In vitro evaluation of a micro-Doppler catheter for detection and aspiration of venous air emboli.
Venous air embolism (VAE) is a potentially fatal complication of surgery when open veins at a surgical site are exposed to ambient air pressure which exceeds the pressure in the venous system. Common techniques of detecting VAE are precordial Doppler monitoring and transesophogeal echocardiography. Precordial Doppler monitoring has poor accuracy and transesophogeal echocardiography is expensive and user-intensive. In both methods, a separate catheter must be inserted into the vena cava so that an embolus may be aspirated if it is detected. We created a micro-Doppler assembly using two ceramic transducers fitted over a 5.8F multiorifice central venous catheter. This micro-Doppler catheter (MDC) was tested in vitro using a static tank and an artificial vena cava (AVC). The MDC was also tested for acoustic pressure and current leakage in the static tank and for heat generation and cavitation in the AVC. The MDC was able to detect bubbles more than 2 mm in diameter with 100% accuracy. A blinded observer was able to identify the onset of vapor lock in 10 of 10 trials. The same observer was able to terminate vapor lock in 10 of 10 trials. The acoustic pressures measured were <1.8 MPa. There was no increase in temperature in the AVC over 24 h and there was no evidence of cavitation in the AVC over 4 h. We have created a MDC that can detect air emboli and relieve vapor lock in a simulated vena cava and atrium. This catheter could be placed percutaneously in the vena cava. Based on the measurements of acoustic pressure, temperature in the AVC and lack of cavitation in the AVC, the device appears to be safe for use in humans. More studies are required to determine if the catheter could be used to detect and aspirate VAE during surgeries where VAE is likely, such as sitting craniotomy.


Fluoro-clomiphene and its synthetic precursors: synthesis and receptor binding.
In an attempt to synthesize compounds with selective estrogen-receptor binding, fluoro- and amino-clomiphene were totally synthesized from benzyl chloride, and their estrogenic/antiestrogenic activity as well as that of some of their chemical intermediates was evaluated. The triazene prepared from the amino-clomiphene was converted into fluoro-clomiphene with 39% yield. In the uterotropic test, both amino- and fluoro-clomiphene exerted mild equipotent estrogenic activity, with minimal saturation doses being 50 and 100 micrograms/rat/day for three days. In the receptor binding test both derivatives demonstrated similar displacement, with an A50% value in the 10(-5) M range, as compared to 10(-6) M for clomiphene and 10(-9) M for diethyl-stilbestrol. This synthesis may be useful for the preparation of 18F-labeled clomiphene for biodistribution studies.


Bilateral same session flexible ureterorenoscopy for endoscopic management of bilateral renal calculi is noninferior to unilateral flexible ureterorenoscopy for management of multiple unilateral renal calculi: outcomes of a prospective comparative study.
The aim of the study was to prospectively evaluate safety and efficacy of bilateral same session ureterorenoscopy (BSS-FURS) for management of bilateral renal calculi. A prospective comparative study was designed to compare the results of BSS-FURS with unilateral flexible ureterorenoscopy (U-FURS) for management of renal calculi between June 2003 and May 2016. A sample size of 55 patients in each arm was calculated considering a 20% increase in the incidence of complications with BSS-FURS over 15% complication rate in U-FURS (alpha = 0.05; Beta = 0.90). Patient demographics, stone burden, total operative time, postoperative creatinine level, duration of hospital stay, perioperative complications and stone free rate (SFR) were compared in both the groups. The literature pertaining to BSS-FURS was reviewed. Although the study group patients had higher overall stone burden (18.60 ± 7.70 mm vs. 13.32 ± 6.43 mm) and significantly longer operative time (48.30 ± 16.71 min vs. 32.95 ± 13.05 min; p < 0.05) as compared to the control group, the length of hospital stay, SFR (67.85% vs. 78.5%; p = 0.436) and perioperative complications were comparable in both the groups. Most patients who developed postoperative fever from both groups had struvite stones. BSS-FURS is a safe and efficient procedure for the management of bilateral renal calculi in the hands of an experienced endourologist. It has comparable SFR and morbidity compared to U-FURS. Caution should be exercised in patients with struvite stones, as they are more likely to develop postoperative fever.


A mantispid larva can preserve its spider egg prey: evidence for an aggressive allomone.
Data indicate that larvae of Mantispa uhleri Banks can halt the development of their spider egg prey. Absence of mechanical injury to the eggs suggests that halting is accomplished with an aggressive allomone. Such a mechanism allows larvae to consume eggs that might otherwise have hatched.


Apolipoprotein A2 -265 T>C polymorphism interacts with dietary fatty acids intake to modulate inflammation in type 2 diabetes mellitus patients.
Several investigations have been conducted regarding the interaction between Apolipoprotein A2 (APOA2) -265 T>C polymorphism and dietary intake of saturated fatty acids (SFAs) on obesity in healthy individuals or type 2 diabetes mellitus (T2 DM) patients. The aim of the present study is to examine the effect of this interaction on inflammatory markers in T2 DM patients. This is a comparative cross-sectional study on 180 T2 DM patients with known APOA2 genotype. Dietary intake was assessed by food-frequency questionnaire and serum levels of inflammatory markers (interleukin [IL]-18, pentraxin 3, and high-sensitivity C-reactive protein [hs-CRP]) were measured. The subjects were dichotomized into "high" and "low" categories, based on the median dietary intake of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), and SFAs. The data were analyzed by analysis of covariance multivariate interaction model. In CC genotype, higher median intake of ω-3 PUFAs and MUFAs was associated with decreased serum levels of IL-18 and hs-CRP (P = 0.014 and 0.008, respectively). In T-allele carriers, higher median intake of SFAs was associated with increased serum hs-CRP level (P < 0.001). There was a significant relationship between APOA2 polymorphism and ω-3 PUFA intake on serum IL-18 level (P interaction = 0.03). Moreover, the relationship between this polymorphism and SFA and MUFA intake on serum hs-CRP level was statistically significant (P interaction = 0.03 and 0.024, respectively). In T2 DM patients, the dietary intake of antiinflammatory fatty acids, such as ω-3 PUFAs and MUFAs, could reduce the inflammatory effects associated with the CC genotype. In addition, proinflammatory fatty acids, such as SFAs, could overcome the antiinflammatory effect of the T-allele. Further studies are needed to confirm these findings.


Inhibitory effect of lysozyme on the intraglomerular immune complex formation in lupus mice.
The effect of lysozyme on intraglomerular immune complex deposition was examined in NZB/W F1 mice undergoing unilateral nephrectomy. Unilateral nephrectomy enhanced the glomerular immune complex deposition and glomerular lesions, which were suppressed by repeated intraperitoneal injections of lysozyme, in spite of unaltered serum anti-DNA antibody titers. DNA binding to the glomerular basement membrane (GBM) examined in vitro and that to glomeruli examined in vitro were also suppressed by lysozyme. An increased survival rate and decreased proteinuria were also induced by this basic protein. The mechanisms of the ameliorative effect were studied in vitro. DNA was bound to the GBM only in the presence of serum, plasma, or fibronectin. A similar inhibitory effect on DNA binding was also obtained by another polycation, hexadimethrine, in place of lysozyme. The in vitro findings suggest that DNA binding to the GBM is mediated by fibronectin, and that lysozyme electrostatically inhibits this binding, thereby possibly reducing the in situ DNA-anti-DNA complex formation in the GBM.


Photoplethysmography-Based Machine Learning Approaches for Atrial Fibrillation Prediction: A Report From the Huawei Heart Study.
Current wearable devices enable the detection of atrial fibrillation (AF), but a machine learning (ML)-based approach may facilitate accurate prediction of AF onset. The present study aimed to develop, optimize, and validate an ML-based model for real-time prediction of AF onset in a population at high risk of incident AF. A primary ML-based prediction model of AF onset (M1) was developed on the basis of the Huawei Heart Study, a general-population AF screening study using photoplethysmography (PPG)-based smart devices. After optimization in 554 individuals with 469,267 PPG data sets, the optimized ML-based model (M2) was further prospectively validated in 50 individuals with paroxysmal AF at high risk of AF onset, and compared with 72-hour Holter electrocardiographic (ECG) monitoring, a criterion standard, from September 1, 2019, to November 5, 2019. Among 50 patients with paroxysmal AF (mean age 67 ± 12 years, 40% women), there were 2,808 AF events from a total of 14,847,356 ECGs over 72 hours and 6,860 PPGs (45.83 ± 13.9 per subject per day). The best performance of M1 for AF onset prediction was achieved 4 hours before AF onset (area under the receiver operating characteristic curve: 0.94; 95% confidence interval: 0.93-0.94). M2 sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (at 0 to 4 hours before AF onset) were 81.9%, 96.6%, 96.4%, 83.1%, and 88.9%, respectively, compared with 72-hour Holter ECG. The PPG- based ML model demonstrated good ability for AF prediction in advance. (Mobile Health [mHealth] technology for improved screening, patient involvement and optimizing integrated care in atrial fibrillation; ChiCTR-OOC-17014138).


Less common applications of simulated moving bed chromatography in the pharmaceutical industry.
Simulated moving bed (SMB) chromatography is often perceived in the pharmaceutical industry as chromatographic method for separating binary mixtures, like racemates. However, SMB can also be used for unbalanced separations, i.e. binary mixtures of varying compositions and multi-component mixtures. These less common application modes of isocratic SMB chromatography are exemplified for four different compounds (racemates and diastereomers) and discussed in view of the so-called 'triangle theory' from an industrial perspective.


Differential amygdala activation to negative and positive emotional pictures during an indirect task.
The role of the amygdala for the processing of valence and arousal is a matter of debate. Using event-related functional magnetic resonance imaging, we tested valence-specific amygdala effects during attentional distraction. Subjects attended to a matching task in the foreground of neutral pictures, and of negative and positive pictures matched for arousal. Negative pictures elicited stronger amygdala activation than neutral or positive pictures, suggesting valence-specific amygdala responses under attentional load.


