Design and modeling of sustainable bioethanol supply chain by minimizing the total ecological footprint in life cycle perspective.
The purpose of this paper is to develop a model for designing the most sustainable bioethanol supply chain. Taking into consideration of the possibility of multiple-feedstock, multiple transportation modes, multiple alternative technologies, multiple transport patterns and multiple waste disposal manners in bioethanol systems, this study developed a model for designing the most sustainable bioethanol supply chain by minimizing the total ecological footprint under some prerequisite constraints including satisfying the goal of the stakeholders', the limitation of resources and energy, the capacity of warehouses, the market demand and some technological constraints. And an illustrative case of multiple-feedstock bioethanol system has been studied by the proposed method, and a global best solution by which the total ecological footprint is the minimal has been obtained.


Long-term follow-up in preschool children after radiofrequency catheter ablation of arrhythmias.
Radiofrequency ablation (RFA) is the standard method of treatment for tachyarrhythmias in school children, and it leads to complete recovery in children without structural heart disease. However, RFA in young children is limited by the risk of complications and unstudied remote effects of radiofrequency lesions. To present the experience of RFA of arrhythmias and the results of follow-up of younger children. RFA procedures (n = 255) were performed in 209 children with arrhythmias from 0 to 7 years old. The arrhythmias were presented with atrioventricular reentry tachycardia with Wolff-Parkinson-White (WPW) syndrome (56%), atrial ectopic tachycardia (21.5%), atrioventricular nodal reentry tachycardia (4.8%), and ventricular arrhythmia (17.2%). The overall effectiveness of RFA, considering the repeated procedures performed due to the primary ineffectiveness and recurrencies, was 94.7%. There was no mortality associated with RFA in patients, including young patients. All cases of "major" complications are associated with RFA of the left-sided accessory pathway and tachycardia foci and are represented by the mitral valve damage in three patients (1.4%). Tachycardia and preexcitation recurred in 44 (21%) patients. There was a correlation between recurrences and parameters of RFA (odds ratio 0.894; 95% confidence interval: 0.804-0.994; p = .039). Reducing the maximum power of effective applications in our study increased the risk of recurrence. The use of the minimum effective parameters of RFA in children reduces the risk of complications, but increases arrhythmia recurrence rate.


[Chemoprevention of (pre)malignant disorders of the head and neck area. Current situation].
A brief review is presented of various ongoing chemoprevention studies on head and neck cancer. Although beta carotene and several retinoids seem to be effective, scientific proof is at yet insufficient. The need of biomarkers as intermediate end-points is stressed.


Effect of histidine on morphine-induced changes in brain histamine.
Chronic morphine administration to rats resulted in a significant decrease in the hypothalamic and cerebro-cortical histamine concentrations. These low histamine values were restored to control levels when L-histidine was administered daily along with morphine treatment. Chronic treatment with L-histidine prevented the midbrain and cerebro-cortical histamine depletion in morphine-withdrawn rats, whereas in the hypothalamus the histamine level remained significantly decreased. The present data suggests that histamine may play a role in morphine dependence and withdrawal.


A simple, inexpensive, disposable electrochemical sensor for clinical and immuno-assay.
An inexpensive, rapid, disposable electrochemical system has been developed for both clinical and immunochemical assays. The three-electrode planar configuration is produced by silk screening graphite paint on to cardboard. Assays are carried out amperometrically using constant voltage and monitoring current produced by the oxidation of an electron mediator. In the case of immuno-assay the system described uses the enzyme glucose oxidase with 1,4-benzoquinone as the mediator. The assay is carried out by effecting a separation of the bound and free fractions of the immunoreactants via immobilizing the antibodies on to magnetic particles which are magnetically concentrated on the electrode surface for analysis. This concentration of the bound antigen-antibody complex with the glucose oxidase label effectively increases the concentration of the reduced mediator in the electrode vicinity, thus increasing the amperometric response to the bound fraction of the label.


FACT-MNG: tumor site specific web-based outcome instrument for meningioma patients.
To formulate Functional Assessment of Cancer Therapy-Meningioma (FACT-MNG), a web-based tumor site-specific outcome instrument for assessing intracranial meningioma patients following surgical resection or stereotactic radiosurgery. We surveyed the relevant literature available on intracranial meningioma surgery and subsequent outcomes (38 papers), making note of which, if any, QOL/outcome instruments were utilized. None of the surgveyed papers included QOL assessment specific to tumor site. We subsequently developed questions that were relevant to the signs and symptoms that characterize each of 11 intracranial meningioma sites, and incorporated them into a modified combination of the Functional Assessment of Cancer Therapy-Brain (FACT-BR) and SF36 outcome instruments, thereby creating a new tumor site-specific outcome instrument, FACT-MNG. With outcomes analysis of surgical and radiosurgical treatments becoming more important, measures of the adequacy and success of treatment are needed. FACT-MNG represents a first effort to formalize such an instrument for meningioma patients. Questions specific to tumor site will allow surgeons to better assess specific quality of life issues not addressed in the past by more general questionnaires.


Proliferative response of bronchoalveolar lymphocytes to beryllium. A test for chronic beryllium disease.
to ascertain whether measuring the proliferative response of bronchoalveolar lymphocytes to beryllium salts is useful for diagnosing chronic beryllium disease. prospective case series compared to normal volunteers and patients with sarcoidosis. university referral center. twenty-three consecutive beryllium workers were evaluated. Fourteen had chronic beryllium disease diagnosed on the basis of histologic evidence of a progressive pulmonary granulomatosis. Four had biopsy evidence of non-beryllium disease. Three had probable chronic beryllium disease but did not have lung biopsies. Two did not have biopsies and had basilar fibrosis on chest roentgenogram suggestive of non-beryllium lung disease. These patients were compared with 6 normal volunteers and 16 patients with sarcoidosis. bronchoalveolar lavage was done and the proliferative response of the lung cells to two beryllium salts was tested. A positive proliferative test was defined as a stimulation index of more than five on two determinations. The sensitivity of this test was 100% in the 14 patients with definite chronic beryllium disease. The specificity of the test was also 100% among the normal volunteers and the 16 patients with sarcoidosis. The test was positive in none of the four patients with biopsy evidence of non-beryllium disease, none out of two patients with lower lobe fibrosis suggestive of non-beryllium disease, and all of three patients with probable chronic beryllium lung disease. the proliferative response of bronchoalveolar lymphocytes to beryllium appears to be a useful test for chronic beryllium disease.


Machine-learning guided elucidation of contribution of individual steps in the mevalonate pathway and construction of a yeast platform strain for terpenoid production.
The production of terpenoids from engineered microbes contributes markedly to the bioeconomy by providing essential medicines, sustainable materials, and renewable fuels. The mevalonate pathway leading to the synthesis of terpenoid precursors has been extensively targeted for engineering. Nevertheless, the importance of individual pathway enzymes to the overall pathway flux and final terpenoid yield is less known, especially enzymes that are thought to be non-rate-limiting. To investigate the individual contribution of the five non-rate-limiting enzymes in the mevalonate pathway, we created a combinatorial library of 243 Saccharomyces cerevisiae strains, each having an extra copy of the mevalonate pathway integrated into the genome and expressing the non-rate-limiting enzymes from a unique combination of promoters. High-throughput screening combined with machine learning algorithms revealed that the mevalonate kinase, Erg12p, stands out as the critical enzyme that influences product titer. ERG12 is ideally expressed from a medium-strength promoter which is the 'sweet spot' resulting in high product yield. Additionally, a platform strain was created by targeting the mevalonate pathway to both the cytosol and peroxisomes. The dual localization synergistically increased terpenoid production and implied that some mevalonate pathway intermediates, such as mevalonate, isopentyl pyrophosphate (IPP), and dimethylallyl pyrophosphate (DMAPP), are diffusible across peroxisome membranes. The platform strain resulted in 94-fold, 60-fold, and 35-fold improved titer of monoterpene geraniol, sesquiterpene α-humulene, and triterpene squalene, respectively. The terpenoid platform strain will serve as a chassis for producing any terpenoids and terpene derivatives.


Autism Spectrum Disorders: Barriers to Implementing Parent-Based Home Programs.
An exploratory survey to identify the barriers experienced by caregivers of children with autism spectrum disorders (ASD) when implementing home programs (HP) was conducted with a newly developed questionnaire, 'barriers in the parent-based home program for ASD (BHPQ-ASD)' in English and Malayalam. The questionnaire has 25 items in Likert scale response format and underwent face validation and cognitive debriefing. It was administered to 50 caregivers of ASD children for factor extraction and reliability analysis. Seven questions under service provider-related barriers emerged to have good psychometric properties in the principal axis factoring method and were grouped to form the 'service provider-related BHPQ-ASD' scale, which has very good internal consistency (Cronbach alpha 0.903). In regression analysis, parents of children not receiving occupational therapy (OT) reported 6.6 times more barriers when compared to those undergoing OT (OR 6.6, CI 1.5-29.7, p = 0.014). BHPQ-ASD is a useful valid tool for detecting the barriers to implementing HPs.


Mutagenicities of xanthone derivatives in Salmonella typhimurium TA100, TA98, TA97, and TA2637.
The mutagenicities of naturally occurring xanthones were tested in Salmonella typhimurium TA100, TA98, TA97, and TA2637 by the preincubation method. Xanthydrol, gentisein, gentisin, isogentisin, 1-hydroxy-3,7-dimethoxyxanthone, 1,3,7-trimethoxyxanthone, desmethylbellidifolin, bellidifolin and dimethylbellidifolin were mutagenic, but unsubstituted xanthone was not mutagenic to TA100, TA98, TA97 and TA2637 with or without a metabolic activation system. The beta-O-glucosides, norswertianolin and swertianolin, were only mutagenic when a metabolic activation system containing beta-glucosidase was used, and the C-glucoside mangiferin was not mutagenic even with this system.


Erratum: Ultrasonic characteristics of the portal venous system of 37 healthy, unsedated, student-owned cats: A prospective study.
[This corrects the article on p. 373 in vol. 63, PMID: 35368397.].


A new method to assess ventricular wall stress in patients with heart failure and its relation to heart rate variability.
Heart failure is characterized by an increase in cardiac load, wall stress and autonomic dysfunction. The neurohumoral imbalance arising from adrenergic activation and parasympathetic withdrawal is associated with worse prognosis. We addressed the hypothesis that an increased left ventricular (LV) wall stress as assessed by cardiac magnetic resonance imaging (CMR) in patients with heart failure is related to a depression of heart rate variability (HRV). Cardiac function and mass were measured in 37 individuals with suspected cardiomyopathy using CMR imaging. A thick-walled sphere model was used to calculate ventricular wall stress. Time domain analysis of HRV was obtained by long-term Holter ECG. Standard deviation of both normal-to-normal (NN) intervals (SDNN) and average NN intervals over 5 minutes (SDANN-i) were negatively correlated with LV enddiastolic wall stress (r = 0.42, P < 0.01). SDNN and SDANN-i were severely decreased (P < 0.01) in patients with increased enddiastolic LV wall stress > 12 kPa (vs. normal range: < 4 kPa). A relation between increased cardiac wall stress and depressed heart rate variability was observed in patients with heart failure. CMR-based measurement of LV volume and mass is appropriate to calculate LV wall stress which should be considered not only as a potential prognostic determinant but also as therapeutic target.


