0-4: OR 8.78), stroke rehabilitation (OR 0.27, 95%CI 0.23-0.30), age (third IQR vs. first IQR: OR 1.57; fourth IQR vs. first IQR: OR 2.23), and in-hospital stroke/TIArecurrence (OR 2.38, 95%CI 2.03-2.78).Conclusions: The findings from this study may help clinicians control the risk of IHM better for patients with AIS.


Resource allocation patterns of two California-Sonoran desert ephemerals.
The patterns of allocation of structural and nonstructural carbon were followed in the co-occurring desert ephemerals Plantago insularis and Camissonia boothii. Patterns of biomass distribution were determined from material harvested at biweekly intervals as were levels of nonstructural sugar and starch. Seasonal patterns of growth and reproduction differed markedly with Plantago allocating significantly more structural and nonstructural carbon to reproduction early in the season. Plantago completed its life cycle in less than 60 days but Camissonia continued both vegetative and reproductive growth to over 100 days. The longer growing season of Camissonia was possible because more energy was allocated to vegetative tissues and storage presumably as investment toward longer life and higher levels of reproduction.


Risk of Synchronous and Metachronous Colorectal Cancer: Population-Based Estimates in Denmark with Focus on Non-Hereditary Cases Diagnosed After Age 50.
The risk of synchronous and metachronous colorectal cancer is influenced by heritable and environmental factors. As a basis for comparative studies, we provide population-based estimates of synchronous and metachronous colorectal cancer with a focus on non-heritable cases. Based on data from national Danish cancer registers, we estimated the proportion of synchronous colorectal cancer and the incidence rates and risks for metachronous colorectal cancer in 28,504 individuals, who developed 577 metachronous colorectal cancer above age 50. Synchronous colorectal cancer was diagnosed in 1.3% of the cases. The risk of metachronous colorectal cancer was associated with sex, tumor location, and age with the strongest influence from the latter. The incidence rate ratios for metachronous colorectal cancer ranged from above 6 in patients below age 65 to <1-3.2 in patients above age 65. The absolute risk of metachronous colorectal cancer was ⩾10% in patients below age 65 and 1.0%-8.0% in patients above age 65. Individuals who develop sporadic, non-inherited colorectal cancer above age 50 are at a significantly increased risk of metachronous colorectal cancer with risk estimates that are strongly affected by age. This observation underscores the need for development of targeted surveillance in the most common clinical subset of colorectal cancer.


Small inward rectifying K+ channels in coleoptiles: inhibition by external Ca2+ and function in cell elongation.
Plant growth requires a continuous supply of intracellular solutes in order to drive cell elongation. Ion fluxes through the plasma membrane provide a substantial portion of the required solutes. Here, patch clamp techniques have been used to investigate the electrical properties of the plasma membrane in protoplasts from the rapid growing tip of maize coleoptiles. Inward currents have been measured in the whole cell configuration from protoplasts of the outer epidermis and from the cortex. These currents are essentially mediated by K+ channels with a unitary conductance of about 12 pS. The activity of these channels was stimulated by negative membrane voltage and inhibited by extracellular Ca2+ and/or tetraethylammonium-CI (TEA). The kinetics of voltage- and Ca(2+)-gating of these channels have been determined experimentally in some detail (steady-state and relaxation kinetics). Various models have been tested for their ability to describe these experimental data in straightforward terms of mass action. As a first approach, the most appropriate model turned out to consist of an active state which can equilibrate with two inactive states via independent first order reactions: a fast inactivation/activation by Ca(2+)-binding and -release, respectively (rate constants >> 10(3) sec-1) and a slower inactivation/activation by positive/negative voltage, respectively (voltage-dependent rate constants in the range of 10(3) sec-1). With 10 mM K+ and 1 mM Ca2+ in the external solution, intact coleoptile cells have a membrane voltage (V) of -105 +/- 7 mV. At this V, the density and open probability of the inward-rectifying channels is sufficient to mediate K+ uptake required for cell elongation. Extracellular TEA or Ca2+, which inhibit the K+ inward conductance, also inhibit elongation of auxin-depleted coleoptile segments in acidic solution. The comparable effects of Ca2+ and TEA on both processes and the similar Ca2+ concentration required for half maximal inhibition of growth (4.3 mM Ca2+) and for conductance (1.2 mM Ca2+) suggest that K+ uptake through the inward rectifier provides essential amounts of solute for osmotic driven elongation of maize coleoptiles.


Integrating metagenomic and amplicon databases to resolve the phylogenetic and ecological diversity of the Chlamydiae.
In the era of metagenomics and amplicon sequencing, comprehensive analyses of available sequence data remain a challenge. Here we describe an approach exploiting metagenomic and amplicon data sets from public databases to elucidate phylogenetic diversity of defined microbial taxa. We investigated the phylum Chlamydiae whose known members are obligate intracellular bacteria that represent important pathogens of humans and animals, as well as symbionts of protists. Despite their medical relevance, our knowledge about chlamydial diversity is still scarce. Most of the nine known families are represented by only a few isolates, while previous clone library-based surveys suggested the existence of yet uncharacterized members of this phylum. Here we identified more than 22,000 high quality, non-redundant chlamydial 16S rRNA gene sequences in diverse databases, as well as 1900 putative chlamydial protein-encoding genes. Even when applying the most conservative approach, clustering of chlamydial 16S rRNA gene sequences into operational taxonomic units revealed an unexpectedly high species, genus and family-level diversity within the Chlamydiae, including 181 putative families. These in silico findings were verified experimentally in one Antarctic sample, which contained a high diversity of novel Chlamydiae. In our analysis, the Rhabdochlamydiaceae, whose known members infect arthropods, represents the most diverse and species-rich chlamydial family, followed by the protist-associated Parachlamydiaceae, and a putative new family (PCF8) with unknown host specificity. Available information on the origin of metagenomic samples indicated that marine environments contain the majority of the newly discovered chlamydial lineages, highlighting this environment as an important chlamydial reservoir.