AIDS in an HIV-seronegative Ghanaian woman with intersubtype A/G recombinant HIV-1 infection.
A 29-year-old Ghanaian woman who developed AIDS while being HIV-antibody seronegative was investigated during a collaborative study aimed at the identification of viral causes of a HIV-seronegative AIDS syndrome in West Africa. Plasma was screened with a panel of EIA tests for antibodies to HIV and HIV-1 p24 antigen. Retroviral infection was investigated by detection of reverse transcriptase (RT) activity in plasma, viral RNA amplification and quantification, and virus isolation. Positive amplification products were sequenced and phylogenetic analyses were carried out. Most EIA tests were unable to demonstrate the presence of anti-HIV anti-bodies, whereas confirmatory assays yielded inconclusive results. Retroviral infection was documented by detection of RT activity, HIV-1-specific genomic amplification and virus isolation. This virus was HIV-1 subtype A with an unusual six amino acid insertion in the gp120 V4 loop and with the nef gene of subtype G. The patient's plasma did not react with either autologous or heterologous viral lysates or HIV-1 peptides, whereas antibodies to other viral antigens were present. In conclusion, the Ghanaian patient exhibited a rare subtype A/G recombinant HIV-1 infection with a near absence of a HIV-specific humoral response. The lack of detectable antibody response might be due to either a highly pathogenic, rapidly fatal, HIV-1 infection preventing the development of the typical humoral immune response or to a host-related dysfunction of the immune system. Direct antigenemia or genomic detection of the virus should be undertaken when clinical or biological data suggests an HIV infection in the absence of serological evidence.


An unusual complication in a 9-year-old patient with hereditary multiple osteochondromatosis.
This case report describes the presentation of a 9-year-old boy with a history of hereditary multiple osteochondromatosis who presented to the outpatient setting with progressive difficulty in ambulation. Magnetic resonance imaging of the spine revealed a thoracic spinal tumor, which was surgically removed. After surgery, the boy's ambulation and spasticity/contractures improved. This case is unique because this complication of hereditary multiple osteochondromatosis was identified at an age and in a region that are not typical. From a clinical standpoint, early identification of this complication is important because surgical treatment typically leads to good outcomes.


Therapeutic significance and indications of pulmonary metastasectomy for hepatocellular carcinoma following liver resection.
To explore the therapeutic significance and indications of pulmonary metastasectomy (PMT) in hepatocellular carcinoma (HCC) patients with pulmonary metastasis (PM) following liver resection (LR). PM-HCC patients who underwent LR were retrospectively enrolled, and survival outcomes and prognostic factors were analyzed. Patients were divided into PMT and non-PMT group, and propensity score matching (PSM) analysis was used for survival comparison. Prognostic analysis and survival comparisons were performed specifically in PMT patients. Ninety-seven patients were enrolled, among which twenty-six underwent PMT while seventy-one did not. Survival outcome was superior in PMT group compared to non-PMT group (33.5 vs. 10.5 months) (p = 0.003), while no statistical difference was found after PSM analysis (33.5 vs. 11.2 months) (p = 0.138). Synchronous PM-HCC, serum alpha fetal protein≥400 ng/ml at PM diagnosis, no intrahepatic treatments (LR, ablation or transarterial chemoembolization) after LR, intrahepatic recurrence or metastasis at repeated PM diagnosis were inferior independent prognostic factors in PMT patients (p < 0.05). Superior survival outcomes were seen in candidate PMT patients when corresponding indications were satisfied (p = 0.014, p = 0.005). PMT might provide potential survival benefits in well selected PM-HCC patients who underwent LR. Well designed, multi-institutional studies with larger patient number were still to be required.


[Inverse PCR amplification of the complete major capsid protein gene of lymphocystis disease virus isolated from Rachycentron canadum and the phylogenetic analysis of the virus].
The major capsid protein of lymphocystis disease virus isolated from Rachycentron canadum (LCDV-rc) was amplified and analysed. The 457bp DNA core fragment was amplified with the degenerate primers designed according to the conserved sequences of MCP gene of iridoviruses, then the flaking sequences adjacent to the core region were amplified by inverse PCR, and the complete sequence was obtained by combining all of them. The open reading frame of the gene is 1380bp in length, encoding a putative protein of 459 aa with molecular weight 51.12 kD and pI 6.87. Constructing the phylogenetic tree for comparing the MCP amino acid of iridoviruses, the results indicated that LCDV-rc is most homologous to the other Lymphocystis viruses and all of them constitute a branch. Accordingly LCDV-rc is identified as Lymphocystivirus.


Axoplasmic asymmetry at the node of Ranvier.
The previously described unilateral condensation of axoplasmic organelles at the node of Ranvier of large diameter fibres in spinal nerve roots has been confirmed in a single normal rabbit. The tendency for this phenomenon to occur on the proximal (neuronal) side of the node, as implied in previous studies, could not be supported by numerical analysis which failed to show statistical significance for any one distribution pattern. This absence of polarization may be related to the existence of both anterograde and retrograde traffic in large diameter fibres.


Metal-organic frameworks: A promising option for the diagnosis and treatment of Alzheimer's disease.
Beta-amyloid (Aβ) peptide is one of the main characteristic biomarkers of Alzheimer's disease (AD). Previous clinical investigations have proposed that unusual concentrations of this biomarker in cerebrospinal fluid, blood, and brain tissue are closely associated with the AD progression. Therefore, the critical point of early diagnosis, prevention, and treatment of AD is to monitor the levels of Aβ. In view of the potential of metal-organic frameworks (MOFs) for diagnosing and treating the AD, much attention has been focused in recent years. This review discusses the latest advances in the applications of MOFs for the early diagnosis of AD via fluorescence and electrochemiluminescence (ECL) detection of AD biomarkers, fluorescence detection of the main metal ions in the brain (Zn2+, Cu2+, Mn2+, Fe3+, and Al3+) in addition to magnetic resonance imaging (MRI) of the Aβ plaques. The current challenges and future strategies for translating the in vitro applications of MOFs into in vivo diagnosis of the AD are discussed.


Colonic production of nitric oxide gas in ulcerative colitis, collagenous colitis and uninflamed bowel.
Nitric oxide (NO) produced in excess by the inflamed human colon is generally considered a pathway of mucosal damage. In an attempt to quantify colonic mucosal production of NO in various forms of colitis we performed 'steady-state' gas perfusion of whole colon in 11 patients with ulcerative colitis, 10 patients with collagenous colitis and 20 controls with uninflamed mucosa. The tip of a Teflon tube was placed in the caecum during colonoscopy. Subsequently, argon was infused at a constant rate for 70-180 min. Argon and NO in gas sampled from the rectum were measured by neutron activation analysis and the chemiluminescence technique, respectively. The use of argon as a marker of colonic NO output was justified by complete recovery (96%+/-2; mean +/- s(x); n = 5) of argon in gas collected from the rectum and a constant output of NO at varying perfusion rates (25, 50 and 75 ml/min coefficient of variation 21%; n = 6). In patients with ulcerative colitis, colonic output of NO was 10-fold higher (P < 0.001) than in controls and positively correlated (P < 0.01) to indices of disease activity. In patients with collagenous colitis, colonic output of NO was 50-fold higher (P < 0.01) than in controls during periods with watery diarrhoea (n = 6), but within the range observed in ulcerative colitis in the absence of diarrhoea (n = 4). Argon gas perfusion of whole colon using chemiluminescence technique for measurement of NO is a reliable method for quantification of colonic mucosal NO production. Increased colonic production of NO in collagenous colitis, which exceeds the output observed even in extensive ulcerative colitis, militates against the theory that NO per se is a cause of mucosal injury.


Anti-coagulation management in pediatric traumatic vascular injuries.
Pediatric traumatic vascular injuries are rare. Given the paucity of data to guide anti-coagulation (AC) management of these injuries in children, who have a lower overall risk for thrombosis compared to their adult counterparts, we sought to examine and summarize our recent experience. We conducted a retrospective review of all patients (<18 years old) who sustained traumatic vascular injuries between 2010-2018 at a Level 1 and Level 2 Pediatric Trauma Center. Ninety-nine patients had traumatic vascular injuries. Eighty-four patients sustained a major arterial injury, 26 had a major venous injury, and 11 had both arterial and venous injuries. The arterial injury cohort had a median age of 13.3 years. Most of the arterial injury patients (65/84, 77%) required vascular repair. In-hospital AC management for the arterial injury patients consisted of a post-operative heparin drip (18%, 15/84), aspirin (39%, 26/84), enoxaparin (23%, 19/84), or none (42%, 43/84). Approximately one-half of the patients with arterial injuries (54%, 45/84) were discharged home on AC therapy, most commonly aspirin. Fifty-six patients (66%) followed up post-injury, of which 25% (14/56) had experienced complications. Pediatric traumatic arterial injuries that require surgical intervention other than ligation should be considered for discharge AC - most commonly aspirin - in the absence of contraindications. Pediatric patients with vascular injuries to the aorta, carotid artery, inferior vena cava, portal vein, or lower extremities that are managed non-operatively should also be considered for AC. The preferred AC for pediatric venous injuries is enoxaparin, in the absence of contraindications. Treatment Study LEVEL OF EVIDENCE: IV.


Assessing chronic toxicity of aluminium, gallium and molybdenum in tropical marine waters using a novel bioassay for larvae of the hermit crab Coenobita variabilis.
A novel bioassay is presented that allows for the estimation of the chronic toxicity of contaminants in receiving tropical marine environments. Relevant procedures to identify contaminants of concern and evaluate hazards associated with contamination in these environments have long remained inadequate. The 6-day bioassay is conducted using freshly hatched planktonic larvae of the hermit crab Coenobita variabilis and is targeted at generating environmentally relevant, chronic toxicity data. The developmental endpoint demonstrated consistently high control performance and was validated through the use of copper as a reference toxicant. In addition, the biological effects of aluminium, gallium and molybdenum were assessed. The endpoint expressed high sensitivity to copper (EC10 = 24 µg L-1) and moderate sensitivity to aluminium (EC10 = 312 µg L-1), whereas gallium and molybdenum elicited no obvious effects, even at high concentrations (EC10 > 6000 µg L-1), providing valuable information on the toxicity of these elements in tropical marine waters for derivation of water quality guidelines or testing of compliance limits.


Demographic perspectives on the mortality of COVID-19 and other epidemics.
To put estimates of COVID-19 mortality into perspective, we estimate age-specific mortality for an epidemic claiming for illustrative purposes 1 million US lives, with results approximately scalable over a broad range of deaths. We calculate the impact on period life expectancy (down 2.94 y) and remaining life years (11.7 y per death). Avoiding 1.75 million deaths or 20.5 trillion person years of life lost would be valued at $10.2 to $17.5 trillion. The age patterns of COVID-19 mortality in other countries are quite similar and increase at rates close to each country's rate for all-cause mortality. The scenario of 1 million COVID-19 deaths is similar in scale to that of the decades-long HIV/AIDS and opioid-overdose epidemics but considerably smaller than that of the Spanish flu of 1918. Unlike HIV/AIDS and opioid epidemics, the COVID-19 deaths are concentrated in a period of months rather than spread out over decades.


