Role of Mg2+ in activation of NADPH oxidase of human neutrophils: evidence that Mg2+ acts through G-protein.
The membrane fraction and three cytosolic proteins of neutrophils, p47-phox, p67-phox and a G-protein, are involved in the cell-free activation of the O2(-)-generating NADPH oxidase in the presence of SDS, though it has been controversial whether the G-protein is required or just enhancing the activity. We have used the three cytosolic factors, the solubilized membrane fraction, GTP gamma S and SDS, and found that both G-protein and GTP gamma S are essential for the activation of the NADPH oxidase. The effect of GTP gamma S is modified by Mg2+: the cations enhance the O2- generation at low concentrations of GTP gamma S, whereas they attenuate the activity at higher concentrations of GTP gamma S. In presence of 10 microM GTP gamma S, the maximal activity is observed at 0.1 microM Mg2+, which is several-fold higher than that at 1 mM Mg2+. The omission of Mg2+ followed by the chelation with EDTA results in loss of the activation, which is completely restored by the addition of Mg2+. Thus, Mg2+ seems to modulate the activation of the NADPH oxidase at the level of the G-protein.


Cancer is not a risk factor for bullous pemphigoid: 10-year population-based cohort study.
Bullous pemphigoid (BP) is the most common autoimmune bullous disease. Whether there is an increased risk for subsequent BP among patients with cancer is still unclear. To evaluate the risk for subsequent BP in patients with cancer. This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Database between 2000 and 2011. A total of 36 838 patients with cancer and 147 352 age-, sex- and index-date-matched controls were recruited. The hazard ratio (HR) of subsequent BP in the patients with cancer was analysed using a Fine-Gray competing risk regression model with mortality as the competing event. The incidence of BP per 100 000 person-years was 17·2 in the patients with cancer and 19·8 in the controls; therefore, the crude incidence rate ratio was 0·87 [95% confidence interval (CI) 0·53-1·36]. The HR of subsequent BP in the patients with cancer was 0·47 (95% CI 0·23-0·94) using the Fine-Gray competing risk regression model. Age (HR 1·05, 95% CI 1·03-1·07), diabetes mellitus (HR 1·69, 95% CI 1·10-2·59) and cerebrovascular disease (HR 2·14, 95% CI 1·36-3·34) were independent risk factors for BP. The incidence of BP in patients with cancer was not higher than in the control group. Cancer is not a risk factor for BP.


New perioperative management reduces bleeding in radical retropubic prostatectomy.
To describe the effect of modifications to radical retropubic prostatectomy (RRP, known to be associated with severe bleeding) on blood loss in a retrospective analysis comparing RRPs by one experienced surgeon before and after the changes. The new method comprised reducing the intravenously applied volume, using a peridural catheter and maintaining a 25-30 degrees Trendelenburg position. The difference in haemoglobin before and after RRP was analysed before the changes (group 1) and after (group 2). If transfusions were required the haemoglobin value was corrected, whereby 1 mL of erythrocyte concentrate increased the patient's haemoglobin by 0.03 g/L. Assessment was possible in 201 of 234 patients, 110 from group 1 and 91 from group 2. The mean transfusion-corrected difference in haemoglobin was 53 g/L in group 1 (20% transfusion rate) and 35.2 g/L in group 2 (1.09% transfusion rate; P > 0.001). The median intravenous volume applied was 5.96 L in group 1 and 3.49 L in group 2 (P < 0.001). The complication rate did not differ between the groups. This new method minimizes the intraoperative blood loss during RRP; transfusions are only necessary in rare cases and the complication rate remained unaltered.


Paraoxonase 1 activity in patients with Alzheimer disease: Systematic review and meta-analysis.
Cumulating evidence links environmental toxicants, such as organophosphate (OP) pesticides, to the pathogenesis of Alzheimer's disease (AD). The calcium-dependent Paraoxonase 1 (PON1) can neutralize these toxicants with good catalytic efficiency, thus protecting from OP-induced biological damage. Although different previous studies have already partially described an association between PON1 activity and AD, this intriguing relationship has not yet been comprehensively examined. To fill this gap, we performed a meta-analysis of existing data comparing the PON1 arylesterase activity in AD and healthy subjects from the general population. Data were obtained by searching MEDLINE, Embase and CENTRAL, Google Scholar, and SCOPUS electronic databases for all studies published at any time up to February 2023, reporting and comparing the PON1- paraoxonase activity between AD patients and controls. Seven studies, based on 615 subjects (281 AD and 356 controls) met the inclusion criteria and were included into the final analysis. A random effect model revealed that PON1 arylesterase activity was significantly lower in the AD group compared to controls, exhibiting low level of heterogeneity (SMD = - 1.62, 95% CI = -2.65 to -0.58, p = 0.0021, I2 = 12%). These findings suggest that PON1 activity might be reduced in AD reflecting a major susceptibility to OPs neurotoxicity. Further studies should be conducted to definitely ascertain this link and to establish the cause-effect relationship between PON1 reduction and AD onset.


Use of levonorgestrel as emergency contraception in overweight women.
Levonorgestrel (LNG) emergency contraception (EC) may have decreased efficacy for women with body mass indices (BMI)≥26kg/m2. This study aims to evaluate the prevalence of LNG EC use and EC counseling among overweight women. The 2013-2015 dataset from the National Survey of Family Growth was analyzed to determine the proportion of women with BMI≥26kg/m2 who report recent use of LNG EC and EC counseling. Overall, 2.4% of respondents reported recent use of LNG EC. Among women using oral LNG for EC, 29.8% of survey participants reported BMI≥26kg/m2. Additionally, 40.2% of women with BMI≥26kg/m2 using oral LNG EC reported having a doctor or medical provider talk to them about emergency contraception within the last 12 months, compared to 18.3% of LNG EC users with BMI<26kg/m2 (p<0.001). Despite recent counseling from clinicians and concerns for decreased efficacy, a significant number of overweight women continue to use LNG for EC. Clinicians should counsel women with BMI≥26kg/m2 on the potential limitations of oral LNG for EC and offer more effective EC methods, including the copper intrauterine device and oral ulipristal acetate.


An EPR analysis of cyanide-resistant mitochondria isolated from the mutant poky strain of Neurospora crassa.
An analysis of the paramagnetic components present in mitochondria isolated from the poky mutant of Neurospora crassa is described. The study was undertaken with a view to shedding light on the nature of the cyanide- and antimycin A-resistant alternative terminal oxidase which is present in these preparations. Of the ferredoxin-type iron-sulfure centers, only Centers S-1 and S-2 of succinate dehydrogenase could be detected in significant quantities. Paramagnetic centers attributable to Site I were virtually absent. In the oxidized state, at least two 'high potential iron sulfur' centers could be distinguished and these were attributed to Center S-3 of succinate dehydrogenase and a second component analogous to that found in mammalian systems. Much of the Center S-3 signal was in a highly distorted state which was apparently dependent upon the presence of an accompanying free radical species. At lower field positions, a succinate-reducible signal peaking around g = 3.15 was found. This signal is caused by a low spin heme species, presumably the cytochrome c which is the only major cytochrome in these mitochondria. At even lower field positions, signals attributable to iron in a field of low symmetry at g = 4.3 and multiple high spin heme species around g = 6, could be distinguished. The effects of salicylhydroxamic acid, an inhibitor of the alternative oxidase, were tested on these components. Effects could be seen on at least one high spin heme component and also partially upon the distorted Center S-3 signal converting part of it to a signal indistinguishable from center S-3. Some increase in the g = 4.3 iron signal was also noted. No effects of the inhibitor on the ferredoxin-type centers were detected.


Animal fat consumption and pancreatic cancer incidence: evidence of interaction with cigarette smoking.
A large difference in fat intake and pancreatic cancer incidence exists among populations worldwide. This study investigated the relation between fat consumption and pancreatic cancer risk at the population level. Fat consumption data for nine periods (1964-1994) and age-standardized pancreatic cancer incidence data for five periods (1973-1997) in 35 countries were derived from the Food and Agriculture Organization and World Health Organization, respectively. A significant positive correlation was found between animal fat consumption and pancreatic cancer incidence in all periods examined (r=0.40-0.74, p=0.021 to < 0.0001 in men and r=0.50-0.66, p=0.01 to 0.0001 in women). After adjustment for smoking and other confounders, animal fat consumption in all nine periods considered was still significantly and positively associated with pancreatic cancer incidence in the 1993 to 1997 period in both sexes. The stratified analysis showed that this association was significant only in countries with below median level of smoking (< 2273 cigarettes/adult/year). A similar but less pronounced effect was observed for total fat consumption. The consumption of fat, especially animal fat, was associated with an increased risk of pancreatic cancer and this association was modified by levels of cigarette smoking.


Sequential administration of methotrexate and asparaginase in relapsed or refractory pediatric acute myeloid leukemia.
The efficacy of combination chemotherapy with methotrexate (MTX) and asparaginase is not well known in relapsed and refractory acute leukemia after contemporary therapy. A retrospective study of pediatric patients with relapsed or refractory acute myeloid leukemia (AML) who received MTX and asparaginase as a salvage therapy at St. Jude Children Research Hospital was performed. MTX was given intravenously followed by a dose of asparaginase intramuscularly or intravenously 24 hours later. The chemotherapy cycle was repeated every 7-10 days. Response, survival, and toxicities were evaluated. Fifteen patients, median age 10.5 years (range, 1.1-18.5 years), were treated. Median number of previous therapeutic regimens was three (range, 1-4). Six patients responded to treatment (three had morphologic complete remission with incomplete blood count recovery, two had partial remission, and one had stable disease for 16 months), and four are still alive. Three of six responders had monoblastic leukemia, and also developed tumor lysis syndrome. The 1- and 2-year overall survival rates are 35.6% and 17.8%, respectively. The most common adverse event was transient elevation of transaminases (nine patients). Two patients developed pancreatitis. Episodes of febrile neutropenia were rare (two patients), and most courses (75 out of 93 total courses) were given in an outpatient setting. Combination chemotherapy with MTX and asparaginase appears to be an effective salvage therapy and well tolerated in patients with relapsed or refractory childhood AML, even in those heavily pretreated with contemporary frontline or salvage therapy.


Wiring and volume transmission in rat amygdala. Implications for fear and anxiety.
The amygdala plays a key role in anxiety. Information from the environment reaches the amygdaloid basolateral nucleus and after its processing is relayed to the amygdaloid central nucleus where a proper anxiogenic response is implemented. Experimental evidence indicates that in this information transfer a GABAergic interface controls the trafficking of impulses between the two nuclei. Recent work indicates that interneuronal communication can take place by classical synaptic transmission (wiring transmission) and by volume transmission in which the neurotransmitter diffuses and flows through the extracellular space from its site of release and binds to extrasynaptic receptors at various distances from the source. Based on evidence from our laboratory the concept is introduced that neurotransmitters in the amygdala can modulate anxiety involving changes in fear learning and memories by effects on receptor mosaics in the fear circuits through wiring and volume transmission modes of communication.