Effectiveness of a 6-week online course in the Canadian Triage and Acuity Scale for emergency nurses.
There is increasing interest in 5-level triage systems in emergency departments; however, the adoption of a new system places heavy training demands on ED department nurses and physicians. One emerging training option is online learning. The purpose of this study was to explore the effectiveness of an online course in the 5-level Canadian Triage and Acuity Scale (CTAS) on the clinical practice of the triage nurse. Interviews were held with 23 emergency nurses from across Canada. A chart audit of triage codes from 367 charts from 6 hospitals was conducted. The most consistent finding was that the majority of RN staff enjoyed the online course and believed it had improved their triage practice. Nurses believed that their patient assessments were more thorough, accurate, and consistent throughout the department. Improved communication between staff and with patients and families was identified. Nurses reported using what they learned to improve triage assessment. Triage accuracy was high; the overall agreement between CTAS graduates and the chart auditor/expert within one CTAS level was 99.7%. Nurses also identified a number of organizational barriers to CTAS implementation after the course. The online format appears to be an effective, efficient, and convenient way to educate large numbers of ED staff in CTAS. Further research is needed regarding the use of multimedia and computer online chat options to further enhance the online learning experience for nurses.


A Subject of Deepest Dread: Seán O'Casey, The Easter Rising, and Tuberculosis.
Seán O'Casey's play The Plough and the Stars presents audiences with a view of life in Dublin's poverty-stricken tenements during the 1916 Easter Rising. Critical consensus holds that it is a play primarily concerned with the Easter Rising set against a backdrop of tenement life. This paper argues instead that this is a play about tuberculosis in Ireland set against the backdrop of the 1916 Easter Rising. The characters in the play place far more importance on tuberculosis and their impoverished state than on politics or even the violence erupting in the streets. The fears and concerns regarding this infectious disease and its impact on poor communities appear in contrast to the characters' annoyance and dismissal of the political events leading up to and including the Rising.


Regional Integrated Multi-Trophic Aquaculture (RIMTA): Spatially separated, ecologically linked.
Aquaculture sustainability is restricted by environmental drawbacks such as the pollution derived from the released organic waste. Integrated multi-trophic aquaculture (IMTA) aims to lower the input of this waste by culturing other species of low trophic level which feed on them. Despite the appealing idea of IMTA, its implementation is very limited in marine ecosystems. Focusing on marine fish farming, in general terms, fish farm waste is not expected to constitute a relevant food source for low-trophic level organisms cultured in the water column. We propose Regional Integrated Multitrophic Aquaculture (RIMTA) as a shift of paradigm in the way IMTA is used to sequester the dissolved exported waste and derived primary production generated by high trophic level cultures. RIMTA advocates for independent allocation of cultures of low and high trophic level species within the same water body. RIMTA implementation should be economically supported through tax benefits or nutrient quota trading schemes. Moving from IMTA to RIMTA should not only foster aquaculture sustainability but also the circular economy and the ecosystem services that the low trophic level cultures provide.


Hyalocyte proliferation and ECM accumulation modulated by bFGF and TGF-beta1.
In cases of severe retinal diseases, the vitreous body has to be removed and replaced by a suitable biomaterial. Currently, however, no satisfying long-term vitreous substitute is in clinical use. A novel therapeutic concept represents the combination of hyalocytes with suitable biomaterials. The goal of the present study was to evaluate the potential of bFGF and TGF-beta1 as tools to control hyalocyte proliferation and the accumulation of extracellular matrix (ECM). In vitro investigation on the influence of different concentrations of bFGF and TGF-beta1 on hyalocyte morphology, proliferation and ECM production. Both growth factors affected hyalocyte morphology; small, round cells could be observed after bFGF supplementation, whereas the cells appeared more completely spread when cultured with TGF-beta1. Hyalocyte proliferation was increased 3-fold by 10 ng/ml bFGF; 1 ng/ml TGF-beta1 in contrast reduced cell proliferation to about 40% of the control. Converse effects of the growth factors could also be observed on the ECM accumulation of hyalocytes; whereas bFGF halved ECM accumulation, TGF-beta1 enhanced the ECM production up to 3-fold. Precultivation of hyalocytes with bFGF for two passages had no influence on their subsequent accumulation of glycosaminoglycans (GAG). However, cells precultivated with bFGF exhibited a doubled accumulation of collagen compared to controls. The observed opposite effects of bFGF and TGF-beta1 on hyalocyte proliferation and ECM accumulation may allow for the control of hyaloycte properties. Therefore, these two growth factors seem to be valuable tools towards the development of a cell-based vitreous substitute.


Correlative light microscopy, scanning electron microscopy, and transmission electron microscopy of osmium-macerated biological tissues.
A method facilitating correlation of light microscopic (LM), scanning electron microscopic (SEM) and transmission electron microscopic (TEM) images was developed. Rat kidney and heart were initially subjected to the osmium maceration procedure and then embedded in acrylic resin. Semithin sections of the tissue blocks were first provided for LM and then examined by SEM after resin removal. Furthermore, the ultrathin sections adjacent to the semithin sections were observed by TEM. The three-dimensional images of intracellular organelles provided an informative adjunct to LM and TEM.


Frequency analysis of electromyographically measured covert speech behavior.
Eleven subjects were asked to silently read slides of the letters "P" and "T," and to view meaningless control slides similarly as they were presented visually. One-eighth-second electromyographic excerpts were sampled from the baseline and response periods. The data were then transformed into the frequency domain for inferential analyses. The mean power spectral frequencies for the response period were significantly lower than those for the base-line in the overall analysis. There were, however, no significant changes from baseline as a function of kind of stimulus (T, P, or Control) or muscle activated (lips or tongue). It was concluded that there was a generalized responding, not unique to the processing of the specific stimuli studied. Frequency analysis of EMG measures of covert behavior holds some promise of yielding unique information not available through traditional analysis procedures, but more sensitive methods than those used here would be required to demonstrate this.