[Epidemiological characteristics of Mycoplasma pneumoniae pneumonia in children].
To study the epidemiological characteristics of Mycoplasma pneumoniae pneumonia (MPP) in children, and to provide a basis for diagnosis and treatment. The serum level of Mycoplasma pneumoniae antibody IgM (MP-IgM) was measured by enzyme-linked immunosorbent assay for 3156 hospitalized children with confirmed community acquired pneumonia from February 2011 to January 2012. The antigens of seven respiratory viruses were detected in the nasopharyngeal secretions of children with MPP. MP-IgM was detected in 427 of the 3156 patients, with a positive rate of 13.53%. The infection rate in female patients was significantly higher than in male patients (16.30% vs 11.70%; P<0.01). The MP-IgM detection rates were 3.6%, 12.5%, 19.2%, and 24.4% in children aged under 1 year, 1-3 years, 3-6 years and 6-14 years respectively (P<0.01), and the total MP-IgM detection rate in children aged under 3 years was significantly lower than in children over 3 years (P<0.01). The MP-IgM detection rate varied with the seasons and was significantly higher in summer and autumn than in winter and spring (19.18% vs 9.61%; P<0.01). Of the 427 MP-IgM-positive children, 60 (14.1%) were infected with respiratory viruses, and the highest proportion of which was respiratory syncytial virus. MPP is sporadic throughout the whole year, with a higher incidence in summer and autumn. MPP occurs mostly in preschool and school-age children, and there is mixed infection of MP and respiratory viruses.


An indolent course of multiple myeloma mimicking a solitary thyroid cartilage plasmacytoma.
Multiple myeloma, solitary plasmacytoma, and extramedullary plasmacytoma constitute a continuum of a disease spectrum, which is called plasma cell neoplasms. These three entities can not be differentiated from each other on a histological basis and, for this reason, clinical evaluation is important in their differential diagnoses. Differential diagnosis guides the proper planning of treatment and helps in estimation of survival. Multiple myeloma located within the larynx is very rare. Because of its rarity, any established diagnostic and treatment criteria do not exist. In this report, a case of laryngeal multiple myeloma is presented for its extraordinary presentation and also for educational purposes.


Impact of wastewaters and hospital effluents on the occurrence of controlled substances in surface waters.
We have investigated the occurrence of controlled drugs in two rivers, two wastewater treatment plants (WWTPs) and five hospital effluents in Taipei, Taiwan, and report here the concentrations of controlled drugs used as prescription medication or drugs of abuse. Of the target drugs, morphine, codeine, methamphetamines and ketamine were observed in significant quantities in hospital effluents, with maximum concentrations of 1240, 378, 260 and 206 ng L(-1), respectively. The other six compounds (including metabolites) were found at trace levels or below the method detection limits. In addition, the high occurrence in river waters of methamphetamine, codeine and ketamine (maximum values 405, 57, and 341 ng L(-1), respectively) indicated the significant prevalence of these controlled drugs. This study demonstrated that effluents from hospitals and clinics and treated WWTP effluents contribute to the controlled substances that eventually reach natural rivers. We hypothesize that the occurrence of controlled drugs in the environment can be attributed to two main sources: (1) substance abuse by individuals and (2) treatment with prescription medication for acute and chronic pain. The presence of these contaminants in the aquatic environment may pose significant risk to aquatic and human life. Further studies are needed for verification and may contribute to the development of sustainable strategies for environmental remediation.


ECEL1 gene related contractural syndrome: Long-term follow-up and update on clinical and pathological aspects.
Autosomal recessive mutations in the ECEL1 gene have recently been associated with a wide phenotypic spectrum including severe congenital contractural syndromes and distal arthrogryposis type 5D (DA5D). Here, we describe four novel families with ECEL1 gene mutations, reporting 15 years of follow-up for four patients and detailed muscle pathological description for three individuals. In particular, we observed mild myopathic features, prominent core-like areas in one individual, and presence of nCAM positive fibres in three patients from 2 unrelated families suggesting a possible problem with innervation. Our findings expand current knowledge concerning the phenotypic and pathological spectrum associated with ECEL1 gene mutations and may suggest novel insights regarding the underlying pathomechanism of the disease.


An unusual procedure in performing brachial plexus block.
A new surgical treatment of pseudarthrosis humeri needed specific anesthesiological management. The relevant problems for the anesthesiologist were the following: one year prior to the present admission the patient suffered from a polytrauma with contusio cerebri and had, as a result of prolonged intubation during the following period of intensive therapy, an excessive tracheal stenosis in the subglottic area, however without any clinical signs. For these reasons, general anesthesia did not seem to be practicable and the conventional way of blocking the brachial plexus appeared to be somewhat problematic owing to the postoperative scar tissue in the previously surgically treated region. For these reasons an unusual anesthetic management was chosen: the brachial plexus was anesthetized in the subaxillar region by surgical exposure of the neurovascular bundle. We feel, that the surgical exposure of the brachial plexus as described here is a practicable alternative to the common techniques of blocking the brachial plexus in very special situations.


Safety and efficacy of corticosteroids in ARDS patients: a systematic review and meta-analysis of RCT data.
Acute respiratory distress syndrome (ARDS) is an acute and critical disease among children and adults, and previous studies have shown that the administration of corticosteroids remains controversial. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to evaluate the safety and efficacy of corticosteroids. The RCTs investigating the safety and efficacy of corticosteroids in ARDS were searched from electronic databases (Embase, Medline, and the Cochrane Central Register of Controlled Trials). The primary outcome was 28-day mortality. Heterogeneity was assessed using the Chi square test and I2 with the inspection level of 0.1 and 50%, respectively. Fourteen RCTs (n = 1607) were included for analysis. Corticosteroids were found to reduce the risk of death in patients with ARDS (relative risk (RR) = 0.78, 95% confidence interval (CI): 0.70-0.87; P < 0.01). Moreover, no significant adverse events were observed, compared to placebo or standard support therapy. Further subgroup analysis showed that variables, such as adults (RR = 0.78; 95% CI: 0.70-0.88; P < 0.01), non-COVID-19 (RR = 0.71; 95% CI: 0.62-0.83; P < 0.01), methylprednisolone (RR = 0.70; 95% CI: 0.56-0.88; P < 0.01), and hydrocortisone (RR = 0.79; 95% CI: 0.63-0.98; P = 0.03) were associated with 28-day mortality among patients who used corticosteroids. However, no association was found, regarding children (RR = 0.21; 95% CI: 0.01-4.10; P = 0.30). The use of corticosteroids is an effective approach to reduce the risk of death in ARDS patients. However, this effect is associated with age, non-COVID-19 diseases, and methylprednisolone and hydrocortisone use. Therefore, evidence suggests patients with age ≥ 18 years and non-COVID-19 should be encouraged during the corticosteroid treatment. However, due to substantial differences in the use of corticosteroids among these studies, questions still remain regarding the dosage, optimal corticosteroid agent, and treatment duration in patients with ARDS.


Serum Glutathione in Patients with Schizophrenia in Dynamics of Antipsychotic Therapy.
Serum concentrations of oxidized and reduced glutathione were measured in 73 patients with schizophrenia at admission and in dynamics of therapy with traditional and atypical antipsychotic drugs. The level of reduced glutathione in patients with schizophrenia with manifest clinical symptoms was lower than in normal subjects. Atypical neuroleptics produced virtually no effects on the glutathione system, while therapy with typical antipsychotics led to further decrease in the levels of reduced glutathione, thus aggravating the imbalance of metabolic processes typical of schizophrenia.


Cysteamine-induced inhibition of mucosal and pancreatic alkaline secretion in rat duodenum.
To determine the effect of cysteamine on the alkaline secretion by the duodenal epithelium, pancreas, and Brunner's glands in relation to the pathogenesis of duodenal ulceration, the alkaline secretion by various types of duodenal loops was comparatively studied. The results obtained were as follows: (1) Cysteamine significantly reduced both mucosal and pancreatobiliary alkaline secretion in the proximal duodenum of rats. (2) The ratio of contribution of pancreatobiliary alkaline secretion to total neutralization of acid in the proximal duodenum was 55.9% under continuous perfusion. (3) There was no significant difference between the amounts of alkali per unit volume of the proximal and distal duodenal loops. (4) The alkaline substance secreted by the proximal duodenal mucosa was confirmed to be the bicarbonate. From these findings, it has been concluded that the impairment of bicarbonate secretion by the mucosal epithelium of proximal duodenum, not by Brunner's glands, plays a causative role in cysteamine-induced duodenal ulceration.


Age-related differences in attention to novelty among cognitively high performing adults.
Age-related differences in attention to novel events were studied in well-matched, cognitively high performing old, middle-aged and young subjects. Event-related potentials were recorded during a visual novelty oddball task in which subjects controlled viewing durations that served as a behavioral measure of attentional allocation. All age groups had a larger P3 amplitude and longer viewing duration to novel than to standard stimuli, with no age-related differences in the magnitude of these effects, indicating old individuals were as engaged by the processing of novelty as younger adults. Old subjects had a larger, more anteriorly distributed P3 component to novels and standards. The increased P3 amplitude differs from prior reports of a diminished P3 response with processes, including aging, that have a potentially deleterious impact on the brain. We hypothesise that cognitively high performing old individuals successfully manage the task by relying on additional neural resources and perhaps more effortful frontal activity than their younger counterparts.


Dipalmitoylphosphatidylcholine membranes modified with carotenoid pigment lutein: experiment versus Monte Carlo simulation study of the membrane organization.
Organization of bilayer lipid membrane formed with dipalmitoylphosphatidylcholine and containing a xanthophyll pigment lutein was studied by both the Monte Carlo simulation and UV-Vis absorption spectroscopy. The simulations were based on ten-state Pink model. The proposed model consisted of two monolayers represented by a two-dimensional triangular lattice with vacancies. The orientation and aggregation state of lutein, obtained from the analysis of the spectroscopic measurements, were used to calibrate intermolecular interactions in the model. In accordance with the experimental data, the model allows two orientations of lutein molecules: one spanning the membrane and the other parallel to its plane. The influence of the intermolecular interactions on the main phase transition as well as on the aggregation of lutein molecules is discussed. The analysis of the model enables us to learn about molecular mechanisms that govern the effects of lutein on the membrane properties as well as the effects of the lipid matrix on lutein organization in the membrane. A concept is discussed according to which increasing domination of parallel lutein orientation, observed at high temperatures, can protect the membrane against penetration by water molecules and reactive oxygen species and against loss of the membrane compactness, especially in the regions of oxidized acyl chains.


