Comparison of sodium, potassium, calcium, magnesium, zinc, copper and iron concentrations of elements in 24-h urine and spot urine in hypertensive patients with healthy renal function.
Sodium, potassium, calcium, magnesium, zinc, copper and iron are associated with the sequela of hypertension. The most reliable method for testing those elements is by collecting 24-h urine samples. However, this is cumbersome and collection of spot urine is more convenient in some circumstance. The aim of this study was to compare the concentrations of different elements in 24-h urine and spot urine. Data was collected from a sub-study of China Salt Substitute and Stroke Study. 240 participants were recruited randomly from 12 villages in two counties in Ningxia, China. Both spot and 24-h urine specimens were collected from each patient. Routine urine test was conducted, and concentration of elements was measured using microwave digestion and Inductively Coupled Plasma-Optical Emission Spectrometry. Partial correlation analysis and Spearman correlation analysis were used to investigate the concentration of different elements and the relationship between 24- h urine and spot urine. A partial correlation in sodium, potassium, calcium, magnesium and iron was found between paired 24-h urine and spot urine samples except copper and zinc: 0.430, 0.426, 0.550, 0.221 and 0.191 respectively. Spot urine can replace 24-h urine for estimating some of the elements in hypertensive patients with normal renal function.


Targeting PKC in microglia to promote remyelination and repair in the CNS.
Microglia and CNS-infiltrating macrophages play significant roles in the pathogenesis of neuroinflammatory and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Prolonged and dysregulated inflammatory responses by these innate immune cells can have deleterious effects on the surrounding CNS microenvironment, which can worsen neurodegeneration and demyelination. However, although chronic activation of pro-inflammatory microglia is maladaptive, other functional microglial subtypes play beneficial roles during CNS repair and regeneration. Therefore, there is a tremendous interest in understanding the underlying mechanism of the activation of these reparative/regenerative microglia. In this review, we focus on the potential role of PKC, a downstream signaling molecule of TREM2 and PLCγ2, and PKC modulators in promoting the activation of reparative/regenerative microglial subtypes as a novel therapy for neuroinflammatory and neurodegenerative diseases.


New antibacterial triterpenoid saponin from Lactuca scariola.
A new antibacterial triterpenoid saponin, 3beta-O-[alpha-L-rhamnopyranosyl]-30-norolean-12,19-diene-28-oic acid 28-O-[beta-D-glucopyranosyl-(1-->4)-O-beta-D-galactopyranosyl]-ester (1); has been isolated from the stems of Lactuca scariola. Its structure was determined by chemical degradations and spectral analysis.


Monitoring patients with left ventricular failure by electrical impedance tomography.
Acute left ventricular failure (LVF) is a common medical emergency but detection and monitoring of pulmonary oedema remains problematic. Fluid is an important determinant of tissue impedance. Electrical impedance tomography (EIT) is a non-invasive technique allowing localisation of impedance changes within tissue. We have investigated the relationship between LVF and the electrical impedance of lung tissue. Twenty patients with a clinical diagnosis of acute left ventricular failure were compared with 30 normal subjects. Patients were monitored using serial chest radiographs and electrical impedance tomography measurements of lung impedance during hospital admission. Radiographs were graded according to the severity of pulmonary oedema by two independent radiologists. Lung impedance was significantly (P<0.0001) lower than normal in patients with left ventricular failure. Values returned towards the normal range as LVF resolved. There was a similar improvement in the score of the chest radiographs. The electrical impedance of the lung is low in left ventricular failure and increases following treatment.


Effect of epileptiform abnormality burden on neurologic outcome and antiepileptic drug management after subarachnoid hemorrhage.
To quantify the burden of epileptiform abnormalities (EAs) including seizures, periodic and rhythmic activity, and sporadic discharges in patients with aneurysmal subarachnoid hemorrhage (aSAH), and assess the effect of EA burden and treatment on outcomes. Retrospective analysis of 136 high-grade aSAH patients. EAs were defined using the American Clinical Neurophysiology Society nomenclature. Burden was defined as prevalence of <1%, 1-9%, 10-49%, 50-89%, and >90% for each 18-24 hour epoch. Our outcome measure was 3-month Glasgow Outcome Score. 47.8% patients had EAs. After adjusting for clinical covariates EA burden on first day of recording and maximum daily burden were associated with worse outcomes. Patients with higher EA burden were more likely to be treated with anti-epileptic drugs (AEDs) beyond the standard prophylactic protocol. There was no difference in outcomes between patients continued on AEDs beyond standard prophylaxis compared to those who were not. Higher burden of EAs in aSAH independently predicts worse outcome. Although nearly half of these patients received treatment, our data suggest current AED management practices may not influence outcome. EA burden predicts worse outcomes and may serve as a target for prospective interventional controlled studies to directly assess the impact of AEDs, and create evidence-based treatment protocols.


Biochemical markers of cultured human prostatic epithelium.
Medium from primary cultures of human prostatic cells was examined for polyamines and carcinoembryonic antigen. Spermine was elevated in medium from 5 of 17 epithelial cell cultures but was not found to be a specific marker for cultured human prostatic epithelial cells. Carcinoembryonic antigen was elevated in all 27 prostate epithelial-cell culture fluids tested, 24 of which had more than 20 ng. carcinoembryonic antigen per milliliter. Medium from other cultured human cells (prostate fibroblasts, genitourinary tumor and non-tumor cells), as well as control medium, contained less than 1 ng. carcinoembryonic antigen per milliliter. Carcinoembryonic antigen, as measured in this study, is a way to demonstrate the presence of human prostatic epithelial cells in culture.


Exploring the relationship between 5'AMP-activated protein kinase and markers related to type 2 diabetes mellitus.
The importance of 5'AMP-activated protein kinase (AMPK) in regulating glucose and fatty acid metabolism is increasing. Thus, it is regarded as a new pharmacological target for treatment of obesity, insulin resistance and type 2 diabetes mellitus (T2DM). In order to explore the relationships between AMPK and diabetes mellitus, urines samples from four groups of C57 mice, i.e., the normal male and female C57 mice, female C57-AMPK gene knocked-out mice, and male C57-AMPK gene knocked-out mice, were studied by coupling GC/MS with a powerful machine learning method, random forest. The experimentation has been designed as two steps: firstly, the normal male and female mice were compared with male and female C57-AMPK gene knocked-out mice, respectively; then the differences between male C57-AMPK gene knocked-out mice and female C57-AMPK gene knocked-out mice were further detected. Finally, not only the differences between the normal C57 mice and C57-AMPK gene knocked-out mice were observed, but also the gender-related metabolites differences of the C57-AMPK gene knocked-out mice were obviously visualized. The results obtained with this research demonstrate that combining GC/MS profiling with random forest is a useful approach to analyze metabolites and to screen the potential biomarkers for exploring the relationships between AMPK and diabetes mellitus.


Prognostic Value of Electrocardiographic Left Ventricular Hypertrophy After Transcatheter Aortic Valve Implantation: Insights from the OCEAN-TAVI Registry.
Electrocardiogram (ECG) left ventricular hypertrophy (LVH) is associated with the prognosis of patients with aortic stenosis. However, the impact of the presence or absence of ECG-LVH on the clinical outcomes after transcatheter aortic valve implantation (TAVI) is limited. This study aimed to assess the prognostic value of ECG-LVH among patients with aortic stenosis treated by TAVI. A total of 1,667 patients who underwent TAVI were prospectively enrolled into the OCEAN-TAVI (Optimized CathEter vAlvular iNtervention-Transcatheter Aortic Valve Implantation) registry. A total of 1,446 patients (mean age 84 years; 29.9% men) were analyzed. The Sokolow-Lyon index was used to determine the presence of ECG-LVH. LVH was also assessed using transthoracic echocardiography (TTE). We investigated the association between ECG-LVH and all-cause and cardiovascular mortality. This study identified ECG-LVH and TTE-LVH in 743 (51.5%) and 1,242 patients (86.0%), respectively. The Kaplan-Meier analysis revealed that all-cause mortality was significantly higher among patients without ECG-LVH than among those with ECG-LVH (log-rank p <0.001). In the multivariable analysis, the absence of ECG-LVH was independently associated with all-cause mortality (hazard ratio 1.98, 95% confidence interval 1.39 to 2.82, p <0.001), regardless of the presence or absence of TTE-LVH. Furthermore, the presence of TTE-LVH with the absence of ECG-LVH was observed in 575 patients (40%), which was associated with cardiovascular mortality (hazard ratio 2.84, 95% confidence interval 1.56 to 5.17, p <0.001). In conclusion, the absence of ECG-LVH was independently associated with an increased risk of all-cause mortality after TAVI. Risk stratification using both ECG-LVH and TTE-LVH is a useful predictor of adverse clinical outcomes after TAVI.


The protistan parasite Perkinsus marinus is resistant to selected reactive oxygen species.
The parasite Perkinsus marinus has devastated natural and farmed oyster populations along the Atlantic and Gulf coasts of North America. When viable P. marinus trophozoites are engulfed by oyster hemocytes, the typical accumulation of reactive oxygen species (ROS) normally associated with phagocyte activity is not observed. One hypothesis to explain this is that the parasite rapidly removes ROS. A manifestation of efficient ROS removal should be a high level of resistance to exogenous ROS. We investigated the in vitro susceptibility of P. marinus to ROS as compared to the estuarine bacterium Vibrio splendidus. We find that P. marinus is markedly less susceptible than V. splendidus to superoxide and hydrogen peroxide (H(2)O(2)), but equally sensitive to hypochlorite. Viable P. marinus trophozoites degrade H(2)O(2) in vitro, but lack detectable catalase activity. However, extracts contain an ascorbate dependent peroxidase activity that may contribute to H(2)O(2) removal in vitro and in vivo.


Stretching health diplomacy beyond 'Global' problem solving: Bringing the regional normative dimension in.
The importance of the regional dimension of health diplomacy is only gaining slow and uneven recognition. This is in many ways surprising. As demonstrated in the work of Deacon on the 'globalization of social policy', global social policy has been animated and debated not only at the multilateral level but at the regional level as well. But at least in the diplomatic literature, the importance of this regional dynamic (with a focus on diverse sites and actors and the pursuit of democratic control) has been missed. The objective of this article is to explore whether health diplomacy is catching up to this larger debate re-shaping the conceptualization and practice of diplomacy more generally. In some ways, the results may be counter-productive in that this shift may encourage an increasingly fragmented process. Yet, it may also point to some breakthroughs, with diplomats, acting as 'go to' personnel on the front lines of operational activity, enabling actors to integrate with one another to produce effective governance. In doing so, the regional dimension is given greater recognition as a component of health diplomacy, albeit in an uneven and sometimes awkward manner. Whereas global diplomacy generally emphasizes problem solving, the regional dimension is animated by a normative orientation.