Evaluation of thyroid functions in leprosy. II. Histopathology of the thyroid.
Open thyroid biopsies from seven patients of bacilliferous leprosy were studied for leprous granuloma or amyloid deposition. None of the patients had clinical evidence of thyroid involvement. Histopathology did not reveal any specific abnormality.


Clinicopathologic discordance-a not unexpected occurrence.
Disagreements between clinical and forensic interpretations of post-mortem findings are sometimes influenced by prior experiences with particular patient cohorts. While patients who present clinically have characteristic indicators of disease (thus enabling diagnosis), symptoms and signs may not have been manifested by those who die suddenly and unexpectedly and present for medicolegal assessment. Thus, the determination of likely or possible lethal mechanisms requires an understanding of occult disease processes and idiosyncratic responses that may be very different from case to case. Summaries of cases should be undertaken with an awareness of the limitations of individual knowledge and may be augmented by collaboration and pooling of expertise.


Preferential expression of a 130,000-Da cell surface protein by vascular wall cells in vitro and in vivo.
Monoclonal antibodies have been raised against cell surface proteins of cultured bovine retinal pericytes. One antibody was selected, designated PC4, which preferentially stained primary cultures of bovine pericytes and smooth muscle cells, but not endothelial cells and fibroblasts. In freshly plated cells a homogeneous cell surface staining was observed, whereas in well-spread cells the antigen was concentrated at cell attachment sites. The antigen remained at these sites after spontaneous detachment of the cells. PC4 monoclonal antibodies reacted with a major protein of 130,000 Da and two minor antigens of 75,000 and 70,000 Da in immunoblots of extracts from cultured pericytes and smooth muscle cells and from fibroblasts cultured for an extended period of time. In frozen sections of bovine tissues the antigen was found in the vascular wall. There was no staining of skeletal muscle cells or duodenal smooth muscle cells, indicating that the antigen may be a specific component of the vascular wall.


The effect of speed of deoxygenation on the percentage of aligned hemoglobin in sickle cells. Application of differential polarization microscopy.
We have used differential polarization microscopy, which provides images of linear dichroism, to measure the percentage of aligned hemoglobin (Hb) in 1086 deoxygenated red blood cells from subjects with sickle cell anemia. The percentage was found to be only slightly dependent on the speed of deoxygenation, thus showing that the percentage of aligned Hb was thermodynamically controlled (as has been found previously for the percentage of polymerized Hb in vitro). A slight decrease in the percentage of aligned Hb due to increasing speed of deoxygenation is primarily due to the increase in the number of cells containing no detectable aligned Hb. This class of cells was also the most variable between the different subjects studied. We were able to identify two other groups of cells that contain different numbers of domains of aligned Hb and show that these groups contain statistically different percentages of aligned Hb. The differences between these classes of cells was shown to be primarily due to different numbers of initial nucleation sites within each cell. It appears that the presence of preformed nucleation sites within cells at ambient oxygen tensions results in the thermodynamic control of aligned Hb polymer.


[Neurophysiological evaluation of cortical excitability in migraine: a review of the literature].
Neurophysiological studies point to altered cortical neuronal excitability in migraine patients. Between attacks, migraine brain seems to be "hyperresponsive" to repetitive stimuli, as suggested by evoked potential studies that show a lack of habituation to sensory stimuli. Transcranial magnetic stimulation suggests an impairment of intracortical inhibitory circuits in migraine, especially in migraine with aura. Controversial results are obtained in migraineurs without aura. Repetitive transcranial magnetic stimulation also shows in migraine with aura a paradoxical enhancement of intracortical facilitation by low frequency stimulation and greater increased facilitatory mechanisms by high-frequency stimulation. Importantly, cortical excitability level fluctuates over time in relation to the migraine cycle. The interictal lack of habituation to sensory stimuli normalizes before and during a migraine attack. Changes of cortical excitability consistent with the theory of cortical spreading depression are also observed during migraine aura with magnetoencephalography. The exact role of cortical excitability changes in migraine pathophysiology and possibly in chronic migraine is still unknown. Further studies are also necessary to clarify the role of migraine preventive drugs on brain excitability. In this review, the results of neurophysiological studies conducted in migraine patients will be described and the associated pathophysiological hypotheses will be discussed.


The Surgical Approach Impacts Component Selection in Total Hip Arthroplasty: A Matched Cohort Study of 7460 Hips.
A higher risk of dislocation following total hip arthroplasty (THA) has been reported for the posterior approach (PA) compared to the anterior approach (AA). Dual mobility implants, larger head sizes, and elevated or face-changing liners can reduce the risk for dislocation. It remains unclear whether the component selection is influenced by the surgical approach. This is a retrospective study of 7,048 patients who underwent 7,460 primary THA with either AA or PA for primary hip osteoarthritis or osteonecrosis of the femoral head between 2019 and 2021. A propensity score model based on age, body mass index, height, and American Association of Anesthesiologists Score was applied. There were 2,502 AA-THA matched with 4,958 PA-THA (2,456 1:2, and 46 1:1). Groups were compared with multiple linear regression analyses/multivariate logistic regressions after controlling for American Association of Anesthesiologists Score and body mass index. In a second step, only hips operated by surgeons using both approaches were matched 1:1 (1,204 PA and AA, respectively). The same statistics were performed after controlling for "surgeon". The PA was associated with a more frequent use of dual mobility implants, elevated liners, face-changing liners, as well as heads with 36 mm or larger diameters, and the implanted cups were significantly larger (P < .001, respectively). These findings were consistent for both matched cohorts. The surgical approach impacts the component selection in THA. Patients undergoing PA-THA are more likely to receive implants with larger head size or stabilizing features compared to AA-THA.


Compact quadruple therapy with the lamivudine/zidovudine combination tablet plus abacavir and efavirenz, followed by the lamivudine/zidovudine/abacavir triple nucleoside tablet plus efavirenz in treatment-naïve HIV-infected adults.
To assess efficacy, safety, and adherence with compact quadruple therapy comprising one lamivudine 150-mg/zidovudine 300-mg tablet (COM) twice daily + one abacavir (ABC) 300-mg tablet twice daily + three efavirenz (EFV) 200-mg capsules at bedtime for 24 weeks, followed by one lamivudine 150-mg/zidovudine 300-mg/ABC 300-mg triple nucleoside tablet (TZV) twice daily + three EFV 200-mg capsules at bedtime for 24 weeks. A pilot 48-week, prospective, open-label trial in which 38 antiretroviral-naïve HIV-infected adults (baseline median HIV-1 RNA 5.1 log(10) copies/mL, CD4+ cell count 285/microL) received the above treatment and were monitored regularly with respect to plasma HIV-1 RNA levels, CD4+ cell counts, T-cell receptor excision circles (TRECs), adherence, and adverse events. At Week 48, intent-to-treat, switch-included analysis showed plasma HIV-1 RNA levels <400 copies/mL in 100% (29/29) of patients and <50 copies/mL in 93% (27/29); 59% of patients who achieved <50 copies/mL had <3 copies/mL (16/27). Similar virologic suppression was observed in patients with baseline HIV-1 RNA above or below 100000 copies/mL. HIV-1 RNA and CD4+ cell counts changed from baseline by a median of -3.4 log(10) copies/mL and +172 cells/microL, respectively. One virologic failure occurred at Week 16. Median TRECs/100000 peripheral blood lymphocytes increased 6-fold between baseline and Week 48. Median adherence rates were consistently 100% by self-report and 94% by pill count. Grade 2-4 treatment-related adverse events included dreams (16%), nausea (13%), decreased white cells (8%), dizziness (8%), sleep disorders (8%), and malaise and fatigue (8%). A suspected ABC hypersensitivity reaction occurred in 8% (3/38) of patients. COM/ABC/EFV or TZV/EFV produced potent, durable virologic suppression and immunologic benefits, was associated with high adherence rates, and was generally well tolerated.


[A preliminary study on effect of electro-acupuncture by the cortical infrared thermography].
To explore the possibility of using cortical infrared thermography (CIT) and temperature in studying the principle of acupuncture and moxibustion. The changes of the cerebral cortical temperature during electro-acupuncture (EA) by CIT in twenty cats were observed. By opening skull before experiments the cortex of animals was revealed. The distribution of the cortical temperature of the awakend animals was studied by AGA Infrared Thermovision, the thermograms were analysed by computer. (1) The thermograms of the profile of the cortex could be displayed clearly, the temperature was higher and lower in ante- and post-cortex respectively than that in other regions. (2) The cortical temperature declined slightly during 30 minutes in cats without EA. (3) After EA, the temperature of cortex generally increased 0.3 to 1.7 degrees centigrade, at 5 min after EA, the temperature increment was the highest, at 10 min after EA, the temperature increment was higher than before EA but lower than 5 min after EA, the cortical temperature recovered 10 min after stopping stimulating. (4) The temperature increment was more obvious in the regions of Ant. Ectosylvian, Ant. Suprasylvian and Ant. Sylvian than that in other regions. No matter where the site of EA was, every group had its region of higher temperature increment. The regions of the temperature increment in the cortex were mainly in the somatesthesia regions. There were similar characteristics between the temperature response in the cortex showing by CIT after EA and the activity of cortical nerve cells after stimulation. The display of the temperature response could be taken as the indication of the nervous activity. CIT could be used to conduct the studies of the acupuncture and brain.