ModInterv: An automated online software for modeling epidemics.
The COVID-19 pandemic has proven the importance of mathematical tools to understand the evolution of epidemic outbreaks and provide reliable information to the general public and health authorities. In this perspective, we have developed ModInterv, an online software that applies growth models to monitor the evolution of the COVID-19 epidemic in locations chosen by the user among countries worldwide or states and cities in the USA or Brazil. This paper describes the software capabilities and its use both in recent research works and by technical committees assisting government authorities. Possible applications to other epidemics are also briefly discussed.


Glucose-6-phosphate dehydrogenase laboratory assay: How, when, and why?
Glucose 6-phosphate dehydrogenase (G6PD) deficiency is the most common defect of red blood cells. Although some different laboratory techniques or methods are employed for the biochemical screening, a strict relationship between biochemists, clinicians, and molecular biologists is necessary for a definitive diagnosis. This article represents an overview on the current laboratory tests finalized to the screening or to the definitive diagnosis of G6PD-deficiency, underlying the problems regarding the biochemical and molecular identification of heterozygote females other than those regarding the standardization of the clinical and laboratory diagnostic procedures. Finally, this review is aimed to give a flow-chart for the complete diagnostic approach of G6PD-deficiency.


Spatiotemporal dynamics of electromagnetic pulses in saturating nonlinear optical media with normal group velocity dispersion.
The nonlinear dynamics of ultrashort optical pulses in nonlinear saturating media with normal group velocity dispersion is examined. The studied saturating nonlinearity changes the sign at the peak intensity of the laser pulses. In the bulk media and the planar wave guides the temporal collapse of the pulse is arrested by its splitting in spatial domain leading to rings formation. The wave collapse in one dimensional geometry cannot be arrested; the field singularity develops for a finite propagation distance.


Transient increase in intraocular pressure during a dose-tapering regime of systemic dexamethasone in preterm infants.
To determine the intraocular pressure (IOP) profile during and after systemic dexamethasone treatment in preterm very low birth weight (VLBW; <1500 g) infants. A cohort study at a university-affiliated tertiary neonatal center. Twenty-seven VLBW infants who received a 3-week dose-tapering course of systemic dexamethasone for treatment of bronchopulmonary dysplasia were consecutively enrolled over a period of 32 months. Intraocular pressure was assessed using a handheld tonometer immediately before (week 0), during (weeks 1 and 3), and after (weeks 5, 7, and 9) commencement of the dexamethasone course. The mixed-effects models were used to evaluate the longitudinal IOP measurements at different time points. To assess the magnitude and duration of increase in IOP during systemic corticosteroid treatment. The IOP at week 1, while the infants were receiving the maximum dose of dexamethasone (0.6 mg/kg/day), was significantly higher than (1) the pretreatment IOP at week 0 (mean [+/- standard deviation]: 19.7 [+/-3.7] vs. 16.4 [+/-3.7] mmHg, respectively) (P<0.0001), (2) the IOP when the infants were receiving the minimum dose of dexamethasone (0.15 mg/kg/day) at week 3 (19.7 [+/-3.7] vs. 15.8 [+/-4.3] mmHg) (P<0.0001), and (3) the IOP after the dexamethasone course had been stopped between week 5 and week 9 (19.7 [+/-3.7] vs. 16.0 [+/-4.0], 15.3 [+/-3.5], and 14.5 [+/-3.3] mmHg for weeks 5, 7, and 9, respectively) (P<0.0001 for all comparisons). In contrast, there was no significant difference between the pretreatment IOP (week 0) and IOP at week 3, 5, 7, or 9 (P = 0.07-0.62) and in the IOP between week 3 and week 5, 7, or 9 (P = 0.27-0.75). The use of a dose-tapering regime of dexamethasone is associated with transient increase of IOP. As IOP was significantly raised during the high-dose but not the low-dose treatment period, we speculate that the physiologic or stress dose of corticosteroids commonly advocated for treatment of serious neonatal conditions should be safe and unlikely to cause significant ocular hypertension in preterm infants.


Development of system B0,+ and a broad-scope Na(+)-dependent transporter of zwitterionic amino acids in preimplantation mouse conceptuses.
The nature and ontogeny of Na(+)-dependent L-alanine transport was examined in mouse eggs and preimplantation conceptuses. Mediated L-alanine uptake was not detected in fertilized or unfertilized eggs, but a small amount of Na(+)-dependent L-alanine transport was detected in 2-cell conceptuses. Na(+)-dependent alanine transport was more rapid at the 8-cell stage of development, and more than 10-fold faster in blastocysts than in 8-cell conceptuses. Analog inhibition analyses were consistent with the interpretation that L-lysine-sensitive and L-lysine-resistant components of transport were present at the 2-cell, 8-cell and blastocyst stages of development. The range of amino acids and their analogs that inhibited the most conspicuous component of alanine transport in blastocysts was consistent with the conclusion that system B0,+ is largely responsible for L-alanine uptake in these conceptuses. Moreover, system B0,+, but not other known systems in blastocysts, became susceptible to activation as these conceptuses approached the time of implantation, so this activation could be involved in implantation. Although the data are consistent with the possibility that system B0,+ is also present in 2-cell and 8-cell conceptuses, the relatively slow L-alanine transport in conceptuses at these earlier stages of development precluded more detailed study of their ability to take up alanine. Similarly, the less conspicuous L-lysine-resistant component of L-alanine transport in blastocysts also may be present in conceptuses as early as the 2-cell stage. The L-lysine-resistant component of L-alanine transport could not be attributed to residual system B0,+ activity, however, because it was inhibited more strongly by trans-OH-L-proline than L-arginine, whereas the reverse was the case for system B0,+. Similarly, L-tryptophan and L-leucine each inhibited system B0,+ more strongly than L-serine or L-cysteine, whereas all four of these amino acids inhibited the L-lysine-resistant component equally well. Moreover, a Hofstee plot for L-alanine influx was consistent with the interpretation that at least two mediated components of Na(+)-dependent L-alanine transport are present in blastocysts. The less conspicuous component of L-alanine transport in blastocysts was relatively susceptible to inhibition by L-leucine and L-tryptophan, but it resisted inhibition by the 'model' system A substrate, MeAIB, and the system ASC inhibitors, L-penicillamine and cationic amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)


Effect of Chronic Kidney Disease on Nonrenal Elimination Pathways: A Systematic Assessment of CYP1A2, CYP2C8, CYP2C9, CYP2C19, and OATP.
Our recent studies have shown that chronic kidney disease (CKD) affects the pharmacokinetics (PKs) of cytochrome P450 (CYP)2D6-metabolized drugs, whereas effects were less evident on CYP3A4/5. Therefore, the effect of CKD on the disposition of CYP1A2-metabolized, CYP2C8-metabolized, CYP2C9-metabolized, CYP2C19-metabolized, and organic anion-transporting polypeptide (OATP)-transported drugs was investigated. We identified dedicated CKD studies with 6, 5, 6, 4, and 12 "model" substrates for CYP1A2, CYP2C8, CYP2C9, CYP2C19, and OATP, respectively. Our analyses suggest that clearance of OATP substrates decreases as kidney function declines. Similar trends were seen for CYP2C8; but overlap between some CYP2C8 and OATP substrates highlights that their interplay needs further investigation. In contrast, the effect of CKD on CYP1A2, CYP2C9, and CYP2C19 was variable and modest compared to CYP2C8 and OATP. This improved understanding of elimination-pathway-dependency in CKD is important to inform the need and conduct of PK studies in these patients for nonrenally eliminated drugs.


Hyperinsulinemia rapidly increases human muscle microvascular perfusion but fails to increase muscle insulin clearance: evidence that a saturable process mediates muscle insulin uptake.
Transport of insulin from the central circulation into muscle is rate limiting for the stimulation of glucose metabolism. By recruiting muscle microvasculature, insulin may promote its own movement into muscle interstitium. We tested whether in humans, as in the rat, insulin exerts an early action to recruit microvasculature within skeletal muscle. We further hypothesized that expansion of the microvascular volume of muscle would enhance muscle insulin clearance. Microvascular volume, total blood flow, and muscle insulin and glucose uptake (forearm balance method) were measured in 14 lean, healthy volunteers before and during a 2-h hyperinsulinemic-euglycemic clamp (1 mU x kg(-1) x min(-1)). Microvascular volume was measured using contrast-enhanced ultrasound. Forearm muscle microvascular volume increased within 20 min of insulin infusion (P < 0.01), whereas an effect to increase total forearm flow was not observed until 100 min. Forearm insulin uptake increased with physiological hyperinsulinemia (15 +/- 3 and 87 +/- 13 fmol x min(-1) x 100 ml(-1) basal vs. last 40 min of clamp, P < 0.001). However, the extraction fraction and clearance of insulin declined (P = 0.02, for each), indicating saturability of muscle insulin uptake at physiological hyperinsulinemia. Skeletal muscle contributes to peripheral insulin clearance both in the basal state and with physiological hyperinsulinemia. Insulin promptly expands human muscle microvascular volume but only slowly increases blood flow. Despite increased microvascular volume available for insulin uptake, muscle insulin clearance decreases significantly. These findings are consistent with the presence of a saturable transport mechanism facilitating the transendothelial transport of insulin into human muscle.


Chilaiditi syndrome - a rare case of pneumoperitoneum in the emergency department: a case report.
Pneumoperitoneum poses an important diagnostic sign determining the urgency of management of patients in an emergency department. Chilaiditi sign is a rare radiologic finding of large intestines transposition between the diaphragm and the liver. If the patient becomes symptomatic, then the condition is called Chilaiditi syndrome. We present a rare case of a 49-year-old Egyptian man who presented to our emergency department complaining of cough and vague abdominal discomfort who was found to have Chilaiditi syndrome diagnosed radiologically by computed tomography scan. He was conservatively managed rather than undergoing invasive non-warranted diagnostic and therapeutic testing that may have resulted in increased morbidity. A review of the current literature on Chilaiditi syndrome is provided with a focus on increasing the familiarity of health care professionals with the conditions and stressing the importance of a physical examination in evaluating patients with what appears to be air under the diaphragm.


Urinary anti diuretic hormone level in essential hypertension.
The present study was aimed to examine the excretory urinary Anti Diuretic Hormone (ADH) pattern in five normotensive and ten hypertensive human subjects. It was observed that Essential hypertensive subjects excreted higher urinary ADH 8.03 +/- 1.17 mU/hr as compared to 3.60 +/- 0.72 mU/hr the difference between the two groups being statistically significant (P less than 0.01). Various renal function parameters evaluated were within normal limits. The results of this study suggest the involvement of ADH in the pathophysiology of Essential hypertension.