Comparison of health effects between individuals with and without skin lesions in the population exposed to arsenic through drinking water in West Bengal, India.
A study was conducted to explore the effect of arsenic causing conjunctivitis, neuropathy and respiratory illness in individuals, with or without skin lesions, as a result of exposure through drinking water, contaminated with arsenic to similar extent. Exposed study population belongs to the districts of North 24 Parganas and Nadia, West Bengal, India. A total of 725 exposed (373 with skin lesions and 352 without skin lesions) and 389 unexposed individuals were recruited as study participants. Participants were clinically examined and interviewed. Arsenic content in drinking water, urine, nail and hair was estimated. Individuals with skin lesion showed significant retention of arsenic in nail and hair and lower amount of urinary arsenic compared to the group without any skin lesion. Individuals with skin lesion also showed higher risk for conjunctivitis ((odd's ratio) OR: 7.33, 95% CI: 5.05-10.59), peripheral neuropathy (OR: 3.95, 95% CI: 2.61-5.93) and respiratory illness (OR: 4.86, 95% CI: 3.16-7.48) compared to the group without any skin lesion. The trend test for OR of the three diseases in three groups was found to be statistically significant. Again, individuals without skin lesion in the exposed group showed higher risk for conjunctivitis (OR: 4.66, 95% CI: 2.45-8.85), neuropathy (OR: 3.99, 95% CI: 1.95-8.09), and respiratory illness (OR: 3.21, 95% CI: 1.65-6.26) when compared to arsenic unexposed individuals. Although individuals with skin lesions were more susceptible to arsenic-induced toxicity, individuals without skin lesions were also subclinically affected and are also susceptible to arsenic-induced toxicity and carcinogenicity when compared to individuals not exposed to arsenic.


Enhanced solubilization and biochemical methane potential of waste activated sludge by combined free nitrous acid and potassium ferrate pretreatment.
The increasing production of waste activated sludge (WAS) from wastewater treatment plants presents an inherent environmental burden. In this study, Free nitrous acid combined with potassium ferrate (FNA + PF) pretreatment was used to enhance solubilization and biochemical methane potential of WAS. Results indicated that the maximum removal rates of total suspended solid by PF, FNA, and PF + FNA pretreatment were 21.84%, 38.09%, and 56.17%, respectively. The biochemical methane potential of WAS without pretreatment reached 61.22 L CH4/kg VSS added while this value increased to 147.07 L CH4/kg VSS added after FNA + PF pretreatment (0.06 g/g TSS NaNO2 and 0.25 g/g TSS K2FeO4). Shotgun metagenomic analysis revealed that FNA + PF pretreatment could increase the diversity and stability of microbial communities by shifting methanogenic pathways from strictly acetoclastic to acetoclastic/hydrogenotrophic, thereby enhancing methane production. This study suggested that FNA + PF pretreatment is a promising technology to reduce WAS and enhance methane production by pretreated WAS during anaerobic digestion.


Ontogeny of guanylin-immunoreactive cells in rat salivary glands.
Guanylin-like peptides regulate electrolyte/water transport through the epithelia. Moreover, these peptides possess antiproliferative activity and regulate the turnover of epithelial cells. In an earlier study we localized guanylin immunoreactivity in secretory ducts of adult rodent salivary glands. In this study we investigated the appearance and distribution pattern of this peptide during the development of rat salivary glands. Guanylin immunoreactivity appeared at the beginning of cell differentiation from solid bud, on embryonic day 17 in the submandibular and sublingual glands and after day 18 in the parotid gland. Guanylin immunoreactivity appeared first in ductal and acinar anlage: its cell distribution pattern and fate differed in these two compartments. In the duct cells guanylin immunoreactivity spread after the duct system developed, whereas in acinar cells it disappeared after cell differentiation. The guanylin immunoreactivity we detected in adult salivary duct cells accords with guanylin's role in regulating electrolyte and water transport through the various epithelia. It does so by activating guanylate cyclase-C receptor, increasing intracellular cGMP concentration, and phosphorylating the cystic fibrosis transmembrane conductance regulator (CFTR) protein by the cGMP-dependent protein kinase II. This signaling cascade couples to the ductal electrolyte/water secretion and modulates finally the electrolyte composition of the saliva. On the other hand, CFTR is also involved in mechanisms of cell growth, by regulating apoptosis, and promoting cell differentiation. The early diffuse guanylin immunoreactivity we observed in ducts and acinar anlage, before the secretory set is operative, suggests guanylin has a role in cell differentiation.


Degradation of spectrin via calpains in the ventral horn after transient spinal cord ischemia in rabbits.
In the present study, we investigated chronological changes of mu-calpain, m-calpain and cleaved spectrin alphaII immunoreactivity in the ventral horn after transient spinal cord ischemia to investigate relationship between calpains and vulnerability to ischemia using abdominal aorta occlusion model in rabbits. Spinal cord sections at the level of L(7) were immunostained with calpains and cleaved spectrin alphaII monoclonal antibodies. mu-Calpain and m-calpain immunoreactivity was significantly increased in the ischemic ventral horn at 30 min and 1 h after ischemia/reperfusion, respectively. Thereafter, they were decreased with time after ischemia/reperfusion: at 48 h after ischemia, their immunoreactivities nearly disappeared in the ischemic ventral horn. Cleaved spectrin alphaII immunoreactivity was significantly increased in the ventral horn of spinal cord at 12 h after ischemia/reperfusion, and thereafter, its immunoreactivity was decreased with time after ischemia/reperfusion. In addition, spectrin alphaII protein level (280 kDa) was decreased from 12 h after ischemia/reperfusion; in contrast, cleaved spectrin alphaII protein level (150 kDa) was significantly increased at 12 h after ischemia/reperfusion. In conclusion, our observations in this study indicate that calpain is associated with neuronal degeneration in the ventral horn at early time after transient spinal cord ischemia via the proteolysis of spectrin alphaII.


The effects of acute ethanol feeding and of chronic benfluorex administration on the activities of some enzymes of glycerolipid synthesis in rat liver and adipose tissue.
Rats were treated for 5 days with benfluorex [1-(3-trifluoromethylphenyl)-2-[N-(2-benzoyloxyethyl)amino]propane] or with suspending medium (controls). They were then intubated with an acute intoxicating dose of ethanol or with glucose of equivalent energy content. Treatment of the control rats with ethanol specifically increases the hepatic activity of the soluble phosphatidate phosphohydrolase by about 5-fold in 6 h. The equivalent increase for the benfluorex-treated rats were about 2-fold. The results are discussed in relation to the effects of ethanol and benfluorex on glycerolipid synthesis.


Cardiovascular effects of patent ductus arteriosus in preterm lambs with respiratory distress.
We created a model for studying the cardiovascular and pulmonary effects of patent ductus arteriosus (PDA) in premature lambs with respiratory distress. In 47 fetal lambs at 129 to 133 days gestation (term, 145 days), we infiltrated the ductus arteriosus with formalin and placed a mechanical occluder about it so that its patency could be regulated. Two days later the lambs were delivered, given sheep surfactant, paralyzed, and their lungs mechanically ventilated. These premature lambs could more than double their left ventricular output when challenged with increasing degrees of left-to-right shunts through the PDA. This was accomplished by an increase in stroke volume, not by an increase in heart rate. During the 40-minute observation period, there was no change in dynamic compliance or functional residual capacity while the ductus was patent. When the ductus was patent, there was a significant increase in arterial PaO2 (even with small left-to-right shunts) and a decrease in PaCO2 (with large shunts). Despite the heart's ability to handle the increased volume load of a PDA, there were significant alterations in individual organ blood flows, resulting from a combination of decreased perfusion pressure and localized vasoconstriction. The abdominal organs had significant reductions in blood flow even with small PDA shunts. This decrease in organ blood flow may explain some of the pathophysiologic manifestations of PDA in preterm infants.


Posterior vermal Purkinje cells in macaques responding during saccades, smooth pursuit, chair rotation and/or optokinetic stimulation.
Anatomical locations of the Purkinje cells (P cells), showing modulations in activity during either saccadic or smooth-pursuit eye movements, during primate chair rotation, or in response to optokinetic stimulation, were studied in the posterior vermes of monkeys trained to move their eyes with a visual target. The majority (68.3%) of the responsive P cells were saccade-related units. They were located exclusively in vermal lobules VIc and VII: the oculomotor vermis. Most P cells sensitive to chair rotation were located in vermal lobules VIa,b and VIII (91.2%), designated as the paraoculomotor vermis. The P cells which modulated activity during smooth-pursuit eye movements, associated with eye position, or during optokinetic stimulation were found in both the oculomotor and paraoculomotor vermis. There were 25 P cells which modulated their activity during smooth pursuit in the oculomotor vermis. Among them, only three responded also to optokinetic stimulation but none was sensitive to chair-rotation stimulation. These findings suggest that the control of saccadic eye movements is the primary function of the oculomotor vermis.


Inguinal Lymphadenopathy After Renal Transplantation Leading to the Diagnosis of Prostate Cancer: A Case Report.
It is extremely rare for a patient with prostate cancer (PCa) to have palpable lymph nodes at the initial presentation. In fact, only 4 case reports of palpable superficial lymph nodes at the first visit led to the diagnosis of PCa. Moreover, no such cases are reported in kidney transplantation (KT) patients. A 72-year-old man who started hemodialysis due to diabetic nephropathy was referred to our hospital for a KT in 2018. Before the KT, he had a negative screen for cancer, including PCa. The postoperative course was good. He felt a lump in the left inguinal region three years after the KT. A computed tomography scan revealed abdominal and left inguinal lymphadenopathy, which was consistent with a post-transplant lymphoproliferative disorder. However, a biopsy of an inguinal lymph node revealed adenocarcinoma with positive prostate-specific antigen (PSA) staining, suggesting lymph node metastasis of PCa. The blood PSA level was 1674.23 ng/mL. A prostate biopsy was performed, the pathologic diagnosis of which was PCa, with a Gleason score of 10. In conclusion, even though the standardized incidence ratio of PCa is not known to increase in KT patients, PCa should be included in the differential diagnosis, along with the possibility of post-transplant lymphoproliferative disorder. We also suggest the importance of regular screening for malignant tumors after organ transplantation.


