Intellectual impairment in school-age children exposed to manganese from drinking water.
Manganese is an essential nutrient, but in excess it can be a potent neurotoxicant. Despite the common occurrence of manganese in groundwater, the risks associated with this source of exposure are largely unknown. Our first aim was to assess the relations between exposure to manganese from drinking water and children's intelligence quotient (IQ). Second, we examined the relations between manganese exposures from water consumption and from the diet with children's hair manganese concentration. This cross-sectional study included 362 children 6-13 years of age living in communities supplied by groundwater. Manganese concentration was measured in home tap water (MnW) and children's hair (MnH). We estimated manganese intake from water ingestion and the diet using a food frequency questionnaire and assessed IQ with the Wechsler Abbreviated Scale of Intelligence. The median MnW in children's home tap water was 34 µg/L (range, 1-2,700 µg/L). MnH increased with manganese intake from water consumption, but not with dietary manganese intake. Higher MnW and MnH were significantly associated with lower IQ scores. A 10-fold increase in MnW was associated with a decrease of 2.4 IQ points (95% confidence interval: -3.9 to -0.9; p < 0.01), adjusting for maternal intelligence, family income, and other potential confounders. There was a 6.2-point difference in IQ between children in the lowest and highest MnW quintiles. MnW was more strongly associated with Performance IQ than Verbal IQ. The findings of this cross-sectional study suggest that exposure to manganese at levels common in groundwater is associated with intellectual impairment in children.


Tumor host relations. I. Increased plasma cortisol in tumor-bearing humans compared with patients with benign surgical diseases.
Plasma cortisol was measured by a protein binding technique in 81 patients with malignant tumors of different extent and various sites and in 82 patients with benign surgical diseases. The mean value of the tumor patients (x +/- s = 165 +/- 69 micrograms cortisol/l plasma) was increased significantly compared with the benign surgical disorders (100 +/- 45 micrograms/l). Within the group of patients with benign surgical disorders there was little variation by the type of disease (cortisol mean values given in brackets): benign breast tumors (95), gall stones (107), ulcer of the stomach and duodenum (96), hernia (78), appendicitis acuta (112), and struma (90). The results are in accordance with the hypothesis that glucocorticoids are involved in the increased protein catabolism of skeletal muscles and other signs of cachectic tumor patients.


Effects of intravenous baclofen on dorsal horn neurons of spinal cats.
Intravenous baclofen (1 mg/kg) abolished or severely attenuated the high threshold late component (but not the low threshold early component of long duration (greater than 150 msec) discharges evoked in cat dorsal horn neurons by intense transcutaneous electrical stimulation. Baclofen similarly reduced the spontaneous activities and discharges evoked by intra-arterial bradykinin in these same cells. These powerful inhibitions of dorsal horn interneurons may be the basis of baclofen's reported analgesic actions and could contribute to depression in reflex excitability of motoneurons.


Pravastatin inhibits advanced glycation end products (AGEs)-induced proximal tubular cell apoptosis and injury by reducing receptor for AGEs (RAGE) level.
Advanced glycation end products (AGEs) and their receptor (RAGE) axis play a role in diabetic nephropathy. Statins have been shown to ameliorate renal function and reduce proteinuria in patients with chronic kidney disease. However, the effects of statin on AGEs-induced tubular cell damage remain unknown. We examined here whether and how pravastatin could block the AGEs-RAGE-elicited tubular cell injury in vitro. Gene expression level was evaluated by real-time reverse-transcription polymerase chain reactions. Reactive oxygen species (ROS) generation was measured with dihydroethidium staining. Apoptosis was analyzed in an enzyme-linked immunosorbent assay. Asymmetric dimethylarginine (ADMA) expression was evaluated by immunostaining. Pravastatin dose-dependently inhibited the AGEs-induced up-regulation of RAGE mRNA level, ROS generation and apoptosis in human renal proximal tubular cells. Further, AGEs decreased mRNA level of dimethylarginine dimethylaminohydrolase-2, an enzyme that mainly degrades asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase and subsequently increased ADMA generation in tubular cells, both of which were also prevented by pravastatin. Geranylgeranyl pyrophosphate (GGPP) treatment blocked all of the effects of pravastatin on tubular cells. We found that rosuvastatin also significantly blocked the AGEs-induced increase in RAGE mRNA level and ROS generation, both of which were prevented by GGPP. Our present study suggests that pravastatin could inhibit the AGEs-induced apoptosis and ADMA generation in tubular cells by suppressing RAGE expression probably via inhibition of GGPP synthesis. Pravastatin may exert beneficial effects on tubular damage in diabetic nephropathy by blocking the AGEs-RAGE axis.