Angiogenesis Assays.
Neoangiogenesis constitutes one of the first steps of tumor progression beyond a critical size of tumor growth, which supplies a dormant mass of cancerous cells with the required nutrient supply and gaseous exchange through blood vessels essentially needed for their sustained and aggressive growth. In order to understand any biological process, it becomes imperative that we use models, which could mimic the actual biological system as closely as possible. Hence, finding the most appropriate model is always a vital part of any experimental design. Angiogenesis research has also been much affected due to lack of simple, reliable, and relevant models which could be easily quantitated. The angiogenesis models have been used extensively for studying the action of various molecules for agonist or antagonistic behaviour and associated mechanisms. Here, we have described two protocols or models which have been popularly utilized for studying angiogenic parameters. Rat aortic ring assay tends to bridge the gap between in vitro and in vivo models. The chorioallantoic membrane (CAM) assay is one of the most utilized in vivo model system for angiogenesis-related studies. The CAM is highly vascularized tissue of the avian embryo and serves as a good model to study the effects of various test compounds on neoangiogenesis.


Frequency changes of sensorimotor EEG rhythm after revascularization surgery.
In a group of 26 patients undergoing extra-intracranial arterial bypass surgery (EIAB), the frequency of sensorimotor rhythms was measured shortly before and 7 days after EIAB surgery. Bipolar EEG recording from both central regions was used for calculation of power spectra and measurement of peak frequency to determine the dominant frequency of the sensorimotor rhythm. Preoperative hemispheric comparisons displayed a statistically significant frequency decrease (-0.47 Hz) on the ischaemic side, only in the group (15 patients) with cortical infarction. The hand pressure, measured electronically, showed a tendency to decrease in the early postoperative stage. Measurement of the frequency, however, showed a significant decrease of -0.35 Hz on the operated side, only in the group with cortical infarction, whereas no frequency decrease was found in the other group. This unilateral postoperative frequency decrease in patients with cortical infarction is interpreted as a temporary deterioration of brain function.


Impact of pulmonary vein anatomy and ostial dimensions on long-term outcome after single-shot device-guided cryoablation for paroxysmal atrial fibrillation.
Cryoballoon (CB)-guided pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). This observational study aimed to assess the role of individual anatomical characteristics to predict long-term freedom from arrhythmia recurrence after CB-guided PVI for paroxysmal AF (PAF). Three hundred fifty three consecutive patients (58 ± 11 years, 56% males), undergoing PVI between 2012 and 2018 were analysed. Individual pulmonary vein (PV) anatomy was assessed using preprocedural cardiac magnetic resonance imaging (MRI). For each PV, the cross-sectional area (CSA) was calculated. The impact of PV characteristics and CSA on long-term AF-free survival was evaluated. Acute PVI was achieved in all patients. Two hundred twenty-three patients (63%) had a normal PV anatomy (2 left- and 2 right-sided PV). Variant PV anatomy was present in 130 patients (37%). During the observation period of 48 months, AF-recurrence was documented in 167 patients (47 %). Patients with AF-recurrence presented with significantly enlarged right-sided PVs and left superior PVs (LSPVs) (p < 0.001). The presence of left common PVs (LCPVs) (n = 75, Log-rank p < 0.001) as well as right variant PVs (n = 35, Log rank p < 0.001) was associated with a significantly impaired long-term AF-free survival rate as compared to patients with normal PV characteristics. Variant PV anatomy is a good predictor for AF-recurrence. A correlation between an enlarged CSA of right-sided PVs as well as LSPVs and AF-recurrence was documented.


The Impact of Pre-Stroke Depressive Symptoms, Fatalism, and Social Support on Disability after Stroke.
Psychological and social factors have been linked to stroke mortality; however, their impact on stroke disability is unclear. The purpose of this study was to evaluate the impact of pre-stroke fatalism, depressive symptoms, and social support on 90-day neurologic, functional, and cognitive outcomes. Ischemic strokes (2008-2011) were identified from the Brain Attack Surveillance in Corpus Christi Project. Validated scales were used to assess fatalism, depressive symptoms, and social support during baseline interviews. The National Institutes of Health Stroke Scale, activities of daily living/instrumental activities of daily living (ADL/IADL) scale, and Modified Mini-Mental State Exam (3MSE) were used to assess 90-day outcomes. The associations between the pre-stroke variables and 90-day outcomes were estimated from regression models adjusting for demographics, risk factors, tissue-type plasminogen activator treatment, and comorbidities. Among 364 stroke survivors, higher pre-stroke fatalism was associated with worse functional (.17 point higher ADL/IADL per interquartile range [IQR] higher fatalism; 95% confidence interval [CI]: .05, .30) and cognitive (2.81 point lower 3MSE per IQR higher fatalism; 95% CI: .95, 4.67) outcomes. Higher pre-stroke depressive symptoms were associated with worse functional (.16 point higher ADL/IADL per IQR higher Patient Health Questionnaire-9; 95% CI: .04, .28) and cognitive (2.28 point lower 3MSE per IQR higher Patient Health Questionnaire-9; 95% CI: .46, 4.10) outcomes. Participants in the middle tertile of social support had better cognitive outcomes (3.75 points higher 3MSE; 95% CI: .93, 6.56) compared with the highest tertile. The associations between pre-stroke fatalism, depressive symptoms, and social support and 90-day outcomes suggest that psychosocial factors play an important role in stroke recovery.


Isolation of a Trypanosoma cruzi antigen by affinity chromatography with a monoclonal antibody. Preliminary evaluation of its possible applications in serological tests.
By affinity chromatography with a monoclonal antibody (163B6), obtained in our laboratory, we have isolated a T. cruzi antigen which could be useful for differential diagnosis of Chagas' disease from leishmaniasis. This antigen, a 52-kD protein, reacted with all sera from Chagas' disease patients tested but not with sera from patients with leishmania, in ELISA. The 52-kD antigen is widely distributed in the Trypanosoma genus since the 163B6 monoclonal antibody reacts with T. rangeli and 8 strains and a clone of T. cruzi epimastigotes.


Direct analysis of trichloropyridinol in human saliva using an Au nanoparticles-based immunochromatographic test strip for biomonitoring of exposure to chlorpyrifos.
A portable immunochromatographic strip-based biosensor for direct detection of trichloropyridinol (TCP), a specific biomarker of exposure to chlorpyrifos, in human saliva sample is presented. In this approach, a series of immunoreactions was performed on the test strip, where the targeted analytes (TCP) bound to the Au nanoparticles-labeled antibodies on the conjugate pad to form analyte-Au-antibody conjugates, and then free Au-labeled antibodies were captured by TCP-BSA in the test zone. Captured Au nanoparticles, increased with decreased levels of analytes, can be observed visibly without any equipment and later quantified by a colorimetric reader. Several experimental parameters were optimized including Au nanoparticle-to-TCP antibody coupling ratio, the amount of Au-labeled TCP antibody, immunoreaction time, the pretreatment of sample pad and the preparation of stock solution of Au-TCP antibody that realize sensitivity, selectivity and direct detection of TCP. Under optimal conditions, this biosensor displays a highly linear range of 0.625-20 ng/mL TCP, with a detection limit of 0.47 ng/mL. Moreover, the immunosensor was successfully used for direct analysis of human saliva sample without any pretreatment. These results demonstrate that this Au nanoparticles-based immunochromatographic test strip (ITS) provides a simple, accurate, and quantitative tool for TCP detection and holds a great promise for point-of-care and in-field analysis of other biomarkers.


Direct growth of MnOOH nanorod arrays on a carbon cloth for high-performance non-enzymatic hydrogen peroxide sensing.
Novel MnOOH nanorod arrays directly growing on a flexible carbon cloth substrate (MnOOH/CC) is first synthesized through a facile hydrothermal technique and utilized as an electrocatalyst for non-enzymatic detection of hydrogen peroxide. The as-prepared MnOOH nanorods are uniformly distributed on the carbon cloth with a 3D porous network structure, which provides a high specific surface area and numerous electroactive sites. The electrode based on the carbon cloth-supported MnOOH nanorod arrays exhibits a higher sensitivity (692.42 μA mM(-1) cm(-2)) and a wider linear range (20 μm-9.67 mM) with a detection limit of 3.2 μM (S/N = 3) compared with the electrode based on the rigid graphite substrate supported the random distributed MnOOH nanorods. Further, the MnOOH/CC possesses an outstanding flexibility and can conveniently be assembled into the required shape for a specific use, thus the arc-shaped MnOOH/CC electrodes are fabricated whose electrocatalytic activity toward the hydrogen peroxide reduction remains nearly unchanged in comparison with the unbent state. Due to its excellent sensitivity, reproducibility, anti-interference and stability, the electrode based on the carbon cloth-supported MnOOH nanorod arrays is believed to be promising for applications in high efficiency flexible hydrogen peroxide sensing.


Multistrand wire retainers: an indirect technique.
A method is described for bonding multistrand retainers indirectly, using a silicone locating splint and visible light curing adhesive. This technique permits construction of the retainer in the laboratory and eliminates the problem of positioning flexible wires in the mouth.


Causes of failure in the surgical treatment of primary hyperparathyroidism: lessons from 51 successful reoperations.
A review of 51 successful reoperations for persisting hypercalcaemia due to primary hyperparathyroidism shows that inadequate anatomical knowledge, inadequate surgical technique and unusual localizations of the parathyroids are the most frequent causes of failure of the primary operation. The majority of these failures are therefore preventable. There is a frequent need for cervical thymectomy in parathyroid surgery. Sternotomy is only very rarely necessary.