Identifying pathogenicity genes in the rubber tree anthracnose fungus Colletotrichum gloeosporioides through random insertional mutagenesis.
To gain more insight into the molecular mechanisms of Colletotrichum gloeosporioides pathogenesis, Agrobacterium tumefaciens-mediated transformation (ATMT) was used to identify mutants of C. gloeosporioides impaired in pathogenicity. An ATMT library of 4128 C. gloeosporioides transformants was generated. Transformants were screened for defects in pathogenicity with a detached copper brown leaf assay. 32 mutants showing reproducible pathogenicity defects were obtained. Southern blot analysis showed 60.4% of the transformants had single-site T-DNA integrations. 16 Genomic sequences flanking T-DNA were recovered from mutants by thermal asymmetric interlaced PCR, and were used to isolate the tagged genes from the genome sequence of wild-type C. gloeosporioides by Basic Local Alignment Search Tool searches against the local genome database of the wild-type C. gloeosporioides. One potential pathogenicity genes encoded calcium-translocating P-type ATPase. Six potential pathogenicity genes had no known homologs in filamentous fungi and were likely to be novel fungal virulence factors. Two putative genes encoded Glycosyltransferase family 28 domain-containing protein and Mov34/MPN/PAD-1 family protein, respectively. Five potential pathogenicity genes had putative function matched with putative protein of other Colletotrichum species. Two known C. gloeosporioides pathogenicity genes were also identified, the encoding Glomerella cingulata hard-surface induced protein and C. gloeosporioides regulatory subunit of protein kinase A gene involved in cAMP-dependent PKA signal transduction pathway.


Patient preference survey: are patients willing to delay surgery if obstructive sleep apnea is suspected?
Screening and optimizing patients for OSA in the perioperative period may reduce postoperative complications. However, sleep studies can be difficult to obtain before surgery. Previous surveys reported that the majority of sleep physicians would delay surgery to diagnose and manage OSA, but most anesthesiologists would not. While disagreements exist, the importance of shared decision making and patient preferences have never been studied on this topic. It is unknown whether patients with suspected OSA, when given information about OSA, would be willing to delay surgery to diagnose and manage their condition preoperatively. This study consisted of a self-administered questionnaire that surveyed patients, patient relatives, or any accompanying members. The survey was conducted in the preoperative clinic or in the perioperative patient and family waiting area at two hospitals in Canada and in the United States. A hypothetical scenario was used: participants were given information about OSA, and asked about their preferences regarding preoperative management should they be at risk for OSA in the setting of pending elective surgery. The objective of this study was to determine whether respondents preferred to 1) proceed with surgery as planned, 2) delay surgery to ensure the medical condition of OSA is diagnosed and optimized, or 3) let his/her physician decide. The final survey contained 19 questions and the survey was conducted from June 2016 to September 2016. Four hundred and seventy-three surveys were collected. Forty-four percent of respondents, when given information about OSA, preferred to delay surgery pending a sleep study and treatment. Forty percent of respondents who preferred to delay surgery would tolerate delaying up to two months. Increasing emphasis and significant value has been placed on shared-decision making between patients and physicians. Educating patients about the risks of OSA and incorporating patient preferences into the perioperative management of OSA may be warranted.


Serum cystatin C is associated with the prognosis in acute myocardial infarction patients after coronary revascularization: a systematic review and meta-analysis.
Our study aimed to assess the association between serum cystatin C levels and prognosis in acute myocardial infarction (AMI) patients after coronary reconstructive surgery. We searched PubMed, Embase, and Cochrane Library up to January 21, 2022 without language restriction. Outcomes were major cardiovascular events (MACEs) and mortality. The risk ratio (RR) and 95% confidence interval (CI) were merged by random-effect models. We included 8 studies with a total of 7,394 subjects in our meta-analysis. Our meta-analysis showed that higher-level of serum cystatin C levels were associated with higher risk of MACEs (RR = 2.52, 95% CI 1.63-3.89, P < 0.001) and mortality (RR = 2.64, 95% CI 1.66-4.19, P < 0.001) in AMI patients after coronary revascularization. Subgroup analysis showed that the serum cystatin C levels were associated with significantly higher risk of MACEs (RR = 2.72, 95% CI 1.32-5.60, P = 0.006) and mortality (RR = 2.98, 95% CI 1.21-7.37, P = 0.020) in AMI patients after percutaneous coronary intervention (PCI). However, in AMI patients after coronary artery bypass surgery, there were no significantly higher risk of MACEs (RR = 2.41, 95% CI 0.98-5.93, P = 0.05) and mortality (RR = 3.15, 95% CI 0.76-13.03, P = 0.10). Further subgroup analysis showed that this significantly higher risk of MACEs and mortality did not change with the study sample size, study population area or study follow-up time. The meta-analysis demonstrated that higher serum cystatin C levels were associated with significantly higher risk of MACEs and mortality in AMI patients after PCI. It is a biomarker for risk stratification for predicting the prognosis in AMI patients after PCI.


Aureocin A70 production is disseminated amongst genetically unrelated Staphylococcus aureus involved in bovine mastitis.
The main aim of this study was to analyse the genetic relationship amongst 46 Staphylococcus aureus Bac(+) strains isolated in Brazil from 12 geographically distant dairy herds, including 34 isolates that produce the antimicrobial peptide aureocin A70. The comparison of 46 Staph. aureus Bac(+) strains was performed by pulsed-field gel electrophoresis (PFGE). Thirteen different pulsotypes were identified, and the subtype A(1) was the most prevalent one. Nine strains belong to pulsotype F, the second most prevalent and mostly confined to a single herd. The PFGE patterns of the 34 Staph. aureus aureocin A70-producers, isolated in Brazil, were also compared with those of strains isolated from bovine mastitis cases in Argentina and revealed that these strains are not genetically related. Although a previous study has suggested that a prevalent pulsotype of aureocin A70-producer Staph. aureus involved in bovine mastitis is disseminated in Argentina, this does not occur in Brazil. Additionally, it was possible to demonstrate that closely related staphylococcal strains can produce distinct staphylococcins. This study corroborates the hypothesis of horizontal gene transfer of aureocin A70 genes amongst distinct staphylococcal strains involved in bovine mastitis, giving them a selective advantage when colonizing the mammary glands.


Naphthalene degradation and biosurfactant activity by Bacillus cereus 28BN.
Biosurfactant activity and naphthalene degradation by a new strain identified as Bacillus cereus 28BN were studied. The strain grew well and produced effective biosurfactants in the presence of n-alkanes, naphthalene, crude oil and vegetable oils. The biosurfactants were detected by the surface tension lowering of the medium, thin layer chromatography and infrared spectra analysis. With (2%) naphthalene as the sole carbon source, high levels of rhamnolipids at a concentration of 2.3 g 1(-1) were determined in the stationary growth. After 20 d of incubation 72 +/- 4% of the initial naphthalene was degraded. This is the first report for a Bacillus cereus rhamnolipid producing strain that utilized naphthalene under aerobic conditions. The strain looks promising for application in environmental technologies.


The effect of oral local anaesthetic and alkali on basal and food-stimulated serum gastrin levels in patients with duodenal ulcer.
Twelve patients with duodenal ulcers were each given on separate days and in random order an oral local anaesthetic (oxethazaine), an alkali (aluminium hydroxide and magnesium hydroxide), a combination of local anaesthetic and alkali (Mucaine), and a similar volume of water (control) followed one hour later by a solution of meat extract (Oxo). The effect of these treatments on serum gastrin levels was measured. None of the treatments altered the normal basal gastrin levels. The gastrin response to ingestion of protein extract was significantly lower in patients who had been pre-treated with local anaesthetic than those who had received alkali, with or without local anaesthetic, or water.


Low colloid osmotic pressure in very low birthweight infants receiving assisted ventilation.
Plasma colloid osmotic pressure (COP) was measured in three groups of very low birthweight infants. Babies in Group 1 (n = 8) were breathing spontaneously and had no respiratory disease. Those in Group 2 (n = 9) received assisted ventilation for hyaline membrane disease (HMD), and those in Group 3 (n = 7) received assisted ventilation for other reasons (five apnoea, two pneumonia). Both assisted ventilation groups had lower mean COP values than spontaneously breathing infants. Mean values (s.e.m.) for Groups 1, 2 and 3, respectively, were: 15.3 (0.6), 11.3 (0.4) and 11.9 mmHg (0.5) (P less than 0.001) on Day 1; and 15.2 (0.4), 12.9 (0.4) and 12.8 mmHg (0.3) (P less than 0.001) on Day 2. The increase from Day 1 to Day 2 was significant for those with HMD (P less than 0.05). Colloid osmotic pressure correlated with mean blood pressure (r = 0.51; P less than 0.001) but not with birthweight, gestation, crystalloid fluid intake or pH. The role of low COP in the pathogenesis of acute respiratory failure in infants with uncomplicated HMD is unclear, but such low COP may contribute to development of pulmonary oedema as a complication, particularly if the ductus arteriosus is still patent and the infants are given high volume intravenous fluids.


Fragmentation mechanisms of oxofatty acids via high-energy collisional activation.
Upon high-energy collisional activation, oxofatty-acid ions undergo fragmentations to produce a unique pattern of product ions by which the position of the ketone is revealed. The reactions occurring in the vicinity of the ketone, which are the subject of this article, produce a spectral pattern that is not symmetrical. Although cleavages of alpha, beta, and gamma C-C bonds occur on the side proximal to the charge site, giving alpha, beta, and gamma ions, respectively, there is only a gamma' ion formed on the side distal to the charge site. The resulting lack of symmetry seemingly contradicts the concept that the reactions are independent of the charge (i.e., that they are charge remote). To eliminate any interaction between the charge and the reaction site, oxofatty acids were linked to glycyrrhetic acid, a steroid with a rigid polycyclic system. The fragmentation pattern remains the same, indicating that the effect does not depend on charge but rather on the ketone. Isotopic labeling and MS/MS/MS studies confirm that the fragmentations of C-C bonds in the vicinity of the ketone are complex, charge-remote processes. Formation of [M-H-H2O]- and [M-H-CO2]- anions and the ion that is formed by homolytic cleavage of the beta bond at the side distal to the charge, however, are charge directed.


Influence of fat pad removal on patellar tendon length during growth.
During various knee operations, the changes caused by the surgical invasion to the infrapatellar fat pad (IPF) is still unknown. If any changes exist, it will have great influence especially on growing generations. Eighty-four Japanese white rabbits (6-month-old) were divided into three groups: the resection group involving resection of the IPF, the graft group involving resection and reimplantation of the IPF, and the no-surgery group. All these surgical procedures were done in right knees. In all left knees, only arthrotomy was performed, serving as the sham side. After 3, 6, 12, and 24 weeks of the operation, the rabbits were killed. Lengths of the patellar tendon and patellar were measured in lateral X-ray. In order to eliminate individual differences in the patellar height, we defined a new index as percent patellar height (PPH) which indicated the percentage of the patellar height of surgery side compared with that of the sham side. The PPH was 90.6% (3 weeks), 83.0% (6 weeks), 73.6% (12 weeks), and 74.7% (24 weeks) in the resection group, while it was 88.4% (6 weeks), and 88.9% (24 weeks) in the graft group. Postsurgical scar tissue formation occurring where the IPF was removed prevented the normal growth of the patellar tendon. Reimplantation of the IPF lessened the adhesion of the patellar tendon to the surrounding tissue, and better growth of the tendon. These results showed that preservation of the IPF in young individuals could be crucial for the normal growth of the patellar tendon, and critical as well for the prevention of the degeneration of the articular surface.