Cucurbitacin E ameliorates airway remodelling by inhibiting nerve growth factor expression in nicotine-treated bronchial epithelial cells and mice: The key role of let-7c-5p up-regulated expression.
Cucurbitacin E (CuE) shows potential to handle airway remodelling. In the current study, the effects of CuE on nicotine-induced airway remodelling were explored by focussing on its interaction with let-7c-5p/NGF axis. The potential microRNA (miR) as the therapeutic target for CuE treatment was determined using a microarray assay. Changes in viability, inflammation and let-7c-5p/NGF pathway in nicotine-treated bronchial epithelial cells (BECs) were detected under CuE treatment (5 μM). The pathways were manipulated with let-7c-5p inhibitor. Mice were subjected to nicotine treatment and handled with CuE. Changes in pulmonary function and structure were detected. Based on the microarray data, let-7c-5p was selected as the therapeutic target. Viability and inflammation of BECs were induced by nicotine and then restored by CuE. At molecular level, nicotine suppressed let-7c-5p while induced NGF, FN1 and COLIA levels. The effects of CuE were counteracted by let-7c-5p inhibition. In a mouse model, nicotine impaired the function and structure of lung, which was attenuated by CuE and then re-impaired by let-7c-5p antagomir. Collectively, CuE protected against nicotine-induced airway remodelling and partially depended on the induction of let-7c-5p; our future work would pay more attention to other downstream effectors of the miR to promote the treatment of nicotine-induced pulmonary disorders.


Biomechanical comparison of the screw-bone interface: optimization of 1 and 2 screw constructs by varying screw diameter.
In vitro biomechanical investigation of 1 and 2-screw anterior scoliosis constructs with varying screw diameters. To determine a possible optimal configuration of screw number and diameter at varying levels within the thoracic spine for anterior vertebral body fixation. Single-rod systems are typical in anterior thoracic and thoracolumbar correction of adolescent idiopathic scoliosis; although dual rod systems may offer more flexural stability. Loss of fixation remains problematic, particularly in the proximal thoracic vertebrae, and it remains unclear how screw diameter or the number of screws within the vertebrae affect fixation. Individual vertebral levels from 10 cadaveric thoracic spines were randomly assigned to either 1 or 2 screws of 5, 6, or 7-mm diameter. Bone-screw interface failures were created in coronal plane cantilever plow, and failure loads were compared across vertebral levels for each instrumentation method. Two-screw constructs had significantly higher failure loads than single-screw constructs, while increasing screw diameter also produced significant changes in fixation strength. Two-screws had improved performance in the mid and lower thoracic spine, while a single screw was more stable in the upper thoracic spine. Failure modes for 1-screw constructs almost entirely (89%) showed gradual plowing through the bone, whereas acute fracture through the vertebral body or pedicles were common forms of failure (85%) for 2-screw constructs.


Application of self-ionization for enhancing stereochemical and positional effects from arylglycosides under electron ionization conditions in an ion trap mass spectrometer.
Ion trap mass spectrometry has been used to structurally characterize and differentiate positional and stereo isomers of arylglycosides having potential antioxidant properties. The use of the self-ionization (SI) technique has allowed to evidence a strong reactivity of fragment ions produced from dissociations of the molecular ion towards the molecules introduced into the trap. Specific structural effects due to positional isomers and anomers have been also envisaged through the occurrence of bimolecular processes inside the ion trap analyzer. Under self-ionization conditions, even-electron ions are produced. The charge is retained on the sugar moiety, in agreement with its proton affinity higher than that of the substituted phenol moiety. Most of the fragmentation pathways involve elimination of acetic acid that protects the hydroxylic groups of the glycoside. SI also produces adduct ions, likely as covalent species, having higher m/z values than the molecular ion. The reaction site is mainly the double bond present in the pyranosidic ring. Even if some fragment ions have lost the initial stereochemistry, their formation can be related to the structure of the parent neutrals introduced into the cell. Collision-induced dissociation (CID) experiments, carried out on ions formed by ion-molecule reactions, have allowed to obtain further information on gas phase ion structures. The study of mass-selected ion-molecule reactions and their kinetics have evidenced a spectacularly different reactivity of the ion at m/z 111 towards the two anomers 2alpha and 2beta, with the latter showing a much more pronounced reactivity. The approach developed in this work revealed to be an useful tool in structural characterization, as well as in stereo and regiochemical differentiation of arylglycosides.


Gingival crevicular fluid transforming growth factor-beta1 in cyclosporine and tacrolimus treated renal transplant patients without gingival overgrowth.
Gingival crevicular fluid (GCF) levels of transforming growth factor-beta(1) (TGF-beta(1)) have been previously investigated in relation to the pathogenesis of cyclosporine-A (CsA)-induced gingival overgrowth (GO) but no clinical data are available regarding the GCF levels of TGF-beta(1) in patients treated with tacrolimus (Tac). However, as gingival inflammation is pronounced at sites of GO and this consequently may lead to an elevation in TGF-beta(1) levels the present study aimed to evaluate gingival crevicular fluid (GCF) TGF-beta(1) levels in renal transplant patients using CsA or Tac without GO. GCF TGF-beta(1) levels were investigated in 30 renal transplant patients without GO medicated with either CsA (n=15) or Tac (n=15). Sixteen gingivitis patients and 15 periodontally healthy subjects were selected as controls. Periodontal status was evaluated by measuring probing depth, plaque index and papilla bleeding index. The TGF-beta(1) levels were analysed by enzyme-linked immunosorbent assay. Both CsA and Tac groups had significantly elevated GCF TGF-beta(1) total amount compared to gingivitis and healthy groups (p<0.008). GCF TGF-beta(1) total amount of CsA and Tac groups was similar (p>0.008). Gingivitis and healthy groups had also similar GCF TGF-beta(1) total amount (p>0.008). Within the limits of the present data it is unlikely that TGF-beta(1) is an exclusive mediator of CsA- or Tac-induced GO. However, pathogenesis of GO is multifactorial and contribution of TGF-beta(1) to the interrelations between cytokines and growth factors with fibrogenic potential cannot be disregarded.


Electric Dreams of Ukiyo: A Series of Japanese Artworks Created by an Artificial Intelligence.
This opinion piece provides insight on the creation of artistic visuals using artificial intelligence. It describes how 3 artists evolving in this field decided to use technology in a derived way, with the help of researchers and enthusiasts working open source, to talk about how our society is developing with regards to technology adoption.