Trends and sources vs air mass origins in a major city in South-western Europe: Implications for air quality management.
This study presents a 17-years air quality database comprised of different parameters corresponding to the largest city in the south of Spain (Seville) where atmospheric pollution is frequently attributed to traffic emissions and is directly affected by Saharan dust outbreaks. We identify the PM10 contributions from both natural and anthropogenic sources in this area associated to different air mass origins. Hourly, daily and seasonal variation of PM10 and gaseous pollutant concentrations (CO, NO2 and SO2), all of them showing negative trends during the study period, point to the traffic as one of the main sources of air pollution in Seville. Mineral dust, secondary inorganic compounds (SIC) and trace elements showed higher concentrations under North African (NAF) air mass origins than under Atlantic. We observe a decreasing trend in all chemical components of PM10 under both types of air masses, NAF and Atlantic. Principal component analysis using more frequent air masses in the area allows the identification of five PM10 sources: crustal, regional, marine, traffic and industrial. Natural sources play a more relevant role during NAF events (20.6 μg · m(-3)) than in Atlantic episodes (13.8 μg · m(-3)). The contribution of the anthropogenic sources under NAF doubles the one under Atlantic conditions (33.6 μg · m(-3) and 15.8 μg · m(-3), respectively). During Saharan dust outbreaks the frequent accumulation of local anthropogenic pollutants in the lower atmosphere results in poor air quality and an increased risk of mortality. The results are relevant when analysing the impact of anthropogenic emissions on the exposed population in large cities. The increase in potentially toxic elements during Saharan dust outbreaks should also be taken into account when discounting the number of exceedances attributable to non-anthropogenic or natural origins.


Epidermal growth factor receptors increase during the differentiation of embryonal carcinoma cells.
Mouse teratocarcinoma stem cells (embryonal carcinoma, or EC cells) bind very small amounts of mouse epidermal growth factor (EGF) and the latter hormone seems to have no stimulatory effect on the growth of two cloned lines of EC cells. However, when EC cells are induced to differentiate into large flat endodern-like cells (END cells), EGF receptors increase in number reaching a plateau in 6 to 8 days. At 8 to 10 days after induction, END cells multiply very slowly, but when EGF is added (3 x 10(-10) M) to the medium, cell division is stimulated and a further change in morphology occurs. This letter describes the binding characteristics and numbers of the EGF receptors on EC and END cells and shows that exogenous retinoic acid increases the numbers of EGF receptors on END cells. We were unable to find endogenous competing factors produced by EC cells. Such factors could account for the lack of detectable binding of EGF on these cells. As EC cells differentiate to END cells, so the ability of the cells to form tumours is reduced. Since this change is accompanied by an increase in the number of EGF receptors there may be a relationship between these two events.


A novel SCN5A mutation demonstrating a variety of clinical phenotypes in familial sick sinus syndrome.
Mutations in SCN5A have been reported to cause several types of hereditary arrhythmias (overlap syndrome). We herein report two patients with the overlapping phenotypes of juvenile sick sinus syndrome (SSS) and Brugada syndrome (BrS). The proband was a man who was in his twenties and had been diagnosed with both SSS and ventricular tachycardia (VT). A pilsicainide challenge test revealed a coved type ST segment elevation. His teenage brother also suffered from SSS, but no VT had been documented. A pilsicainide challenge failed to produce a Brugada-type ST elevation, but there was a marked prolongation of the His-ventricle interval. Their electrocardiograms at rest did not display any Brugada-type ST elevations. We identified a novel SCN5A (F1775Lfs*15) mutation in both patients, even though there was a phenotype discrepancy.


Identification of Prognostic Factors in Patients With Streptococcus Bloodstream Infection.
The purpose of this study was to explore prognostic factors of bloodstream infections (BSIs), a common severe infection and a major cause of mortality worldwide, so as to construct a prognosis model of patients with BSI. Clinical and biochemical test data were obtained retrospectively from the medical records of 562 patients with BSI who had been treated at a single center; the end point was 60 days of all-cause death. The chi-square test was used to compare the mortality of patients grouped by the types of antibiotic treatment. The logistic regression analysis was adopted to identify prognostic factors; the Kaplan-Meier survival curve and log-rank test were conducted to compare the survival rate of patients with different prognostic factors; the receiver operating characteristic (ROC) curve was used to estimate the predictive value of different prognostic factors. Of the 562 patients, 455 survived (80.96%), and 107 died (19.04%). The mortality rate of patients treated with a combination of antibiotics (25.40%) was higher than that treated with a single antibiotic (15.82%). Univariate analysis identified 19 prognostic factors for patients with BSI, including gender, age, diabetes, malignant tumor (non-blood system), total hospitalization time, alanine aminotransferase, aspartate aminotransferase, total protein, albumin, total bilirubin, direct bilirubin, creatinine, ratio of granulocytes, fibrinogen, D-dimer, platelet, C-reactive protein, shock, and respiratory failure (P < 0.05). Multivariate analysis indicated that albumin (odds ratio [OR] = 0.94, 95% confidence interval [CI]: 0.89-0.99), fibrinogen (OR = 0.61, 95%CI: 0.46-0.82), shock (OR = 16.61, 95%CI: 7.00-39.41), and respiratory failure (OR = 47.53, 95%CI: 19.93-133.64) were independent factors. The combination of four indicators demonstrated a favorable predictive value for the 60-day outcome of patients with BSI, with an area under the ROC of 0.96 (95%CI: 0.94-0.99), sensitivity of 90.65%, specificity of 94.95%, and accuracy of 94.13%. Shock, respiratory failure, albumin, and fibrinogen are potential independent prognostic factors for 60-day mortality.


Smoking characteristics and lung functions among university athletes.
Cigarette smoking has negative effects on the respiratory system, particularly pulmonary functions. This study aimed to determine smoking prevalence and characteristics among university athletes. We conducted a cross-sectional study of Thammasat University athletes in Thailand from July to October 2018. Demographic and smoking data were recorded. Exhaled carbon monoxide (CO) levels and lung function data were analysed. A total of 433 subjects (56% men) were included. Mean age was 19.8 ± 1.3 years. Asthma was reported in 5.5%. The prevalence of current cigarette smoking was 23.8%. Tobacco use was 3.0 ± 3.2 cigarettes per day. The Fagerstrom score for nicotine dependence was 0.76 ± 1.47. Compared to non-smokers, smokers were predominately males (70.6% vs 29.4%, P < 0.001), had higher exhaled CO levels (3.75 ± 3.08 ppm vs 2.18 ± 0.73 ppm, P < 0.001), higher FVC (89.65 ± 17.61% vs 83.22 ± 15.72%, P = 0.001), higher FEV1 (92.60 ± 15.36% vs 87.77 ± 11.23%, P = 0.002), but lower FEV1/FVC (78.21 ± 5.38% vs 79.70 ± 5.60%, P = 0.015). Moreover, athletes who smoke, were more likely to: drink alcohol, have a family member who smokes, have a friend who smokes or have a university instructor who smokes. In conclusion, smoking prevalence among university athletes was relatively high, although low nicotine addiction level and good lung functions were found. Home and institute environments had important influences on cigarette use in students.Trial registration: TCTR20180917001.


Space division multiplexing chip-to-chip quantum key distribution.
Quantum cryptography is set to become a key technology for future secure communications. However, to get maximum benefit in communication networks, transmission links will need to be shared among several quantum keys for several independent users. Such links will enable switching in quantum network nodes of the quantum keys to their respective destinations. In this paper we present an experimental demonstration of a photonic integrated silicon chip quantum key distribution protocols based on space division multiplexing (SDM), through multicore fiber technology. Parallel and independent quantum keys are obtained, which are useful in crypto-systems and future quantum network.


Mechanisms of killing spores of Bacillus subtilis by acid, alkali and ethanol.
To determine the mechanisms of killing of Bacillus subtilis spores by ethanol or strong acid or alkali. Killing of B. subtilis spores by ethanol or strong acid or alkali was not through DNA damage and the spore coats did not protect spores against these agents. Spores treated with ethanol or acid released their dipicolinic acid (DPA) in parallel with spore killing and the core wet density of ethanol- or acid-killed spores fell to a value close to that for untreated spores lacking DPA. The core regions of spores killed by these two agents were stained by nucleic acid stains that do not penetrate into the core of untreated spores and acid-killed spores appeared to have ruptured. Spores killed by these two agents also did not germinate in nutrient and non-nutrient germinants and were not recovered by lysozyme treatment. Spores killed by alkali did not lose their DPA, did not exhibit a decrease in their core wet density and their cores were not stained by nucleic acid stains. Alkali-killed spores released their DPA upon initiation of spore germination, but did not initiate metabolism and degraded their cortex very poorly. However, spores apparently killed by alkali were recovered by lysozyme treatment. The data suggest that spore killing by ethanol and strong acid involves the disruption of a spore permeability barrier, while spore killing by strong alkali is due to the inactivation of spore cortex lytic enzymes. The results provide further information on the mechanisms of spore killing by various chemicals.


Prognosis of 6644 resected non-small cell lung cancers in Japan: a Japanese lung cancer registry study.
For the scheduled future revision of the TNM staging system for lung cancer, it is important that the present 1997 version be evaluated in a large population. In 2001, the Japanese Joint Committee of Lung Cancer Registry sent a questionnaire to 320 Japanese institutions regarding the prognosis and clinicopathological profiles of patients who underwent the resection for primary lung neoplasms in 1994. We compiled the data for 7408 patients from 303 institutions (94.7%). Among these, 6644 patients with non-small cell histology were studied in terms of prognosis. The 5-year survival rate of the entire group was 52.6%. The 5-year survival rates by clinical (c-) stage were as follows: 72.1% for IA (n = 2423), 49.9% for IB (n = 1542), 48.7% for IIA (n = 150), 40.6% for IIB (n = 746), 35.8% for IIIA (n = 1270), 28.0% for IIIB (n = 366) and 20.8% for IV (n = 147). The difference in prognosis between neighboring stages was significant except for between IB and IIA and between IIIB and IV. The 5-year survival rates by pathological (p-) stage were as follows: 79.5% for IA (n = 2009), 60.1% for IB (n = 1418), 59.9% for IIA (n = 232), 42.2% for IIB (n = 757), 29.8% for IIIA (n = 1250), 19.3% for IIIB (n = 719) and 20.0% for IV (n = 259). The difference in prognosis between neighboring stages was significant except for between IB and IIA and between IIIB and IV. The survival curves of stages IB and IIA were almost superimposed in both c- and p-settings. These findings indicated that the present stages IB and IIA should be merged into the same stage category. Otherwise, the present TNM staging system seemed to well characterize the stage-specific prognosis in non-small cell lung cancer. The future revision should focus on the subdivision of stages I and II.