A review of bioanalytical methods for chronic lymphocytic leukemia drugs and metabolites in biological matrices.
Quantitation of drugs used for the treatment of chronic lymphocytic leukemia in various biological matrices during both pre-clinical and clinical developments is very important, often in routine therapeutic drug monitoring. The first developed methods for quantitation were traditionally done on LC in combination with either UV or fluorescence detection. However, the emergence of LC with mass spectrometry in tandem in early 1990s has revolutionized the quantitation as it has provided better sensitivity and selectivity within a shorter run time; therefore it has become the choice of method for the analysis of various drugs. In this article, an overview of various bioanalytical methods (HPLC or LC-MS/MS) for the quantification of drugs for the treatment of chronic lymphocytic leukemia, along with applicability of these methods, is given.


Myelosuppression and acute hematological complications of sulfur mustard exposure in victims of chemical terrorism.
Sulfur mustard (SM) is a vesicant chemical warfare agent. Recent studies reported alleged use of SM by non-state actors in Syria and Iraq. It has been shown that SM induced immunological and hematological complications. The aim of this study was to determine acute toxic effects of SM exposure on hematological parameters. Blood samples from a group of Syrian exposed to SM in 2016 were taken daily during the follow-up of the patients in intensive care unit. Initial leukocytosis was observed in all patients (100%) on the first 48 h after exposure. Following leukocytosis, isolated lymphopenia was observed in all patients (100%) between 2nd and 4th days. A decrease in hemoglobin level was noted in five patients (62.5%) between 4th and 5th days. Thrombocytopenia was observed in 75% of patients between 4th and 6th days for mild cases and between 9th and 11th days for severe cases. Three patients (37.5%) developed distinct leucopenia/neutropenia on 11th and 12th days. It was observed that human exposure to high dose of SM has direct toxic effect on hematological cells and bone marrow. New strategies on treatment of SM-induced myelosuppression could reduce the effects of hematological complications and could increase the survival rate in these patients.


Conservative treatment of early breast cancer.
At our Institution, the treatment policy for early carcinoma of the breast (T1-2, NO, AJC) is lumpectomy followed by radiotherapy to the breast and peripheral lymphatics. From October 1976 until December 1982, 171 patients have been admitted and treated. Radiotherapy was administered with 60 Co, 5.000 cGy in 5 weeks to the breast and lymphatics plus a boost to the scar giving q.s.p. 6.400 cGy at maximum tumor depth. With a minimum follow-up of 3 years and a median follow-up of 61.7 months the locoregional control was 94.2% and survival at 8 years with no evidence of disease (NED) was 77.2% with an overall survival rate of 90%. No difference in NED survival rate was found between Stage I and II. There was a tendency to better survival rate in those patients older than 50 years and also for post menopausal patients, however the difference did not reach statistical significance (66.7% NED survival at 8 years for premenopausal and 81.8% NED survival for post menopausal, also at 8 years, p = 0.056 Gehan). The time elapsed between surgery and radiation therapy (between 1 and 2 months) was found to be nonsignificant. Only 1 out of 171 patients had axillary dissection. The importance or lack of it, is discussed.


Pulmonary artery dissection leading to cardiac tamponade as a cause of maternal death in a woman with pulmonary hypertension: a case report.
Severe pulmonary hypertension in pregnancy is known to carry a 40% risk of death for the mother. The most common cause of death in cases of pulmonary hypertension is heart failure. We present a case of maternal death due to dissection of the pulmonary artery resulting in cardiac tamponade. The sudden onset of severe chest pain radiating to the back should alert the clinician to the possibility of pulmonary artery dissection in pregnant patients with pulmonary hypertension. Severe chest pain may not be accompanied by changes in vital signs or oxygen saturation. Immediate delivery should be considered. However, delivery may worsen the mother's condition due to postpartum cardiovascular changes.


Influence of target location, task complexity, and gender on children's use of their preferred foot.
The goal of the present study was to compare the choice of foot of right-footed children with varying strengths of foot preference when performing two tasks of different levels of complexity at three spatial locations. 30 right-footed children were tested. The results showed that the general tendency to use one's preferred foot to interact with an object is more or less pronounced depending on the object's location and the complexity of the task. The children used their non-preferred left foot more often during the simple task and when the object was presented to the left. Our findings also revealed interactions between gender, age, and spatial location. At five, girls used globally less their left foot than boys. In addition, girls used their preferred right foot more frequently than boys when the object was presented to the left. Based on these results, it can be concluded that foot selection depends on foot preference, task demand, environmental context, and biological factors associated with motor dominance.


The original Akagi line is the most reliable: a systematic review of landmarks for rotational alignment of the tibial component in TKA.
There is no present consensus on the most reliable anatomical landmarks or axes for tibial rotational alignment in total knee arthroplasty (TKA). The goal was therefore to review the literature and compare accuracy and repeatability of different axes for tibial baseplate rotation in TKA. Medline and Embase were searched for articles that reported accuracy in terms of error or discrepancy from the trans-epicondylar axes (TEA), and/or repeatability in terms of intraclass correlation coefficient, of one or more axes used for tibial baseplate rotation in TKA. Twenty-one articles met criteria, and their data were extracted and tabulated. The selected articles evaluated 15 different axes, 13 for reliability, 12 for repeatability. The lowest errors or discrepancies from the projected TEA were reported for the original 'Akagi line' (posterior cruciate ligament posteriorly to medial border of tibial tuberosity), its variant using the sulcus of the tibial spines as anterior landmark, as well as the anterior tibial border and the curve-on-curve technique. The best inter-observer repeatabilities were reported for 'Akagi line' variants that use the geometric centre of the tibial plateau posteriorly and the medial border of the tibial tuberosity, or the medial sixth of the patellar tendon anteriorly. Considering accuracy and repeatability simultaneously, only two axes were found to satisfy both criteria consistently: the original 'Akagi line' and the anterior tibial border. Because of the small number of studies found, the collected evidence remains insufficient to recommend reference axes for intra-operative rotational alignment of the tibial baseplate in TKA. A combination of two or more anatomical landmarks or projected axes could be used to ensure adequate tibial baseplate rotation, while considering individual patient morphology and implant design to optimize knee kinematics and prevent prosthetic overhang. Level IV, systematic review of level III and IV studies.


Pseudomonas syringae infection assays in Arabidopsis.
Pseudomonas syringae pv. tomato DC30000 (Pst DC3000) infection of Arabidopsis thaliana has been widely used to elucidate many of the general principles underlying the plant immune response and bacterial pathogenesis. Study of Pst DC3000 virulence factors has also proven useful in the discovery and elucidation of fundamental mechanisms in plant biology. In particular, Pst DC3000 produces a phytotoxin, coronatine, that is a remarkable molecular mimic of the active form of the plant hormone jasmonate. Here we illustrate several common methods used for Pst DC3000-based assays, including preparation of Pst DC3000 inocula, inoculation of soil-grown Arabidopsis plants, and subsequent bacterial quantification in planta. We also describe how Pst DC3000 infection can be applied to study gene expression and protein degradation associated with jasmonate signaling.


Molecular analysis and risk factors for Escherichia coli producing extended-spectrum β-lactamase bloodstream infection in hematological malignancies.
Patients with hematologic malignancies have greater risk-factors for primary bloodstream infections (BSI). From 2004-2009, we analyzed bacteremia caused by extended-spectrum beta-lactamase Escherichia coli (ESBL-EC) (n = 100) and we compared with bacteremia caused by cephalosporin-susceptible E. coli (n = 100) in patients with hematologic malignancies. To assess the clinical features, risk factors, and outcome of ESBL-EC BSI in patients with hematologic malignancies, and to study the molecular epidemiology of ESBL-EC isolates. The main diagnosis was acute leukemia in 115 patients (57.5%). Death-related E. coli infection was significantly increased with ESBL-EC (34% vs. control group, 19%; p = 0.03). Treatment for BSI was considered appropriate in 64 patients with ESBL-EC (mean survival, 245 ± 345 days), and in 45 control patients this was 443 ± 613 (p = 0.03). In patients not receiving appropriate antimicrobial treatment, survival was significantly decreased in cases compared with controls (26 ± 122 vs. 276 ± 442; p = 0.001). Fifty six of the ESBL-EC isolates were characterized by molecular analysis: 47 (84%) expressed CTX-M-15, two (3.6%) SHV, and seven (12.5%) did not correspond to either of these two ESBL enzymes. No TLA-1 enzyme was detected. Patients who had been previously hospitalized and who received cephalosporins during the previous month, have an increased risk of ESBL-EC bacteremia. Mortality was significantly increased in patients with ESBL-EC BSI. A polyclonal trend was detected, which reflects non-cross transmission of multiresistant E.coli isolates.


Direct inhibitory synaptic linkage of pontomedullary reticular burst neurons with abducens motoneurons in the cat.
1. Unit spikes of burst neurons were extracellularly recorded in the pontomedullary reticular formation of the cat. These neurons were identified by their burst activity coincident with the quick inhibitory phase of the contralateral abducens nerve during vestibular nystagmus and their antidromic activation from the contralateral abducens nucleus. 2. When the extracellular field potentials in and near the abducens nucleus were triggered by spikes of a contralateral burs neuron, the averaged potential consisted of an early di- or triphasic spike and a late slow positive wave. The early spike was an action current caused by impulses conducting along the axon of the burst neuron. 3. The action potentials of a contralateral burst neuron. 3. The action potentials of a contralateral burst neuron were employed to trigger a post-spike average of the membrane potential of abducens motoneurons. Then unitary IPSPs with monosynaptic latencies were revealed. This provided direct evidence that the burst neurons are inhibitory in nature. The amplitudes of unitary IPSPs ranged from 18 to 220 mu V. Each inhibitory burst neuron branched widely in the abducens nucleus and was estimated to make inhibitory connections with approximately 60% of the motoneuron pool. 4. The post-spike average of compound potentials of the abducens nerve triggered by action potentials of contralateral single inhibitory burst neurons revealed inhibition of spike activity with latencies and time courses compatible with those of unitary IPSPs in motoneurons. The inhibition was observed with all inhibitory burst neurons tested.