Sutureless aortic valves in isolated and combined procedures: Thirteen years of experience in 784 patients.
The aim of this study was to evaluate the outcome and experience of the Perceval sutureless valve at our institution (UZ Leuven). Between 2007 and 2019, 784 patients underwent sutureless aortic valve replacement using the Perceval valve (isolated or combined with other procedures). We performed a retrospective analysis of the postoperative and follow-up data. Mean age was 78 years with a median European System for Cardiac Operative Risk Evaluation II score of 4.2% (interquartile range, 2.6%-7.2%). Isolated aortic valve replacement accounted for 45% of cases; 30% of cases were aortic valve replacement in combination with coronary artery bypass grafting and the remaining 25% were other combined procedures. The median crossclamp times were 38 minutes in single aortic valve replacement, 70 minutes in cases with coronary artery bypass grafting, and 89 minutes in multiple valve cases. Device success was 99.1% and in-hospital mortality was 3.3%. Postoperative stroke or transient ischemic attack occurred in 1.9% of patients and 1% of patients had a new need for dialysis after surgery and median survival time was 7.0 years with a cumulative follow-up of 2797.8 patient-years. The 1-, 5-, and 10-year freedom from reintervention were 99%, 97%, and 94%, respectively. These data represent the longest follow-up available, to our knowledge, for the Perceval sutureless valve. We observed favorable early outcomes, and low rates of early mortality, stroke, and other major complications. Valve durability is promising with low rates of valve degeneration and a limited need for reintervention.


Retracted: Spare Parts Stocking Decision Strategy and Service Logistics Cost Optimization of Two-Echelon Service Logistics System considering Multifailure Mode.
[This retracts the article DOI: 10.1155/2022/7607985.].


A Biosensor Based on Interchain Reactions for the Detection of Acetamiprid and the Construction of Basic Logic Gates OR and AND.
An enzyme-free and label-free fluorescent DNA aptasensor was constructed with computer assistance based on thermodynamic deviation driving interchain reactions. In this work, in the presence of target acetamiprid, the released trigger strand C-apt could open hairpin Hp1, which in turn triggered the strand displacement reaction and catalyzed the self-assembly of hairpins Hp1 and Hp2, so that the guanine base rich stem in Hp2 was opened. In the presence of K+ and NMM, the G-rich moiety could form a G-quadruplex and emit strong fluorescence at a specific excitation wavelength. The proposed strategy enables sensitive detection of acetamiprid at concentrations as low as 54.3 pM. Most importantly, computer-assisted analysis of the thermodynamic properties of nucleic acid strands and simulation of the reaction process and conditions of the proposed model before conducting biological experiments theoretically proves this strategy feasible and may simplify subsequent biological experiments. In addition, basic molecular logic gates, including OR and AND, were constructed based on this detection principle, and simulation tests and biological experiments were performed. The final results show that this strategy can not only have some applications in the field of food safety and environmental monitoring, but also provide a certain way for the development of molecular logic computing.


Polyuria in patients with lower urinary tract symptoms: Prevalence and etiology.
Patients with lower urinary tract symptoms (LUTS) can be subcategorized into polyuria, normal or oliguria groups. Polyuria may be caused by pathologies including diabetes mellitus (DM), chronic kidney disease (CKD), diabetes insipidus (DI), or primary polydipsia (PPD). While fluid restriction is appropriate for some, doing so in all may result in serious complications. This study investigates the prevalence of these pathologies in LUTS patients with polyuria. Two databases were retrospectively queried for men and women who filled out a lower urinary tract symptom score (LUTSS) questionnaire, 24-h bladder diary (24HBD) and were polyuric (>2.5 L/day). Patients were divided into four groups: poorly controlled DM, DI, an CKD grade 3 and PPD. One-way analysis of variance compared 24HBD and LUTSS questionnaires. Pearson correlation examined LUTSS and bother with 24-h voided volume (24 HVV), maximum voided volume (MVV) and total voids. Among 814 patients who completed a 24HBD, 176 had polyuria (22%). Of the patients with complete data, 7.8% had poorly-controlled DM, 3.1% had DI, 4.7% had CKD grade 3% and 84.4% had PPD. Amongst the four different sub-groups, significant differences were seen in 24 HVV (p < 0.001), nocturnal urine volume (NUV) (p < 0.001), MVV (p = 0.003), daytime voids (p = 0.05), nocturnal polyuria index (NPi) (p < 0.001) and nocturia index (Ni) (p = 0.002). Significance was also seen between LUTSS and bother subscore (r = 0.68, p < 0.001), LUTSS and total voids (r = 0.29, p = 0.001) and bother sub-score and total voids (r = 0.21, p = 0.019). 22% of patients with LUTS were found to have polyuria based on a 24HBD. Within this cohort, four sub-populations were identified as being demonstrating statistically significant differences in 24 HVV, NUV, MVV, daytime voids, NPi and Ni. Identifying the underlying etiology of polyuria should be carried out to safely treat patients with LUTS.


Intranasal Delivery of Recombinant AAV Containing BDNF Fused with HA2TAT: a Potential Promising Therapy Strategy for Major Depressive Disorder.
Depression is a disturbing psychiatric disease with unsatisfied therapy. Not all patients are sensitive to anti-depressants currently in use, side-effects are unavoidable during therapy, and the cases with effectiveness are always accompanied with delayed onset of clinical efficacy. Delivering brain-derived neurotrophic factor (BDNF) to brain seems to be a promising therapy. However, a better approach to delivery is still rudimentary. The purpose of our present work is to look for a rapid-onset and long-lasting therapeutic strategy for major depressive disorder (MDD) by effectively delivering BDNF to brain. BDNF, fused with cell-penetrating peptides (TAT and HA2), was packaged in adenovirus associated virus (AAV) to construct the BDNF-HA2TAT/AAV for intranasally delivering BDNF to central nervous system (CNS) via nose-brain pathway. Intranasal administration of BDNF-HA2TAT/AAV to normal mice displayed anti-depression effect in forced swimming test when the delivery lasted relatively longer. The AAV applied to mice subjected to chronic mild stress (CMS) through intranasal administration for 10 days also alleviated depression-like behaviors. Western-blotting analysis revealed that BDNF-HA2TAT/AAV nasal administration enhanced hippocampal BDNF content. These results indicate intranasal administration of constructed BDNF-HA2TAT/AAV exerts anti-depression effect in CMS mice by increasing hippocampal BDNF, suggesting that this strategy holds a promising therapeutic potential for MDD.


Investigations on spinal cord fMRI of cats under ketamine.
Functional magnetic resonance imaging (fMRI) of the spinal cord has been the subject of intense research for the last ten years. An important motivation for this technique is its ability to detect non-invasively neuronal activity in the spinal cord related to sensorimotor functions in various conditions, such as after spinal cord lesions. Although promising results of spinal cord fMRI have arisen from previous studies, the poor reproducibility of BOLD activations and their characteristics remain a major drawback. In the present study we investigated the reproducibility of BOLD fMRI in the spinal cord of cats (N=9) by repeating the same stimulation protocol over a long period (approximately 2 h). Cats were anaesthetized with ketamine, and spinal cord activity was induced by electrical stimulation of cutaneous nerves of the hind limbs. As a result, task-related signals were detected in most cats with relatively good spatial specificity. However, BOLD response significantly varied within and between cats. This variability was notably attributed to the moderate intensity of the stimulus producing a low amplitude haemodynamic response, variation in end-tidal CO(2) during the session, low signal-to-noise ratio (SNR) in spinal fMRI time series and animal-specific vascular anatomy. Original contributions of the present study are: (i) first spinal fMRI experiment in ketamine-anaesthetized animals, (ii) extensive study of intra- and inter-subject variability of activation, (iii) characterisation of static and temporal SNR in the spinal cord and (iv) investigation on the impact of CO(2) end-tidal level on the amplitude of BOLD response.


Elastin peptides prepared from piscine and mammalian elastic tissues inhibit collagen-induced platelet aggregation and stimulate migration and proliferation of human skin fibroblasts.
We obtained pure elastin peptides from bovine ligamentum nuchae, porcine aorta, and bonito bulbus arteriosus. The inhibitory activity of these elastin peptides on platelet aggregation induced by collagen and the migratory and proliferative responsivenesses of human skin fibroblasts to these elastin peptides were examined. All of bonito, bovine, and porcine elastin peptides found to inhibit platelet aggregation, but bonito elastin peptides showed a higher inhibitory activity than bovine and porcine elastin peptides did. All elastin peptides enhanced the proliferation of fibroblasts 3.5- to 4.5-fold at a concentration of 10 µg/ml. Bovine and porcine elastin peptides stimulated the migration of fibroblasts, with the optimal response occurring at 10(-1) µg/ml, while maximal response was at 10(2) µg/ml for bonito elastin peptides. Furthermore, pretreatment of fibroblasts by lactose depressed their ability to migrate in response to all elastin peptides, suggesting the involvement of elastin receptor in cell response. These results suggest that both mammalian and piscine elastin peptides can be applied as useful biomaterials in which elasticity, antithrombotic property, and the enhancement of cell migration and proliferation are required.


Color enhances Mach bands detection threshold and perceived brightness.
We have previously argued that unless color and luminance are shown to be processed independently, using isoluminant stimuli may not reveal the full contribution of color to visual functioning. Here we study the interaction of color and luminance in a task, Mach bands detection and perceived brightness, where color by itself is not effective at all. Subjects viewed luminance or color/luminance ramps and had to determine in either case the luminance contrast necessary for detecting Mach bands and, in another experiment, to compare the brightness of the bands in the luminance and in the combined displays. Isoluminant color displays did not generate any Mach bands, but the addition of color to the luminance display lowered Mach bands detection thresholds and enhanced their perceived brightness. It is thus concluded that the failure to perceive Mach bands in an isoluminant display is not indicative of the lack of color contribution to spatial vision but rather indicates that the strong effect that color has on contrast enhancement mechanisms can be revealed if color and luminance are allowed to interact.