Microsatellite polymorphism in the heme oxygenase-1 gene promoter and cardiac allograft vasculopathy.
The heme oxygenase-1 (HO-1) isoenzyme has recently been suggested to protect transplants from ischemia-reperfusion and immunologic injury. Inducibility of this enzyme is modulated by a (GT)n dinucleotide length polymorphism in the HO-1 gene promoter. Short (class S) repeats are associated with greater up-regulation of HO-1 than are long repeats. In the present study, we investigated the impact of the promoter polymorphism on the development of cardiac allograft vasculopathy (CAV) in human heart transplants. We enrolled 152 recipients of a heart allograft with at least 1 year survival post-transplantation in this retrospective study. The HO-1 genotype was assessed using genomic DNA isolated from paraffin-embedded allograft biopsy specimens. Patients were followed angiographically for CAV. Angiographic vessel-wall abnormalities were defined as CAV, and a stenosis of more than 50% in at least 1 vessel area was defined as severe CAV. Eighty-seven patients (57%) had received a heart from a donor with at least 1 class S allele. Within the mean follow-up period of 9 years, 95 patients (63%) showed signs of CAV, among which 60 patients (40%) developed severe CAV. The frequency of CAV and severe CAV was not significantly different between class S allele recipients and non-recipients (CAV, 57/87 vs 38/65, p = 0.12; severe CAV, 35/87 vs 25/65, p = 0.30). In contrast to recent findings in renal allografts and vascular injury, the HO-1 gene promoter polymorphism does not show an association with the development of CAV in heart transplants.


Chronic fluoxetine treatment attenuates post-septic affective changes in the mouse.
It has been previously demonstrated that the induction of sepsis in rodents results in persistent impairments in affective and cognitive domains. In this study we have examined the impact of chronic treatment with the antidepressant fluoxetine on affective behaviours and hippocampal neuroinflammation and stem cell proliferation in animals that have previously undergone sepsis induced by peripheral treatment with lipopolysaccharide. We find that fluoxetine significantly attenuates post-septic increases in behavioural despair and motivated exploration, whilst also reversing the effects of previous sepsis on activated microglia and stem cell proliferation. These results indicate that conventional antidepressants may be effective in the management of mood disorders in survivors of sepsis.


Skeletal age estimation based on medial clavicle--a test of the method reliability.
In order to establish a reliable age indicator in the period when all other epiphyseal age indicators have already been inactivated, medial clavicle as the bone with the longest period of growth became the object of various investigations. However, the lack of population-specific method often made it unreliable in some regions. The current study involved a Balkan population and it was designed in order to examine whether morphological, radiological, and histological analyses of medial clavicles could be applied with success in age assessment of individuals beyond their twenties in anthropological and forensic practice. The medial clavicular specimens were collected from contemporary Serbian population, autopsied in the period from 1998 to 2001, encompassing 67 individuals (42 males and 25 females) with the age range from 20 to 90 years. The conducted analyses of morphological features identified the epiphyseal union timing, signs of lipping in the region of the notch for the first rib as well as exostoses and bone overgrowths of the articular surface margin as age-dependent attributes. Trabecular bone volume fraction and minimum trabecular width were also highlighted as age-distinctive microscopic features. Sex difference was ascertainable in epiphyseal union timing, morphology of the notch for the first rib, margin of the articular surface, and basic morphology of articular surface as well as in two microscopic characteristics: trabecular bone volume fraction and minimum trabecular width. The study managed to identify several age- and sex-related features that could be applied as additional guidance for age estimation in Serbian population.


Cyclic AMP and cyclic GMP in germinating conidia of Neurospora crassa.
A new method for obtaining synchronous germination allowed accurate time-course studies of endogenous levels of cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-phosphate in germinating conidia of Neurospora crassa. The levels of both cyclic nucleotides remained constant throughout germination, showing that they neither signal nor respond to any of the biochemical changes which are known to occur in the germination process. Conidal germination was approximately normal in three cr-1 mutants of Neurospora which have been shown to be deficient in adenylate cyclase activity. Cyclic AMP levels in the mycelia of cr-1 mutants were low, but surprisingly, the levels in conidia were normal.


The TNFα/TNFR2 axis mediates natural killer cell proliferation by promoting aerobic glycolysis.
Natural killer (NK) cells are predominant innate lymphocytes that initiate the early immune response during infection. NK cells undergo a metabolic switch to fuel augmented proliferation and activation following infection. Tumor necrosis factor-alpha (TNFα) is a well-known inflammatory cytokine that enhances NK cell function; however, the mechanism underlying NK cell proliferation in response to TNFα is not well established. Here, we demonstrated that upon infection/inflammation, NK cells upregulate the expression of TNF receptor 2 (TNFR2), which is associated with increased proliferation, metabolic activity, and effector function. Notably, IL-18 can induce TNFR2 expression in NK cells, augmenting their sensitivity toward TNFα. Mechanistically, TNFα-TNFR2 signaling upregulates the expression of CD25 (IL-2Rα) and nutrient transporters in NK cells, leading to a metabolic switch toward aerobic glycolysis. Transcriptomic analysis revealed significantly reduced expression levels of genes involved in cellular metabolism and proliferation in NK cells from TNFR2 KO mice. Accordingly, our data affirmed that genetic ablation of TNFR2 curtails CD25 upregulation and TNFα-induced glycolysis, leading to impaired NK cell proliferation and antiviral function during MCMV infection in vivo. Collectively, our results delineate the crucial role of the TNFα-TNFR2 axis in NK cell proliferation, glycolysis, and effector function.


The liquid condensed diffusional transition of dipalmitoylphosphoglycerocholine in monolayers.
The fine details of the phase transition of dipalmitoylphosphoglycerocholine (DPPC) monolayers at air/NaCl solution interfaces were investigated at 21 +/- 1 degrees C by using the fluorescence after photobleaching technique employing 12-(9-anthroyloxy)stearic acid as fluorescent probe. The mode of compression of the monolayer (i.e., continuous compression or successive additions of the lipid at fixed area) together with the ionic strength of the subphase (0.1 or 1.0 M NaCl) were particularly studied. The photobleaching results show that the lateral diffusion coefficient of the probe molecules decreases drastically within the liquid-condensed phase, i.e., from the end of the liquid-expanded-liquid-condensed phase transition to the beginning of the solid-condensed phase. The molecular areas at which the phase transition occurs under the various experimental conditions, together with a parallel analysis of the hydration states and related molecular areas of the DPPC molecules in multilayers, strongly suggest that the steric hindrance associated with the hydration water of the polar head of DPPC molecules in the monolayer is responsible for the drastic decrease in diffusion coefficient in the liquid-condensed phase. Furthermore, the fluorescence characteristics of the probe molecules also show that, together with the aforementioned reorganization of the polar head, a structural reorganization of the aliphatic chains of the lipid molecules also takes place in the liquid-condensed phase. The liquid-condensed phase therefore appears as a transition region from liquid to solid phases in which the lipid molecules present a significant decrease in their lateral diffusion related to a structural reorganization of both their polar and aliphatic components.


A dual role in regulation and toxicity for the disordered N-terminus of the toxin GraT.
Bacterial toxin-antitoxin (TA) modules are tightly regulated to maintain growth in favorable conditions or growth arrest during stress. A typical regulatory strategy involves the antitoxin binding and repressing its own promoter while the toxin often acts as a co-repressor. Here we show that Pseudomonas putida graTA-encoded antitoxin GraA and toxin GraT differ from other TA proteins in the sense that not the antitoxin but the toxin possesses a flexible region. GraA auto-represses the graTA promoter: two GraA dimers bind cooperatively at opposite sides of the operator sequence. Contrary to other TA modules, GraT is a de-repressor of the graTA promoter as its N-terminal disordered segment prevents the binding of the GraT2A2 complex to the operator. Removal of this region restores operator binding and abrogates Gr aT toxicity. GraTA represents a TA module where a flexible region in the toxin rather than in the antitoxin controls operon expression and toxin activity.


Agranulocytosis, aplastic anemia, and leukemia: relevance to arachidonic acid metabolism.
Several agents including drugs, chemicals and viruses are known to induce agranulocytosis, aplastic anemia, and leukemia. The recent identification, characterization and cloning of several peptide regulatory factors, including granulocyte-macrophage-colony stimulating peptide regulatory factor (GM-CSF), erythropoietin, and interleukins and a study of their actions, suggest that agents producing agranulocytosis, aplastic anemia, and leukemia may interfere with the action of these factors. The agents that are capable of inducing these diseases and the various peptide regulatory factors have positive and/or negative actions on the prostaglandin system. Prostaglandins are known to be involved in the maturation and differentiation of the progenitor cells of the bone marrow and in erythropoietin-mediated erythropoiesis. Since prostaglandins influence immune response, modify genetic damage induced by drugs and chemicals, modulate gene action, and have feed-back control on the actions of peptic regulatory factors, it is likely that prostaglandins are involved in the pathogenesis of agranulocytosis, aplastic anemia, and leukemia. If so, this may lead to new therapeutic strategies in these hematological conditions.


At the core of nucleotide excision repair.
Nucleotide excision repair (NER) is unique in its ability to identify and remove vastly different lesions from DNA. Recent advances in the structural characterization of complexes involved in detection, verification, and excision of damaged DNA have reshaped our understanding of the molecular architecture of this efficient and accurate machinery. Initial damage recognition achieved through transcription coupled repair (TC-NER) or global genome repair (GG-NER) has been addressed by complexes of RNA Pol II with different TC-NER factors and XPC/RAD23B/Centrin-2 with TFIIH, respectively. Moreover, transcription factor IIH (TFIIH), one of the core repair factors and a central NER hub was resolved in different states, providing important insights how this complex facilitates DNA opening and damage verification. Combined, these recent advances led to a highly improved understanding of the molecular landscape of NER core processes, sharpening our view on how NER is successfully achieved.


Mortality of Escalation and Modulation Antithrombotic Therapy in Coronary Artery Disease Patients: A Meta-analysis of Randomized Controlled Trials.
The net clinical benefit of antithrombotic therapy (ATT) reflects the concomitant effects of bleeding and ischemic events. We sought to assess the overall effect of the modulation or escalation of ATT on all-cause mortality as well as ischemic and bleeding events. We performed a meta-analysis of randomized controlled trials comparing escalation or modulation of ATT versus standard ATT in patients with coronary artery disease. A total of 32 studies with 160,659 subjects were enrolled in this analysis. Neither escalation nor modulation of ATT has significant effect on all-cause mortality (escalation: relative risk [RR]: 0.94, 95% confidence interval [CI]: 0.85-1.04; modulation: RR: 0.90; 95% CI: 0.81-1.01). Compared with standard ATT therapy, escalation of ATT was associated with lower risk of myocardial infarction (MI; RR: 0.84, 95% CI: 0.76-0.94), but had a higher risk of major or minor bleeding (RR: 1.38, 95% CI: 1.15-1.66). Modulation of ATT was associated with a similar risk of MI (RR: 1.07, 95% CI: 0.96-1.19), but a reduced risk for major or minor bleeding (RR: 0.58, 95% CI: 0.51-0.66). Meta-regression combining both escalation and modulation studies found that the heterogeneity of all-cause mortality was mainly attributed to the heterogeneity of major or minor bleeding (adjusted R-squared = 100.00%, p = 0.004), but not to MI. Either escalation or modulation of ATT has little benefit in all-cause mortality. The variability of the treatment effects on all-cause mortality was mainly attributed to the variability of major or minor bleeding, but not to MI.