Testing the neurocognitive framework for regulation expectation: The relationship between actual/ideal self-esteem and proactive/reactive autonomic stress regulation.
According to the Neurocognitive Framework for Regulation Expectation (NFRE), actual and ideal self-esteem are related to how individuals anticipate and respond to a stressful event. Based on this framework, we investigated whether in individuals with low ideal self-esteem (moderator), a positive relationship between actual self-esteem and reactive autonomic regulation would be mediated by the amount of anticipatory autonomic regulation. Forty-five healthy females prepared a speech (i.e., anticipation) and performed it in front of a camera (i.e., stressor). Actual and ideal self-esteem were measured with the Implicit Relational Assessment Procedure. Anticipatory and reactive autonomic stress regulation were indexed by heart rate variability, and affective responses were assessed via self-report. Results were in line with predictions based on the NFRE: when ideal self-esteem was low, higher actual self-esteem was associated with higher reactive autonomic regulation, and this association was mediated by higher anticipatory autonomic regulation. Because only female undergraduates were recruited, replication within a more heterogeneous sample is necessary to further generalize these findings. These results support the hypothesis, based on the NFRE, that actual and ideal self-esteem interact in predicting the relationship between anticipatory and reactive stress regulation, and are a step forward in the understanding of the mechanisms underlying successful stress regulation.


Src kinase-targeted anti-inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7 cells.
Mushrooms are popular both as food and as a source of natural compounds of biopharmaceutical interest. Some mushroom-derived compounds such as beta-glucan have been shown to be immunostimulatory; this study explores the anti-inflammatory properties of hispidin analogues derived from the mushroom, Inonotus xeranticus. We sought to identify the molecular mechanism of action of these hispidin analogues by determining their effects on lipopolysaccharide (LPS)-mediated inflammatory responses in a macrophage cell line. The production of inflammatory mediators was determined by Griess assay, reverse transcription-PCR and ELISA. The inhibitory effect of davalliactone on LPS-induced activation of signalling cascades was assessed by western blotting, immunoprecipitation and direct kinase assay. In activated RAW264.7 cells, davallialactone strongly downregulated LPS-mediated inflammatory responses, including NO production, prostaglandin E2 release, expression of proinflammatory cytokine genes and cell surface expression of co-stimulatory molecules. Davallialactone treatment did not alter cell viability or morphology. Davallialactone was found to exert its anti-inflammatory effects by inhibiting a signalling cascade that activates nuclear factor kappa B via PI3K, Akt and IKK, but not mitogen-activated protein kinases. Treatment with davallialactone affected the phosphorylation of these signalling proteins, but not their level of expression. These inhibitory effects were not due to the interruption of toll-like receptor 4 binding to CD14. In particular, davallialactone strongly inhibited the LPS-induced phosphorylation and kinase activity of Src, implying that Src may be a potential pharmacological target of davallialactone. Our data suggest that davallialactone, a small molecule found in edible mushrooms, has anti-inflammatory activity. Davallialactone can be developed as a pharmaceutically valuable anti-Src kinase agent.


Drug resistant TB spine in a two year old child: A case report.
Spinal tuberculosis (TB) is a disease of high morbidity that is associated with deformity and neurological sequelae, especially in growing children. Children diagnosed with spinal TB need to be monitored closely for clinical improvements. Previous history of antituberculous therapy (ATT), poor adherence to previous ATT, contact with persons having known drug-resistant (DR) TB, or clinical worsening despite regular ATT are strong indicators for the diagnosis of DR TB of the spine. We report a case of spinal DRTB in a two year old child with no previous history of ATT and contact with a person on irregular treatment for drug sensitive TB that did not show regression of the spinal lesions despite standard ATT.


Prospective audit of aminoglycoside usage in a general hospital with assessments of clinical processes and adverse clinical outcomes.
A comprehensive, multiphasic review of gentamicin and tobramycin utilization was undertaken with audits of the microbiological sensitivity of Gram-negative pathogens; indications for the prescription of aminoglycoside agents; the utilization of assay services; the adequacy of clinical drug delivery by measures of serum antibiotic levels; and the assessment of adverse outcomes by markers of nephrotoxicity. The great majority of clinical isolates of target organisms (n = 4208) was more sensitive to gentamicin (96%) and to tobramycin (99%) than to all alternative agents, including first- and third-generation cephalosporin agents. A review of the indications for the prescription of aminoglycoside agents by clinical criteria showed that in 85.6% of 278 documented cases, the choice of agent was appropriate by clinical and microbiological criteria. In a substantial (77.6%) proportion of the 511 patients who were receiving therapeutic courses of an aminoglycoside agent, serum drug assays had been performed. Assay data could not be interpreted adequately in 52.6% of 3079 assayed cases as a result of inadequate data on administration regimens (39.7%) or sampling regimens (12.9%). Where sampling was documented adequately, there was extreme variation (zero to five hours) in post-dose sampling. In only 33.2% of cases could it be concluded unambiguously that the patients were receiving safer, adequate therapy for clinically significant infections, 5.6% of patients were receiving potentially toxic doses, and 8.6% of patients showed suboptimal concentration profiles. The majority of potentially toxic levels were associated with adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)


AMPK and Raptor: matching cell growth to energy supply.
In a recent issue of Molecular Cell, Gwinn et al. (2008) suggest a novel mechanism by which AMPK signals to mTOR, and they provide new insight into how information about cellular energy status is fed into decisions about cell growth and proliferation.


Congenital cardiac anomalies: prenatal readings versus neonatal outcomes.
The purpose of this study was to determine the variation between prenatal and postnatal diagnosis of congenital cardiac lesions diagnosed by both fetal center primary physicians and fetal pediatric cardiologists at a single tertiary referral center in the United States and evaluate why cases were misdiagnosed. A retrospective review of all cardiac abnormalities identified prenatally by level II sonography at a tertiary referral fetal center between January 2006 and December 2008 was performed to include any patient with a fetal cardiac abnormality and with a documented autopsy or neonatal follow-up. Congenital heart disease diagnoses were classified as correct, incorrect, or incorrect but within the same spectrum of disease. Cases of correct diagnosis by primary physicians and pediatric cardiologists were compared. Sixty patients with fetal heart abnormalities were identified among 8894 patients who had level II sonography. The combined detection rate for fetal heart abnormalities for both primary physicians and pediatric cardiologists together was 81.7%. The detection rates of congenital heart disease were not statistically different between primary physicians and pediatric cardiologists: 77.9% (46 of 59) versus 85.0% (34 of 40; P = .3). The most common cardiac abnormalities misdiagnosed in our study population included pulmonic stenosis, ventricular septal defect, myxoma, truncus arteriosus, and coarctation of the aorta. Congenital heart disease is misdiagnosed in tertiary care centers by both pediatric cardiologists and fetal imaging specialists. We believe that this occurrence is related to multiple factors, including evolution of congenital heart disease, maternal body habitus, associated congenital anomalies, decreased amniotic fluid volume, gestational age at evaluation, imaging techniques, and, most importantly, the experience of the sonographer.


Plumbagin inhibits cancer stem-like cells, angiogenesis and suppresses cell proliferation and invasion by targeting Wnt/β-catenin pathway in endocrine resistant breast cancer.
Fifty percent of advanced stage ER-positive breast cancer patients develop endocrine resistance. Aberrant activation of Wnt/β-catenin is associated with stem-like phenotypes and epithelial-mesenchymal transition (EMT) process which confers resistance to endocrine therapy. Cancer stem-like cells (CSLCs) can be a vital source of proangiogenic factors including fibroblast growth factor 2 (FGF2) which drives angiogenesis and leads to tumor growth and metastasis. Therefore, targeting Wnt and FGF2 may provide effective treatment for endocrine resistant breast cancer. Our previous in vitro study reported that plumbagin (PLB) was a potent anticancer agent and was able to inhibit EMT in endocrine-resistant cells. This study aimed to further investigate the inhibitory effects of PLB on cancer stem-like phenotypes, tumorigenicity and angiogenesis. The results demonstrated Wnt/β-catenin signaling was activated and was able to form mammospheres with increased cancer stem cell markers (ALDH1, NANOG, and OCT4) in endocrine-resistant cells. PLB significantly inhibited colony-forming, mammosphere formation and decreased cancer stem cell markers. The inhibitory effects of PLB on cell proliferation and invasion were mediated by Wnt signaling pathway. PLB also significantly reduced Wnt responsive genes and β-catenin. Moreover, PLB treatment at doses of 2 and 4 mg/kg/day inhibited tumor growth, angiogenesis and metastasis without any adverse effects on body weight and blood coagulation in orthotopic xenograft nude mice. In conclusion, PLB exerted anti-cancer activity and eliminated stem-like properties by attenuating Wnt/β-catenin signaling and FGF2 expression. These findings suggest that PLB could be a promising agent to treat endocrine resistant breast cancer.


Superoxide dismutase in an animal model of otitis media.
Cu, Zn superoxide dismutase (SOD) is a metalloprotein that catalyzes the dismutation of the superoxide anion into O2- and H2O2, and therefore functions to maintain a low intracellular concentration of an otherwise toxic metabolite of oxygen. SOD protects living tissue from the destructive effects of free radicals. Increasing evidence implicates free radicals, including the superoxide radical (O2-), in the pathogenesis of disease, including otitis media. In an effort to elucidate the role free radicals play in the pathogenesis of otitis media, SOD was localized immunocytochemically to determine its cellular distribution in specimens of guinea pig middle ear. In normal ears, SOD was found concentrated in the epithelium of the middle ear mucosa. Low quantities were characteristic of connective tissue, bone, and cartilage. In streptococcus-infected ears, SOD localized similarly, concentrating in the epithelium. The infected ears had extensive submucosal edema which stained poorly and appeared to have less SOD than did normal ears. This was confirmed by an assay using laser densitometry of Western blots to quantify the amount of SOD in the mucosa of normal versus infected middle ears. This demonstrated a value of SOD in normal mucosa of 1.77 +/- 0.48 micrograms/mg of protein compared with 1.02 +/- 0.28 micrograms/mg in the infected mucosa. The two groups were significantly different at P < 0.05. These findings are discussed, and suggestions for future experimentation addressed.


Effect of methyl parathion on Na(+)-K+ and Mg2+ adenosine triphosphatase activity in developing central nervous system in rats.
Developing rat pups exposed to sublethal doses of methyl parathion exhibit marked alteration in the activities of Na(+)-K+ and Mg2+ ATPases. The results suggest that the first post natal week developing animals are more sensitive to organophosphorous insecticide compared to higher age group animals.


Draft Genome Sequence of a Chlorinated-Ethene Degrader, Cupriavidus necator Strain PHE3-6 (NBRC 110655).
Cupriavidus necator strain PHE3-6 grows on phenol as a sole carbon source and cometabolizes cis- and trans-dichloroethenes and trichloroethene. Here, we report the draft genome sequence of PHE3-6, which provides insights into the degradation system of phenol and chlorinated ethenes.