All-Cause and Cardiovascular-Related Mortality in CKD Patients With and Without Heart Failure: A Population-Based Cohort Study in Kaiser Permanente Southern California.
Heart failure and chronic kidney disease (CKD) frequently coexist reflective of the strong interplay between these organ systems. A better understanding of the prevalence of different types of heart failure (preserved and reduced ejection fraction) and their subsequent mortality risks among advanced CKD patients would provide important epidemiologic insights and may pave the way for more focused and proactive management strategies. Retrospective cohort study. Patients aged ≥18 years with incident CKD (estimated glomerular filtration rate ≤45 mL/min/1.73 m2) with and without heart failure in a large integrated health care system in Southern California. Heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF). All-cause and cardiovascular-related mortality within one year of CKD identification. HRs were estimated using Cox proportional-hazards model for risk of all-cause mortality and Fine-Gray subdistribution hazard model for risk of cardiovascular-related mortality within 1 year. The study cohort included 76,688 patients with incident CKD between 2007 and 2017, of which 14,249 (18.6%) had prevalent heart failure. Among these patients, 8,436 (59.2%) had HFpEF and 3,328 (23.3%) had HFrEF. Compared with patients without heart failure, the HR for 1-year all-cause mortality was 1.70 (95% CI, 1.60-1.80) among patients with heart failure. The HRs were 1.59 (95% CI, 1.48-1.70) for patients with HFpEF and 2.43 (95% CI, 2.23-2.65) for patients with HFrEF. Compared with patients without heart failure, the 1-year cardiovascular-related mortality HR for patients with heart failure was 6.69 (95% CI, 5.93-7.54). Cardiovascular-related mortality HR was even higher among those with HFrEF (HR, 11.47; 95% CI, 9.90-13.28). Retrospective design with a short 1-year follow-up period. Additional variables including medication adherence, medication changes, and time-varying variables were not accounted for in this intention-to-treat analysis. Among patients with incident CKD, heart failure was highly prevalent with HFpEF accounting for over 70% among patients with known ejection fraction. Although the presence of heart failure was associated with higher 1-year all-cause and cardiovascular-related mortality, patients with HFrEF were the most vulnerable.


Steady-state and dynamic photosynthetic response of Adenocaulon bicolor (Asteraceae) in its redwood forest habitat.
The gas exchange characteristics under steadystate and transient light conditions were determined for a redwood forest understory herb Adenocaulon bicolor, that depends on use of sunflecks for a large fraction of its daily carbon gain. Measurements under steady-state conditions indicated that this species has photosynthetic characteristics that are typical for understory plants. The mean light-saturated assimilation rate was 5.26 μmol CO2 m-2 s-1; the light saturation and compensation occurred at 243 and 2 μmol photons m-2 s-1, respectively. This light compensation point was much less than the photon flux density under diffuse light in the understory so that positive assimilation could be maintained throughout the day. When leaves that had been in diffuse light for at least 2 h were exposed to a sudden increase in PFD to saturating levels, 10-30 min were required for both assimilation and stomatal conductance to reach maximum values. Calculation of intercellular CO2 pressures, however, suggest that for the first 10 min after the light increase, biochemical factors were responsible for most of the increase in assimilation. Thereafter stomatal opening caused a further increase in assimilation that was no more than 25% of the total. When fully induced leaves were returned to low light, induction was rapidly lost even though stomatal conductance decreased only slowly. This rapid loss of induction limited the capacity of A. bicolor to use sunflecks after low light periods that lasted longer than 1-2 min. However, during periods when sunflecks are more frequent there is probably little loss of induction. Under these conditions, sunflecks are used with high efficiency for assimilation.


Insulin receptor and altered glucose transport in a monensin-resistant mutant of Chinese hamster ovary cell.
A monensin-resistant mutant Monr-31, derived from Chinese hamster ovary (CHO) cell line, has been shown to have a reduced number of insulin receptors and a reduction in glucose uptake in response to insulin. We have further investigated the possibility that altered glucose uptake in Monr-31 cells is related to an alteration in the activity of the insulin receptor. Uptake of glucosamine, 2-deoxy-D-glucose, and 3-O-methyl-D-glucose in Monr-31 cells was one-half to one-third that of CHO cells. The cellular content of the glucose transporter in Monr-31 was reduced to about one-third that of CHO as assayed by use of an antiglucose transporter antibody. After transfection with the human insulin receptor cDNA, we obtained clones CIR-0 from CHO, and MIR-2 and MIR-15 from Monr-31; CIR-0 expressed a tenfold higher level of the insulin-binding activity than did CHO, and MIR-2 and MIR-15 expressed a 20-fold higher level than did Monr-31. Glucose uptake in both CHO and CIR-0 was significantly enhanced by exogenous insulin, but not in Monr-31, MIR-2, and MIR-15. The beta-subunits of insulin receptor in CHO, CIR-0, Monr-31, and MIR-2 were similarly phosphorylated. The decreased glucose transport activity in Monr-31 cells is discussed in relation to the absence or presence of insulin receptor expression.


Validation of an in vitro contractility assay using canine ventricular myocytes.
Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscope at ~36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration-effect curves were constructed for each compound in 4-30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6-8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds.


Gender Differences in Demographic and Clinical Correlates among Veterans with Musculoskeletal Disorders.
Studies suggest that women may be at greater risk for developing chronic pain and pain-related disability. Because musculoskeletal disorders (MSD) are the most frequently endorsed painful conditions among veterans, we sought to characterize gender differences in sociodemographic and clinical correlates among veterans upon entry into Veterans Health Administration's Musculoskeletal Disorders Cohort (n = 4,128,008). Women were more likely to be younger, Black, unmarried, and veterans of recent conflicts. In analyses adjusted for gender differences in sociodemographics, women were more likely to have diagnoses of fibromyalgia, temporomandibular disorders, and neck pain. Almost one in five women (19.4%) had more than one MSD diagnosis, compared with 15.7% of men; this higher risk of MSD multimorbidity remained in adjusted analyses. Adjusting for sociodemographics, women with MSD were more likely to have migraine headache and depressive, anxiety, and bipolar disorders. Women had lower odds of cardiovascular diseases, substance use disorders, and several MSDs, including back pain conditions. Men were more likely to report "no pain" on the pain intensity Numeric Rating Scale, whereas more women (41%) than men (34%) reported moderate to severe pain (Numeric Rating Scale 4+). Because women veterans are more likely to have conditions such as fibromyalgia and mental health conditions, along with greater pain intensity in the setting of MSD, women-specific pain services may be needed.


Metabolism and toxicokinetics of the mycotoxin ochratoxin A in F344 rats.
Male (n=18) and female (n=18) F344 rats were administered a single dose of OTA (0.5 mg/kg b.w.) in corn oil by gavage. Animals (n=3) were sacrificed 24, 48, 72, 96, 672 and 1,344 hours after OTA administration and concentrations of OTA and OTA-metabolites in urine, feces, blood, liver and kidney were determined by HPLC with fluorescence detection and/or by LC-MS/MS. Recovery of unchanged OTA in urine amounted to 2.1% of dose in males and 5.2% in females within 96 h. In feces, only 5.5% resp. 1.5% of dose were recovered. The major metabolite detected was OTalpha, low concentrations of OTA-glucosides were also present in urine. Other postulated metabolites were not observed. The maximal blood levels of OTA were observed between 24 and 48h after administration and were app. 4.6 µmol/l in males and 6.0 µmol/l in females. Elimination of OTA from blood followed first-order kinetics with a half-life of app. 230h calculated from 48h to 1344h. In liver of both male and female rats OTA-concentrations were less than 12 pmol/g tissue, with a maximum at 24h after administration. In contrast, OTA accumulated in the kidneys, reaching a concentration of 480 pmol/g tissue in males 24h after OTA-administration. In general, tissue concentrations in males were higher than in females. OTalpha was not detected in liver and kidney tissue of rats administered OTA and OTalpha concentrations in blood were low (10-15 nmol/1). The high concentrations of OTA in kidneys of male rats may explain the organ- and gender-specific toxicity of OTA.


[Influence of anti-ICOS antibody on quantity and function of CD4(+);CD25(+);Foxp3(+);Treg from lymph and blood of rats with bronchial asthma].
To investigate the influences of anti-ICOS antibody (anti-ICOSAb) on quantity and function of CD4(+);CD25(+);Foxp3(+);Treg cells from lymph and peripheral blood of rats with bronchial asthma. The mononuclear cells (MNC) from lymph and blood were co-cultured with anti-ICOSAb, and then the percentage of CD4(+);CD25(+);Foxp3(+);Treg cells were analyzed by flow cytometer (FCM) and the levels of IL-10 and TGF-β1 in supernatants were determined by ELISA. The MNC were collected from lymph and blood at 0, 24 and 48 h after the last challenge, respectively, and the cells were cultured for 96 h in vitro. The percentage of CD4(+);CD25(+);Foxp3(+);Treg cells in the MNC from lymph was significantly higher than that from blood in each group (P<0.05); The percentage of CD4(+);CD25(+);Foxp3(+);Treg cells in the MNC from lymph and blood in asthma group was significantly lower compare with the normal control group (P<0.05); The percentage of CD4(+);CD25(+);Foxp3(+);Treg cells in the MNC from lymph and blood in the anti-ICOSAb group obviously decreased compare with the asthma group (P<0.05). At 0 h after the last challenge, the level of IL-10 in the supernatant of MNC from lymph and blood in the anti-ICOSAb group were significantly lower than that of the control and asthma groups (P<0.05), while there were no significant differences of TGF-β1 expression in the supernatant of MNC from lymph and blood in each group at different time points. Blocking the ICOS/ICOSL signaling pathway by anti-ICOSAb could exacerbate the deficiency of CD4(+);CD25(+);Foxp3(+);Treg cells from lymph and blood in bronchial asthmatic rat, meanwhile inhibit the CD4(+);CD25(+);Foxp3(+);Treg cells secreting IL-10 at 0 h after the last challenge, but have no significant effect on the secretion of TGF-β1.


Influence of temperature on growth rate and lag phase of fungi isolated from Argentine corn.
The influence of temperature on the growth of nine strains of fungi belonging to the genera Eurotium, Aspergillus, Penicillium and Fusarium has been investigated for the temperature range 15-35 degrees C. The lag phase and the growth rate were evaluated by using a laboratory medium. The maximum growth rate for E. repens, A. wentii and P. chrysogenum was observed at about 25 degrees C, for P. citrinum near 30 degrees C and for F. semitectum and F. moniliforme between 20 and 25 degrees C. The growth rate of A. niger, A. flavus and A. parasiticus increased with increasing temperatures in the range studied. For all strains studied it appeared that the higher the growth rate the lower the lag phase was.