Involvement of estradiol-17beta and its membrane receptor, G protein coupled receptor 30 (GPR30) in regulation of oocyte maturation in zebrafish, Danio rario.
The orphan G protein coupled receptor, GPR30, has the characteristics of a high affinity, specific estrogen membrane receptor on Atlantic croaker oocytes and mediates estrogen inhibition of oocyte maturation in this perciform fish. In order to determine the broad applicability of these findings to other teleosts, similar experiments were conducted in a cyprinid fish, zebrafish, in the present study. GPR30 mRNA expression was detected in zebrafish oocytes but not in the ovarian follicular cells. Both spontaneous and 17, 20beta-dihyroxy-4-pregnen-3-one (DHP)-induced maturation of follicle-enclosed zebrafish oocytes was significantly decreased when they were incubated with either estradiol-17beta, or the GPR30 agonists, ICI 182 780 and tamoxifen, or with the GPR30 specific agonist G-1. On the other hand spontaneous oocyte maturation increased two-fold when zebrafish ovarian follicles were incubated with an aromatase inhibitor, ATD. Moreover, the stimulatory effects of ATD on germinal vesicle breakdown (GVBD) were partially reversed by co-treatment with 100 nM of E2 or G-1. These results suggest that endogenous estrogens acting through GPR30 are involved in maintaining meiotic arrest of zebrafish oocytes.


Enhancing biofuels production by engineering the actin cytoskeleton in Saccharomyces cerevisiae.
Saccharomyces cerevisiae is widely employed as a cell factory for the production of biofuels. However, product toxicity has hindered improvements in biofuel production. Here, we engineer the actin cytoskeleton in S. cerevisiae to increase both the cell growth and production of n-butanol and medium-chain fatty acids. Actin cable tortuosity is regulated using an n-butanol responsive promoter-based autonomous bidirectional signal conditioner in S. cerevisiae. The budding index is increased by 14.0%, resulting in the highest n-butanol titer of 1674.3 mg L-1. Moreover, actin patch density is fine-tuned using a medium-chain fatty acid responsive promoter-based autonomous bidirectional signal conditioner. The intracellular pH is stabilized at 6.4, yielding the highest medium-chain fatty acids titer of 692.3 mg L-1 in yeast extract peptone dextrose medium. Engineering the actin cytoskeleton in S. cerevisiae can efficiently alleviate biofuels toxicity and enhance biofuels production.


External Ear Disease: Keratinaceous Lesions of the External Auditory Canal.
Keratosis obturans (KO) and external auditory canal cholesteatoma (EACC) are two distinct keratinaceous lesions of the external ear. This article reviews the signs, symptoms, pathophysiology, workup, and treatment of each. Patients with either pathology can often be managed in the clinic with debridement; however, EACC is more likely to involve osteonecrosis and require more extensive operative management if disease is not confined to the canal on account of the bony erosion characteristic of cholesteatoma. If required for extensive disease, surgical approaches to both pathologies are similar.