Myocardial protection for coronary bypass grafting: the Toronto Hospital perspective.
The contemporary results of coronary artery bypass grafting using a variety of myocardial preservation techniques are excellent. In recent years, the number of "high-risk" patients referred for operation has increased, thus necessitating continued advances in surgical myocardial protection. In this article, we review recent advances in clinical myocardial protective techniques and emphasize studies conducted at The Toronto Hospital. Further, on the basis of promising current research, we speculate on future prospects for myocardial protection. At The Toronto Hospital, we converted from crystalloid to intermittent cold blood cardioplegia in 1985. We demonstrated that "continuous" cardioplegic strategies may help resuscitate the ischemic myocardium and reduce operative complications in high-risk patients. Further improvements in myocardial protection will require refinements in cardioplegic solution temperature, direction of delivery, and additives to "precondition" the myocardium against ischemic damage. Major advances that meet the requirements of an increasingly high risk patient population have been made in surgical myocardial protection in recent years. The future is bright for continued progress in this area.


An Update on Perinatal Cannabis Use.
Since the legalization of non-medical cannabis, many questions have arisen regarding cannabis use during pregnancy. Obstetrical care providers can minimize the harms of prenatal cannabis use using evidence-based information. This commentary describes populations at highest risk for use, the predictors of use, the reasons birthing people continue or stop using cannabis during pregnancy, and short- and long-term outcomes for infants and children exposed to cannabis prenatally. Our goal is to equip providers with knowledge from the literature to inform practical decision-making.


Lichen sclerosus and eosinophilic fasciitis as manifestations of chronic graft-versus-host disease: expanding the sclerodermoid spectrum.
Chronic cutaneous graft-versus-host disease (GVHD) is classically divided into two major clinical categories--lichenoid and sclerodermoid. Although diffuse areas of sclerosis as in scleroderma characterize the more advanced stages of the sclerodermoid form, the initial circumscribed plaques would be more correctly described as morpheaform. Eosinophilic fasciitis (EF) (a fibrosing disorder related to deep morphea) and lichen sclerosus (LS) have also been reported as manifestations of sclerodermoid GVHD. However, these two presentations of GVHD have not been emphasized in the dermatologic literature. We describe 6 patients, all of whom developed LS and two of whom also developed EF in the context of chronic GVHD. Each patient presented clinically with hypopigmented plaques that exhibited wrinkling, scaling, and follicular plugging. These lesions demonstrated the classic histologic features of LS including epidermal atrophy; a subepidermal zone of pale-staining, homogenized collagen; and a bandlike lymphocytic infiltrate. Although all patients eventually developed morpheaform and/or sclerodermoid GVHD, LS was a prominent part of the initial presentation of chronic cutaneous GVHD in every case. The LS lesions tended to occur on the neck and upper to mid aspect of the trunk, whereas morpheaform lesions favored the lower aspect of the trunk. EF involved the extremities (sparing the hands and feet), and was characterized clinically by an acute onset of pain and edema followed by induration with a rippled appearance. This case series serves to expand the spectrum of sclerodermoid GVHD, with LS as the most superficial and EF as its deepest manifestation.


Increased fragmentation of rest-activity patterns is associated with a characteristic pattern of cognitive impairment in older individuals.
Aging is accompanied by changes in cognitive function, and changes in rest-activity patterns. Previous work has demonstrated associations between global rest-activity measures and cognitive performance on a number of tasks. Recently, we demonstrated that aging is associated with changes in the minute-to-minute fragmentation of rest-activity patterns in addition to changes in amounts of rest and activity. Given the body of experimental evidence linking sleep fragmentation with decrements in cognitive function in animals and humans, we hypothesized that increased fragmentation of rest-activity patterns would be associated with decreased cognitive function in older individuals. Cross-sectional. 700 community-dwelling individuals from the Rush Memory and Aging Project. We obtained up to 11 days of actigraphic recordings in subjects' home environments and quantified the fragmentation of rest and activity using a recently developed state transition metric. We tested the associations between this metric and performance in 5 cognitive domains. Greater fragmentation of both rest and activity were associated with lower levels of cognitive performance, and this association was independent of total amounts of rest or activity. There was a characteristic pattern of cognitive deficits associated with rest and activity fragmentation, with preferential involvement of perceptual speed, semantic memory, working memory, and visuospatial abilities, and relative sparing of episodic memory. The fragmentation of periods of rest and activity is a clinically important characteristic of rest-activity patterns that correlates with cognitive performance in older individuals.


High-rate biological denitrification in the cyclic rotating-bed biological reactor: Effect of COD/NO3(-), nitrate concentration and salinity and the phylogenetic analysis of denitrifiers.
The effects of COD/NO3(-) ratio, nitrate concentration and salinity was tested on the performance of the CRBR in denitrification with catechol as carbon source. The maximum nitrate reduction attained at COD/NO3(-) ratio of 1. The CRBR operated at optimum COD/NO3(-) ratio could completely denitrify the nitrate at inlet concentration up to 1250mg/L without nitrite accumulation. The maximum denitrification rate in the CRBR was 3.56kgNO3(-)/m(3)d with a nitrate reduction efficiency of 99% when the bioreactor was operated at inlet nitrate loading rate of 3.6kgNO3(-)/m(3)d. The denitrification performance of the CRBR was not affected significantly by NaCl concentrations up to 20g/L. 16S rRNA fragment and phylogenetic analysis identified Pseudomonas resinovorans, Stenotrophomonas maltophilia and Bacillus cereus as the most abundant denitrifiers in biomass. Accordingly, the CRBR is a high-rate bioreactor and appropriate technology for treatment of nitrate-laden industrial wastewaters containing phenolic compounds and salinity.


Strabismus After Ahmed Glaucoma Valve Implantation.
Most reports of strabismus after glaucoma drainage device implantation study larger devices and rarely note the incidence of strabismus after Ahmed glaucoma valve (AGV) implantation. It is unknown if the pattern of strabismus is similar with smaller devices. We investigated characteristics of strabismus after AGV implantation. Retrospective review. Institutional study of 732 patients at our institution undergoing AGV implantation between 2013 and 2018. Rate and characteristics of strabismus were the primary outcome; age, gender, and location of AGVs were also analyzed. We identified 29 patients who developed new-onset strabismus postoperatively after initial AGV implantation, for 4% incidence of strabismus. Twenty-one (72%) of these had diplopia. AGVs were implanted superotemporally in 21, superonasally in 5, inferotemporally in 1, and inferonasally in 2. Three patients were esotropic, 11 were exotropic, 4 had hypertropia, 2 had hypotropia, and 9 patients had combined horizontal/vertical strabismus (esotropia/hypotropia [n = 1] or exotropia/hypertropias [n = 8]). Exotropia was the most common type of strabismus in both the superotemporal and superonasal (60%) AGV groups. Superotemporal AGVs were more commonly associated with ipsilateral hypertropia (43%) than superonasal AGVs. Treatments included strabismus surgery (n = 14), prisms (n = 6), or an occlusive lens (n = 1). In the largest single-center series of patients undergoing initial AGV implantation, the overall incidence of postoperative strabismus was 4%. This is comparable to strabismus incidence following implantation of other types of glaucoma drainage devices, even larger devices. The possibility of this complication should be discussed with patients prior to surgery.


Cryo-EM structures of the human surfactant lipid transporter ABCA3.
The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter ABCA3 plays a critical role in pulmonary surfactant biogenesis. Mutations in human ABCA3 have been recognized as the most frequent causes of inherited surfactant dysfunction disorders. Despite two decades of research, in vitro biochemical and structural studies of ABCA3 are still lacking. Here, we report the cryo-EM structures of human ABCA3 in two distinct conformations, both at resolution of 3.3 Å. In the absence of ATP, ABCA3 adopts a "lateral-opening" conformation with the lateral surfaces of transmembrane domains (TMDs) exposed to the membrane and features two positively charged cavities within the TMDs as potential substrate binding sites. ATP binding induces pronounced conformational changes, resulting in the collapse of the potential substrate binding cavities. Our results help to rationalize the disease-causing mutations in human ABCA3 and suggest a conserved "lateral access and extrusion" mechanism for both lipid export and import mediated by ABCA transporters.


Risk factors for non-invasive/invasive ventilatory support in patients with COVID-19 pneumonia: A retrospective study within a multidisciplinary approach.
To investigate risk factors for non-invasive/invasive ventilatory support (NI/I-VS) in patients with coronavirus disease 2019 (COVID-19). All consecutive patients admitted to the Infectious Diseases Unit and Intensive Care Unit (ICU) of Santa Maria Annunziata Hospital (Florence, Italy), from February 25 to April 25, 2020, with a confirmed COVID-19 diagnosis were enrolled in this retrospective cohort study. NI/I-VS was defined as the need for continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BPAP) (non-invasive ventilation) or mechanical ventilation, not including low-flow systems of oxygen therapy such as the Venturi mask or nasal cannula. Ninety-seven patients were enrolled; 61.9% (60/97) were male and the median patient age was 64 years. The in-hospital mortality was 9.3%. Thirty-five of the 97 patients (36%) required ICU admission and 94.8% (92/97) were prescribed oxygen therapy: 10.8% (10/92) by nasal cannula, 44.5% (41/92) by Venturi mask, 31.5% (29/92) by CPAP, 2.2% (2/92) by BPAP, and 10.8% (10/92) by mechanical ventilation following intubation. On univariate analysis, patients with a body mass index >30, type II diabetes mellitus, and those presenting with dyspnoea, asthenia, SOFA score ≥2 points, PaO2/FiO2 <300, temperature >38 °C, increased levels of lactate dehydrogenase (LDH), alanine aminotransferase, and C-reactive protein, and a d-dimer >1000 ng/mL at admission more frequently underwent NI/I-VS. Multivariate logistic regression analysis confirmed temperature >38 °C (odds ratio (OR) 21.2, 95% confidential interval (95% CI) 3.5-124.5, p = 0.001), LDH >250 U/l (OR 15.2, 95% CI 1.8-128.8, p = 0.012), and d-dimer >1000 ng/mL (OR 4.5, 95% CI 1.2-17.3, p = 0.027) as significantly associated with the requirement for NI/I-VS. A non-significant trend (p = 0.051) was described for PaO2/FiO2 <300. Temperature >38 °C, LDH > 250 U/l, and d-dimer >1000 ng/mL were found to be independent risk factors for NI/I-VS in COVID-19 patients. In order to quickly identify patients likely at risk of developing a critical illness, inflammatory markers should be assessed upon hospital admission.