Prostate cancer screening-stepping forward with MRI.
To comprehensively review the literature on the integration of MRI as a diagnostic tool in prostate cancer screening and offer practical recommendations for optimising its use. Existing research studies, clinical guidelines and expert opinions were reviewed to support the optimisation standards for MRI use in screening. Consolidated screening principles were used to make appropriate recommendations regarding the integration of MRI into the diagnostic pathway. To strike a balance between the potential benefits of early detection on mortality and minimising the harm of over-diagnosing indolent cancers, it is necessary to have a clear understanding of the context of MRI use. The key to optimisation is patient selections and MRI-targeted biopsies. For men at higher-than-average risk, it is essential to use screening-specific MRI protocols and establish accuracy levels and interpretation criteria. Optimisation of readings by the automation of data acquisition, image quality monitoring, post-processing, radiologist certification and deep-learning computer-aided software is needed. The optimal utilisation of MRI involves its integration into a multistep diagnostic pathway, supported by a quality-assured and cost-effective infrastructure that ensures community-wide access to imaging. MRI in the prostate cancer screening pathway can bring substantial diagnostic benefits. By carefully considering its advantages, limitations and safety concerns and integrating it into a multistep diagnostic pathway, clinicians can improve outcomes while minimising harm to screening participants. The manuscript discusses the role of MRI in prostate cancer screening, highlighting its potential to improve accuracy and reduce overdiagnosis. It emphasises the importance of optimising protocols and integrating MRI into a multistep diagnostic pathway for successfully delivering screening benefits. • Population screening for prostate cancer is a new indication for prostate MRI that allows the detection of high-risk cancers while reducing the need for biopsies and associated harm. • To optimise prostate cancer screening using MRI, it is essential to redefine MRI protocols; establish accuracy levels, reliability and interpretation criteria; and optimise reading (including post-processing, image quality, radiologist certification, and deep-learning computer-aided software). • The optimal utilisation of MRI for prostate cancer screening would involve its integration into a multistep diagnostic pathway, supported by a quality-assured and cost-effective infrastructure that ensures community-wide access to imaging.


In situ potentiometric method to evaluate bacterial outer membrane-permeabilizing ability of drugs: example using antiprotozoal diamidines.
We introduced a new assay system, combining tyrocidine A and a K(+)-selective electrode, to evaluate the bacterial outer membrane-permeabilizing ability of drugs. Tyrocidine A, in the presence of an outer membrane permeabilizer, increased the permeability to K(+) of the cytoplasmic membrane of Escherichia coli, because this antibiotic could markedly increase the permeability of phospholipid layers constituting the cytoplasmic membrane, while it acted weakly on the outer membrane. Hence, the novel function of agents increasing the permeability of the outer membrane could be examined directly by monitoring the tyrocidine A-induced leakage of K(+) from the bacterial cytoplasm using a K(+)-selective electrode. We found that antiprotozoal diamidines, such as diminazene, pentamidine, and 4',6-diamidino-2-phenylindole (DAPI), can increase the permeability of the bacterial outer membrane and appropriate lipophilicity is important for diamidines to permeabilize the outer membrane.


[Review of the post-COVID-19 syndrome associated to acute telogen effluvium].
Coronavirus disease 2019 (COVID-19) has impacted our society in numerous ways. So far (November 2022) around 640 million SARS-CoV-2 infections have been confirmed worldwide. It is known that this disease has a main affection at the cardiopulmonary level, however, it affects almost all the organs and systems of the body, including the skin. Post-COVID-19 syndrome occurs in some patients, leaving significant sequelae that impact their quality of life. Among the most common sequelae are: cough, dyspnea, chronic fatigue, hyposmia and dysosmia. In addition to these, other sequelae not related to respiratory syndrome have been reported, such as hair loss, which has been observed in around 20% of post-COVID-19 patients, this could be attributable to acute telogen effluvium (TE). To date, no study has been conducted to determine the relationship of ET in those who have had COVID-19. Acute ET is defined as diffuse, non-scarring hair loss, usually self-limited, lasting for about 6 months. Within its etiology, severe systemic febrile illness, pregnancy, restrictive diets, severe stress and various drugs have been described. It seriously affects the quality of life of patients and is often associated with loss of confidence and low self-esteem.


Odour intensity and taste acceptability of spices in minced fish products.
Minced fish products, like pastes, sausages and hamburgers, usually are produced with the addition of spices, and the amount of the individual flavouring ingredients is chosen hitherto on basis of the trial and error method. A more efficient approach, based on predictor equations, is described in this paper.


Deteriorated high-fat diet-induced diabetes caused by pancreatic β-cell-specific overexpression of Reg3β gene in mice.
Reg family proteins have long been implicated in islet β-cell proliferation, survival, and regeneration. In our previous study, we reported that Reg3β overexpression did not increase islet growth but prevented streptozotocin-induced islet damage by inducing specific genes. In order to explore its role in type 2 diabetes (T2D), we established high-fat diet (HFD)-induced obesity and diabetes in RIP-I/Reg3β mice. Glucose and insulin tolerance tests, immunofluorescence for insulin, eIF2α, and GLUT2 in islets, Western blots on phosphorylated AMPKα and hepatic histology were performed. Both RIP-I/Reg3β and wild-type mice gained weight rapidly and became hyperglycemic after 10 weeks on the HFD. However, the transgenic mice exhibited more significant acceleration in blood glucose levels, further deterioration of glucose intolerance and insulin resistance, and a lower intensity of insulin staining. Immunofluorescence revealed similar magnitude of islet compensation to a wild-type HFD. The normal GLUT2 distribution in the transgenic β-cells was disrupted and the staining was obviously diminished on the cell membrane. HFD feeding also caused a further decrease in the level of AMPKα phosphorylation in the transgenic islets. Our results suggest that unlike its protective effect against T1D, overexpressed Reg3β was unable to protect the β-cells against HFD-induced damage.


Modelling Adaptive Learning Behaviours for Consensus Formation in Human Societies.
Learning is an important capability of humans and plays a vital role in human society for forming beliefs and opinions. In this paper, we investigate how learning affects the dynamics of opinion formation in social networks. A novel learning model is proposed, in which agents can dynamically adapt their learning behaviours in order to facilitate the formation of consensus among them, and thus establish a consistent social norm in the whole population more efficiently. In the model, agents adapt their opinions through trail-and-error interactions with others. By exploiting historical interaction experience, a guiding opinion, which is considered to be the most successful opinion in the neighbourhood, can be generated based on the principle of evolutionary game theory. Then, depending on the consistency between its own opinion and the guiding opinion, a focal agent can realize whether its opinion complies with the social norm (i.e., the majority opinion that has been adopted) in the population, and adapt its behaviours accordingly. The highlight of the model lies in that it captures the essential features of people's adaptive learning behaviours during the evolution and formation of opinions. Experimental results show that the proposed model can facilitate the formation of consensus among agents, and some critical factors such as size of opinion space and network topology can have significant influences on opinion dynamics.


The effects of economic growth on carbon dioxide emissions in selected Sub-Saharan African (SSA) countries.
This research article concerns a study of economic growth influences on carbon dioxide emissions in 20 selected Sub Saharan African (SSA) countries. The study also intends to reexamine energy consumption, tourism sector and population effect on carbon dioxide emissions. The empirical research applies panel linear regression model for the data obtained in these 20 SSA countries throughout 2000 to 2020. The empirical estimation techniques employed in the analysis consist of pooled ordinary least square (OLS), fixed effects model (FEM), random effects model (REM) and robust fixed model, including diagnostic tests such as endogeneity, heteroscedasticity and other measurements. The empirical analysis using the robust fixed effects model has established significant associations between economic growth, energy consumption, tourism sector and population on carbon dioxide emissions in SSA countries between 2000 and 2020. This study has established that a 1% increase in economy growth increases the carbon dioxide emission level by approximately 0.02%. A study has identified that SSA countries' energy consumption, especially from oil, will only contaminate air quality. A study confirmed that international tourist arrivals are one of the factors that significantly caused air quality reduction among SSA countries. However, increasing population and future international agreements and protocols could also mean that carbon emissions can potentially cause less environmental degradation in the region.


Heme biosynthesis in mammalian systems: evidence of a Schiff base linkage between the pyridoxal 5'-phosphate cofactor and a lysine residue in 5-aminolevulinate synthase.
5-Aminolevulinate synthase is the first enzyme of the heme biosynthetic pathway in nonplant higher eukaryotes. Murine erythroid 5-aminolevulinate synthase has been purified to homogeneity from an Escherichia coli overproducing strain, and the catalytic and spectroscopic properties of this recombinant enzyme were compared with those from nonrecombinant sources (Ferreira, G.C. & Dailey, H.A., 1993, J. Biol. Chem. 268, 584-590). 5-Aminolevulinate synthase is a pyridoxal 5'-phosphate-dependent enzyme and is functional as a homodimer. The recombinant 5-aminolevulinate synthase holoenzyme was reduced with tritiated sodium borohydride and digested with trypsin. A single peptide contained the majority of the label. The tritiated peptide was isolated, and its amino acid sequence was determined; it corresponded to 15 amino acids around lysine 313, to which pyridoxal 5'-phosphate is bound. Significantly, the pyridoxyllysine peptide is conserved in all known cDNA-derived 5-aminolevulinate synthase sequences and is present in the C-terminal (catalytic) domain. Mutagenesis of the 5-aminolevulinate synthase residue, which is involved in the Schiff base linkage with pyridoxal 5'-phosphate, from lysine to alanine or histidine abolished enzyme activity in the expressed protein.


[Dopamin-beta-hydroxylaseaktivität im Plasma von Dialysepatienten (author's transl)].
Plasma dopamin-b-hydroxylase (DBH) was studied in 70 healthy control persons and in 37 hemodialysed patients. Basal DBH in controls corresponded to 50.0 +/- 29.3 IU. There was was no significant difference between males (53.9 +/1 33.8 IU) and females (47.4 +/- 25 IU); no correlation could be found between age and plasma DBH. In hemodialysed patients basal DBH levels were significantly (p less than 0.01) decreased (32.5 %/- 17.6 IU), suggesting lowered sympathetic activity and/or abnormalities in release, distribution space, or metabolism of DBH. During hemodialysis plasma DBH activity rose during ultrafiltration. This finding indicates a directionally appropriate sympathetic reflex response to volume depletion in dialysed patients.