[Hip fracture surgery in the elderly patient: epidemiological data and risk factors].
Health care administration is concerned about the escalating cost of geriatric trauma care and more specifically hip fracture (HF). By 2050, the wordwide annual incidence of HF among elderly people will be 4.5 million (predictible incidence in France: 150,000) and prevention will be more important than ever. The risk of hip fracture in older people increases exponentially with age. The main other risk factors are osteoporosis and osteopenia, gender, weight, physical activity. The most important cause of osteoporosis is the gradual bone loss that occurs after the menopause. Similarly, there is a strong association with gender: the female-to-male ratio of HF is greater than 2/1 in people over 50 years of age (mean age: 83.2 yrs in female and 79.6 yrs in male in France). One year mortality after hip fracture is remarkably high, around 20 to 30%.


Possible thermal and chemical stabilization of body-centred-cubic iron in the Earth's core.
The nature of the stable phase of iron in the Earth's solid inner core is still highly controversial. Laboratory experiments suggest the possibility of an uncharacterized phase transformation in iron at core conditions and seismological observations have indicated the possible presence of complex, inner-core layering. Theoretical studies currently suggest that the hexagonal close packed (h.c.p.) phase of iron is stable at core pressures and that the body centred cubic (b.c.c.) phase of iron becomes elastically unstable at high pressure. In other h.c.p. metals, however, a high-pressure b.c.c. form has been found to become stabilized at high temperature. We report here a quantum mechanical study of b.c.c.-iron able to model its behaviour at core temperatures as well as pressures, using ab initio molecular dynamics free-energy calculations. We find that b.c.c.-iron indeed becomes entropically stabilized at core temperatures, but in its pure state h.c.p.-iron still remains thermodynamically more favourable. The inner core, however, is not pure iron, and our calculations indicate that the b.c.c. phase will be stabilized with respect to the h.c.p. phase by sulphur or silicon impurities in the core. Consequently, a b.c.c.-structured alloy may be a strong candidate for explaining the observed seismic complexity of the inner core.


Lysine transport across rat jejunum: distribution between the transcellular and the paracellular routes.
Transport of lysine across the rat jejunum has been studied measuring transmural fluxes, Jms and Jsm, under short-circuit conditions, influx across the brush-border membrane, Jmc, under open-circuit and voltage-clamp conditions, and steady-state uptake by the isolated mucosa. 1. Jlysmc can be described as the sum of a saturable process with a Kt of 3 mM and a Jmax of 2.25 micromole/cm2.hr and a diffusional component corresponding to a lysine permeability of 0.014 cm/hr. Also Jlysms is well described as the sum of a saturable process and a diffusional contribution described by the same permeability as for Jlysmc. 2. The effects of the transmural p.d. on Jlysmc indicate that at 60 mM this flux includes a diffusional contribution, which corresponds to a lysine permeability of 0.014 cm/hr. 3. The passage of an electrical current across the gut wall changes the electrical conductance as expected for a cation-selective epithelium. The effect of a mucosa to serosa current on the Jms value of mannitol provides confirmation of the expected current effect on transepithelial volume flow. These effects on conductance and solute flux, together with the electrostatic effect on lysine movements, suffice to account for the p.d. effects on Jmc, Jms, and Jsm of lysine. 4. Jlyssm is in a saturable manner stimulated by increasing concentrations of D-glucose. At higher (10 mM) concentrations of lysine this effect leads to a net secretion of lysine. Qualitatively and quantitatively these effects are consistent with the model of a glucose-induced fluid circuit between the mucosal solution and the lateral intercellular spaces. 5. All observations are consistent with a paracellular, transepithelial pathway for lysine, which includes the lateral intercellular spaces. 6. The transport of lysine across the basolateral membrane is analysed. Togethet the data on transcellular passage of lysine are very similar to those reported for rabbit ileum, except that more than one transport process could not be demonstrated.