Trace metal concentrations in tropical mangrove sediments, NE Brazil.
Sediment cores were taken from the mangroves of the Coreaú River estuary off the northeast coast of Brazil. They were analyzed for grain size, CaCO3, organic matter, and trace metal (Cd, Pb, Zn, Cu, Al, and Fe) contents. Mud texture was the predominant texture. Levels of trace metals in surface sediments indicated strong influence of anthropogenic processes, and diagenetic processes controlled the trace metal enrichment of core sediments of this estuary. The positive relationships between trace metals and Al and Fe indicate that Cu, Zn, Pb, and Cd concentrations are associated mainly with Al and Fe oxy-hydroxides and have natural sources.


Clinical Experience with Telavancin: Real-World Results from the Telavancin Observational Use Registry (TOUR™).
Telavancin-a lipoglycopeptide antibacterial agent active against Gram-positive pathogens including methicillin-sensitive and -resistant Staphylococcus aureus (MRSA)-is approved in the USA for once-daily intravenous use. This registry study captured patient characteristics, prescribing patterns, and treatment outcomes associated with telavancin use in real-world clinical practice. This prospective, multicenter, observational study will characterize current real-world practice patterns for the use of telavancin in the USA by describing demographic and clinical conditions, examining the process of care and rationale for use, and describing the clinical effectiveness and selected safety outcomes among patients treated with telavancin. The Telavancin Observational Use Registry (TOUR™) is an observational multicenter registry study. Clinical data-including patient demographics, pathogens, telavancin dosing and treatment duration, and adverse events-along with investigators' assessments of outcome, were collected through retrospective medical chart review. Data from 1063 patients were collected from 45 US sites. Of these patients, 29.4% were ≥ 65 years of age [mean age ± standard deviation, 55.2 ± 15.4 years; median age (interquartile range), 57.0 (46.0-66.0)], 53.4% were male, and 83.4% were White. The primary infections in these patients included complicated skin and skin-structure infection (48.7%), bone and joint infections (27.4%), bacteremia and endocarditis (14.2%), and lower respiratory tract infections (8.5%). The predominant pathogen identified was MRSA (37.7%). The mean telavancin dose and duration of treatment were 741.7 ± 194.3 mg and 17 ± 17 days, respectively. Of the 964 (90.7%) patients for whom an end-of-treatment assessment was available, 77.7% had a positive clinical response, 10.1% failed treatment, and 12.2% had indeterminate outcomes. Real-world data collected from the TOUR study show once-daily telavancin is being used for the treatment of a variety of Gram-positive infections with generally positive clinical outcomes.


Bucking the health establishment: Alexander Milne and the fight for a New Zealand hepatitis B immunization program.
In order to successfully combat a disease it is necessary that their exists an individual or a group willing to 'champion' that ailment by arguing that it is serious enough to warrant the expenditure of scarce resources. In the case of hepatitis B such champions have often arisen outside of the public health establishments that are mandated to play that role. In New Zealand it was left up to one unusual and determined man to not only discover the seriousness of the hepatitis B epidemic but to practically single-handedly force a reluctant government to acknowledge the threat and act to contain it. He accomplished this by combining high quality scientific research with unrelenting political pressure generated by appeals to the public by means of the mass media. Alexander Milne demonstrates the vital role that the concerned citizen can make even in an age of timid bureaucracies.


Different repertoires of mouse T cells for bovine insulin presented by syngeneic and allogeneic cells.
Splenic T cells were primed, after removal of alloreactive cells, to beef insulin on allogeneic antigen-presenting cells (APC). The fine specificity of in vitro secondary response was tested in combinations H-2b (responder) T cell-H-2k (nonresponder) APC, and vice versa, using separated chains of beef and pork insulin. The response in both combinations exhibited identical specificity patterns demonstrating that both responder and nonresponder APC could present the same array of insulin epitopes to allogeneic T cells. The determinants presented to allogeneic T cells include the A-chain loop epitope and the B-chain determinant(s) that were found to be immunogenic for H-2b and H-2d T cells, respectively, in the context of syngeneic major histocompatibility complex (HC) molecules. In addition, minor determinants were detected in the A chain outside the loop that are not immunogenic in syngeneic T cell-APC combinations. Inhibition of T cell proliferation with monoclonal antibodies has shown that class II MHC molecules of the nonresponder (Ak alpha Ak beta, Ek alpha Ek beta) as well as those of the responder APC (Ab alpha Ab beta) are equally capable of presenting virtually all insulin epitopes recognizable by T cells. The data, therefore, demonstrate that the selective recognition of different insulin epitopes observed in syngeneic or semisyngeneic T cell-APC combinations does not result from determinant selection at the level of APC.


Significant Increase in Deliberate Self-Poisonings Among Adolescents During the Second Year of the COVID-19 Pandemic.
The COVID-19 pandemic has been associated with a decline in mental health of adolescents. The aim of this study was to analyze the rate of deliberate self-poisonings (DSPs) among adolescents reported to the Dutch Poisons Information Center before and during the COVID-19 pandemic. A retrospective study from 2016 until 2021 was performed to characterize DSPs among adolescents, and to analyze trends in the number of DSPs. All DSPs among adolescents with the age of 13 up to and including 17 years were included. DSP characteristics included: age, gender, bodyweight, used substance, dose, and treatment advice. Trends in the number of DSPs were analyzed using time series decomposition and Seasonal Autoregressive Integrated Moving Average models. Six thousand nine hundred fifteen DSPs in adolescents were recorded from January first 2016 until December 31st 2021. Females were involved in 84% of adolescent DSPs. A strong increase in the number of DSPs was observed in 2021 (45% increase compared to 2020), which deviated from the predicted trend based on previous years. This increase was most prominent in 13-, 14-, and 15-year-old female adolescents. Commonly involved drugs were paracetamol, ibuprofen, methylphenidate, fluoxetine, and quetiapine. The contribution of paracetamol rose from 33% in 2019 to 40% in 2021. The strong increase in the number of DSPs during the second year of the COVID-19 pandemic suggests that long-term containment measures such as quarantines, lockdowns, and school closures may enhance self-harm behavior among adolescents, especially among younger females (13-15 years of age), with a preference for paracetamol as DSP substance.


The Association Between Employment Status and Mental Health in Young Adults: A Nationwide Population-Based Study in Korea.
There has been limited evidence on the association between employment status and mental health among young adults. Therefore, this study investigated the association between employment status and mental health in Korean young adults. Data from 15,649 adults aged 19-39 years who participated in the Korea National Health and Nutrition Examination Survey (2007-2013, 2015, and 2017) were analyzed. Employment status was categorized by those who worked in paid jobs or those who did unpaid work for relatives. Mental health problems included depressive mood and suicide ideation. We performed a multiple logistic regression analysis. Of the participants, 33.5% were unemployed. The odds ratio (OR) of depressive mood (1.28, 95% CI: 1.06-1.55) was higher in unemployed 20-year-olds than employed ones and ORs of suicide ideation were higher among unemployed males (1.59, 1.16-2.20) and 30-year-olds (1.38, 1.13-1.70) than employed ones, respectively. Further, compared to employed males, the ORs of depressive mood (3.10, 2.54-3.77) and suicide ideation (4.44, 3.57-5.53) were the highest among unemployed females. This study could not explain the causal relationship between employment status and mental health because it was a cross-sectional study. We did not include the relationship between mental health and employment status before the last week. Among young adults, unemployed status was significantly associated with an increased risk of mental health problems such as depressive mood and suicide ideation. Multifaceted efforts are required to reduce these mental health issues among unemployed young adults.


Tobacco consumption in New Zealand: why did it fall?
To estimate the relative contributions of trends in smoking prevalence and trends in smoking intensity (average number of cigarettes smoked per day) to the observed decline in per capita tobacco consumption in New Zealand from 1984 to 2004. Tobacco consumption and smoking prevalence time series data were sourced from Statistics New Zealand and the ACNielsen Omnibus Survey respectively and checked for accuracy against other sources. The contribution of changes in smoking prevalence to the observed decline in tobacco consumption was estimated by counterfactual modelling. The corresponding contribution of trends in smoking intensity was then calculated by difference. Changes in smoking prevalence accounted for 48% of the decline in per capita tobacco consumption from 1984-89 and for 39% thereafter. Correspondingly, changes in smoking intensity accounted for 52% of the consumption decline during the first five years of the study period and 61% thereafter (i.e. from 1990 to 2004). Understanding the relative contributions of trends in smoking prevalence and smoking intensity to the observed decline in per capita tobacco consumption is important, because the relationship between smoking intensity and health effects is non-linear. Our results indicate that the dramatic fall in tobacco consumption in New Zealand over the past 30 years will not be accompanied by an equivalent reduction in tobacco-attributable morbidity and mortality. Furthermore, our findings raise doubts as to how much longer tobacco consumption will continue to decline, given that smoking intensity is already low. The key message for the tobacco control program is to re-focus on helping smokers to quit and stay quit.


Psychological stress-induced lower serum zinc and zinc redistribution in rats.
In humans, long-term exposure to uncontrollable and unpredictable life stressors is a major precipitant in the development of depressive disorders. There are strong evidences that depression is accompanied by lower serum zinc. The aim of present study is to assess the effects of repeated psychological stress (PS) on the zinc metabolism in rat. The rats were divided into control group and PS group which were subdivided into three subgroups: 7-day group, 14-day group, and recovery group (ten rats in each subgroup). PS model was created by a communication box which contains room A and room B. Rats in room A were only exposed to the responses of rats which were randomly given electrical shock for 30 min in room B. PS was given to rats for 30 min every morning for 14 days. The serum corticosterone (CORT), zinc in serum and tissues, and zinc apparent absorption after PS exposure were investigated. The results showed that the serum CORT increased and serum zinc decreased after 7 and 14 days of PS treatment. The zinc concentration in the liver was increased by 14 days PS exposure, whereas its concentration in the hippocampus was decreased by 7 and 14 days of PS exposure. There were no significant changes in zinc concentration in the heart, spleen, kidney, duodenum, cortex, and cerebellum. A decrease in the zinc apparent absorption was observed in the 7- and 14-day PS groups. The increased serum CORT and liver zinc concentrations and decreased serum zinc and apparent absorption of zinc recovered to normal concentrations 7 days away from PS exposure. The results suggest that PS could induce lower serum zinc, which might be correlated with decreased zinc absorption in the small intestine and increased liver zinc accumulation after PS exposure. The consequent effects of decreased hippocampal and serum zinc and increased CORT concentration after PS exposure on stress-related diseases await further research.