Quercetin may act as a cytotoxic prooxidant after its metabolic activation to semiquinone and quinoidal product.
In the last ten years, there has been an important increase in interest in quercetin action as a unique antioxidant, but its putative role in numerous prooxidant effects is also being continually updated. The mechanism underlying this undesirable ability seems to involve its metabolic oxidoreductive activation. Based on the structural properties of quercetin, we have investigated whether its catechol moiety may be the potential tool for revealed toxicity. We demonstrated, with an ESR spin-stabilization technique coupled to conventional spectrophotometry, that o-semiquinone and o-quinone are indeed the products of enzymatically catalyzed oxidative degradation of quercetin. The former radical might serve to facilitate the formation of superoxide and depletion of GSH, which could confer a specificity of its prooxidative action in situ. The observed one-electron reduction of o-quinone may enrich the semiquinone pool, thereby magnifying its effect. The two-electron reduction of quinone can result in constant resupply of quercetin in situ, thereby also modulating another pathway of its known biological activities. We have also tried to see whether the intracellular oxidative degradation of quercetin can be confirmed under the controlled conditions of model monolayer cell cultures. The results are indicative of the intracellular metabolic activation of quercetin to o-quinone, the process which can be partially associated with the observed concentration-dependent cytotoxic effect of quercetin.


The pathway of melatonin biosynthesis in common wheat (Triticum aestivum).
Melatonin (Mel) is a multifunctional biomolecule found in both animals and plants. In plants, the biosynthesis of Mel from tryptophan (Trp) has been delineated to comprise of four consecutive reactions. However, while the genes encoding these enzymes in rice are well characterized no systematic evaluation of the overall pathway has, as yet, been published for wheat. In the current study, the relative contents of six Mel-pathway-intermediates including Trp, tryptamine (Trm), serotonin (Ser), 5-methoxy tryptamine (5M-Trm), N-acetyl serotonin (NAS) and Mel, were determined in 24 independent tissues spanning the lifetime of wheat. These studies indicated that Trp was the most abundant among the six metabolites, followed by Trm and Ser. Next, the candidate genes expressing key enzymes involved in the Mel pathway were explored by means of metabolite-based genome-wide association study (mGWAS), wherein two TDC genes, a T5H gene and one SNAT gene were identified as being important for the accumulation of Mel pathway metabolites. Moreover, a 463-bp insertion within the T5H gene was discovered that may be responsible for variation in Ser content. Finally, a ASMT gene was found via sequence alignment against its rice homolog. Validations of these candidate genes were performed by in vitro enzymatic reactions using proteins purified following recombinant expression in Escherichia coli, transient gene expression in tobacco, and transgenic approaches in wheat. Our results thus provide the first comprehensive investigation into the Mel pathway metabolites, and a swift candidate gene identification via forward-genetics strategies, in common wheat.


Copper(II)-disulfiram loaded melanin-dots for cancer theranostics.
Copper(II) diethyldithiocarbamate complex (CuET), the metabolite of disulfiram complexed with copper, is the component responsible for cancer treatment efficacy of disulfiram. But the hydrophobic property of CuET limits its use in vivo, and an appropriate drug delivery system needs to be developed. Ultrasmall melanin nanoparticle (M-Dot) with excellent biosafety and biocompatibility properties has been synthesized in our previous studies. Herein we prepared CuET loaded with M-Dots through hydrophobic interaction, which could enhance the water solubility significantly. After the administration of M-Dots-CuET in mice tumor models, the nanoparticles showed good tumor accumulation as evidenced by the enhanced photoacoustic signal in tumor regions. M-Dots-CuET also displayed excellent tumor inhibition capability, and the tumor growth inhibition value (TGI) was 45.1%. When combined with photothermal therapy, the TGI reached up to 78.6%. In summary, M-Dots-CuET provide a new potential strategy for cancer theranostics.


Clinical impact of intra-aortic balloon pump during extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock.
There is no available data on clinical outcome in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock who are supported by an intra-aortic balloon pump (IABP) in combination with extracorporeal life support (ECLS). We analysed 96 consecutive patients with AMI and complicating cardiogenic shock who were assisted by an ECLS system between January 2004 and December 2011. The primary outcome was in-hospital mortality. The secondary outcomes were the success rate of weaning from ECLS and the lactate clearance for 48 hours (%). A combination of IABP and ECLS was used in 41 (42.7%) patients. In-hospital mortality occurred for 51 patients (ECLS with IABP versus ECLS alone; 51.2% vs. 54.5%, p = 0.747). The success rate of weaning from ECLS was similar between the two groups (63.4% vs. 58.2%, p = 0.604). Complications such as ischemia of a lower extremity or bleeding at the ECLS insertion site (p = 0.521 and p = 0.667, respectively) did not increase when ECLS was combined with IABP. Among patients who survived for 24 hours after intervention, lactate clearance was not significantly different between patients who received ECLS alone and those who received ECLS with IABP (p = 0.918). The combined use of ECLS and IABP did not improve in-hospital survival in patients with AMI complicated by cardiogenic shock.


Amine-functionalized ionic liquids for CO2 capture.
In petroleum industry, the release of more and more carbon dioxide (CO2) brings greenhouse effect and even results in climate change, leading CO2 capture to become an urgent issue. To design ideal and effective absorbent, interaction mechanism for CO2 capture was systematically investigated in a series of imidazolium-based ionic liquids (ILs). The potential effects of alkyl side chain, electron-philic halogen (F, Cl, Br) atom(s), electron-denoting groups OH and NH2 (bound on cation or/and anion), and water solvent were disclosed on CO2 capture using CAM-B3LYP functional with SMD-GIL solvation model, and the most potential green effective absorbent was predicted. This work provides an explicit idea and theoretical basis about the design of desired IL for CO2 capture. Graphical abstract In present work, no/halogen/amino/hydroxy-functionalized imidazolium tetrafluoroborate ILs were studied for CO2 absorption at the CAM-B3LYP/6-311++G** level of theory by SMD-GIL solvation model. NH2 is more potent group in absorbing CO2 than halogen and OH, and its number is proportional to the adsorption capacity of IL. A potentially high-capacity CO2 absorbent with four NH2 groups was predicted. In addition, the mixture of water could further enhance such chemical absorption by lowering the activation energy barriers and viscosity of IL.


SHMTool: a webserver for comparative analysis of somatic hypermutation datasets.
The somatic hypermutation (SHM) of Immunoglobulin variable (V) regions is a key process in the generation of antibody diversity. The growing number of datasets of point mutations that occur during SHM in mice and humans often include comparisons between wild-type and individuals or strains genetically defective in the repair mechanisms that contribute to SHM. However, it has been difficult to compare the results of different studies because the analyses have not been standardized for criteria such as correction for base composition and the inclusion of unique mutations. If many mutations are involved, the analysis can also be time consuming. To overcome these problems and facilitate a standardized analysis and display of similar data, we present a webserver (SHMTool) for comparing SHM datasets, available at http://scb.aecom.yu.edu/shmtool.


Hepatitis C virus (HCV) E1 and E2 protein regions that specifically bind to HepG2 cells.
Identify hepatitis C virus (HCV) sequences in E1 and E2 protein binding to HepG2. Synthetic 20-mer long, ten-residue overlapped peptides, from E1 and E2 proteins, were tested in HepG2 or Raji cell-binding assays. Affinity constants, binding site number per cell and Hill coefficients were determined by saturation assay for high activity binding peptides (HABPs). Receptors for HepG2 cell were determined by cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Twelve HABPs were found in HCV genotype 1a, allowing six hepatocyte-binding sequences (HBSs) to be defined: two peptide-binding regions in E1 HABPs 4913 (YQVRNSTGLYHVTNDCPNSS) and 4918 (MTPTVATRDGKLPATQLRRHY). Four hepatocyte-binding regions were defined in E2: region-I, peptide 4931 (ETHVTGGSAGHTVSGFVSLLY); region-II, 4937-4939 (HHKFNSSGCPERLASCRPLTDFDQGWGPISYANGSGPDQR); region-III, 4943-4945 (PVYCFTPSPVVVGTTDRSGAPTYSWGENDTDVFVLNNTR) and region-IV, 4949-4952 (CGAPPCVIGGAGNNTLHCPTDCFRKHPDATYSRCGSGPWITPRCLVDYPY). The underlined sequences are most relevant in the binding process. HABPs 4913 and 4938 also bind to CD81 positive Raji cells. Region-II 4938 HABPs bind to 50 and 60kDa HepG2 cell membrane surface proteins. Six HVRs to the HepG2 were identified. Some HABPs have been previously found to be antigenic and immunogenic. HABPs, 4918 (from E1), 4938, 4949, 4950, 4951 and 4952 (from E2) have not been previously recognised. These HABPs could be relevant to HCV invasion of hepatocytes.


Cadmium-treatment efficiency and membrane fouling during electrodialysis of wastewater discharged from zinc smelting.
Zinc smelting wastewater contains high concentrations of Cd. Here, the treatment efficiency of Cd using electrodialysis was evaluated. In addition, scale accumulation of ion-exchange membrane (IEM) was analyzed, and fouling control was studied. The results showed that spacers effectively improved the limiting current density but accelerated foulant accumulation. The Cd-treatment efficiency improved to 85.4% without a spacer. Dissolved organic carbon (DOC) and hydrophobic DOC levels in diluted water decreased by 0.65 mg L-1 and 2.1 mg L-1, respectively; in contrast, hydrophilic DOC level increased by 1.45 mg L-1. Some of the hydrophobic DOC in the diluted water was converted to hydrophilic DOC and subsequently to low-molecular-weight (LMW) DOC. DOC level in the concentrated water did not change substantially, but the LMW fraction of the hydrophilic DOC increased. In the cation-exchange membrane, a material composed of calcium sulfate accumulated in the bottom layer, and hydroxides of divalent and trivalent ions accumulated on top of it. In contrast, the anion-exchange membrane was fouled by humic substances. In terms of fouling control, physical and acid cleaning of IEMs was more effective than the reversal operation.


Type 1 Brugada Pattern Associated with Nicotine Toxicity.
Brugada pattern (BrP) findings on electrocardiogram (ECG) are mandatory for the diagnosis of Brugada syndrome (BrS). BrS is an incompletely understood cause of sudden cardiac death. Our patient was a young woman who was using topical nicotine for assistance in smoking cessation at a relatively high dose compared to her daily cigarette intake. She presented with symptoms of mild nicotine toxicity and had an ECG with a type 1 BrP. An ECG the next day was normal and electrophysiology consultation was conducted. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Recognition of a BrP ECG by emergency physicians is critical because this is the first step in diagnosing BrS, a condition that is characterized by ventricular dysrhythmias and sudden cardiac death. In addition, ECG abnormalities can be transient in nature, requiring vigilance by the emergency physician to prevent the patients' potential life threat from going undiagnosed. We present the first case to our knowledge of a BrP associated with nicotine toxicity. We also discuss treatment and disposition recommendations.