Multispecies resistance of cattle gastrointestinal nematodes to long-acting avermectin formulations in Mato Grosso do Sul.
The use of long-acting avermectins (AVMs) in cattle to treat infections with gastrointestinal nematodes was common in Brazil until its prohibition by state authorities. The prohibition; however, was rescinded in 2015, but a scientific discussion of the pros and cons of the use of these formulations is necessary. We evaluated the levels of resistance to 1.0 and 3.5% doramectin and to 3.15% ivermectin in cattle. The worms in animals treated with 3.5% doramectin were characterized by the suppression of oviposition and by a higher proportion of adult females carrying no eggs. Haemonchus placei, Cooperia punctata, C. pectinata, C. spatulata, and Oesophagostomum radiatum were resistant to the above compositions. The administration of long-acting AVM formulations did not result in a higher efficacy against these helminth populations.


Affected enzyme activities in Alzheimer's disease are sensitive to antemortem hypoxia.
Many enzyme activities in Alzheimer's disease (AD) are changed. Some of these enzyme activities are related to certain neurotransmitter systems. Enzymes in the brain can also be sensitive to antemortem hypoxia. In the present study it was determined if enzyme activities that are altered in AD are also subject to alteration by antemortem hypoxia. As an indicator of antemortem hypoxia brain lactate concentration was used. Enzyme activities measured were those of prolyl endopeptidase (PE), aminopeptidase (AP), phosphatidylinositol (PI) kinase, phosphatidylinositol phosphate kinase, alpha-ketoglutarate dehydrogenase (alpha-KGDH), choline acetyltransferase and beta-glucuronidase. All of these enzyme activities have been measured in AD patients before and several of them have been found to be decreased. In accordance with previous findings, PE, alpha-KGDH and ChAT activities were reduced in AD patients. PI kinase and beta-glucuronidase activities, however, were not reduced, contrary to previous findings. All enzyme activities, except that of beta-glucuronidase, correlated with brain lactate concentration, suggesting that antemortem hypoxia has a major influence on the activity of enzymes in the brain. PE, AP, alpha-KGDH and ChAT activities were still different between AD and control samples when these were matched for lactate concentration. The enzyme activities that were changed in AD were also significantly correlated with lactate concentration, an indicator of antemortem hypoxia, in brain specimens. This suggests that antemortem hypoxia and AD have some factor in common that may be responsible for changes in enzyme activities. Since both PE and alpha-KGDH are known to be sensitive to oxidative stress this factor could be oxidative stress.


Genetics of hereditary large vessel diseases.
Recent progress in the study of hereditary large vessel diseases such as Marfan syndrome (MFS) have not only identified responsible genes but also provided better understanding of the pathophysiology and revealed possible new therapeutic targets. Genes identified for these diseases include FBN1, TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3, SKI, EFEMP2, COL3A1, FLNA, ACTA2, MYH11, MYLK and SLC2A10, as well as others. Their dysfunction disrupts the function of transforming growth factor-β (TGF-β) signaling pathways, as well as that of the extracellular matrix and smooth muscle contractile apparatus, resulting in progression of structural damage to large vessels, including aortic aneurysms and dissections. Notably, it has been shown that the TGF-β signaling pathway has a key role in the pathogenesis of MFS and related disorders, which may be important for development of strategies for medical and surgical treatment of thoracic aortic aneurysms and dissections.


Retrograde axonal transport of dopamine beta hydroxylase antibodies by neurons in the trigeminal ganglion.
In this study we describe a population of neurons in the adult rat trigeminal ganglion (TG) that express dopamine beta-hydroxylase (DBH) and tyrosine hydroxylase (TH), and transport anti-DBH from their terminals. We have used NGF and NT3 labeled with biotin and anti-p75NTR labeled with FITC to examine the transport of neurotrophins and their receptors by these cells. In both the superior cervical ganglion (SCG) and the TG all neurons that transported anti-DBH transported NGF. While 100% of the DBH positive neurons in the TG also transported NT3, approximately 25% of these neurons in the SCG failed to transport NT3. In the SCG virtually all the neurons transported anti-p75NTR with the neurotrophins while in the TG more than 25% of these neurons failed to transport anti-p75NTR with the neurotrophins. These findings suggest that DBH positive neurons in the TG depend upon target-derived NGF and NT3 for their noradrenergic phenotype.