Inhibitors of prostaglandin synthesis and the cornea.
Low doses of indomethacin were applied topically to rabbit eyes in an experimental model of immunologically provoked inflammatory keratitis. Leucocyte infiltration was potentiated but not the concomitant neovascularization.


Association between intake of total vs added sugar on diet quality: a systematic review.
Given its potential effect on nutrient and energy density, the sugar content of the diet is a subject of controversy. The aim of this review was to examine the cross-sectional or prospective evidence for associations between the intake of total sugar or added sugar (high vs low intakes) and diet quality or nutrient intakes in the general population. The following databases were searched for English-language articles published between 1972 and 2012: CINAHL Plus, EBM Reviews, ERIC, MEDLINE, PREMEDLINE, PsycINFO, PubMed, and ScienceDirect. The search identified studies that examined the association between intake of total sugar and/or added sugar and diet quality (n = 22) or nutrient intakes (n = 30). The following data were extracted: sample size and population, dietary assessment method, source of added sugar data, source of funding, comparator, association between total sugar or added sugar and diet quality, and the direction and magnitude of the association. Of 22 studies, all except 1 found a higher intake of added sugar to be associated with poorer diet quality, and the exceptional study did not adjust for total energy intake. Twenty-one of 30 studies found a negative association between added sugar and micronutrient intakes. The same association was not found for total sugar intake. Any negative association between dietary sugar and diet quality is better exposed by referring to added sugar rather than total sugar. There was substantial variation in features of study quality, including sample size, so the magnitude of the observed effect was generally small and may not be of clinical significance. Furthermore, the positive influence that core foods such as fruit and milk exert on total sugar values may bias the association between total sugar and diet quality.


Trend detection via temporal difference model predicts inferior prefrontal cortex activation during acquisition of advantageous action selection.
The process of accurately predicting which actions are associated with advantageous versus disadvantageous outcomes is an important function of daily life. An integral part of this process is being able to detect when the association between an action and an outcome changes. This investigation examined the hypothesis that the inferior prefrontal cortex is critical for the detection of trends and that a trend process derived from the temporal difference model accomplishes this detection. Nineteen normal right-handed volunteers completed 120 4-s trials of a Rock Paper Scissors (RPS) task during functional magnetic resonance imaging. Subjects acquired the selection of advantageous actions during the RPS task. Activations in the medial frontal gyrus (BA 10), left ventrolateral frontal gyrus (BA 11/47), and left pallidum were significantly higher during trials in which subjects acquired the advantageous action. The time course of individually derived trend detection functions was found to be time-locked to the hemodynamic changes in the inferior frontal gyrus. These findings are consistent with the hypothesis that the inferior prefrontal cortex computes a trend from previously experienced action-outcome sequences based on a value function derived from the temporal difference model.


Toward interactive scheduling systems for managing medical resources.
Managers of medico-hospital facilities are facing two general problems when allocating resources to activities: (1) to find an agreement between several and contrasting requirements; (2) to manage dynamic and uncertain situations when constraints suddenly change over time due to medical needs. This paper describes the results of a research aimed at applying constraint-based scheduling techniques to the management of medical resources. A mixed-initiative problem solving approach is adopted in which a user and a decision support system interact to incrementally achieve a satisfactory solution to the problem. A running prototype is described called Interactive Scheduler which offers a set of functionalities for a mixed-initiative interaction to cope with the medical resource management. Interactive Scheduler is endowed with a representation schema used for describing the medical environment, a set of algorithms that address the specific problems of the domain, and an innovative interaction module that offers functionalities for the dialogue between the support system and its user. A particular contribution of this work is the explicit representation of constraint violations, and the definition of scheduling algorithms that aim at minimizing the amount of constraint violations in a solution.


"Denkfaulheit" in frontotemporal dementia: a preliminary analysis.
The initial recognition of frontotemporal dementia is often difficult. Frontotemporal dementia presents with subtle personality changes in the absence of a definitive biomarker. The authors report an analysis of cognitive shallowness, or "Denkfaulheit," in patients with frontotemporal dementia early in its course.


Risk factors for community-associated methicillin-resistant Staphylococcus aureus infection in Hong Kong.
The risk factors for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection were not well understood. The objective of this study was to identify risk factors associated with CA-MRSA infection in Hong Kong. We carried out a matched case control study. Cases and controls were recruited from 14 acute public hospitals in Hong Kong. One control was individually matched to one case based on sex, age, admission date and ward location. We interviewed each case and control by telephone using a standard questionnaire. We used a conditional logistic regression model for multivariate analysis. We successfully recruited 127 pairs of matched case and control. We found that sharing of personal items with other persons had a higher risk of CA-MRSA infection (Adjusted matched odds ratio [aOR]: 4.71, 95% confidence interval [CI] 1.43-15.59). On the other hand, patients who had frequent hand washing practice (aOR: 0.21, 95%CI 0.06-0.72) and those who reported history of acne (aOR: 0.12, 95%CI 0.02-0.74) had a lower risk of CA-MRSA infection. We concluded that sharing of personal items with other persons is a risk factor for CA-MRSA infection while frequent hand washing is a protective factor against the infection.


metaSHARK: a WWW platform for interactive exploration of metabolic networks.
The metaSHARK (metabolic search and reconstruction kit) web server offers users an intuitive, fully interactive way to explore the KEGG metabolic network via a WWW browser. Metabolic reconstruction information for specific organisms, produced by our automated SHARKhunt tool or from other programs or genome annotations, may be uploaded to the website and overlaid on the generic network. Additional data from gene expression experiments can also be incorporated, allowing the visualization of differential gene expression in the context of the predicted metabolic network. metaSHARK is available at http://bioinformatics.leeds.ac.uk/shark/.


Importance of liquid fragility for energy applications of ionic liquids.
Ionic liquids (ILs) are salts that are liquid close to room temperature. Their possible applications are numerous, e.g., as solvents for green chemistry, in various electrochemical devices, and even for such "exotic" purposes as spinning-liquid mirrors for lunar telescopes. Here we concentrate on their use for new advancements in energy-storage and -conversion devices: Batteries, supercapacitors or fuel cells using ILs as electrolytes could be important building blocks for the sustainable energy supply of tomorrow. Interestingly, ILs show glassy freezing and the universal, but until now only poorly understood dynamic properties of glassy matter, dominate many of their physical properties. We show that the conductivity of ILs, an essential figure of merit for any electrochemical application, depends in a systematic way not only on their glass temperature but also on the so-called fragility, characterizing the non-canonical super-Arrhenius temperature dependence of their ionic mobility.


Personalized, 3D- printed fracture fixation plates versus commonly used orthopedic implant materials- biomaterials characteristics and bacterial biofilm formation.
Additive manufacturing enabled the development of personalized, ideally fitting medical devices. The topography of the surface of the 3D-printed implant may not only facilitate its integration but also cause its rejection, as the surface may become a reservoir for different bacterial strains. In this study, the innovative, raw, 3D- printed fracture fixation plates, manufactured by using selective laser melting (SLM) from Ti-6Al-4V were compared with commercially available, surface-modified plates commonly used in orthopedic surgery. The topography surface of the plates was studied by atomic force microscopy. Susceptibility to the development of biofilm was tested for Staphylococcus epidermidis, Staphylococcus aureus and Streptococcus mutans by using crystal violet staining of biomass, confocal, and scanning electron microscopy (SEM). 3D- printed plates showed higher roughness (Sa=131.0 nm) than commercial plates (CP1 and CP2), Sa= 60.67 nm and Sa=55.48 nm, respectively. All strains of bacteria colonized 3D- printed raw plates more densely than commercial plates. The microscopic visualization showed biofilm mostly in irregular cavities of printed plates while on commercial plates it was mainly located along the edges. The research has indicated that there is need for further development of this technology to optimize its effectiveness and safety.


Research on the Relationship Between High-Commitment Work Systems and Employees' Unethical Pro-organizational Behavior: The Moderating Role of Balanced Reciprocity Beliefs.
Based on the social exchange theory, this paper explores the indirect impact of high-commitment work systems on employees' unethical pro-organizational behavior. Through the analysis of multisource data from 139 companies (including 139 human resource managers and 966 employees), a multilevel structuring equation model is used to verify the study's hypotheses. The research results show the following findings: (1) High-commitment work systems are significantly positively related to employees' unethical pro-organizational behavior. (2) High-commitment work systems have indirect effects on the employees' unethical pro-organizational behavior through the relational psychological contract. The relational psychological contract plays a mediating role in this process. (3) Employees' balanced reciprocity beliefs significantly enhance the positive effect of relational psychological contracts on employees' unethical pro-organizational behavior. It can also positively moderate the mediating effect of high-commitment work systems that affect employees' unethical pro-organizational behavior via relational psychological contract.


Relationships Between Initial COVID-19 Risk Perceptions and Protective Health Behaviors: A National Survey.
Perceptions of health risks inform decisions about protective behaviors, but COVID-19 was an unfamiliar risk as it began to spread across the U.S. In the initial stage of the epidemic, authors examined perceived risks for COVID-19 infection and infection fatality and whether these risk perceptions were associated with protective behaviors. They also examined whether findings differed between later versus earlier responders. Between March 10 and March 31, 2020, a cross-sectional online survey was conducted with a nationally representative U.S. sample (n=6,684). Half responded before March 13, 2020 (versus later). Participants assessed their risks of COVID-19 infection and infection fatality (0%-100%) which were transformed into quartiles (1-4). They reported their implementation of protective behaviors like handwashing and social distancing (yes/no). Analyses were conducted in April‒May 2020. Median perceived risk was 10.00% for COVID-19 infection and 5.00% for infection fatality, but respondents showed large disagreement. An increase of 1 quartile in perceived infection risk was associated with being 1.45 times (95% CI=1.33, 1.58) more likely to report handwashing, with perceived infection fatality risk showing no significant association. When predicting social distancing behaviors such as avoiding crowds, both quartile-based risk perceptions were significant (OR=1.24, 95% CI=1.17, 1.30 for infection and OR=1.19, 95% CI=1.13, 1.26 for infection fatality). Perceived COVID-19 infection risk, protective behaviors, and their relationship increased among later (versus earlier) responders. Despite disagreements about the risks, people perceiving greater risks were more likely to implement protective behaviors-especially later (versus earlier) in March 2020. These findings have implications for risk communication.