Risk factors of mortality among patients hospitalised with COVID-19 in a critical care or hospital care unit: analysis of the French national medicoadministrative database.
To explore mortality risk factors for patients hospitalised with COVID-19 in a critical care unit (CCU) or a hospital care unit (HCU). Retrospective cohort analysis using the French national (Programme de médicalisation des systèmes d'information) database. Any public or private hospital in France. 98 366 patients admitted with COVID-19 for more than 1 day during the first semester of 2020 were included. The underlying conditions were retrieved for all contiguous stays. In-hospital mortality and associated risk factors were assessed using frailty Cox models. Among the 98 366 patients included, 25 765 (26%) were admitted to a CCU. The median age was 66 (IQR: 55-76) years in CCUs and 74 (IQR: 57-85) years in HCUs. Age was the main risk factor of death in both CCUs and HCUs, with adjusted HRs (aHRs) in CCUs increasing from 1.60 (95% CI 1.35 to 1.88) for 46 to 65 years to 8.17 (95% CI 6.86 to 9.72) for ≥85 years. In HCUs, the aHR associated with age was more than two times higher. The gender was not significantly associated with death, aHR 1.03 (95% CI 0.98 to 1.09, p=0.2693) in CCUs. Most of the underlying chronic conditions were risk factors for death, including malignant neoplasm (CCU: 1.34 (95% CI 1.25 to 1.43); HCU: 1.41 (95% CI 1.35 to 1.47)), cirrhosis without transplant (1.41 (95% CI 1.22 to 1.64); 1.27 (95% CI 1.12 to 1.45)) and dementia (1.30 (95% CI 1.16 to 1.46); 1.07 (95% CI 1.03 to 1.12)). This analysis confirms the role of age as the major risk factor of death in patients with COVID-19 irrespective to admission to critical care and therefore supports the current vaccination policies targeting older individuals.


Exogenous H2S prevents high glucose-induced damage to osteoblasts through regulation of KATP channels.
Association between diabetes and osteoporosis has been extensively investigated. However, whether the effects of H2S on osteoblast function under high glucose (HG) condition relate to ATP-sensitive potassium (KATP) channels is unclear. This study aimed to investigate the effects of H2S on the proliferation, apoptosis, and mineralization of osteoblasts under HG condition, and observe whether H2S exert this effect through the KATP channels. Primary osteoblasts (POBs) were obtained from the calvaria of Sprague-Dawley rats. Cells were pre-treated with 400 μmol/L NaHS (a H2S donor), and/or 0.1 mmol/L non-selective KATP channel opener pinacidil (Pia), and/or KATP channel inhibitor glibenclamide (Gli). They then were cultured in DMEM with 26.5 mmol/L (HG) or 5.5 mmol/L (control) glucose. Cell proliferation, apoptosis, and mineralization were determined. In addition, the expression of KATP SUR1 was also determined. NaHS pretreatment significantly inhibited the down-regulation of KATP SUR1 expression in POBs. NaHS also significantly prevented osteoblast injury induced by HG, through decreasing the rate of cell proliferation and increasing the number of apoptotic cells, which was similar with the effects of Pia. In addition, NaHS significantly deterred the HG-induced POB mineralization inhibition. H2S prevents the HG-induced osteoblast damage through regulating KATP channels.


Communicating pancreatic and splenic pseudocysts: A case report.
A splenic pseudocyst is an encapsulated mature collection located within the splenic tissues. It is usually asymptomatic and is detected incidentally during either radiological workup or laparoscopy for other reasons. Our patient is a 66-year-old male presenting with a history of weight loss, early satiety, and constipation, found to have a splenic pseudocyst communicating with a preexisting pancreatic cyst. Cystic lesions of the spleen can be divided into primary and secondary types. Secondary splenic cysts (pseudocysts) are residues of either earlier infection, trauma, or infarction. Management approaches to splenic cysts are either conservative or surgical according to the symptoms and size of these cysts. Most splenic cysts are discovered incidentally either during radiological workup or laparoscopy. Such entities require the combined effort of surgeons, gastroenterologists, and radiologists to provide the maximum care for these patients.


Defining animal welfare standards in hunting: body mass determines thresholds for incapacitation time and flight distance.
Shooting is an important tool for managing terrestrial wildlife populations worldwide. To date, however, there has been few quantitative methods available enabling assessment of the animal welfare outcomes of rifle hunting. We apply a variety of factors to model flight distance (distance travelled by an animal after bullet impact) and incapacitation from the moment of bullet impact. These factors include body mass, allometric and isometric scaling, comparative physiology, wound ballistics and linear kinematics. This approach provides for the first time a method for quantifying and grading the quality of shooting processes by examining only body mass and flight distance. Our model is a universally applicable tool for measuring animal welfare outcomes of shooting regimes both within and among species. For management agencies the model should be a practical tool for monitoring and evaluating animal welfare outcomes regarding shooting of mammalian populations.


[The treatment of melanoma of the choroid using localized radiation of cobalt 60 applicators (author's transl)].
Sixty one cases of melanoma of the choroid have been treated conservatively in our Department over the last 9 years, using Cobalt 60 applicators. Analysis of these cases has shown that the tumours most susceptible to, and which react favourably to this treatment, are those of less than 11 mm diameter which are not in contact either with the macula or the optic nerve.


The influence of liver dysfunction on the pharmacokinetics of carprofen.
The pharmacokinetics of the investigational agent carprofen were examined in 12 patients with liver dysfunction (hepatic cirrhosis) and in six normal volunteers following single 100-mg oral administration of carprofen. In addition, three patients with acute hepatitis received a single 100-mg dose during the acute phase of the disease, and two of these patients received the same dose after they had convalesced. The pharmacokinetic parameters and urinary excretion data did not differ significantly (P greater than 0.05) between patients with hepatic cirrhosis and healthy volunteers. The mean +/- SD area under plasma concentration-time curve and apparent oral plasma clearance values were 57.8 +/- 11.7 micrograms X h/mL and 30.0 +/- 6.3 mL/min, respectively, in patients and 52.4 +/- 11.3 micrograms X h/mL and 33.1 +/- 7.2 mL/min in normals. The respective harmonic mean elimination half-lives were 10.5 and 9.4 hours. The 0-24 hour urinary recovery of intact drug and the glucuronide conjugate were 7.0 +/- 4.9% and 28.9 +/- 11.0%, respectively, in patients compared to 5.5 +/- 7.1% and 20.1 +/- 12.3% in normal subjects. The results of this study showed that liver dysfunction (hepatic cirrhosis) had no effect on the pharmacokinetic profile of carprofen. In the two patients with acute hepatitis who completed the study, the results suggest that the apparent oral clearance of carprofen may increase during the acute phase of the disease.


Influence of seed and root exudations on the rhizosphere effect in Sorghum vulgare and Crotalaria juncea.
The influence of seed and root exudations on the rhizosphere effect of Sorghum vulgare and Crotalaria juncea was examined. While the quantitative occurrence of certain morphological and physiological groups of bacteria on the seeds and rhizospheres of the two plant species differed, there were similarities in the occurrence of certain physiological and nutritional groups of bacteria on the seed as well as on the rhizosphere. The occurrence of some genera of fungi on the seeds and in the rhizosphere indicated the influence of both seeds and root exudations on the rhizosphere effect. Increase in root exudations of amino acids and sugars correlated with a concomitant increase in microbial activity in the rhizosphere on the 15th day of growth in both plant species but there was a delayed effect of the exuded chemicals on the rhizosphere microflora after 30 d of plant growth.


The power of the 3' UTR: translational control and development.
Many crucial decisions, such as the location and timing of cell division, cell-fate determination, and embryonic axes establishment, are made in the early embryo, a time in development when there is often little or no transcription. For this reason, the control of variation in gene expression in the early embryo often relies on post-transcriptional control of maternal genes. Although the early embryo is rife with translational control, controlling mRNA activity is also important in other developmental processes, such as stem-cell proliferation, sex determination, neurogenesis and erythropoiesis.


Fertility stakeholders' concerns regarding payment for egg and sperm donation in New Zealand and Australia.
New Zealand and Australia are countries which currently prohibit donor payment and require open-identity forms of donation. This study explored the concerns of fertility stakeholders regarding payment which would constitute financial reward for gamete donation, and factors predicting such concerns. A total of 434 participants from across New Zealand and Australia completed an online survey anonymously. Participants included those with infertility and treatment experience, donors, recipients, donor-conceived people and clinic professionals. Results indicated that participants' concerns related to their assumptions about the type of donor motivated by financial reward, and the possibility that, if paid, donors might conceal information relevant to treatment and the donor-conceived person. Furthermore, participants were concerned about increasing recipient costs. Participants with personal experience of infertility held stronger concerns overall. Professionals expressed concerns of clinical relevance, such as the withholding of donor information relevant to treatment outcomes. The lowest levels of concern were expressed in relation to payment devaluing the meaning of human life. Qualitatively, themes highlighted concerns regarding payment enticing the 'wrong' type of donor, increased cost to recipients, and concern about the wellbeing of donor-offspring. Collectively, such concerns must be understood against the New Zealand and Australia open-identity donation context which enables the possibility of contact between donors and offspring. These findings indicate that donor recruitment campaigns need to account for different stakeholder concerns, and consider ways to address donor shortages effectively while remaining compliant with legislative requirements.


Deadspace estimation from CO2 versus molar mass measurements in infants.
Estimation of respiratory deadspace is often based on the CO2 expirogram, however presence of the CO2 sensor increases equipment deadspace, which in turn influences breathing pattern and calculation of lung volume. In addition, it is necessary to correct for the delay between the sensor and flow signals. We propose a new method for estimation of effective deadspace using the molar mass (MM) signal from an ultrasonic flowmeter device, which does not require delay correction. We hypothesize that this estimation is correlated with that calculated from the CO2 signal using the Fowler method. Breath-by-breath CO2, MM and flow measurements were made in a group of 77 term-born healthy infants. Fowler deadspace (Vd,Fowler) was calculated after correcting for the flow-dependent delay in the CO2 signal. Deadspace estimated from the MM signal (Vd,MM) was defined as the volume passing through the flowhead between start of expiration and the 10% rise point in MM. Correlation (r = 0.456, P < 0.0001) was found between Vd,MM and Vd,Fowler averaged over all measurements, with a mean difference of -1.4% (95% CI -4.1 to 1.3%). Vd,MM ranged from 6.6 to 11.4 ml between subjects, while Vd,Fowler ranged from 5.9 to 12.0 ml. Mean intra-measurement CV over 5-10 breaths was 7.8 +/- 5.6% for Vd,MM and 7.8 +/- 3.7% for Vd,Fowler. Mean intra-subject CV was 6.0 +/- 4.5% for Vd,MM and 8.3 +/- 5.9% for Vd,Fowler. Correcting for the CO2 signal delay resulted in a 12% difference (P = 0.022) in Vd,Fowler. Vd,MM could be obtained more frequently than Vd,Fowler in infants with CLD, with a high variability. Use of the MM signal provides a feasible estimate of Fowler deadspace without introducing additional equipment deadspace. The simple calculation without need for delay correction makes individual adjustment for deadspace in FRC measurements possible. This is especially important given the relative large range of deadspace seen in this homogeneous group of infants.