Vericiguat reduced a composite of CV death or HF hospitalization in patients with HF and reduced LVEF.
Armstrong PW, Pieske B, Anstrom KJ, et al. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med. 2020;382:1883-93. 32222134.


Electric double layer-mediated polarization field for optimizing photogenerated carrier dynamics and thermodynamics.
Photocatalytic hydrogen evolution efficiency is limited due to unfavorable carrier dynamics and thermodynamic performance. Here, we propose to introduce electronegative molecules to build an electric double layer (EDL) to generate a polarization field instead of the traditional built-in electric field to improve carrier dynamics, and optimize the thermodynamics by regulating the chemical coordination of surface atoms. Based on theoretical simulation, we designed CuNi@EDL and applied it as the cocatalyst of semiconductor photocatalysts, finally achieved a hydrogen evolution rate of 249.6 mmol h-1 g-1 and remained stable after storing under environmental conditions for more than 300 days. The high H2 yield is mainly due to the perfect work function, Fermi level and Gibbs free energy of hydrogen adsorption, improved light absorption ability, enhanced electron transfer dynamics, decreased HER overpotential and effective carrier transfer channel arose by EDL. Here, our work opens up new perspectives for the design and optimization of photosystems.


Occupational exposures in constrictive bronchiolitis.
Bronchiolitis obliterans is a clinical entity which results from a variety of etiologies and has a detrimental impact on patients' quality of life when it remains undiagnosed and untreated. Due to its non-pathognomic clinical symptoms and signs, physicians often proceed to radiological examination, especially with high resolution chest tomography. Histological examination reveals constrictive bronchiolitis, the pathological definition of bronchiolitis obliterans. Due to an almost normal aspect of the lung parenchyma this condition can be missed. However, its recognition and the identification of a possible exposure are important for removing the patient from the incriminating agent. We present a case of constrictive bronchiolitis in a metal-cutting worker, highlighting the principal findings of this disease.


S-ketamine anesthesia increases cerebral blood flow in excess of the metabolic needs in humans.
Animal studies have demonstrated neuroprotective properties of S-ketamine, but its effects on cerebral blood flow (CBF), metabolic rate of oxygen (CMRO2), and glucose metabolic rate (GMR) have not been comprehensively studied in humans. Positron emission tomography was used to quantify CBF and CMRO2 in eight healthy male volunteers awake and during S-ketamine infusion targeted to subanesthetic (150 ng/ml) and anesthetic (1,500-2,000 ng/ml) concentrations. In addition, subjects' GMRs were assessed awake and during anesthesia. Whole brain estimates for cerebral blood volume were obtained using kinetic modeling. The mean +/- SD serum S-ketamine concentration was 159 +/- 21 ng/ml at the subanesthetic and 1,959 +/- 442 ng/ml at the anesthetic levels. The total S-ketamine dose was 10.4 mg/kg. S-ketamine increased heart rate (maximally by 43.5%) and mean blood pressure (maximally by 27.0%) in a concentration-dependent manner (P = 0.001 for both). Subanesthetic S-ketamine increased whole brain CBF by 13.7% (P = 0.035). The greatest regional CBF increase was detected in the anterior cingulate (31.6%; P = 0.010). No changes were detected in CMRO2. Anesthetic S-ketamine increased whole brain CBF by 36.4% (P = 0.006) but had no effect on whole brain CMRO2 or GMR. Regionally, CBF was increased in nearly all brain structures studied (greatest increase in the insula 86.5%; P < 0.001), whereas CMRO2 increased only in the frontal cortex (by 15.7%; P = 0.007) and GMR increased only in the thalamus (by 11.7%; P = 0.010). Cerebral blood volume was increased by 51.9% (P = 0.011) during anesthesia. S-ketamine-induced CBF increases exceeded the minor changes in CMRO2 and GMR during anesthesia.