Role of physical properties of resistance vessel wall in regulating peripheral blood flow--II. Structural and mechanical behavior.
In order to examine the structural and mechanical properties of the vessel wall resistance when subjected to autoregulatory flow control, a mechanical model for the vascular wall was derived from a mathematical model. The mechanical model was an analogue model which connected in series the Maxwell model (elastic modulus: K3) with the parallel elements of Hill's model (elastic modules: K2) and Hooke's elastic model (elastic modulus: K1); it was also mathematically equivalent to the Spring model (see part I). The structural and mechanical properties of the resistance vessel wall were characterized by the three elastic moduli (K1, alpha K2 and K3) [mmHg]. The parameter alpha was a modification factor of the elastic modulus K2 given by the myogenic mechanism. After a numerical analysis of the experimental data given by the mechanical model, we confirmed that the arterial pressure range for autoregulatory flow controls shifted to the upper region with an increase of the elastic modulus K1 and the flow regulation was reduced.


Auditory development in the mouse: structural maturation of the middle ear.
The development of middle-ear structures in the mouse was examined in nine groups of pups between 1 and 45 days of age. The area of the tympanic membrane (pars tensa and pars flaccida), the length of the lever arms of the malleus and incus, the surface area of the oval window, and the volume of the bulla all showed systematic changes during neonatal life. The area of the oval window reached maturity first and the lever arms achieved 90% of their adult size on day 11. The tympanic membrane achieved the same criterion on day 18. These data help us further to understand the processes that contribute to the functional ontogeny of the middle ear.


[Molecular cloning and analysis of cDNA sequences encoding serine proteinase and Kunitz type inhibitor in venom gland of Vipera nikolskii viper].
Serine proteinases and Kunitz type inhibitors are widely represented in venoms of snakes from different genera. During the study of the venoms from snakes inhabiting Russia we have cloned cDNAs encoding new proteins belonging to these protein families. Thus, a new serine proteinase called nikobin was identified in the venom gland of Vipera nikolskii viper. By amino acid sequence deduced from the cDNA sequence, nikobin differs from serine proteinases identified in other snake species. Nikobin amino acid sequence contains 15 unique substitutions. This is the first serine proteinase of viper from Vipera genus for which a complete amino acid sequence established. The cDNA encoding Kunitz type inhibitor was also cloned. The deduced amino acid sequence of inhibitor is homologous to those of other proteins from that snakes of Vipera genus. However there are several unusual amino acid substitutions that might result in the change of biological activity of inhibitor.


International Normalized Ratio and Mortality Risk in Acute Heart Failure and Nonvalvular Atrial Fibrillation Patients Receiving Vitamin K Antagonists.
Heart failure patients with nonvalvular atrial fibrillation (NVAF) on treatment with vitamin K antagonists (VKA) often have suboptimal international normalized ratio (INR) values. Our aim was to evaluate the association between INR values at admission due to acute heart failure and mortality risk during follow-up. In this observational study, we retrospectively assessed INR on admission in 1137 consecutive patients with acute heart failure and NVAF who were receiving VKA treatment. INR was categorized into optimal values (INR = 2-3, n = 210), subtherapeutic (INR < 2, n = 660), and supratherapeutic (INR > 3, n = 267). Because INR did not meet the proportional hazards assumption for mortality, restricted mean survival time differences were used to evaluate the association among INR categories and the risk of all-cause mortality. During a median [interquartile range] follow-up of 2.15 years [0.71-4.29], 495 (43.5%) patients died. On multivariable analysis, both patients with subtherapeutic and supratherapeutic INR showed higher risks of all-cause mortality, as evidenced by their restricted mean survival time differences at 5 years' follow-up: -0.50; 95%CI, -0.77 to -0.23 years; P < .001; and -0.40; 95%CI, -0.70 to -0.11 years; P = .007, respectively, compared with INR 2-3. In acute heart failure patients on treatment with VKA for NVAF, INR values out of normal range at admission were independently associated with a higher long-term mortality risk.


Fungicidal elements accumulated in Cryptothecia punctulata (Ascomycetes lichen) of an arecanut orchard in South India.
Different nutrient elements were analyzed in the lichen Cryptothecia punctulata collected from the arecanut trees which were exposed to several sprays of a fungicide Bordeaux mixture. The study revealed the accumulation of fungicidal elements such as Cu, Ca and S in higher concentration of 575.4, 10,000 and 21,000 microg g(-1), respectively.


X-rays induced IL-8 production in lung cancer cells via p38/MAPK and NF-κB pathway.
It is reported inflammatory cytokine interleukin-8 (IL-8) could predict radiation-induced lung toxicity (RILT). RILT is believed to be a consequence of a cascade of cytokine production. It is considered that vascular endothelial cell and macrophages are the mainly source of cytokines. This study was investigated the production of IL-8 from cancer cells induced by X-rays may involve in the radiation-induced inflammation. We analyzed IL-8 in human lung cancer cell lines after expose to X-rays, and we also detect IL-8 in HUVEC cells and THP1 cells as endothelial cell and macrophage model to identify the change in normal cells after expose. Furthermore, we added the inhibitors to the culture with or without radiation to identify the role of MAPK and NF-κB pathways on the radiation-induced secretion of IL-8. Radiation could induce IL-8 production both in non-lung cancer cells (HUVECs and THP1 cells) and in lung cancer cells (A549 cells, H446 cells, PC-9 cells). Simultaneously, radiation activated p38/MAPK and NF-κB signal pathways in lung cancer cells. Moreover, p38/MAPK inhibitor SB203580 and NF-κB inhibitor BAY11-7082 could block the IL-8 up-regulated by X-rays but JNK inhibitor SP600125, ERK inhibitor U0126, ROS Scavenger NAC could not inhibit this phenomenon. X-rays could induce IL-8 production in lung cancer cells, which may be related to the activation of p38/MAPK and NF-κB signaling pathway, providing a new point for elucidating the mechanism of radiation pneumonitis.


Unexpected complication of arteriovenous fistula of the left common carotid to internal jugular vein following central venous catheterization.
Incidence of inadvertent arterial puncture secondary to central venous catheter insertion is not common with an arterial puncture rate of <1%. This is due to the advancements and wide availability of ultrasound to guide its insertion. Formation of arteriovenous fistula after arterial puncture is an unexpected complication. Till date, only five cases (including this case) of acquired arteriovenous fistula formation has been described due to inadvertent common carotid puncture. The present case is a 26-year-old man sustained traumatic brain injuries, chest injuries and multiple bony fractures. During resuscitative phase, attempts at left central venous catheter via left internal jugular vein under ultrasound guidance resulted in inadvertent puncture into the left common carotid artery. Surgical neck exploration revealed that the catheter had punctured through the left internal jugular vein into the common carotid artery with formation of arteriovenous fistula. The catheter was removed successfully and common carotid artery was repaired. Postoperatively, the patient recovered and clinic visits revealed no neurological deficits. From our literature review, the safest method for removal is via endovascular and open surgical removal. The pull/push technique (direct removal with compression) is not recommended due to the high risk for stroke, bleeding and hematoma formation.


Polypeptide growth factors augment interleukin 1-induced release of prostaglandin E2 by rheumatoid arthritis synovial cells in vitro.
When stimulated with increasing amounts of interleukin 1 beta (IL 1 beta) rheumatoid arthritis (RA), as compared with osteoarthritis (OA), synovial cells grown in RPMI plus fetal bovine serum (FBS), released significantly more prostaglandin E2 (PGE2) (p less than 0.05; paired t test, two-tailed). PGE2 release by IL 1 beta-stimulated RA synovial cells grown for 14 days in serum-free RPMI was significantly less than that released by the same cells grown in medium plus 10% FBS (p less than 0.03; two-tailed). Since these data suggest that growth factors present in FBS may augment the effects of IL 1 beta, experiments were conducted to study the influence of four polypeptide growth factors--transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), on IL 1 beta-induced release of PGE2 by cultured RA synovial cells. Both EGF and bFGF significantly enhanced IL 1 beta-induced release of PGE2 (p less than 0.05; paired t test, one-tailed), while PDGF was synergistic with IL 1 beta, significantly increasing release of PGE2 by these cultured cells (p less than 0.02; two-tailed). No such effect was seen when TGF-beta was added to the culture medium. Taken together, these data lend support to the concept that within the synovial micro-environment small quantities of individual growth factors may potentiate the effects of IL 1 beta to amplify intra-articular inflammation.


Mechanism of angiotensin I converting enzyme inhibition by SQ20,881 (less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) in vivo. Further evidence for extrapulmonary conversion.
The mechanism by which the angiotensin I (AI) converting enzyme inhibitor SQ20,881 (less than Glu-Trp-Pro-Arg-Pro-Glu-Ile-Pro-Pro) blocks the pressor response to exogenous AI was studied in vivo in the intact anesthetized dog. When administered as a single dose 250 times that of injected AI (250 nmoles/kg) into either the pulmonary or systemic circulation, SQ20,881 produced inhibition of pulmonary conversion of exogenous AI to AII that lasted for more than 6 hours as judged by the absence of immunoreactive or labeled AII in the pulmonary venous effluent. In contrast, the pressor response to exogenous AI began to reappear within 1 hour of SQ20,881 administration. Six hours following SQ20,881, the pressor response to AI had nearly returned to normal, still in the absence of demonstrable intrapulmonary conversion and without release of detectable amounts of AII into the pulmonary venous effluent. These experiments demonstrated that AI has a pressor effect in the presence of SQ20,881 that is independent of pulmonary conversion. Studies with (Des-Asp) AII and (Des-Asp, Arg) AII showed that the delayed pressor response to AI following SQ20,881 administration could not be accounted for by circulating peptide metabolites of AI or AII. A competitive inhibitor of AII, (D-Asp, Ile) AII completely blocked the returning pressor response, suggesting that extrapulmonary generation of AII was responsible. The data strongly suggest that the systemic vascular bed taken as a whole contains large amounts of AI converting enzyme that is capable of rapid generation of AII without releasing the peptide into circulation. The extrapulmonary enzyme is more resistant to long-lasting blockade by SQ20,881 than pulmonary converting enzyme. The physiological role of extrapulmonary conversion systemic and local circulatory homeotasis remains to be assessed.