Vasculitis reminds us that 'Ockham's razor' may still apply in the elderly.
A 76-year-old woman with a history of stage IV chronic kidney disease and hypertension was admitted to the hospital for progressive weakness and acute on chronic kidney injury. She was found to have anaemia requiring transfusion. On the evening of admission, she had worsening respiratory status with subsequent diagnosis of a non-ST-elevation myocardial infarction, pulmonary oedema on chest x-ray presumed to be a result of heart failure, and a possible transfusion reaction. A kidney biopsy performed as part of her ongoing nephrology evaluation revealed granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis). Subsequent bronchoalveolar lavage confirmed diffuse alveolar haemorrhage as the explanation for her anaemia and respiratory decline. She underwent immunosuppressive therapies and initiated dialysis, but subsequently chose hospice care and died 2 months after her diagnosis.


Effects of experimental excision arthroplasty of the hip joint.
The experimental results are reported on a series of sheep in which unilateral hip excision arthroplasty was performed. These sheep were slaughtered at regular postoperative intervals. Radiography and histology were performed on the normal and excised hip joints of the experimental sheep to provide information of the formation of the pseudarthrosis that develops following excision arthroplasty. The efficiency of the false joint that develops is good, judged on a clinical basis. Continuous remodelling of the acetabulum and resected face was noted throughout the experimental period. A sequence of degenerative changes in the acetabular cartilage was observed followed by filling in of the acetabular favity with new bone. New bone also developed on the cemoral component of the pseudarthrosis in the form of osteophytes situated around the perimeter of the resected surface. Growth deformities of the contralateral, nonoperated limb were induced.


Consultations During COVID: Effects of a Pandemic on Neurosurgical Care.
COVID-19 has impacted neurosurgical care around the world. But reports describing patient admission trends during the pandemic have provided limited time frames and diagnoses. The purpose of this paper was to analyze the impact of COVID-19 on neurosurgical care provided to our emergency department during the outbreak. Patient admission data were collected based on a list of 35 ICD-10 codes, which were placed into 1 of 4 categories: head and spine trauma ("Trauma"), head and spine infection ("Infection"), degenerative spine ("Degenerative"), and subarachnoid hemorrhage/brain tumor ("Control"). Emergency department (ED) consultations to the Neurosurgery Department were collected from March 2018 to March 2022, representing 2 years before COVID and 2 years of pandemic. We hypothesized that Control cases would remain stable throughout the 2 time periods while Trauma and Infection would decrease. Because of widespread clinic restrictions, we postulated Degenerative (spine) cases presenting to the ED would increase. During the first 2 years of the COVID pandemic, Neurosurgical Trauma and Degenerative ED patients decreased compared with prepandemic levels, while Cranial and Spinal infections increased and continued to do so during the pandemic period studied. Brain tumors and subarachnoid hemorrhages (Control cases) did not change in a significant way throughout the 4-year analysis. The COVID pandemic significantly altered the demographics of our Neurosurgical ED patient population and continues to do so.


Calorie and protein intake in acute rehabilitation inpatients with traumatic spinal cord injury versus other diagnoses.
Obesity and its consequences affect patients with spinal cord injury (SCI). There is a paucity of data with regard to the dietary intake patterns of patients with SCI in the acute inpatient rehabilitation setting. Our hypothesis is that acute rehabilitation inpatients with SCI consume significantly more calories and protein than other inpatient rehabilitation diagnoses. To compare calorie and protein intake in patients with new SCI versus other diagnoses (new traumatic brain injury [TBI], new stroke, and Parkinson's disease [PD]) in the acute inpatient rehabilitation setting. The intake of 78 acute rehabilitation inpatients was recorded by registered dieticians utilizing once-weekly calorie and protein intake calculations. Mean ± SD calorie intake (kcal) for the SCI, TBI, stroke, and PD groups was 1,967.9 ± 611.6, 1,546.8 ± 352.3, 1,459.7 ± 443.2, and 1,459.4 ± 434.6, respectively. ANOVA revealed a significant overall group difference, F(3, 74) = 4.74, P = .004. Mean ± SD protein intake (g) for the SCI, TBI, stroke, and PD groups was 71.5 ± 25.0, 61.1 ± 12.8, 57.6 ± 16.6, and 55.1 ± 19.1, respectively. ANOVA did not reveal an overall group difference, F(3, 74) = 2.50, P = .066. Given the diet-related comorbidities and energy balance abnormalities associated with SCI, combined with the intake levels demonstrated in this study, education with regard to appropriate calorie intake in patients with SCI should be given in the acute inpatient rehabilitation setting.


The intrinsic contributions of tyrosine, serine, glycine and arginine to the affinity and specificity of antibodies.
Synthetic antibody libraries with restricted chemical diversity were used to explore the intrinsic contributions of four amino acids (Tyr, Ser, Gly and Arg) to the affinity and specificity of antigen recognition. There was no correlation between nonspecific binding and the content of Tyr, Ser or Gly in the antigen-binding site, and in fact, the most specific antibodies were those with the highest Tyr content. In contrast, Arg content was clearly correlated with increased nonspecific binding. We combined Tyr, Ser and Gly to generate highly specific synthetic antibodies with affinities in the subnanomolar range, showing that the high abundance of Tyr, Ser and Gly in natural antibody germ line sequences reflects the intrinsic capacity of these residues to work together to mediate antigen recognition. Despite being a major functional contributor to co-evolved protein-protein interfaces, we find that Arg does not contribute generally to the affinity of naïve antigen-binding sites and is detrimental to specificity. Again, this is consistent with studies of natural antibodies, which have shown that nonspecific, self-reactive antibodies are rich in Arg and other positively charged residues. Our findings suggest that the principles governing naïve molecular recognition differ from those governing co-evolved interactions. Analogous studies can be designed to explore the roles of the other amino acids in molecular recognition. Results of such studies should illuminate the basic principles underlying natural protein-protein interactions and should aid the design of synthetic binding proteins with functions beyond the scope of natural proteins.