Sleep-wake dynamics pre- and post-exposure to chronic social stress.
An analytical approach combining the statistical distributions of the sleep-wake bouts and the Markov transition matrix is used to explain the under-examined association between the microarchitecture of the sleep-wake cycle and susceptibility to chronic social stress in C57BL/6J mice. We separated the sleep-wake transitions into distinct sleep-wake sequences, NREM↔Wake and NREM→REM→Wake, which are controlled by independent neural circuits. Our findings imply greater pull toward the wake leading to early termination and fragmentation of the sleep bouts in the light in both sleep-wake sequences pre- and post-stress. Moreover, the stability of NREM in the NREM↔Wake transition was lower, and the probability of transitioning to wake was higher in susceptible relative to resilient or stress-naïve mice pre- and post-stress. Our findings help elucidate the mechanistic interplay between sleep and mood by suggesting the potential neural underpinnings of sleep disturbances responsible the aberrant transitions of sleep-wake bouts exhibited by the stress-susceptible phenotype.


Stable isotopes, beaks and predators: a new tool to study the trophic ecology of cephalopods, including giant and colossal squids.
Cephalopods play a key role in the marine environment but knowledge of their feeding habits is limited by lack of data. Here, we have developed a new tool to investigate their feeding ecology by combining the use of their predators as biological samplers together with measurements of the stable isotopic signature of their beaks. Cephalopod beaks are chitinous hard structures that resist digestion and the stable isotope ratios of carbon (delta13C) and nitrogen (delta15N) are indicators of the foraging areas and trophic levels of consumers, respectively. First, a comparison of delta13C and delta15N values of different tissues from the same individuals showed that beaks were slightly enriched in 13C but highly impoverished in 15N compared with lipid-free muscle tissues. Second, beaks from the same species showed a progressive increase in their delta15N values with increasing size, which is in agreement with a dietary shift from lower to higher trophic levels during cephalopod growth. In the same way, there was an increase in the delta15N signature of various parts of the same lower beaks in the order rostrum, lateral walls and wings, which reflects the progressive growth and chitinization of the beaks in parallel with dietary changes. Third, we investigated the trophic structure of a cephalopod community for the first time. Values of delta15N indicate that cephalopods living in slope waters of the subantarctic Kerguelen Islands (n=18 species) encompass almost three distinct trophic levels, with a continuum of two levels between crustacean- and fish-eaters and a distinct higher trophic level occupied by the colossal squid Mesonychoteuthis hamiltoni. delta13C values demonstrated that cephalopods grow in three different marine ecosystems, with 16 species living and developing in Kerguelen waters and two species migrating from either Antarctica (Slosarczykovia circumantarctica) or the subtropics (the giant squid Architeuthis dux). The stable isotopic signature of beaks accumulated in predators' stomachs therefore revealed new trophic relationships and migration patterns and is a powerful tool to investigate the role of the poorly known cephalopods in the marine environment.


Microbial pathogen primary sequence inversely correlates with blood group antigen immunogenicity.
It is well known that specific groups of patients immunologically respond more readily than others to red blood cell (RBC) antigens. While allogeneic RBC antigen exposure is the primary determinant of alloantibody formation, other variables are also involved. Given the significant primary sequence identity between common RBC and microbial antigens, we hypothesized that certain individuals may be immunologically primed to form RBC alloantibodies via environmental exposure to cross-reactive microbial epitopes, and that such a correlation may be linked to blood group antigen immunogenicity. We examined the relationship between RBC-microbe peptide homology and the formation of alloantibodies to the most immunogenic RBC antigens, using the BLASTp homology database. Thirteen-residue peptides centered on the polymorphic amino acids of K, Jka , Lua , E, c, M, C, and S antigens were queried for identity with microbial peptides using the BLASTp database. Results were restricted to bacteria and fungi, with a selective threshold of >80% identity for inclusion, to allow for minor peptide variability. Significant peptide identity was found between RBC antigens and pathogenic organisms including B. fragilis, P. aeruginosa, and Candida spp., among others. Linear regression and k-medoids clustering analysis of the microbial genera meeting the inclusion criteria showed a statistically significant inverse correlation with RBC immunogenicity (b = -0.0017, r2 = 0.624 & p = 0.0197), with lower immunogenicity antigens associated with larger number of genera. Our findings raise a potential relationship between microbial exposure and alloantibody formation, and lead to interesting questions regarding the potential relationship between RBC antigen immunogenicity and microbial prevalence.