Subclinical atherosclerosis, but normal autonomic function after Kawasaki disease.
To compare the carotid artery intima-media-thickness (IMT) of children with Kawasaki disease with normative data for Western children. Forty-eight children (20 patients after Kawasaki disease, mean age 12.1 +/- 4.7 years; 28 age- and sex-matched healthy controls, mean age 12.0 +/- 3.1 years) were studied. Mean (IMT differed significantly (0.449 +/- 0.02 vs 0.424 +/- 0.01, P < .001) as well as IMT standard deviation score (1.2 +/- 0.6 vs 0.3 +/- 0.1, P < .001). Patients with coronary arterial involvement (n = 15) showed a further increase of the IMT (0.459 +/- 0.01 vs 0.436 +/- 0.01, P < .05). There was no difference regarding short-term blood pressure regulation. In this small patient group, signs of subclinical atherosclerosis after Kawasaki disease have been detected. These preliminary data indicate that these patients may be at risk for cardiovascular disease even in the absence of permanent alterations of the coronary arteries.


Microstructural observation of the swollen catalyst layers of fuel cells by cryo-TEM.
It is important to understand and control the fine structure of the fuel cell catalyst layer in order to improve the battery characteristics of the fuel cell. A major challenge in observing the microstructure of the catalyst layer by electron microscopy is the visualization of ionomers, which have low contrast and are susceptible to damage by electron beam irradiation. Previous papers have reported transmission electron microscopy (TEM) observations of ionomers neutralized with cesium (Cs) ions. However, this approach involves chemical reactions and indirect visualization of ionomers. In contrast, we have previously revealed the microstructure of ionomers in frozen catalyst inks by cryogenic (cryo) scanning electron microscopy and cryo-TEM. In general, ionomers are basically used under high-temperature and humid conditions while the fuel cell is operating. Therefore, in this study, ultrathin sections prepared from the fuel cell catalyst layer (membrane electrode assemblies) were incubated in a chamber under high-temperature and humid conditions and then rapidly frozen for observation by cryo-TEM. As a result, we succeeded in observing the pore structure of the catalyst layer in the swollen state of the ionomer. The swollen ionomer surrounded and enclosed the Pt/C aggregates and bridged over the pores in the catalyst layer.


Microfluidic sperm sorting improves ICSI outcomes in patients with increased values of Double-Strand Breaks in sperm DNA.
Delays in embryo kinetics, implantation failures in ICSI treatments and recurrent miscarriages have been associated with high values of Double-Strand Breaks (DSB) in sperm DNA. While conventional methods for semen preparation have been shown to be inefficient reducing DSB values, Microfluidic Sperm Sorting (MSS) devices are promising tools to reduce this damage. To study the clinical utility of an MSS device in ICSI treatments when the male partner presents increased DSB values, as compared to the use of conventional methods based on sperm motility. This retrospective cohort study included 28 infertile couples undergoing ICSI treatments. Only couples where the male partner presented increased values of DSB were included. DSB values were evaluated in semen samples by the Neutral Comet assay. Couples performed a first ICSI cycle using conventional methods for semen preparation (Density Gradients and Swim-up) and a second ICSI cycle using the ZyMōt™ICSI (formerly named FertileChip®) microfluidic device. Embryology and clinical outcomes were compared between ICSI cycles. Semen parameters and the number of obtained and fertilized oocytes did not show differences between ICSI rounds. Clinical outcomes were statistically better when MSS was used: the biochemical pregnancy rate increased 28.31%; the clinical pregnancy rate increased 35.56% and the number of live births increased 35.29%, as compared to the first ICSI cycle in this group of patients. The ZyMōt™ICSI microfluidic device improved the reproductive outcomes in couples where the male partner presented increased DSB values, when compared to the use of conventional semen preparation techniques.


Diet and physical activity are associated with suboptimal weight loss and weight regain 10-15 years after Roux-en-Y gastric bypass: A cross-sectional study.
Suboptimal weight loss (SWL) after bariatric surgery affects approximately 30% of the patients in the long-term. Diet and physical activity (PA) are likely to modulate long term weight loss outcomes after Roux-en-Y gastric bypass (RYGB). To compare food habits and PA levels between those experiencing SWL and optimal weight loss (OWL), and between those experiencing weight regain (WR) and no weight regain (NWR), 10-15 years after RYGB, in addition to a pre-operative control group. Participants were recruited from the Bariatric Surgery Observation Study (BAROBS), ≥ 10 y after RYGB. Food intake was assessed by a Food Frequency Questionnaire (FFQ) and PA levels with Sensewear armbands. 75 participants (79% females) were recruited. Excess weight loss (EWL) was 17 ± 19% and 87 ± 22% in the SWL and OWL groups, respectively and WR was 31 ± 15% and 1 ± 11% in the WR and NWR groups, respectively (P < 0.001 for both). The OWL group reported a lower energy intake (P = 0.012) than the control group. The control group reported a higher intake of milk, cream and cheese than both SWL group (P = 0.008) and OWL group (P < 0.001). The SWL group reported a higher intake of processed meat products than the OWL group, while the OWL group reported a lower intake of sauces than both the SWL and the control groups (P < 0.001 and P = 0.005, respectively). The OWL group reported a lower intake of cakes, sugar and sweets than both SWL group (P = 0.035) and control group (P = 0.021). The WR group reported a lower PA duration (P = 0.046) compared with the NWR group. EWL was positively, and WR negatively, correlated with average PA duration. A high intake of energy-dense foods and low PA is associated with poor weight loss outcomes, namely SWL and WR, 10-15 years after RYGB.


Arterial chemoreceptors, ventilation and heart rate in man.
1. Transient changes of heart rate (HR) and ventilation were recorded following step changes in alveolar gas composition in three healthy subjects. From a steady state of normo- or slightly hypercapnic hypoxia (PA,CO2 38-46 torr, PA,O2 50-60 torr) arterial chemoreceptor stimulation was transiently relieved by breathing a CO2-free mixture for two breaths, either pur O2 (causing a fall in PA,CO2 and a rise in PA,O2; O2 test) or a low O2 mixture (causing a fall in PA,CO2 without any change in PA, O2; CO2 test). For both test types ventilation was either allowed to change freely ('free-breathing' tests) or was consciously maintained at the pre-test level by the subjects ('controlled-breathing tests). The circulatory delay from the lungs to the ear was measured with a sensitive ear oximeter. 2. In all 'free-breathing' tests ventilation decreased significantly after a mean latency of 5.2 sec; the average lung-ear circulation time was 4.9 sec. HR increased slightly above pre-test levels in eighty-one of one hundred and four tests of all types, the changes being significant after a latency identical to that of the ventilatory changes. Except in the 'controlled-breathing' CO2 tests this early tachycardia was followed by a decrease in HR within the following 5-6 sec. 3. These findings indicate that the primary effect of withdrawal of arterial chemoreceptor stimulation in conscious man as in the anesthetized animal is tachycardia. The secondary development of bradycardia in 'free-breathing' CO2 tests is probably due to the operation of a lung reflex sensing changes in ventilation. The absence of bradycardia in 'controlled-breathing' CO2 tests and its presence in 'controlled-breathing' O2 tests, finally, suggest that relief of systemic hypoxia causes a slowing of the heart not due to lung reflexes but to some other mechanism which operates with a latency nearly twice as long as the arterial chemoreflex.


Onset of Chiari type 1 malformation: insights from a small series of intrauterine MR imaging cases.
Morphometric studies on idiopathic Chiari malformation type 1 (CM1) pathogenesis have been mainly based on post-natal neuroimaging. Prenatal clues related to CM1 development are lacking. We present pre- and post-natal imaging time course in idiopathic CM1 and assess fetal skull and brain biometry to establish if clues about CM1 development are present at fetal age. Multicenter databases were screened to retrieve intrauterine magnetic resonance (iuMR) of children presenting CM1 features at post-natal scan. Syndromes interfering with skull-brain growth were excluded. Twenty-two morphometric parameters were measured at fetal (average 24.4 weeks; range 21 to 32) and post-natal (average 15.4 months; range 1 to 45) age; matched controls were included. Among 7000 iuMR cases, post-natal scans were available for 925, with postnatal CM1 features reported in seven. None of the fetuses presented CM1 features. Tonsillar descent was clear at a later post-natal scan in all seven cases. Six fetal parameters resulted to be statistically different between CM1 and controls: basal angle (p = 0.006), clivo-supraoccipital angle (p = 0.044), clivus' length (p = 0.043), posterior cranial fossa (PCF) width (p = 0.009), PCF height (p = 0.045), and PCFw/BPDb (p = 0.013). Postnatally, only the clivus' length was significant between CM1 cases and controls. Pre- and post-natal CM1 cases did not share striking common features, making qualitative prenatal assessment not predictive; however, our preliminary results support the view that some of the pathogenetic basis of CM1 may be embedded to some extent already in intrauterine life.


Sleep-waking discharge profiles of dorsal raphe nucleus neurons in mice.
We have recorded, for the first time, in non-anesthetized, head-restrained mice, a total of 407 single units throughout the dorsal raphe nucleus (DR), which contains serotonin (5-hydroxytryptamine, 5-HT) neurons, during the complete wake-sleep cycle. The mouse DR was found to contain a large proportion (52.0%) of waking (W)-active neurons, together with many sleep-active (24.8%) and W/paradoxical sleep (PS)-active (18.4%) neurons and a few state-unrelated neurons (4.7%). The W-active, W/PS-active, and sleep-active neurons displayed a biphasic narrow or triphasic broad action potential. Of the 212 W-active neurons, 194 were judged serotonergic (5-HT W-active neurons) because of their triphasic long-duration action potential and low rate of spontaneous discharge, while the remaining 18 were judged non-serotonergic (non-5-HT W-active neurons) because of their biphasic narrow action potential and higher rate of spontaneous discharge. The 5-HT W-active neurons were subdivided into four groups, types I, II, III, and IV, on the basis of differences in firing pattern during wake-sleep states, their waking selectivity of discharge being in the order type I>type II>type III>type IV. During the transition from sleep to waking, the vast majority of waking-specific or waking-selective type I and II neurons discharged after onset of waking, as seen with non-5-HT W-specific neurons. Triphasic DR W/PS-active neurons were characterized by a low rate of spontaneous discharge and a similar distribution to that of tyrosine hydroxylase-immunoreactive, dopaminergic neurons. Triphasic DR slow-wave sleep (SWS)-active and SWS/PS neurons were also characterized by slow firing. At the transition from sleep to waking, sleep-selective neurons with no discharge activity during waking ceased firing before onset of waking, while, at the transition from waking to sleep, they fired after onset of sleep. The present study shows a marked heterogeneity and functional topographic organization of both serotonergic and non-serotonergic mouse DR neurons and suggests that they play different roles in behavioral state control and the sleep/waking switch.