Effect of prostaglandins E1 and F2 alpha on neuromuscular transmission in the frog sartorius muscle.
End plate potentials (e.p.p.s.) and miniature end plate potentials (m.e.p.p.s.) were recorded intracellularly at the neuromuscular junction of the frog sartorius muscle. Addition of as little as 8.5 x10(-8)M PGE1 reduced the mean m.e.p.p. frequency. The mean amplitude of m.e.p.p.s was not changed, the mean amplitude of the e.p.p.s and the quantum content of the transmitter released by a nerve impulse was slightly reduced. A decrease in mean m.e.p.p. frequency was also seen in response to the administration of 8.5 x 10(-8)M PG2 alpha. The mean amplitude of e.p.p.s and m.e.p.p.s and the quantum content remained unchanged. The possible presynaptic mode of action of PGs in the preparation of discussed.


Newborn with transverse facial cleft associated with polyhydramnios.
We describe here the case of a female newborn baby with a bilateral complete transverse facial cleft. Obstetrical ultrasound had revealed an increased amount of amniotic fluid from 28 weeks' gestation without fetal hydrops or congenital anomalies. A 1900-g baby girl born at 36 weeks' gestation presented with bilateral wide facial clefts with macrostomia, microphthalmia, nose, and auricular deformities. Her breathing was dependent on life support, which was discontinued 2 hours after birth. An autopsy revealed no congenital malformations in vital organs but the absence of the olfactory nerves. Polyhydramnios and respiratory arrest after birth were presumed to be due to central disintegration of swallowing and breathing, in this case with brain anomaly.


Variation of the glenohumeral and scapulothoracic motion in progressive severity of glenohumeral osteoarthritis.
The aim of this study is to investigate the variation of the glenohumeral and scapulothoracic motion in progressive severity of glenohumeral osteoarthritis using a 3-D-motion analysis. Moreover, the variation of the Constant Score is evaluated. The hypothesis is that the motion of the scapulothoracic joint may partly compensate for the loss of the glenohumeral joint movement in patients with increasing severity of glenohumeral osteoarthritis. A total of 21 patients with primary osteoarthritis of the glenohumeral joint were clinically examined, divided in three groups (SP1-SP3) according to size of their caudal osteophyte. The contribution of the scapulothoracic (acromioclavicular and sternoclavicular) joint to the total arm (humerothoracical) elevation in sagittal and frontal plane was measured with 3D motion analysis and the Constant Score was evaluated. In sagittal plane elevation (anteversion) the contribution of the scapulothoracic joint to the total elevation was while arm raising 32.7% (SD 8.0%) in Group SP1, 36.6% (SD 11.0%) in Group SP2 and 49.6% (SD 9.0%) in Group SP3 (p=0.002). The contribution of the scapulothoracic joint to the total elevation while arm lowering was 31.4% (SD 9.0%) in Group SP1, 39.0% (SD 13.0%) in Group SP2 and 49.7% (SD 12.0%) in Group SP3 (p=0.043). In frontal plane elevation (abduction) the contribution of the scapulothoracic joint was while arm raising 33.7% (SD 8.0%) in Group SP1, 34.0% (SD 10.0%) in Group SP2 and 42.3% (SD 9.0%) in Group SP3 (p=0.071). While arm lowering the contribution of the scapulothoracic joint was 30.8% (SD 10.0%) in Group SP1, 36.3% (SD 12.0%) in Group SP2 and 44.8% (SD 8.0%) in Group SP3 (p=0.022). The group SP1 achieved a Constant Score of 78.00 (SD 9.823) points. The group SP2 achieved a Constant Score of 53.57 (SD 13.92) and the group SP3 38.64 (SD 10.40). There is a significant difference between the three groups (p<0.001). Increasing severity of glenohumeral osteoarthritis leads to a reduced motion of the glenohumeral joint. Instead the magnitude of the scapulothoracic motion increases. V, Case Series.


IPMP Global Fit - A one-step direct data analysis tool for predictive microbiology.
The objective of this work is to develop and validate a unified optimization algorithm for performing one-step global regression analysis of isothermal growth and survival curves for determination of kinetic parameters in predictive microbiology. The algorithm is incorporated with user-friendly graphical interfaces (GUIs) to develop a data analysis tool, the USDA IPMP-Global Fit. The GUIs are designed to guide the users to easily navigate through the data analysis process and properly select the initial parameters for different combinations of mathematical models. The software is developed for one-step kinetic analysis to directly construct tertiary models by minimizing the global error between the experimental observations and mathematical models. The current version of the software is specifically designed for constructing tertiary models with time and temperature as the independent model parameters in the package. The software is tested with a total of 9 different combinations of primary and secondary models for growth and survival of various microorganisms. The results of data analysis show that this software provides accurate estimates of kinetic parameters. In addition, it can be used to improve the experimental design and data collection for more accurate estimation of kinetic parameters. IPMP-Global Fit can be used in combination with the regular USDA-IPMP for solving the inverse problems and developing tertiary models in predictive microbiology.


Advances in the treatment of mitochondrial epilepsies.
Epilepsy is frequently a severe and sinister symptom in primary mitochondrial diseases, a group of more than 350 different genetic disorders characterized by mitochondrial dysfunction and extreme clinical and biochemical heterogeneity. Mitochondrial epilepsy is notoriously difficult to manage, principally because the vast majority of primary mitochondrial diseases currently lack effective therapies. Treating the underlying mitochondrial disorder is likely to be a more effective strategy than using traditional antiepileptic drugs. This review, initially presented at the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures at the Francis Crick Institute in London, summarizes the currently available and emerging therapies for mitochondrial epilepsy. Potentially treatable mitochondrial diseases include disorders of coenzyme Q10 biosynthesis and a group of mitochondrial respiratory chain complex I subunit and assembly factor defects that respond to riboflavin (vitamin B2). Approaches that have been adopted in actively recruiting clinical trials include redox modulation, harnessing mitochondrial biogenesis, using rapamycin to target mitophagy, nucleoside supplementation, and gene and cell therapies. Most of the clinical trials are at an early stage (Phase 1 or 2) and none of the currently active trials is specifically targeting mitochondrial epilepsy. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".


Efficacy of resin infiltration of proximal caries in primary molars: 1-year follow-up of a split-mouth randomized controlled clinical trial.
The main purpose of this split month, randomized, controlled clinical trial was evaluate the efficacy of caries infiltration in controlling the progression of non-cavitated proximal lesions in primary molars. Anxiety and time required for the caries infiltration was also evaluated. Fifty healthy children, 5 to 9 years, presenting two primary molars with proximal caries lesions (1/2 of the enamel or outer 1/3 of dentin), were included. Lesions were randomly allocated to the test group (fluoridated toothpaste + flossing + infiltration) or to the control group (fluoridated toothpaste + flossing). Caries risk was based on the Cariogram model. The main outcome after 1-year radiographic follow up was assessed by an independent blinded examiner A facial image scale (FIS) was applied to assess dental anxiety and time required to perform the infiltration was recorded. Of the sample, 92.9% corresponded to high or medium caries risk. In 42 patients (1-year follow up), caries progression was observed in 11.9% (5/42) of the test lesions compared with 33.3% (14/42) of the control lesions (p < 0.05). Five control and three test lesions progressed to the middle 1/3 of dentin and were restored. No side effects were observed. Anxiety was both low before and after the treatment, and mean time required for the infiltration was 11.29 min (± 1.16 min). Caries infiltration of proximal caries lesions in primary molars is significantly more efficacious than standard therapy alone (fluoride toothpaste + flossing). Caries infiltration is an applicable and well-accepted method be used in children, representing a promising micro-invasive approach.


Neurokinin-1 receptor antagonists modulate brain noradrenaline and serotonin interactions.
Substance P (neurokinin-1; NK1) receptor antagonists represent a putative new class of antidepressant/anxiolytic drugs. Using in vivo electrophysiological paradigms in rats, this study examined the effects of acute, sub-acute and long-term administration of these drugs on the firing of rat noradrenaline and serotonin (5-HT) neurons. In the locus coeruleus, neither a 2-day treatment with the tachykinin NK1 receptor antagonists [(2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl) methyl]-1-azabicyclo[2.2.2]octan-3-amine (CP-96,345, 10 mg/kg/day, i.p.), CP-99,994 (10 mg/kg/day, i.p.), nor a 14-day of treatment with (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994, 10 mg/kg/day, s.c.) significantly modified the firing rate of noradrenaline neurons. However, all these treatments attenuated the inhibitory action of the alpha(2)-adrenoceptor agonist clonidine on noradrenaline neuronal firing. While acute administration of the tachykinin NK1 receptor antagonist CP-96,345 (10 mg/kg, i.p.) attenuated the responsiveness of dorsal raphe 5-HT(1A) autoreceptors, lesioning noradrenaline neurons with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) prevented the enhancing action of a 2-day treatment with CP-96,345 on 5-HT neuronal firing, suggesting that tachykinin NK1 receptor antagonists influence 5-HT system via noradrenaline neurons independently of their firing rate.


Control of 1D wave versus 2D honeycomb CoIIICdIICuI heterotrimetallic architectures by Delta L-Lambda L diastereoisomerism of L-cysteinatocobalt(III) building units.
The reactions of the Delta L and Lambda L isomers of [Co( l-Hcys- N, S)(en) 2] (2+) ( l-H 2cys = l-cysteine) with CuCl in aqueous HCl gave Co (III)Cu (I) dinuclear complexes with the same S-bridged structures, Delta L- 1 and Lambda L- 1. When Delta L- 1 was treated with CdCl 2 in water, a 1D wavelike (Co (III) 2Cd (II)Cu (I)) n polymeric complex ( 2) was produced. On the other hand, similar treatment of Lambda L- 1 led to the formation of a 2D honeycomb-like (Co (III) 3Cd (II) 3Cu (I)) n polymeric complex ( 3), supported by the presence of counter-monoanions.