Preparing for the Maximum Emergency with a Simulation: A Table-Top Test to Evaluate Bed Surge Capacity and Staff Compliance with Training.
The sudden increase in the number of critically ill patients following a disaster can be overwhelming. The main objective of this study was to assess the real number of available and readily freeable beds ("bed surge capacity") and the availability of emergency operating rooms (OR) in a maximum emergency using a theoretical simulation. The proportion of dismissible patients in four areas (Medical Area, Surgical Area, Sub-intensive Care Units, Intensive Care Units) and three emergency OR was assessed at 2 and 24 hours after a simulated maximum emergency. Four scenarios were modeled. Hospitalization and surgical capacities were assessed on weekdays and holidays. The creation of new beds was presumed by the possibility of moving patients to a lower level of care than that provided at the time of detection, of dislocation of patients to a discharge room, with care transferred to lower-intensity hospitals, rehabilitation, or discharge facilities. The Phase 1 table-top simulations were conducted during the weekday morning hours. In particular, the 24-hour table-top simulations of a hypothetical event lasted about 150 minutes compared to those conducted at 2 hours, which were found to be longer (about 195 minutes). Phase 2 was conducted on two public holidays and a quick response time was observed within the first 40 minutes of the start of the test (about 45% of departments). The availability of simulated beds was greater than that indicated in the maximum emergency plans (which was based solely on the census of beds). Patients admitted to Intensive Care and The Sub-Intensive Area may be more difficult to move than those in low-intensity care. The availability of emergency OR was not problematic. Age influenced the possibility of remitting/transferring patients. Simulation in advance of a maximum emergency is helpful in designing an efficient response plan.


Full scale composting of food waste and tree pruning: How large is the variation on the compost nutrients over time?
The aim of the study was to evaluate if a composting unit on a commercial scale can produce, during 15 months, an organic compost according to the guarantees and tolerance margins required by Brazilian legislation for its nutrient content. For this, a food and tree pruning waste compost produced in a composting unit located in Belo Horizonte (Brazil) was evaluated. Noncompliance regarding tolerance margins for nitrogen, phosphorus and potassium were 3, 17 and 28% on a dry matter basis and 19, 31 and 33% on a fresh matter basis. Noncompliance can be mainly attributed to difference in the initial condition among piles (mass used in the piles preparation, proportion of food and pruning waste, initial nutrient content in the mixture, etc.) and differences in the operational activities among the piles. Together, these factors explained 64 to 86% of the variation in the nutrient content of the compost.


Evaluation of the single-incision Elevate system to treat pelvic organ prolapse: follow-up from 15 to 45 months.
The aim of this study was to assess the 2-year clinical outcomes of pelvic reconstructive surgery with the single-incision Elevate system (American Medical Systems, Minnetonka, MN, USA). This retrospective study was conducted from November 2010 to August 2013, and included 210 patients with pelvic organ prolapse stage 3 or 4 who underwent pelvic reconstructive surgery with an Elevate system and were followed for 1 to 3 years postoperatively. Assessments included pre- and postoperative Pelvic Organ Prolapse Quantification (POP-Q) stage, Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7) and multi-channel urodynamic examinations. Anatomical success was defined as postoperative POP-Q stage 0 or I. The anatomical success rates were 95 % for the anterior vaginal wall, 99 % for the posterior vaginal wall and 94 % for the apical vaginal wall after a median 27 months of follow-up. POP-Q, UDI-6 and IIQ-7 scores, maximal flow rate and post-voiding residual urine all improved significantly after surgery. Complications included 1 case of internal bleeding, 4 cases of mesh exposure, 5 cases of recurrent prolapse that required salvage operations, and 3 cases of urine retention that required intermittent catheterization. There were no bladder or bowel injuries during surgery. Pelvic reconstructive surgery with the Elevate system yielded good anatomical outcomes and symptom improvement after 2 years of follow-up.


Influence of acid surrogates toward potency of VLA-4 antagonist.
A series of VLA-4 antagonist were synthesized wherein carboxylic acid was replaced by various acid surrogates. The effect of these acid surrogates toward potency was evaluated in a binding assay. A number of acid surrogates were potent antagonist of VLA-4, albeit significantly less potent than the corresponding carboxylic acid. Heterocyclic acid surrogate, oxadiazolidinone 3, demonstrated an improved pharmacokinetic property when dosed intravenously.


A simple method for the removal of mycoplasma contamination from paramyxovirus stocks.
A simple and quick method of detecting mycoplasmas in virus stocks using the fluorochrome Hoechst 33258 is described. Different methods of removal of mycoplasmas from stocks are discussed. The simple but effective method using gentamicin (0.2 mg/ml) or chloramphenicol (5 micrograms/ml) is demonstrated and chosen as the most efficient as judged using both the Hoechst stain and the direct assessment of mycoplasma RNA species labelled with [5-3H]uridine.


Effect of exogenous melatonin on X-ray induced cellular toxicity in lymphatic tissue of Indian tropical male squirrel, Funambulus pennanti.
The radioprotective ability of melatonin was investigated in the Indian tropical rodent, Funambulus pennanti during its reproductively inactive phase (RIP) when peripheral melatonin is high and the animal is under the influence of environmental stresses. Fifty male squirrels were divided into two sets of 25 each; with set 1 receiving 0.9% saline and set 2 receiving 25 mug melatonin/100 g body weight/day for four weeks during evening hours. Five saline-treated and five-melatonin treated squirrels were sacrificed at times of 4, 24, 48 and 72 hours following 2.06 Gy X-ray radiation. Remaining squirrels that were not exposed to X-ray were used as control and melatonin treated, respectively. Total leukocyte count (TLC) and lymphocyte count (LC) in peripheral blood and lipid peroxidation (LPO) status, superoxide dismutase (SOD) activity, total antioxidant status (TAS), apoptotic percentage on the basis of morphological changes and DNA fragmentation and caspase-3 activity were measured in the spleens of squirrels. Peripheral blood and spleens with higher intrinsic levels of environmental and X-radiation induced free radical generation had inhibited TLC, LC, SOD activity and TAS and increased LPO and apoptosis. Melatonin pre-treatment significantly reduced and altered the changes brought on by X-radiation. Exogenous melatonin with its anti-apoptotic and antioxidant properties additively increased the immunity of the squirrels, by protecting their hematopoietic system and lymphoid organs against X-ray radiation induced cellular toxicity.


Respiratory metabolism of Cyclops bicuspidatus (sensu stricta) (Claus) (Copepoda: Cyclopoida) from Esthwaite Water, Cumbria.
The respiration rate of all stages of Cyclops bicuspidatus (s. str.) (Claus), a benthic copepod, from Esthwaite Water in the English Lake District, was determined at a range of field temperatures, 4° C-12° C, using cartesian diver microrespirometry. The population of C. bicuspidatus in Esthwaite Water was found to be adapted to low temperatures, with an optimum rate of metabolism at 8° C. Weight varied with temperature, in general the largest weights occurred at the lower temperatures. Adult males had higher rates of respiration than adult females, which were on average twice the size of males. Gravid and non-gravid females had similar levels of metabolism. Regression coefficients (b), derived from regressions of log oxygen consumption against log dry weight were low, ranging between 0.25-0.51 according to temperature.


Customized adjuncts with clear aligner therapy: "The Golden Circle Model" explained!
Clear aligners are the most debated infusion of technology into the orthodontic stratosphere and currently account for a sizable chunk of the orthodontic commercial market. Data indicate that a series of plastic aligners alone cannot resolve all the variants of malocclusion routinely treated by our specialty. Current literary consensus exists that the discrepancy between the predicted and actual clinical outcomes with clear aligner therapy (CAT) is around 50% or more, necessitating midcourse corrections, refinement, or additional aligners, or even a conversion to fixed appliances before the end of treatment. A practical panacea to improve the predictability of CAT is the addition of creative and customized adjuncts to CAT. This article, inspired by the "Golden Circle Model", addresses questions such as the "WHY, HOW, and WHAT" of adjuncts used in combination with CAT and depicts an "inside out" approach (from WHY to WHAT) to present the rationale, stepwise clinical workflow, and the advantages of these adjuncts. The bootstrap, mini pin-supported mesialization or distalization, Yin-Yang attachments, Beneslider, Mesialslider, BMX Expander, and Computer-Aided Design (CAD) / Computer-Aided-Manufacturing (CAM)...based innovative appliance designs among others, are presented as adjuncts to CAT in this article. These adjuncts can either be used concomitantly with the aligners or planned as a separate phase of treatment before the commencement of the actual CAT, based on the type of tooth movement required and whether the planned tooth movement is indicated for a single tooth or a group of teeth. An astute clinician who wishes to expand the repertoire of malocclusions that can be successfully managed by CAT should judiciously plan the inclusion of such adjunct appliances in their aligner treatment planning.


Physiology and pathophysiology of iron in hemoglobin-associated diseases.
Iron overload and iron toxicity, whether because of increased absorption or iron loading from repeated transfusions, can be major causes of morbidity and mortality in a number of chronic anemias. Significant advances have been made in our understanding of iron homeostasis over the past decade. At the same time, advances in magnetic resonance imaging have allowed clinicians to monitor and quantify iron concentrations noninvasively in specific organs. Furthermore, effective iron chelators are now available, including preparations that can be taken orally. This has resulted in substantial improvement in mortality and morbidity for patients with severe chronic iron overload. This paper reviews the key points of iron homeostasis and attempts to place clinical observations in patients with transfusional iron overload in context with the current understanding of iron homeostasis in humans.


In vivo quantitative imaging of dopamine receptors in human brain using positron emission tomography and [76Br]bromospiperone.
The brain regional distribution and kinetics of [76Br]bromospiperone, a derivative of a neuroleptic (spiperone) labeled with the positron emitter bromine-76, were studied by time-of-flight tomography after i.v. injection in man. In a control subject the kinetic distribution study showed an accumulation of radioactivity which reached a maximum 3 h postinjection in the frontal cortex and cerebellum regions and 4-5 h postinjection in the basal ganglia. Thereafter the striatal activity remained essentially constant over a period of 25 h. In a group of 13 control subjects, the mean value for the striatum-to-cerebellum ratio, at 4.5 h postinjection, was 1.84 (S.D. 0.21). In two schizophrenics treated with high doses of haloperidol, this ratio was found to be only 1.22. These data indicate that radiolabeled bromospiperone is very suitable for human pharmacological or pathological investigations of the central dopaminergic system.


Risk perception of driving as a function of advanced training aimed at recognizing and handling risks in demanding driving situations.
The present study examined in 224 individuals whether an advanced driving training aimed at recognizing, avoiding and handling risks in demanding driving situations, affected perceived risk of driving situations (measured by a questionnaire). The training, which involved both experience and feedback on real performance, specifically intended to emphasize the dangers in loss of control of a vehicle. With that emphasis, it was hypothesized that perceived risk would increase after as compared to before the training. In addition, this study examined whether risk perception was dependent on gender or on age. A mixed ANOVA performed on mean scores on the questionnaire yielded significant main effects for training (before/after), gender, and age. Higher levels of perceived risk were reported after the training as compared to before it, by females than by males, and by older adult drivers than by younger adult drivers. An analysis of the data of a smaller sample showed that the increment in perceived risk was still present 2 months after the training, and that it did not decrease significantly as compared to immediately after the training. These results are discussed in relation to relevant methodological issues and future research.