Parathyroid crisis as first manifestation of primary hyperparathyroidism.
We report the case of a 61-year-old woman who suffered a parathyroid crisis due to a parathyroid adenoma. The patient presented with the typical clinical symptoms of hypercalcemia. Ca(+2) and PTH were markedly increased. Initially, she was treated conservatively until Ca(+2) returned to normal levels. Then, she underwent surgical excision of a newly diagnosed parathyroid adenoma. Parathyroid crisis (PC), also known as parathyroid storm or acute primary hyperparathyroidism, is a rare and serious complication of primary hyperparathyroidism (PH). Fewer than 200 cases have been described in the literature. Prognosis is poor: mortality is 100% in non-operable cases and 20% in cases in which parathyroidectomy is performed. We emphasize the importance of early diagnosis and aggressive treatment.


Ascending aorta dilatation is associated to hard cardiovascular events, follow-up from multicentric ARGO-Perspective project.
Aortic root dilatation has been proposed as hypertension-mediated organ damage (HMOD). Nevertheless, the role of the aortic root dilatation as a possible additional HMOD is still unclear since studies conducted so far are quite heterogeneous regarding the type of population analyzed, the aortic tract considered, and the type of outcomes accounted for. The aim of the present study is to assess whether the presence of aortic dilatation is associated with strong cardiovascular (CV) events (MACE: heart failure, CV death, stroke, acute coronary syndrome, myocardial revascularization) in a population of patients affected by essential hypertension. Four hundred forty-five hypertensive patients from six Italian hospitals were recruited as part of ARGO-SIIA study1. For all centers, follow-up was obtained by re-contacting all patients by telephone and through the hospital's computer system. Aortic dilatation (AAD) was defined through absolute sex-specific thresholds as in previous studies (41 mm for males, 36 mm for females). Median follow-up was 60 months. AAD was found to be associated with the occurrence of MACE (HR = 4.07 [1.81-9.17], p < 0.001). This result was confirmed after correction for main demographic characteristics such as age, sex and BSA (HR = 2.91 [1.18-7.17], p = 0.020). At penalized Cox regression, age, left atrial dilatation, left ventricular hypertrophy and AAD were identified as best predictor of MACEs and AAD resulted a significant predictor of MACEs even after correction for these confounders (HR = 2.43 [1.02-5.78], p = 0.045). The presence of AAD was found to be associated with an increased risk of MACE independently of for major confounders, including established HMODs. AAD ascending aorta dilatation, LAe left atrial enlargement, LVH left ventricular hypertrophy, MACEs major adverse cardiovascular events, SIIA Società Italiana dell'Ipertensione Arteriosa (Italian Society for Arterial Hypertension).


Exogenous somatotropin alters IGF axis in porcine endometrium and placenta.
The aim of this study was to examine whether exogenous somatotropin (ST) can alter the insulin-like growth factor (IGF) axis in the porcine epitheliochorial placenta. Crossbred gilts were injected either 6 mg of recombinant porcine ST or vehicle from days 10 to 27 after artificial insemination (term day 116). Control and ST-treated gilts were euthanized on day 28 (8 control/5 treated), day 37 (4 control/6 treated), and day 62 (4 control/6 treated) of gestation. Endometrium and placental tissue samples were collected and subjected to mRNA analyses. In control gilts, somatotropin receptor (STR) and IGF-I mRNA abundance in the endometrium decreased with gestation. Conversely, the amounts of IGF-II mRNA and of IGF binding protein (BP)-2 and -3 mRNA, which were analyzed in endometrium and placental chorion, increased with gestation. The endometrium contained less IGF-II mRNA but more IGFBP-2 and-3 mRNA than the placental chorion. In response to pST treatment, the amounts of endometrial STR and IGF-I mRNA were lower at days 28 and 37, but higher at day 62 of gestation. The content of IGF-II mRNA was higher in the endometrium of pST-treated than control gilts on day 37. The amount of IGFBP-2 mRNA was increased on day 37 in endometrium and placenta of pST-treated gilts, whereas no changes in IGFBP-3 mRNA were observed. The IGF-II/IGFBP-2 ratio was higher in the placenta in response to pST on day 28 of gestation. Results show that pST treatment of pregnant gilts during early gestation alters IGF axis in maternal and fetal placental tissues and suggest pST may exert an effect on fetal growth by altering the relative amount of IGFBPs and IGFs at the fetal-maternal interface.


A Ni(i)Fe(ii) analogue of the Ni-L state of the active site of the [NiFe] hydrogenases.
[Ni(L(1))Fe((t)BuNC)4](PF6)2 is a robust Ni(II)Fe(II) complex that undergoes a reversible one-electron reduction. Spectroscopic and theoretical studies show that [Ni(L(1))Fe((t)BuNC)4](+) is an unprecedented Ni(I)Fe(II) species that reproduces the electronic configuration of the Ni-L state of the [NiFe] hydrogenases.


Artificial erection by perfusion of penile arteries.
The dorsal and cavernous arteries of the penis in 14 cadavers and 4 surgical specimens were studied, and the role of these vessels in producing erection was evaluated. For the first time, erection was produced in a cadaver by the perfusion of the cavernous artery. Perfusing the dorsal artery resulted in distention but not erection, and the dorsal artery showed extensive anastomoses between all six arteries of the penis. The cavernous artery appears to be very important for erection, with the dorsal artery playing a relatively smaller role. Surgically, however, both vessels may lend themselves to vascular shunts in the treatment of vasculogenic impotence.


Effects of anoxia and ischemia on uptake2 of catecholamines in perfused rat heart.
The effects of 30 min periods of either anoxia or ischemia (stop-flow) on the uptake2 of isoprenaline and on the production of O-methyl-isoprenaline, a major metabolite of isoprenaline formed by catechol-O-methyltransferase (COMT), were examined in the perfused rat heart. After either glucose deprivation or anoxia, the uptake2 of isoprenaline in hearts subsequently perfused with isoprenaline and 3',4'-dihydroxy-2-methyl-propiophenone, a COMT inhibitor, was similar to control values. However, uptake2 was decreased following either anoxia in association with glucose deprivation or ischemia. In the absence of the COMT inhibitor, neither glucose deprivation nor anoxia alone had any effect on the production of [3H]3-O-methyl-isoprenaline from [3H]isoprenaline, but both anoxia together with glucose deprivation and stop-flow ischemia decreased it. These findings indicate that both anoxia coupled with glucose deprivation and ischemia inhibit both uptake2 and COMT activity and suggest that such inhibition may be responsible for the high concentration of catecholamines released locally following myocardial infarction.