The effect of pesticide spraying on the rate and severity of ED asthma.
We report on the incidence of emergency department (ED) asthma presentations and admissions to the Lincoln Hospital, located in the South Bronx of New York City, during the 1999 eradication program of the mosquito vector for West Nile virus. Spraying of Malathion and Resmethrin occurred in the hospital's geographic area over 4 days in September 1999. During that time, 1318 pediatric and adult patients were seen in the ED for asthma-related symptoms. Of these, 222 (16.8%) were hospitalized. Emergency department visits, during days when spraying occurred, were compared with visits during days when no spraying occurred. Comparisons were made with previous years as a reference point. Findings showed that the spraying of insecticides did not increase the rate or severity of asthma presentations as measured by the Lincoln Hospital's ED asthma census or hospital admissions for asthma.


How to improve total factor energy efficiency under climate change: does export sophistication matter?
Climate change has a profound impact on human survival and development. Climate change is an energy and economic issue, which should be driven by technology. Total factor energy efficiency (TFEE) improvement is undoubtedly a breakthrough in solving energy problems. In this paper, the fixed effect model, impulse response function, and threshold regression model are used to test the complex relationship between export sophistication and TFEE. The results reveal that export sophistication improvement leads to higher TFEE. The impulse response results verify the existence of a phased and positive correlation between export sophistication and TFEE. Finally, the relationship between export sophistication and TFEE significantly varied across different threshold levels of regional corruption score, economic development, and openness. This article led the foundation for supporting China's export sophistication promotion strategy and also provides a reference for energy efficiency improvement and energy crisis response in the post-pandemic era.


The pattern ERG in response to colored stimuli.
The pattern-evoked electroretinogram (PERG) was studied in response to square-wave stripe patterns contrasting either between dark and colored stripes ("red-black" or "green-black" luminance contrast pattern) or between the two colors (red-green chromatic contrast pattern). All lights were matched in photopic luminance. A two-channel Maxwellian view system was used to present the stimuli in the onset-offset mode. When no pattern was present a mixture of both colors was seen. Different spatial frequencies were studied and the amplitudes of the onset response were evaluated. When the two luminance contrast patterns were presented, the responses showed a spatial selectivity. However the combination of the two colors (red-green contrast) resulted in a monotonic decrease of the response with spatial frequency. The spatially selective behavior of the response to luminance contrast patterns could be associated with the on-off center-surround organization of retinal receptive fields. The behavior of the response to chromatic-contrast patterns, on the other hand, could be explained by the action of color-opponent center-surround receptive fields as described in the primate.


Adjunctive armodafinil for major depressive episodes associated with bipolar I disorder.
In a previous study, adjunctive armodafinil 150 mg/day significantly improved depressive symptoms associated with bipolar I disorder. Multicenter, double-blind study of patients with a major depressive episode despite bipolar I disorder maintenance therapy randomized to adjunctive placebo or adjunctive armodafinil 150 or 200mg/day for 8 weeks; for logistical reasons, assignment to armodafinil 200mg/day was discontinued early. Primary efficacy was measured by change from baseline to week 8 in 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) total score. Patients were randomized to adjunctive placebo (n=230), adjunctive armodafinil 150 mg/day (n=232), or adjunctive armodafinil 200mg/day (n=30; analyzed for safety only). Least-square mean change in IDS-C30 total score was numerically superior for adjunctive armodafinil 150 mg/day vs adjunctive placebo, but was not statistically significant (p=0.13). Armodafinil was well-tolerated. Adverse events (AEs) observed in >5% with adjunctive armodafinil 150 mg/day and more frequently than with adjunctive placebo were headache (16% [38/231] vs 13% [30/229]) and nausea (7% [17/231] vs 2% [5/229]). The most common AEs with adjunctive armodafinil 200mg/day were diarrhea and dry mouth (17% [5/30] each vs 6% [13/229] and 1% [3/229], respectively, with adjunctive placebo). Early study discontinuation for logistical reasons by the sponsor limited adjunctive armodafinil 200-mg/day assessment. FDA-approved bipolar I depression treatments are limited. Adjunctive armodafinil 150 mg/day reduced depressive symptoms associated with bipolar I disorder to a greater extent than adjunctive placebo, although the difference failed to reach statistical significance. Safety data indicate treatment with adjunctive armodafinil was well-tolerated.


Impact of adapted bicycle riding on outcomes for children and adolescents with disabilities: A systematic review.
To review the evidence for the effects of adapted bicycle riding on body structures and functions, activity, participation, and quality of life outcomes in children with disabilities, along with family-level participation outcomes. A systematic review with searches of nine electronic databases to identify studies involving participants with a developmental disability aged 4 to 18 years who used a dynamic adapted bicycle was completed in August 2021. Risk of bias was assessed based on individual study designs. A narrative synthesis integrated the findings of the included studies. Certainty of evidence was synthesized using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Ten studies were included with 234 participants. Five studies reported outcomes at the body structures and functions level, ten reported activity-level outcomes, two reported participation-related outcomes, and none assessed quality of life or family participation in social and recreational activities. Adapted bicycle riding interventions may improve gross motor function, enhance lower-limb muscle strength, and promote physical activity; however, certainty of evidence of effects was rated very low using GRADE. Further research is required to understand the impact of adapted bicycle riding on the participation outcomes of children and adolescents with disabilities and on family-level participation in social and recreational activities. Adapted bicycle riding interventions may improve motor functions and physical activity. Evidence about participation outcomes after adapted bicycle riding is limited. Research on adapted bicycle riding interventions in natural settings is needed.


Long-term sleep deprivation by hypothalamic stimulation in cats.
Several techniques were developed to prevent sleep in animals in order to examine the biological role fulfilled by sleep; however, most were either stressful or difficult to accomplish routinely, especially in such a large animal as the cat. Electrical stimulation of activating structures in the brain presents a very attractive alternative to peripheral stimulation used by the usual sleep deprivation methods although it has been rarely tried. The paper describes a microcomputer-based system used to achieve sleep deprivation in cats by stimulating the hypothalamic predatory area with short trains. During control days and deprivation the electrocorticogram (EEG), electromyogram (EMG) and electrooculogram (EOG) were continuously digitalized by the computer in 5 s epochs and the integrated power of the 4 usual frequency bands of the EEG (alpha, beta, delta, theta) as well as the variance of EMG and EOG signals were calculated. Criteria for stimulus delivery were based on the integrated power of the delta band and on the variance of EMG but the flexibility of the computer ensures that any other parameter can be used to achieve total or selective sleep deprivation.


Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate.
Cell fate transitions are frequently accompanied by changes in cell shape and mechanics. However, how cellular mechanics affects the instructive signaling pathways controlling cell fate is poorly understood. To probe the interplay between shape, mechanics, and fate, we use mouse embryonic stem cells (ESCs), which change shape as they undergo early differentiation. We find that shape change is regulated by a β-catenin-mediated decrease in RhoA activity and subsequent decrease in the plasma membrane tension. Strikingly, preventing a decrease in membrane tension results in early differentiation defects in ESCs and gastruloids. Decreased membrane tension facilitates the endocytosis of FGF signaling components, which activate ERK signaling and direct the exit from the ESC state. Increasing Rab5a-facilitated endocytosis rescues defective early differentiation. Thus, we show that a mechanically triggered increase in endocytosis regulates early differentiation. Our findings are of fundamental importance for understanding how cell mechanics regulates biochemical signaling and therefore cell fate.


Acute Normovolemic Hemodilution in Spinal Deformity Surgery.
Objective To prospectively compare the clinical and laboratorial aspects of patients undergoing spine deformity surgery, using the acute normovolemic hemodilution technique with tranexamic acid, versus a control group with tranexamic acid alone, and to evaluate the influence of hemodilution in intraoperative bleeding and the need for homologous transfusion. Materials and Methods Comparative prospective study with patients aged between 12 and 65 years undergoing spine deformity surgery with the acute normovolemic hemodilution technique associated with tranexamic acid versus a control group to which only tranexamic acid (15 mg/kg) was administered. Laboratorial exams were performed and analyzed in three different moments. Results A total of 30 patients were included in the present study: 17 in the hemodilution group, and 13 in the control group. The mean duration of the surgery in the hemodilution group was longer. The number of levels submitted to surgery ranged from 7 to 16 in the hemodilution group, and from 4 to 13 in the control group. Osteotomy, predominantly of the posterior kind, was performed in 20 patients. There was more intraoperative bleeding in the control group. All patients were stable during the procedures. Only 6 participants needed homologous blood transfusion, mostly from the control group ( p > 0.05). Conclusion There was no significant difference between the two groups regarding the need for blood transfusion and intraoperative bleeding. The severity of the deformity was the main determinant for homologous blood transfusion.


Use of the life table method in determining attrition from treatment.
Life table analysis of attendance at an outpatient clinic indicates levels of attrition similar to those reported by follow-up and other studies of treatment for drug dependence. With appropriate qualifications, rates of attrition may be viewed as measures of treatment outcome.


Bioaccumulation of polybrominated diphenyl ethers in harbor seals from the northwest Atlantic.
Polybrominated diphenyl ethers (PBDEs) were analyzed in blubber of harbor seals (Phoca vitulina concolor) collected between 1991 and 2005 along the northwest Atlantic. summation operatorPBDE concentrations (mono- to hexa-BDEs) detected in blubber samples (n=42) ranged from 80 to 25720 ng g(-1)lw, (overall mean 2403+/-5406 ng g(-1)lw). By age, mean summation operatorPBDE concentrations were: 3645+/-7388, 2945+/-5995, 1385+/-1265, and 326+/-193 ng g(-1)lw in pups, yearlings, adult males, and adult females, respectively. Unlike the trend for PCBs, no decreasing gradient from urban to rural/remote areas was observed for PBDEs in these samples, likely reflecting inputs from local sources. No significant temporal trend was observed for PBDEs in harbor seals between 1991 and 2005, although congener profiles shifted over time. Tetra-BDE-47 was the dominant congener, followed by BDEs-99, -100, -153, -154, and -155 in varying order, suggesting exposure to the penta-BDE product. In adult males, the hexa-BDEs contributed more to the total (22%) than BDEs-99 and -100 (14%), and concentrations of BDE-155 were elevated compared with -154. Higher BDEs were detected in a subset of seals (n=12) including hepta-BDE-183, the marker for the octa-BDE mixture, and octa-BDE-197, along with several unidentified hepta- and octa- congeners. BDE-209 was detected in seal blubber at concentrations ranging from 1.1 to 8 ng g(-1)lw, indicating that deca-BDE is bioavailable in this marine food web. This is the first study to document the accumulation of BDE-209 at measurable levels in wild harbor seals. While the PBDE patterns in blubber indicate exposure to all three BDE commercial mixtures, the data also suggest that BDE-209 debromination by seal prey fish may contribute to the loading of lower brominated congeners (hexa- to octa-BDEs) in these seals.