Children With Food Allergy Are at Risk of Lower Lung Function on High-Pollen Days.
Grass pollen exposure is a risk factor for childhood asthma hospital attendances. However, its short-term influence on lung function, especially among those with other allergic conditions, has been less well-studied. To investigate this association in a population-based sample of children. Within the HealthNuts cohort, 641 children performed spirometry during the grass pollen season. Grass pollen concentration was considered on the day of testing (lag 0), up to 3 days before (lag 1-lag 3), and cumulatively (lag 0-3). We used linear regression to assess the relevant associations and examined potential interactions with current asthma, hay fever or eczema, and food allergy. Associations were observed only in children with allergic disease (P value for interaction ≤ 0.1). In children with food allergy, grass pollen concentration was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) and lower mid-forced expiratory flows (FEF25%-75%) at all lags (eg, at lag 2, FEV1/FVC z-score = -0.50 [95% CI -0.80 to -0.20] and FEF25%--75% z-score = -0.40 [-0.60 to -0.04] per 20 grains/m3 pollen increase), and increased bronchodilator responsiveness (BDR) at lag 2 and lag 3 (eg, at lag 2, BDR = (31 [95% CI -0.005 to 62] mL). In children with current asthma, increasing grass pollen concentration was associated with lower FEF25%-75% and increased BDR, whereas children with current hay fever or eczema had increased BDR only. A proactive approach needs to be enforced to manage susceptible children, especially those with food allergy, before high-grass pollen days.


IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients.
Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences. We collected the data of 37 unpublished patients (18 males and 19 females) with IQSEC2 pathogenic variants and 5 individuals with variants of unknown significance and reviewed published variants. We compared variant types and phenotypes in males and females and performed an analysis of IQSEC2 isoforms. IQSEC2 pathogenic variants mainly led to premature truncation and were scattered throughout the longest brain-specific isoform, encoding the synaptic IQSEC2/BRAG1 protein. Variants occurred de novo in females but were either de novo (2/3) or inherited (1/3) in males, with missense variants being predominantly inherited. Developmental delay and intellectual disability were overall more severe in males than in females. Likewise, seizures were more frequently observed and intractable, and started earlier in males than in females. No correlation was observed between the age at seizure onset and severity of intellectual disability or resistance to antiepileptic treatments. This study provides a comprehensive overview of IQSEC2-related encephalopathy in males and females, and suggests that an accurate dosage of IQSEC2 at the synapse is crucial during normal brain development.


Ruthenium(II) coordination chemistry of a fused donor-acceptor ligand: synthesis, characterization, and photoinduced electron-transfer reactions of [{Ru(bpy)2}(n)(TTF-ppb)](PF6)(2n) (n = 1, 2).
A pi-extended, redox-active bridging ligand 4',5'-bis(propylthio)tetrathiafulvenyl[i]dipyrido[2,3-a:3',2'-c]phenazine (L) was prepared via direct Schiff-base condensation of the corresponding diamine-tetrathiafulvalene (TTF) precursor with 4,7-phenanthroline-5,6-dione. Reactions of L with [Ru(bpy)(2)Cl(2)] afforded its stable mono- and dinuclear ruthenium(II) complexes 1 and 2. They have been fully characterized, and their photophysical and electrochemical properties are reported together with those of [Ru(bpy)(2)(ppb)](2+) and [Ru(bpy)(2)(mu-ppb)Ru(bpy)(2)](4+) (ppb = dipyrido[2,3-a:3',2'-c]phenazine) for comparison. In all cases, the first excited state corresponds to an intramolecular TTF --> ppb charge-transfer state. Both ruthenium(II) complexes show two strong and well-separated metal-to-ligand charge-transfer (MLCT) absorption bands, whereas the (3)MLCT luminescence is strongly quenched via electron transfer from the TTF subunit. Clearly, the transient absorption spectra illustrate the role of the TTF fragment as an electron donor, which induces a triplet intraligand charge-transfer state ((3)ILCT) with lifetimes of approximately 200 and 50 ns for mono- and dinuclear ruthenium(II) complexes, respectively.


Critical bandwidth determined by masking in the presence of two narrow-band noises.
In this experiment, the critical band (CB)-widths were measured using two narrow-band noises (NBNs) with steep cut-off slopes as a masker, varying their spectral level and center-frequency. The following results were obtained: (i) The CB-widths at all center-frequencies were narrower than the classical CB-widths estimated by Zwicker et al [J Acoust Soc Am 29:548-557 (1957)], and decreased continuously toward the lower frequency at the center-frequencies below 500 Hz, though Zwicker's data were constant in the same range. These results barely coincided with the frequency dependence of the equivalent rectangular bandwidth (ERB) which was estimated from the shape of the auditory filter measured directly. (ii) Level dependence of masking noise in CB was constant beyond 20 dB of the masked threshold. This depends on the use of NBN as a masker. (iii) The CB was influenced by distortion products and off-frequency listening. Accordingly, the bandwidths might differ with the experimental method.


Correlation of metabolic acidosis with outcome following injury and its value as a scoring tool.
This study looked at preresuscitation arterial pH as a predictor of outcome in injury. Seriously injured patients admitted to the Trauma Service over a 5-month period were evaluated prospectively. Data collected included basic patient demographics, initial arterial blood gas determinations (ABGs) including pH, bicarbonate (HCO3), base deficit or excess (BASE), admitting trauma score (TS), discharge injury severity score (ISS), total blood products used for initial resuscitation (TBP), and outcome. There were 191 patients averaging 34.7 years old with average TS 13.6, ISS 19.5, initial pH 7.38 +/- 0.09, HCO3 20.9 +/- 4.0, and BASE -3.3 +/- 4.7. The average TBP was 1309 cc, and overall mortality was 13/191 (6.8%). Comparing survivors to nonsurvivors, the ISS (18.2 vs. 38.3), TS (14.1 vs. 7.8), TBP (976 vs. 5881 cc), HCO3 (21.1 vs. 17.6), and BASE (-3.1 vs. -5.8) data were significantly different; pH (7.38 vs. 7.36) and age (34.4 vs. 38.5) were not. Using multiple regression with TBP as the dependent variable, BASE, age, TS, and to a lesser extent pH and HCO3 correlated (r = 0.536; p < 0.001); using outcome as the dependent variable, only TS and age correlated (r = 0.465; p < 0.0001). Although metabolic acidosis (pH, HCO3, BASE) predicts the TBP used, it does not improve on TS and age for predicting outcome.


Oil prices volatility and economic performance during COVID-19 and financial crises of 2007-2008.
We examine the time-frequency dynamics of spillovers between oil price shocks and economic performance globally. We use both time and frequency domains simultaneously to find the response of macroeconomic performance to changes in oil prices during the global financial and pandemic crises. Using Wavelet analysis, this seminal study explores the connectedness between oil price shocks and economic activities during COVID-19 and the financial crises of 2008. This study finds that both economic activities and oil prices have shown high power during the period of global financial crises. The recently COVID-19 outbreak indicates significant volatility in economic activities and oil prices during the period of crisis. Moreover, we observe a strong interconnectedness between oil prices and economic activities during global financial crises and COVID-19 crises. We argue that a shock to oil prices in global financial crises and the COVID-19 outbreak has serious repercussions for economic activities. The highest total connectedness between oil prices and economic activities is observed during the COVID-19 outbreak, which advocates that the speed of information transmission amid oil prices and economic activities is greater in the era of the COVID-19 outbreak as compared to other global financial crises. The results of this study have significant implications for policymakers.


Effects of tetrandrine on left ventricle hypertrophy in deoxycorticosterone acetate-salt hypertensive rats.
The effect of regression of left ventricular hypertrophy was studied in deoxycorticosterone-acetate-salt hypertensive rats (DOCA-salt hypertensive rats) treated with tetrandrine. Treatment with tetrandrine (by gastric intubation, 50 mg/kg per day for 9 weeks) lowered systolic blood pressure, left ventricular weight, Ca2+ of mitochondria, and markedly decreased the density (Bmax) and total number of dihydropyridine binding sites in hypertrophic left ventricle (P < 0.001). There was no difference between groups in dissociation constant (Kd) values of dihydropyridine binding sites. These facts indicate that tetrandrine decreased cardiac mass in DOCA-salt hypertensive rats through mechanisms that may be associated with the density and the total number of dihydropyridine binding sites, Ca2+ and blood pressure control.


Two-hybrid analysis of human salivary mucin MUC7 interactions.
MUC7 is a low molecular weight monomeric mucin secreted by submandibular, sublingual and minor salivary glands. This mucin has been implicated in the non-immune host defense system in the oral cavity since it binds and agglutinates a variety of oral microbes. To investigate interactions between this mucin and other secretory salivary proteins, a submandibular gland prey library was screened with baits encoding the N- and C-terminal regions of MUC7 in the yeast two-hybrid system. The N-terminal region interacted with several secretory salivary proteins, whereas the C-terminal region did not. Interacting proteins included amylase, acidic proline-rich protein 2, basic proline-rich protein 3, lacrimal proline-rich protein 4, statherin and histatin 1. Formation of complexes between these proteins and the N-terminal region of MUC7 was confirmed in Far Western blotting experiments. Interactions between mucin and non-mucin proteins in saliva could protect complex partners from proteolysis, modulate the biological activity of complexed proteins or serve as a delivery system for distribution of secretory salivary proteins throughout the oral cavity.


A Longitudinal Study of Joint Attention, Motor Imitation and Language Development in Young Children with Autism Spectrum Disorder in Taiwan.
This longitudinal study examined early predictors of language development in 74 young children with Autism Spectrum Disorder (ASD) in Taiwan. Participants were assessed twice (initial age between 17 and 35 months) on responding to joint attention (RJA), initiating joint attention (IJA), motor imitation with objects (object imitation; OI) and without objects (manual imitation; MI), and receptive and expressive language. The two assessments were 18 months apart. Results showed that both RJA and MI concurrently and longitudinally predicted receptive and expressive language across the two assessments. These findings were not entirely consistent with the limited and mixed findings of Western longitudinal studies. However, they have implications for early interventions aiming to facilitate language development in children with ASD internationally.