Postmortem changes in actomyosin dissociation, myofibril fragmentation and endogenous enzyme activities of grass carp (Ctenopharyngodon idellus) muscle.
The changes of actomyosin, proteolytic activities and myofibril fragmentation during the postmortem aging of grass carp were studied. The study revealed dramatically increased actomyosin dissociation within 6 h of storage postmortem in grass carp, and it was associated with the drop of pH from 6.9 to 6.7, while liberated actin remained almost unchanged after 6 h postmortem. The myofibril fragmentation also increased significantly with the storage time in 6 h, and a highly positive correlation (P<0.01) existed between MFI and cathepsin B, D, H activities. The study indicated both actomyosin dissociation and cathepsin B, D, H played a role in postmortem tenderization and textural changes in grass carp.


A porous poly(acrylonitrile-co-acrylic acid) film-based glucose biosensor constructed by electrochemical entrapment.
A novel glucose biosensor was constructed by electrochemical entrapment of glucose oxidase (GOD) into porous poly(acrylonitrile-co-acrylic acid), which was synthesized via radical polymerization of acrylonitrile and acrylic acid. The obtained biosensor showed a better stability and higher sensitivity than the biosensor prepared by simple physical adsorption. Effects of some experimental variables such as immobilization time, enzyme concentration, pH, applied potential, and temperature on the amperometric response of the sensor were investigated. The biosensor exhibited a rapid response to glucose (< 30s) with a linear range of 5 x 10(-6) to 3 x 10(-3)M and a sensitivity of 6.82 mAM(-1)cm(-2). The apparent Michaelis-Menten constant (K(M)(app)) was 7.3mM.


B-Mode and Contrast Enhanced Ultrasonography Features of Gastric Inflammatory and Neoplastic Diseases in Cats.
Alimentary lymphoma (AL) is the most common malignancy of the feline gastrointestinal tract and may cause variable mild to severe alteration of the gastric wall on ultrasonography (US) that can be very similar to those caused by inflammation (INF). The aim of this prospective study is to establish the value of B-mode and contrast-enhanced US (CEUS) in describing specific features of normal, inflammatory, and neoplastic gastric diseases in feline species. B-mode US and CEUS of the stomach were performed in anesthetized cats with or without gastric disorders. Gastric wall qualitative and quantitative parameters were evaluated on B-mode US and CEUS examination. A total of 29 cats were included: six healthy (HEA) cats as the control group; nine INF; three low-grade lymphoma (LGAL); 10 high-grade lymphoma (HGAL). On B-mode US, there were significant differences in thickness, the wall's layer definition and echogenicity between HGAL and all the other groups (<0.001). For CEUS, statistical differences between groups were found in the following: HGAL vs. HEA, HGAL vs. INF; HGAL vs. LGAL; INF vs. HEA. Diagnostic accuracy (AUC) and cut-off value were calculated and found to be significant for thickness (3.8 mm) for INF vs. LGAL (AUC > 0.70) and "benign" vs. "malignant" (AUC > 0.90) as well as peak enhancement (34.87 dB) for "benign" vs. "malignant" (AUC > 0.70). INF and LGAL showed an overlap of qualitative and quantitative parameters both on B-mode and CEUS, while HGAL usually appears as a severe wall thickening with absent layer definition, high-contrast uptake, a specific enhancement pattern, regional lymphadenopathy and local steatitis. Thickness and peak enhancement can be useful parameters in the characterization of gastric infiltrates in cats.


Understanding unipolar electrograms and global activation from noninvasive mapping for diagnosing arrhythmias.
In the past several decades Electrocardiographic Imaging has been developed, validated, and recently commercialized for clinical use (Medtronic CardioInsight™). The technology noninvasively maps cardiac electrical potentials by combining multi-channel body surface electrocardiograms and patient specific heart-torso geometry. Unlike contact catheter mapping where bipolar electrograms are commonly used, noninvasive mapping is unipolar in nature. While bipolar electrograms reflect local activation time, noninvasive mapping reflects both local and global information. Characterizing arrhythmias using noninvasive mapping requires a different approach than what is used with bipolar mapping during electrophysiological studies. With multiple example cases, this article aims to demonstrate how in-depth analysis of noninvasive electrogram features and global activation patterns can reveal clinically important characteristics of arrhythmias, which may not be evident on the automatically generated maps. These characteristics include transmural location of the ectopic focus, differential locations within structural proximity, engagement of bundle or specific tissue, and substrate properties. The analysis approach involves applying unipolar potential fundamentals and relating electrogram features, global activation with underlying electrophysiology and cardiac anatomy to explain specific mapping phenomenon. If validated, easy-to-use diagnostic criteria or algorithms can be built and automated as product features in the commercial system to facilitate future noninvasive mapping in patients.


Glacier retreat reorganizes river habitats leaving refugia for Alpine invertebrate biodiversity poorly protected.
Alpine river biodiversity around the world is under threat from glacier retreat driven by rapid warming, yet our ability to predict the future distributions of specialist cold-water species is currently limited. Here we link future glacier projections, hydrological routing methods and species distribution models to quantify the changing influence of glaciers on population distributions of 15 alpine river invertebrate species across the entire European Alps, from 2020 to 2100. Glacial influence on rivers is projected to decrease steadily, with river networks expanding into higher elevations at a rate of 1% per decade. Species are projected to undergo upstream distribution shifts where glaciers persist but become functionally extinct where glaciers disappear completely. Several alpine catchments are predicted to offer climate refugia for cold-water specialists. However, present-day protected area networks provide relatively poor coverage of these future refugia, suggesting that alpine conservation strategies must change to accommodate the future effects of global warming.