Community mental health nursing in Alberta, Canada: an oral history.
Community mental health nurses had a central role in the construction of new rehabilitative practices and community mental health services in the 1960s and 1970s. The purpose of this article is, first, to explore how nurses understood and created their new role and identity in the turbulent context of deinstitutionalization. The development of after care services for patients discharged from Alberta Hospital in Ponoka (AH-Ponoka), a large mental institution in Calgary, in the Canadian province of Alberta, will be used as a case study. I specifically focus on the establishment of outpatient services in a new psychiatric department at Foothills General Hospital in Calgary. Second, I examine how deinstitutionalization itself shaped community mental health nurses' work. Oral history interviews with nurses and other mental health professionals, who had a central role in this transformation process, provide a unique lens through which to explore this social change. The article concludes that new rehabilitative, community-based mental health services can better be understood as a transformation of former institutional practices rather than as a definite break with them.


Correlating efficacy and immunogenicity in malaria vaccine trials.
The availability of an effective and appropriately implemented malaria vaccine would form a crucial cornerstone of public health efforts to fight this disease. Despite many decades of research, however, no malaria vaccine has yet shown satisfactory protective efficacy or been rolled-out. Validated immunological substitute endpoints have the potential to accelerate clinical vaccine development by reducing the required complexity, size, duration and cost of clinical trials. Besides facilitating clinical development of existing vaccine candidates, understanding immunological mechanisms of protection may drive the development of fundamentally new vaccination approaches. In this review we focus on correlates of protection in malaria vaccine development: Does immunogenicity predict malaria vaccine efficacy and why is this question particularly difficult? Have immunological correlates accelerated malaria vaccine development in the past and will they facilitate it in the future? Does Controlled Human Malaria Infection represent a valid model for identifying such immunological correlates, or a correlate of protection against naturally-acquired malaria in itself?


Vestibular evoked myogenic potentials in patients with contralateral delayed endolymphatic hydrops.
We studied vestibular evoked myogenic potentials (VEMPs) in nine patients with unilateral profound hearing loss followed by contralateral delayed hearing fluctuation and episodic vertigo. This condition has been called contralateral delayed endolymphatic hydrops. Five of nine ears with profound hearing loss (56%) showed an absence of VEMPs. One ear (11%) showed decreased responses, and three ears (33%) had normal responses. Of the ears with fluctuation of hearing, six (67%) showed an absence of responses, and three ears (33%) showed normal responses. In four patients we recorded VEMPs before and after oral administration of glycerol. Three hours after glycerol administration, two of four ears with fluctuating hearing loss showed the appearance of VEMPs although there was an absence of VEMPs before glycerol administration. These results suggested that saccular dysfunction could exist not only in the ears with profound hearing loss but also in ears with fluctuating hearing loss and that saccular endolymphatic hydrops could exist in the ears with fluctuating hearing loss. "Contralateral delayed endolymphatic hydrops" might be an appropriate term.