Efficacy of topical blockade of interleukin-1 in experimental dry eye disease.
To evaluate the therapeutic efficacy of topical interleukin-1 receptor antagonist (IL-1Ra) in the treatment of dry eye disease. Laboratory investigation. Dry eye disease was induced in C57BL/6 female mice through exposure to a desiccating environment within a controlled environment chamber. Topical formulations containing 5% IL-1Ra, 1% methylprednisolone, 0.05% cyclosporin A, and a vehicle control containing carboxymethylcellulose sodium were applied after the induction of dry eye. Corneal fluorescein staining was performed by a masked observer in the different treatment groups. Immunohistochemical studies were undertaken to enumerate corneal CD11b+ cells, as well as to evaluate corneal lymphangiogenesis. Real-time polymerase reaction was used to quantify the expression of interleukin-1β in the cornea. A significant decrease in corneal fluorescein staining was observed after topical treatment with 5% IL-1Ra (P < .01), 1% methylprednisolone (P < .01), and 0.05% cyclosporin A (P < .03). Additionally, a significant decrease in the numbers of central corneal CD11b+ cells (P < .05), corneal lymphatic growth (P < .05), and corneal interleukin-1β expression (P < .003), compared with vehicle treated, were demonstrated only after treatment with 5% IL-1Ra and 1% methylprednisolone, and were absent after cyclosporin A treatment. Topical treatment with IL-1Ra is effective in ameliorating the clinical signs of the dry eye disease, as well as in reducing underlying inflammation. These effects are comparable with those resulting from treatment with topical methylprednisolone. Topical IL-1Ra may hold promise as a novel therapeutic strategy in the treatment of dry eye.


Ex vivo culture rescues hematopoietic stem cells with long-term repopulating capacity following harvest from lethally irradiated mice.
High-dose ionizing radiation can cause lethal myeloablation in exposed individuals. We examined whether ex vivo culture could rescue hematopoietic stem cells with repopulating capacity following harvest from lethally irradiated animals. We exposed B6.SJL mice to 1050 cGy, harvested their irradiated bone marrow (BM), and examined whether ex vivo culture of the irradiated BM mononuclear cells (MNC) with porcine microvascular endothelial cells (PMVEC) or cytokines alone could rescue hematopoietic cells with in vitro colony-forming activity, in vivo radioprotective capacity, and long-term repopulating potential. PMVEC coculture supported the recovery of fourfold and 80-fold greater numbers of total cells and colony-forming cells (CFC) compared to cyokines alone following 1050 cGy irradiation. All control mice irradiated with 1050 cGy died by day 30, as did mice transplanted with 1050 cGy-irradiated BM MNC. In contrast, transplantation of 1050 cGy-irradiated/PMVEC-cultured BM was fully radioprotective in 12 of 16 recipient mice (75%) exposed to 1050 cGy. Six of the 12 CD45.2+ mice (50%) transplanted with 1050 cGy-irradiated/PMVEC-cultured cells showed long-term (>6 months) multilineage repopulation derived from irradiated donor CD45.1+ cells. Surprisingly, transplantation of identical doses of 1050 cGy-irradiated/cytokine-cultured BM was also radioprotective in 50% of irradiated recipient mice and 50% of these mice demonstrated donor-derived repopulation. Fully functional BM stem and progenitor cells can be rescued following harvest from lethally irradiated animals via ex vivo culture with PMVEC or cytokines alone. This method can serve as a model for the rapid ex vivo rescue and transplantation of autologous BM progenitors in the treatment of victims of radiation injury.


Correction to: The old CEACAMs find their new role in tumor immunotherapy.
Correction is needed to the original version of this article.


Phyllodes tumors of the breast: ultrasonographic findings and diagnostic performance of ultrasound-guided core needle biopsy.
We evaluated ultrasonography (US) findings between benign and malignant phyllodes tumors and analyzed diagnostic performance of US-guided core needle biopsy (CNB) for phyllodes tumors. Surgically removed phyllodes tumors of 168 women were divided into two groups according to the benign and malignant (including borderline tumor) groups and 116 were benign and 52 were malignant. On US, the complex cystic echogenicity (p = 0.021), presence of cleft (p = 0.005) and higher final US assessment (p = 0.008) were more frequent in the malignant group. The sensitivity of CNB including fibroepithelial tumors was 67.9% (114/168) and the concordant rate between CNB and surgical excision was 82.1% (32/39) and 5.8% (3/52) in the benign and malignant group. Our results suggested that the US findings of complex cystic echogenicity, cleft, higher final US assessment were more frequent in malignant phyllodes tumors. The sensitivity of CNB was 67.9% (114/168) and malignant phyllodes tumors were rarely diagnosed as malignant by US-guided CNB.


Single and combined effects of microplastics and cadmium on the cadmium accumulation, antioxidant defence and innate immunity of the discus fish (Symphysodon aequifasciatus).
Microplastics (MPs) have the potential to interact with the toxicity of other common environmental contaminants, such as heavy metals. Here, we investigated the impacts of polystyrene-MPs (32-40 μm), cadmium (Cd) and their combination on early juveniles of the discus fish (Symphysodon aequifasciatus) in relation to Cd accumulation, antioxidant defence and innate immunity. Animals were exposed to three concentrations of MPs (0, 50 or 500 μg L-1) crossed with two levels of Cd (0 or 50 μg L-1) for 30 days. Our findings showed that MPs and Cd had no adverse effects on growth and survival. Under exposure to Cd, however, accumulation of Cd in the body of fish decreased with increasing MP concentrations as supported by a reduced metallothionein content. The activities of superoxide dismutase and glutathione peroxidase increased with MPs but decreased with Cd. MPs, Cd or the mixture increased catalase activity, despite an antagonistic interaction between the two stressors. Glutathione levels increased when exposed to high MP concentrations but decreased when co-exposed to Cd. Malondialdehyde content was only influenced by MPs and increased with elevated MPs. MPs or Cd alone did not increase protein carboxyl content but showed a synergistic effect and increased content. MPs or Cd alone showed no effect on lysozyme activity but had a synergistic effect and activated activity. Activities of both acid phosphatase and alkaline phosphatase were enhanced by MPs, Cd or their mixture, although there was an antagonistic interaction between the two stressors. In contrast, MPs, Cd or their mixture decreased complement 3 content, despite an antagonistic interaction between the two stressors. Collectively, this study suggests that exposure to Cd led to reduced Cd accumulation in the presence of MPs. Nevertheless, co-exposure could induce severe oxidative stress and stimulate innate immunity in the juvenile S. aequifasciatus.


Impact of diabetes on long term follow-up of elderly patients with chronic total occlusion post percutaneous coronary intervention.
The prognosis of elderly patients with chronic total occlusion (CTO) and diabetes mellitus (DM) treated with percutaneous coronary intervention (PCI) is not known. To investigate the effect of diabetes on long-term follow-up of CTO after PCI in elderly patients. A total of 153 elderly patients (age > 65 years old) with CTO lesions which were successfully treated with PCI were enrolled. Fifty one patients with diabetes and 102 without diabetes were compared for long-term outcomes (mean follow up: 36 ± 12 months). Major adverse cardiac events (MACE) which include death, myocardial infarction or target lesion revascularization (TLR) were considered as a combined endpoint. The combined endpoint occurred in 29.4% of diabetes patients, and 11.3% of the patients without diabetes (P < 0.05). The Cox proportional hazards model identified: drug eluting stent (DES) or bare metal stent (BMS) (HR: 0.13, 95% confidence interval (95% CI): 0.03-0.62, P = 0.004), DM (HR: 6.69, 95% CI: 1.62-15.81, P = 0.01) and final minimal lumen diameter (MLD) (HR: 0.37, 95% CI: 0.13-0.90, P = 0.03 ) as independent predictors of MACE, DM with renal impairment (HR: 6.64, 95% CI: 1.32-33.36, P = 0.02), HBA1C on admission (HR: 1.79, 95% CI: 1.09-2.94, P = 0.02), as independent predictors of MACE at long term follow-up. The study demonstrates that DM is a predictive factor for MACE in elderly CTO patients treated with PCI, type of stent, final minimal lumen diameter and DM with renal impairment, and HBA1C level on admission are predictors of MACE.


Commissioning and comprehensive quality assurance of commercial 3D treatment planning system using IAEA Technical Report Series-430.
The purpose of this work is to report the results of commissioning and to establish a quality assurance (QA) program for commercial 3D treatment planning system (TPS) based on IAEA Technical Report Series 430. Eclipse v 7.3.10, (Varian Medical Systems, Palo Alto, CA, U.S.A.) TPS was commissioned for a Clinac 6EX (Varian Medical Systems, Palo Alto, CA, USA) linear accelerator. CT images of a phantom with various known in-homogeneities were acquired. The images were transferred to TPS and tested for various parameters related to patient data acquisition, anatomical modeling, plan evaluation and dose calculation. Dosimetric parameters including open, asymmetric and wedged shaped fields, oblique incidence, buildup region behavior and SSD dependence were evaluated. Representative clinical cases were tested for MU calculation and point doses. The maximum variation between the measured and the known CT numbers was 20 +/- 11.7 HU (1 SD). The results of all non-dosimetric tests were found within tolerance, however expansion at the sharp corners was found distorted. The accuracy of the DVH calculations depends on the grid size. TPS calculations of all the dosimetric parameters were in good agreement with the measured values, however for asymmetric open and wedged fields, few points were found out of tolerance. Smaller grid size calculation showed better agreement of dose calculation in the build-up region. Independent tests for MU calculation showed a variation within +/-2% (relative to planning system), meanwhile variation of 3.0% was observed when the central axis was blocked. The test results were in agreement with the tolerance specified by IAEA TRS 430. A subset of the commissioning tests has been identified as a baseline data for an ongoing QA program.


Treatment of congenital pseudarthrosis of the tibia by microsurgical fibula transfer.
Conventional methods for the treatment of congenital pseudarthrosis of the tibia (CPT) often lead to unsatisfactory results and so microsurgical fibula transfer (MFT) has appeared as an option to treat this challenging problem. In this series of 27 patients with CPT, we obtained satisfactory results in 23 as assessed by the timing of bone union and bone hypertrophy of the fibular transplant. The overall functional results were also good; in 18 patients, the residual shortening was less than 2 cm (with no limb shortening in 4) and in 7, shortening ranged between 2 and 4 cm. All 25 patients resumed normal walking without the help of braces after an average of 12 months. This report suggests that microvascular fibula transfers provide superior results in the treatment of CPT, especially when considering that many of such cases represented previous surgical failures.


Challenges and opportunities in the global methane cycle.
To control the atmospheric methane concentration for Paris Agreement and Global Methane Pledge, it is urgent to elucidate global methane budget, in the context of dangerous high growth rate of atmospheric methane concentration in the past three years (2020-2022). Interdisciplinary research can definitely help answer the open questions about methane budget, as some examples shown in this Special Issue on "Methane emissions, sinks, and mitigation".