Effect of gamma irradiation on mechanical properties of human cortical bone: influence of different processing methods.
The secondary sterilisation by irradiation reduces the risk of infectious disease transmission with tissue allografts. Achieving sterility of bone tissue grafts compromises its biomechanical properties. There are several factors, including dose and temperature of irradiation, as well as processing conditions, that may influence mechanical properties of a bone graft. The purpose of this study was to evaluate the effect of gamma irradiation with doses of 25 or 35 kGy, performed on dry ice or at ambient temperature, on mechanical properties of non-defatted or defatted compact bone grafts. Left and right femurs from six male cadaveric donors aged from 46 to 54 years, were transversely cut into slices of 10 mm height, parallel to the longitudinal axis of the bone. Compact bone rings were assigned to the eight experimental groups according to the different processing method (defatted or non-defatted), as well as gamma irradiation dose (25 or 35 kGy) and temperature conditions of irradiation (ambient temperature or dry ice). Axial compression testing was performed with a material testing machine. Results obtained for elastic and plastic regions of stress-strain curves examined by univariate analysis are described. Based on multivariate analysis it was found that defatting of bone rings had no significant effect on any mechanical parameter studied, whereas irradiation with both doses decreased significantly the ultimate strain and its derivative toughness. The elastic limit and resilience were significantly increased by irradiation with the dose 25 kGy, but not 35 kGy, when the time of irradiation was longer. Additionally, irradiation at ambient temperature decreased maximum load, elastic limit, resilience, and ultimate stress. As strain in the elastic region was not affected, decreased elastic limit resulted in lower resilience. The opposite phenomenon was observed in the plastic region, where in spite of the lower ultimate stress, the toughness was increased due to the increase in the ultimate strain. The results of our study suggest that there may be an association between mechanical properties of bone tissue grafts and the damage process of collagen structure during gamma irradiation. This collagen damage in cortical bone allografts containing water does not depends on the temperature of irradiation or defatting during processing if dose of gamma irradiation does not exceed 35 kGy.


Pre-hospital triage performance and emergency medical services nurse's field assessment in an unselected patient population attended to by the emergency medical services: a prospective observational study.
In Sweden, the rapid emergency triage and treatment system (RETTS-A) is used in the pre-hospital setting. With RETTS-A, patients triaged to the lowest level could safely be referred to a lower level of care. The national early warning score (NEWS) has also shown promising results internationally. However, a knowledge gap in optimal triage in the pre-hospital setting persists. This study aimed to evaluate RETTS-A performance, compare RETTS-A with NEWS and NEWS 2, and evaluate the emergency medical service (EMS) nurse's field assessment with the physician's final hospital diagnosis. A prospective, observational study including patients (≥16 years old) transported to hospital by the Gothenburg EMS in 2016. Three comparisons were made: 1) Combined RETTS-A levels orange and red (high acuity) compared to a predefined reference emergency, 2) RETTS-A high acuity compared to NEWS and NEWS 2 score ≥ 5, and 3) Classification of pre-hospital nurse's field assessment compared to hospital physician's diagnosis. Outcomes of the time-sensitive conditions, mortality and hospitalisation were examined. The statistical tests included Mann-Whitney U test and Fisher's exact test, and several binary classification tests were determined. Overall, 4465 patients were included (median age 69 years; 52% women). High acuity RETTS-A triage showed a sensitivity of 81% in prediction of the reference patient with a specificity of 64%. Sensitivity in detecting a time-sensitive condition was highest with RETTS-A (73%), compared with NEWS (37%) and NEWS 2 (35%), and specificity was highest with NEWS 2 (83%) when compared with RETTS-A (54%). The negative predictive value was higher in RETTS-A (94%) compared to NEWS (91%) and NEWS 2 (92%). Eleven per cent of the final diagnoses were classified as time-sensitive while the nurse's field assessment was appropriate in 84% of these cases. In the pre-hospital triage of EMS patients, RETTS-A showed sensitivity that was twice as high as that of both NEWS and NEWS 2 in detecting time-sensitive conditions, at the expense of lower specificity. However, the proportion of correctly classified low risk triaged patients (green/yellow) was higher in RETTS-A. The nurse's field assessment of time-sensitive conditions was appropriate in the majority of cases.


On-line sensors for coagulation proteins: concept and progress report.
The assessment of blood damage and of the activation of the coagulation, complement and/or inflammatory systems by cardiovascular and extracorporeal devices is difficult at best. Immunoassay methods are now available for the measurement of many of the proteins, enzymes and peptides involved in coagulation, thrombosis, complement and inflammation. We present a long-range project and plan to develop an array of remote, on-line, semicontinuous immunosensors for selected coagulation proteins, based on fluoroimmunoassay principles. The free/bound separation step is performed optically. Excitation of fluorescence is performed via an evanescent wave produced by total internal reflection and waveguide optics. Fluorescence emission is collected only in the near field. Means to deliver fluorescently-labelled reagent and to modify the antigen-antibody binding constant are presented and discussed. The results of non-specific binding, plasma-blood fluorescence, and blood compatibility are also discussed.


Effects of pioglitazone on survival and omental adipocyte function in mice with sepsis induced by cecal ligation and puncture.
To examine the effects of pioglitazone, peroxisome proliferator-activated receptor-gamma (PPAR-γ), on mortality and omental adipocyte function in mice with cecal ligation and puncture (CLP). Male mice were assigned to receive (1) vehicle/sham-operation, (2) pioglitazone/CLP, or (3) vehicle/CLP. Pioglitazone was injected intraperitoneally for 7 d before operation. Serum and omental tissue were collected before, 24, and 48 h after CLP. Serum levels of adiponectin, cytokine, and chemokine were measured with ELISA. mRNA expressions in omental tissues were determined by RT-PCR. Survival was monitored for 7 d after CLP. Survival after CLP was significantly better in the pioglitazone/CLP than in the vehicle/CLP. Serum adiponectin levels before CLP were higher in the pioglitazone/CLP than in the vehicle/CLP. Treatment with pioglitazone significantly inhibited the increases in the serum interleukin-6 and monocyte chemoattractant protein-1 (MCP-1) levels after CLP and lowered the mRNA expressions of proinflammatory cytokines, interleukin-6, and MCP-1 in omental tissue after CLP. The anti-inflammatory effects of pioglitazone on omental adipocyte function appear to be mediated in part by PPAR-γ activation, which down-regulates the production of inflammatory mediators.