Perceptual-Speech, Nasometric, and Cephalometric Results After Modified V-Y Palatoplasties With or Without Mucosal Graft.
Although the goal of cleft palate (CP) repair is to achieve normal speech, no standard procedure ensures that patients' speech will be at the same level as speech in children without CP. In this study, postoperative speech outcomes following primary CP repair combined with or without a mucosal graft was analyzed in comparison with that of control subjects without CP. Eighty-two patients who underwent modified V-Y palatoplasty with a mucosal graft on the nasal side for symmetrical muscular reconstruction during 2006-2012 (MG group) and 109 patients who previously underwent modified V-Y palatoplasty without a mucosal graft (non-MG group) were enrolled in this study. Speech data on 37 Japanese subjects without CP were used as a control. Perceptual rating of resonance and nasal emission and nasometry were carried out for all participants. Furthermore, cephalometric analyses were performed to assess postoperative velopharyngeal morphology and velar movement. Normal resonance was achieved at a significantly higher rate (90.3% of patients) in the MG group than in the non-MG group (68.8%) (P < .01). The mean nasalance scores in the MG group were significantly lower (P < .01) and were almost at the same level as in controls. Cephalometric analyses revealed a greater velar length and velar elevation angle during phonation in the MG group (P < .01 and P < .05, respectively). Modified V-Y palatoplasty combined with a mucosal graft on the nasal side of the velum for symmetrical muscular reconstruction facilitates speech outcomes for children with cleft palate that are comparable with those for peers without CP.


Hemodynamic and recirculation performance of dual lumen cannulas for venovenous extracorporeal membrane oxygenation.
Venovenous extracorporeal membrane oxygenation (ECMO) can be performed with two single lumen cannulas (SLCs) or one dual-lumen cannula (DLC) where low recirculation fraction ([Formula: see text]) is a key performance criterion. DLCs are widely believed to have lower [Formula: see text], though these have not been directly compared. Similarly, correct positioning is considered critical although its impact is unclear. We aimed to compare two common bi-caval DLC designs and quantify [Formula: see text] in several positions. Two different commercially available DLCs were sectioned, measured, reconstructed, scaled to 27Fr and simulated in our previously published patient-averaged computational model of the right atrium (RA) and venae cavae at 2-6 L/min. One DLC was then used to simulate ± 30° and ± 60° rotation and ± 4 cm insertion depth. Both designs had low [Formula: see text] (< 7%) and similar SVC/IVC drainage fractions and pressure drops. Both cannula reinfusion ports created a high-velocity jet and high shear stresses in the cannula (> 413 Pa) and RA (> 52 Pa) even at low flow rates. Caval pressures were abnormally high (16.2-23.9 mmHg) at low flow rates. Rotation did not significantly impact [Formula: see text]. Short insertion depth increased [Formula: see text] (> 31%) for all flow rates whilst long insertion only increased [Formula: see text] at 6 L/min (24%). Our results show that DLCs have lower [Formula: see text] compared to SLCs at moderate-high flow rates (> 4 L/min), but high shear stresses. Obstruction from DLCs increases caval pressures at low flow rates, a potential reason for increased intracranial hemorrhages. Cannula rotation does not impact [Formula: see text] though correct insertion depth is critical.


Having and being an other-sex crush during early adolescence.
This study examined other-sex crush experiences (both having and being perceived as an other-sex crush) among 544 young adolescents (mean age=12.74 years). Results indicated that 56% had at least one current other-sex crush, with little overlap between crushes, friends, and boyfriends/girlfriends. Significant associations between other-sex crush scores (scores reflecting the number of crush nominations received) and physical attractiveness, relational aggression, physical aggression, and popularity, as reported by same-sex and other-sex peers, were found. In addition, crush scores were (a) associated with same-sex likeability for boys (but not girls) and (b) uniquely related to peer nominations of popularity and physical attractiveness, as reported by other-sex peers. Neither having nor being perceived as an other-sex crush was uniquely related to loneliness. Taken together, the findings suggest that other-sex crushes are normative experiences during early adolescence that warrant further research attention.


Effects of registered nurse staffing levels, work environment, and education levels on adverse events in nursing homes.
This study examined the effects of nurse staffing levels, work environment, and education levels on adverse events in nursing homes. A cross-sectional study was conducted involving 216 nurses working in 62 nursing homes in South Korea, using self-reported questionnaires and data from the National Health Insurance Service of South Korea. A logistic regression model was used to investigate the effects of nurse staffing levels, work environment, and nursing education levels on the adverse events experienced by residents. An increase of one resident per nurse was significantly associated with a higher incidence of medication error, pressure ulcers and urinary tract infections. A poor work environment increased the incidence of adverse events. Compared to nurses with a bachelor's degree or higher, those with diplomas reported increased incidence rates of pressure ulcers. Improving the health outcomes of residents in nursing homes requires efforts that strengthen the nursing workforce in terms of numbers and educational level, and which improve their work environment at institutional and policy levels.


Protective behavioral strategies predict alcohol-related problems among injured patients following a brief intervention.
Alcohol protective behavioral strategies (PBS) have been proposed as mechanisms of change underlying interventions for reducing alcohol use and alcohol-related problems. Few studies have examined PBS use among non-college student populations and no study has examined PBS use among adult injured patients. The current study tested types of PBS as mediators of the effects of a brief motivational intervention (BMI) delivered in the trauma care setting on alcohol-related problems. Secondary data analyses were conducted using data from a multisite randomized controlled trial of brief intervention in the trauma care setting. The current study used data from a subset of participants who reported having consumed alcohol at least once at 3-month follow-up (N = 324). Following a baseline assessment, participants were assigned to either brief advice (BA; n = 107), BMI (n = 119), or BMI with a telephone booster (BMI + B; n = 98). Participants completed measures of PBS at 3-month follow-up and of alcohol-related problems at baseline and 6-month follow-up. A multiple mediation model was conducted to simultaneously test the mediation effects of types of PBS. BMI and BMI + B relative to BA did not increase PBS use. However, more frequent use of certain types of PBS at 3-month follow-up were predictors of greater reductions in alcohol-related problems from baseline to 6-month follow-up. There were no statistically significant mediation effects. The present study suggests that PBS use reduces alcohol-related problems among trauma patients and implications for future studies are discussed.


Single-cell transcriptomic atlas of primate cardiopulmonary aging.
Aging is a major risk factor for many diseases, especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019 (COVID-19). Resolving cellular and molecular mechanisms associated with aging in higher mammals is therefore urgently needed. Here, we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung, heart and artery, the top tissues targeted by SARS-CoV-2. Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging. With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. We found that interleukin 7 (IL7) accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner. Furthermore, treatment with vitamin C blocked IL7-induced ACE2 expression. Altogether, our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2, suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly.


Alcohol-induced behavioral changes in zebrafish: The role of dopamine D2-like receptors.
The dopaminergic system has been proposed to mediate alcohol-induced locomotor activity, yet the mechanisms underlying this behavioral response remain poorly understood. This study was conducted to investigate the role of dopamine D2-like receptors in mediating alcohol-induced behavioral responses. In experiment 1, we examined the effects of high concentrations (0, 2.5, 5, 10 μM) of haloperidol on motor responses. In experiment 2, we examined the effects of low concentrations (0, 0.625, 1.25, 2.5 μM) of haloperidol on anxiety-like behavioral responses using the novel tank test. In experiment 3, we examined the effect of pre-treating zebrafish with different concentrations of haloperidol (0, 0.625, 2.5 μM) and subsequently exposing them to 0 or 1 % alcohol. In experiment 1, haloperidol induced an inverted U-shaped concentration-dependent increase in locomotor activity. In experiment 2, haloperidol (2.5 μM) reduced the absolute turn angle and freezing behavior in a new environment. In experiment 3, acute alcohol exposure significantly increased locomotor activity and decreased anxiety-like behavioral responses. Pre-treating zebrafish with the lower dose of haloperidol (0.625 μM) abolished the alcohol-induced locomotor activity, without altering anxiety-like behavioral responses. However, pre-treating with the higher dose of haloperidol (2.5 μM) abolished both alcohol-induced increase of locomotor activity and reduction of anxiety-like behavioral responses. The results suggest alcohol-induced locomotor hyperactivity in zebrafish is mediated via activation of dopamine D2-like receptors, whereas anxiety-like behavioral responses may only be altered by a high haloperidol concentration, at which dose the drug may affect receptors other than D2-R.


Biliverdin reductase activity in cattle, sheep, rabbits and rats.
1. Biliverdin reductase (BVR) activity was measured in post-microsomal supernatants of livers of cattle, sheep, rabbits and rats. BVR activities in bovine and ovine livers were 4.7 and 5.0%, respectively, of rat liver activity. 2. The finding of BVR activity in ruminants is in contrast to a previous report and may be due to the use of a different assay system. 3. Lapine liver had the lowest BVR activity of only 0.37% of rat liver activity. 4. Increasing the available heme by phenylhydrazine administration did not induce increased hepatic or splenic BVR activity in rabbits. 5. Maximal BVR activities were attained using NADPH as cofactor at pH 8.7 in sheep and rabbits and at pH 8.4 in cattle. 6. Differing concentrations of bovine or human albumins enhanced or inhibited BVR activity quite differently in the various species. 7. The finding of a very low, but measurable BVR activity in lapine liver and spleen may explain, in part, why rabbits, unlike rats, cattle and sheep, excrete primarily biliverdin (70%) into bile.


Multiple survival signals are delivered by dendritic cells to naive CD4+ T cells.
The molecular mechanisms by which dendritic cells (DC) favor naive T cell survival in mice have been examined in co-cultures of DC and naive CD4+ T cells. Naive T cells can survive in the presence of IL-4 or IL-7, but DC-induced T cell survival requires direct cell-cell interactions and does not seem to be mediated by these or other soluble factors. Classical MHC II molecules on DC are not necessary for T cell survival as long as hybrid AalphaEbeta MHC class II molecules are present. In the total absence of MHC II molecules on DC, T cell survival is reduced by half, and CD3zeta phosphorylation fully disappears. These results contrast with the classical view that naive T cell survival is associated with CD3zeta phosphorylation and depends mostly on IL-7 and MHC-TCR interactions. We demonstrate that DC-induced T cell survival is a multi-factorial process that also involves CD28, LFA-1 and another (as yet undefined) surface molecule that requires the activity of src (but not phosphatidylinositol-3-) kinase.