Brainstem auditory evoked potentials in syndromes of decerebration, the bulbar syndrome and in central death.
The results are reported of serial brainstem auditory evoked potentials recordings in 51 patients with decerebration and bulbar syndrome. In contrast to the stability of latencies of single components of the potential in healthy subjects, patients with decerebration syndromes show considerable instability and an increase in the latency of all the components of the potential. In 34 decerebrate patients the P-I latency and the interpeak latencies for the medullo-pontine and ponto-mesencephalic segments as well as the central conduction time were significantly increased. There was marked reduction of the amplitude of P-V and P-III and deformation of the single components of the potential with widening and smoothing. The amplitude ratios A-V to A-I and A-III to A-I were significantly decreased. The findings are interpreted as due to mesencephalic and pontine functional disturbance during decerebration. The brainstem auditory evoked potential can be used to estimate the time of brain death. Possible causes of misinterpretation are discussed.


Single cell protein and oil production from solid cocoa fatty acid distillates co-fed ethanol.
The use of solid lipid sidestreams have been overlooked as a feedstock for the production of microbial biomass for food and feed applications and little to no recent work has examined the utilization of solid fatty acid distillates (FADs), which are a significant residue from vegetable oil processing. Yarrowia lipolytica and Rhodosporidium toruloides cultivated on cocoa fatty acid distillates (CFAD) generated final cell dry weight values > 40 g/L, with strong productivity (3.3 g/L·h) and rich protein (>45%) and lipid content (>25%). Interestingly, microbial oils were > 65% unsaturated fatty acids, compared < 20% unsaturated content in FAD. Importantly, to overcome mass-transfer limitations associated with bioconversion of solid lipid residues, ethanol was applied as a co-substrate to solubilize FAD residues. Here, FAD residues from cocoa deodorization have been demonstrated to be high energy feedstocks that represent an attractive substrate for the production of both single cell protein and oil (SCPO).


Glucose induced activation of canonical Wnt signaling pathway in hepatocellular carcinoma is regulated by DKK4.
Elevated glycemic index, an important feature of diabetes is implicated in an increased risk of hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of this association are relatively less explored. Present study investigates the effect of hyperglycemia over HCC proliferation. We observed that high glucose culture condition (HG) specifically activates canonical Wnt signaling in HCC cells, which is mediated by suppression of DKK4 (a Wnt antagonist) expression and enhanced β-catenin level. Functional assays demonstrated that a normoglycemic culture condition (NG) maintains constitutive expression of DKK4, which controls HCC proliferation rate by suppressing canonical Wnt signaling pathway. HG diminishes DKK4 expression leading to loss of check at G0/G1/S phases of the cell cycle thereby enhancing HCC proliferation, in a β-catenin dependent manner. Interestingly, in NOD/SCID mice supplemented with high glucose, HepG2 xenografted tumors grew rapidly in which elevated levels of β-catenin, c-Myc and decreased levels of DKK4 were detected. Knockdown of DKK4 by shRNA promotes proliferation of HCC cells in NG, which is suppressed by treating cells exogenously with recombinant DKK4 protein. Our in vitro and in vivo results indicate an important functional role of DKK4 in glucose facilitated HCC proliferation.


Divergent reactivity of nitric oxide with metal-metal quintuple bonds.
Reactions of NO with the quintuple bonded chromium and molybdenum amidinate dimers, respectively, gave dichromium nitrosyl nitrito amidinato complexes, and the quadruple bonded dimolybdenum nitrito amidinato species with a paddlewheel configuration.


Separation and determination of degradation products of acid orange 7 by capillary electrophoresis/capacitively coupled contactless conductivity detector.
Capillary electrophoresis (CE) with capacitively coupled contactless conductivity detector (C(4)D) was developed to separate azo-dyestuff acid orange 7 (AO7) and its six degradation products. The analyzed products were sulfamic acid, oxalic acid, benzenesulfonic acid, 4-hydroxybenzene sulfonic acid, phthalic acid, and 4-aminobenzene sulfonic acid. In developing the method, types and concentrations of running buffers, injecting voltage and time, and applied voltage were tested to obtain optimum conditions to analyze target compounds. The separation was successfully achieved within 10 min using a fused-silica capillary under the following conditions: 20 mmol L(-1) acetate acid buffer, electrokinetic injection of -12 kV × 10 s, and applied voltage of -13 kV. The developed method was applied to analyze degradation products in situ during the reaction of AO7 with Fenton reagent (Fe(II)+H2O2 at pH 4.0).


Young bone marrow transplantation preserves learning and memory in old mice.
Restoration of cognitive function in old mice by transfer of blood or plasma from young mice has been attributed to reduced C-C motif chemokine ligand 11 (CCL11) and β2-microglobulin, which are thought to suppress neurogenesis in the aging brain. However, the specific role of the hematopoietic system in this rejuvenation has not been defined and the importance of neurogenesis in old mice is unclear. Here we report that transplantation of young bone marrow to rejuvenate the hematopoietic system preserved cognitive function in old recipient mice, despite irradiation-induced suppression of neurogenesis, and without reducing β2-microglobulin. Instead, young bone marrow transplantation preserved synaptic connections and reduced microglial activation in the hippocampus. Circulating CCL11 levels were lower in young bone marrow recipients, and CCL11 administration in young mice had the opposite effect, reducing synapses and increasing microglial activation. In conclusion, young blood or bone marrow may represent a future therapeutic strategy for neurodegenerative disease.


In vitro studies on potentiation of cytotoxic effects of anticancer drugs by interferon on a human neoplastic cell line (HeLa).
Experiments were performed to ascertain whether the antitumor effect of various anticancer drugs might be enhanced by interferon, using cultures of HeLa cells originating from a human carcinoma of the uterine cervix. The effects of drugs were assessed by counting cell colonies formed in culture. The drugs studied included 4 metabolic antagonists: cytosine arabinoside (Ara-C), 5-fluorouracil (5-FU), 6-mercaptopurine (6-MP) and methotrexate (MTX), 7 antibiotics: aclacinomycin (ACM), adriamycin (ADM), actinomycin D (ACD), cycloheximide, mitomycin C (MMC), peplomycin (PEP) and puromycin; 2 alkylating agents: nimustine hydrochloride (ACNU) and melphalan, and 3 other drugs, vincristine (VCR), cisplatin (CDDP) and hydroxyurea (HU). Interferon was a preparation of the beta-type produced by human fibroblasts. A specific additive or synergistic potentiation of the cytotoxic effect by concomitant application of interferon was observed with PEP, ACNU, ACM, CDDP, 5-FU and ADM; the drug concentration given a 50% inhibition of cell growth was reduced by one-half or more in cultures with the combination of interferon and these drugs. The treatment of cells with interferon alone caused only 10-30% inhibition of cell proliferation.


Inhibitory effects of hot water extract of the Stevia stem on the contractile response of the smooth muscle of the guinea pig ileum.
The effects of a hot water extract of the stem of Stevia rebaudiana on the smooth muscle of isolated guinea pig ileum were investigated. The butyl alcohol layer of the extract antagonized the contractions of the isolated guinea pig ileum induced by histamine (1 x 10(-5) M) and acetylcholine (1 x 10(-5) M) in a concentration-dependent manner. The butyl alcohol layer of the extract also showed inhibition of CaCl(2) (1 x 10(-3)-3.8 x 10(-1) M)-induced contractions. The antagonism of the extract was considered to be non-specific, but this action might be related to an influx of extracellular Ca(2+). With column chromatography preparation, the active component was assumed to be as stevioside. The antagonistic effects exerted by the stem extract of Stevia rebaudiana contributed to the gastroprotective activity of the extract in animals fed dietary histamine.


Plasmodium falciparum: administration of anti-sporozoite antibodies during sporogony results in production of sporozoites which are not neutralized by human anti-circumsporozoite protein vaccine sera.
Five days after receiving a Plasmodium falciparum NF54 infectious blood meal, Anopheles stephensi mosquitoes were fed rat anti-P, falciparum sporozoite or rabbit anti-R32tet32 antibodies. Sporozoites isolated from salivary glands were tested by the inhibition of sporozoite invasion (ISI) assay using monoclonal antibody (Mab) 2A10 to P. falciparum circumsporozoite protein or sera from human volunteers immunized with P. falciparum R32tet32 or (NANP)3-TT vaccines. Whereas sporozoites from control mosquitoes were neutralized by Mab 2A10 and vaccine sera, only the Mab and not the vaccine sera neutralized sporozoites from immune-fed mosquitoes. The implications of these results in vaccine design and the impact on transmission are discussed.


Temperature-dependent, competitive 1,3-acyl shift versus decarbonylation of a cyclopropanone intermediate.
Photooxygenation of 1,1,3-trimethyl-1,2-dihydropentalene gives an unstable endoperoxide which upon decomposition delivers a bicyclic cyclopropanone intermediate; this species either extrudes CO to give a cycloheptadienone or undergoes a 1,3-acyl shift, both processes occurring most likely in a stepwise manner via diradical intermediates. Alternatively, C3a-C4 cleavage in the dioxygen diradical derived from the endoperoxide yields a 2-cyclopropyl substituted cyclopentadienone epoxide.


[Methods for investigation and estimation of individual chemosensitivity of tumors (review)].
A review of the current methods for the estimation of tumor sensitivity to antiblastomic drugs is presented. Methods for the in vitro and in vivo cultivation of tumor cells are discussed. Among them the following methods are reviewed: the method for the cultivation of tumor heterotransplants in diffusion chambers and its various modifications, the method for the cultivation of human tumors under the kidney capsule, the method for the cell cultivation in primary short-term suspensions, the methods using enriched media, the methods for the cell cultivation on acetate cellulose fibres, in monolayers, etc.


[Neuropsychological functioning in hebephrenic patients. Comparison between visual and auditory stimuli initially projected either in one or in both cerebral hemispheres].
The performances of 14 hebephrenic patients and 14 normal subjects were studied through visual and auditory tests concerning the comparison of the number of stimuli projected either in the left, or in the right, or in both cerebral hemispheres. Schizophrenic patients were less efficient than normal subjects and, in both populations, no difference in the performances with regard to the locus of projection was observed. This suggests that information processing in schizophrenia might be deficient not only at the level of interhemispheric connections, but also in intrahemispheric functioning.