Construct validity of the Physiotherapy Evidence Database (PEDro) quality scale for randomized trials: Item response theory and factor analyses.
There is an agreement that the methodological quality of randomized trials should be assessed in systematic reviews, but there is a debate on how this should be done. We conducted a construct validation study of the Physiotherapy Evidence Database (PEDro) scale, which is widely used to assess the quality of trials in physical therapy and rehabilitation. We analyzed 345 trials that were included in Cochrane reviews and for which a PEDro summary score was available. We used one- and two-parameter logistic item response theory (IRT) models to study the psychometric properties of the PEDro scale and assessed the items' difficulty and discrimination parameters. We ran goodness of fit post estimations and examined the IRT unidimensionality assumption with a multidimensional IRT (MIRT) model. Out of a maximum of 10, the mean PEDro summary score was 5.46 (SD = 1.51). The allocation concealment and intention-to-treat scale items contributed most of the information on the underlying construct (with discriminations of 1.79 and 2.05, respectively) at similar difficulties (0.63 and 0.65, respectively). The other items provided little additional information and did not distinguish trials of different quality. There was substantial evidence of departure from the unidimensionality assumption, suggesting that the PEDro items relate to more than one latent trait. Our findings question the construct validity of the PEDro scale to assess the methodological quality of clinical trials. PEDro summary scores should not be used; rather, the physiotherapy community should consider working with the individual items of the scale.


Flexible cystoscopy in men: is topical anaesthesia with lignocaine gel worthwhile?
The value of 2% lignocaine gel as a topical anaesthetic for flexible cystoscopy in men was tested in a prospective, randomized, double-blind, placebo controlled trial. A total of 138 patients were entered into the study. Group A patients (n = 75) received 10 ml of 2% lignocaine gel intraurethrally whilst 10 ml of plain lubricating gel was instilled in the remaining 63 patients (Group B). Patient discomfort was recorded by means of a four-point descriptive pain scale (completed by both surgeon and patient) and a 100 mm non-graphic rating visual analogue scale (patient only). The results showed no significant difference between the two treatments irrespective of the method of recording. This study shows that 2% lignocaine gel offers no advantage over plain lubricating gel in providing analgesia for flexible cystoscopy. In this situation good lubrication may be a more important factor than topical anaesthesia.


Out Sourcing of Head and Neck Oncologic Surgery: Cost Considerations.
165 surgeries for head and neck cancer have been performed by a team of the Indian Institute of Head and Neck Oncology IIHNO in 1 year. Integration of private players was necessitated because of need to share available facilities without losing objective of reducing the cost. These surgeries were performed at a private hospital using their resources for the operation theatre and post-operative intensive care services, since the IIHNO does not as yet have an operation theatre facility. The pre-op facilities and post-operative care was done at IIHNO a charitable cancer center under the Indore Cancer Foundation a public charitable trust. Cost analysis of these procedures has been done and the system of integration of the two have been analysed.


Assessing sleep in opioid dependence: a comparison of subjective ratings, sleep diaries, and home polysomnography in methadone maintenance patients.
Comparisons of subjective and objective sleep measures have shown discrepancies between reported sleep and polysomnography (PSG) in non-drug dependent individuals with and without insomnia. Sleep may affect behavioral and physiologic aspects of drug abuse and dependence; patients in methadone maintenance therapy (MMT) for opioid dependence frequently report sleep problems. Whether subjective sleep reflects objective sleep in MMT patients is unknown. We undertook these analyses to establish the correlations among subjective and objective sleep measures in MMT patients. We compared one week of daily sleep diaries, one night of home PSG, a questionnaire completed the morning after PSG, and the Pittsburgh Sleep Quality Inventory (PSQI) as well as demographics and drug use measures in 62 MMT patients with disturbed sleep (PSQI score > 5). Subjective and objective sleep durations were similar in this sample; average sleep times for the diary, morning questionnaire, and PSG were 340, 323, and 332 min, respectively. Average diary sleep time, subjective ratings of feeling rested, and PSG sleep efficiency were correlated significantly with PSQI score. Age was inversely correlated with PSG sleep time. Participants whose urine toxicology showed benzodiazapine use reported significantly longer sleep times on the morning questionnaire. Objective sleep measures confirm subjective measures in MMT patients with disturbed sleep. The high prevalence of sleep complaints in this population likely reflects pathology rather than sleep misperception. Both objective and subjective measures are useful in research and clinical settings for assessing sleep in opioid-dependent patients.


Long-term efficacy of high-frequency (10 kHz) spinal cord stimulation for the treatment of painful diabetic neuropathy: 24-Month results of a randomized controlled trial.
To evaluate the long-term efficacy of high-frequency (10 kHz) spinal cord stimulation (SCS) for treating refractory painful diabetic neuropathy (PDN). The SENZA-PDN study was a prospective, multicenter, randomized controlled trial that compared conventional medical management (CMM) alone with 10 kHz SCS plus CMM (10 kHz SCS+CMM) in 216 patients with refractory PDN. After 6 months, participants with insufficient pain relief could cross over to the other treatment. In total, 142 patients with a 10 kHz SCS system were followed for 24 months, including 84 initial 10 kHz SCS+CMM recipients and 58 crossovers from CMM alone. Assessments included pain intensity, health-related quality of life (HRQoL), sleep, and neurological function. Investigators assessed neurological function via sensory, reflex, and motor tests. They identified a clinically meaningful improvement relative to the baseline assessment if there was a significant persistent improvement in neurological function that impacted the participant's well-being and was attributable to a neurological finding. At 24 months, 10 kHz SCS reduced pain by a mean of 79.9% compared to baseline, with 90.1% of participants experiencing ≥50% pain relief. Participants had significantly improved HRQoL and sleep, and 65.7% demonstrated clinically meaningful neurological improvement. Five (3.2%) SCS systems were explanted due to infection. Over 24 months, 10 kHz SCS provided durable pain relief and significant improvements in HRQoL and sleep. Furthermore, the majority of participants demonstrated neurological improvement. These long-term data support 10 kHz SCS as a safe and highly effective therapy for PDN. ClincalTrials.gov Identifier, NCT03228420.