Central Autonomic Network Regions and Hypertension: Unveiling Sympathetic Activation and Genetic Therapeutic Perspectives.
Hypertension, a leading cause of death, was investigated in this study to understand the role of specific brain regions in regulating blood pressure. The lateral parabrachial nucleus (LPBN), Kolliker-fuse nucleus (KF), and periductal grey matter (PAG) were examined for their involvement in hypertension. Lentiviral vectors were used to alter the activity of these brain regions in hypertensive rats. Over a 75-day period, blood pressure, heart rate, reflex responses, and heart rate variability were measured. Decreasing the activity in the LPBN resulted in a reduced sympathetic outflow, lowering the blood pressure and heart rate. In the KF, the sympathetic activity decreased and chemoreflex variation was attenuated, without affecting the blood pressure. Silencing the PAG had no significant impact on blood pressure or sympathetic tone, but decreased cardiac baroreflex gain. These findings highlight the significant role of the LPBN in hypertension-related sympathetic activation. Additionally, LPBN and KF neurons appear to activate mechanisms that control respiration and sympathetic outflow during chemoreceptor activation. The study provided insights into the contribution of the midbrain and pontine regions to neurogenic hypertension and offers potential avenues for future genetic interventions and developing novel treatment approaches.


Ontario score and cardiac risk during waiting for elective coronary bypass grafting.
Waiting lists for coronary bypass grafting are of major concern in several countries and prioritisation systems to the surgery have been proposed. The aim of this study was to verify the adequacy of Ontario score in predicting cardiac events during the waiting for elective coronary bypass grafting. A composite end-point (sudden or cardiac death, myocardial infarction, unstable angina or hospital admission) and sudden, cardiac death were analysed in 460 patients referred to the surgery. The relation between Ontario score and events was verified. Median waiting time was 126 days. The composite end-point and sudden, cardiac death occurred in 21.7% and 2.7% of the cases, respectively. In relation to Ontario score > or = 6.00, considered the lower-risk subset, only patients in score <4.00 (7.2% of whole study population) presented a higher chance of the composite end-point during the waiting. ROC curve did not show adequate accuracy of Ontario score in predicting the composite end-point (area under the curve 0.53, p = 0.36). Ontario score could not predict the risk of death. Total complications and death occurred within acceptable waiting times by Ontario recommendation in 47.8% and 36.4% of the cases, respectively. Waiting longer than maximum wait defined by Ontario was not associated with an excess of complications. Ontario score showed a limited value in predicting cardiac events during the waiting for elective coronary bypass grafting. The results emphasise the need for shortening the wait in order to reduce complications in the period.


Interrelationship of thermal and sleep-wakefulness changes elicited from the medial preoptic area in rats.
The study investigated the possible interrelationship between changes in sleep-wakefulness and body temperature, primarily induced by manipulation of the noradrenergic system in the medial preoptic area. Saline, norepinephrine, and its alpha- and beta-blockers were injected in the medial preoptic area and in some control areas of rats, during their sleeping and active periods. 5-Hydroxytryptamine was injected in the medial preoptic area in another group of animals. Simultaneous changes in sleep-wakefulness and the body temperature were continuously recorded. Norepinephrine produced hypothermia and arousal, whereas alpha-adrenergic blockers induced hyperthermia and sleep. These changes in body temperature and in sleep-wakefulness did not follow an identical time course. 5-Hydroxytryptamine induced hyperthermia without affecting sleep-wakefulness. It is suggested that there are different neuronal mechanisms in the medial preoptic area that bring about the drug-induced changes in temperature and sleep-wakefulness.


Response of bacterial community in composition and function to the various DOM at river confluences in the urban area.
River confluences result in mixture and transformation of dissolved organic matter (DOM), influencing the phylogeny of microbial community, furthermore, the integrity and function of river systems. The relationship between the microbial community and DOM is complex, especially in the confluence zone. Previous reports focused on shifts in the different bacterial community in response to exposure to the same terrestrial DOM. However, the transformation of bacterial community induced by convergent DOM remains unknown. This study showed the shifts of DOM components at the junction via excitation-emission matrices parallel factor analysis. Metabolic differences were also determined via phylogenetic investigation of communities by reconstruction of unobserved states. The results demonstrated a direct link between the microbial metabolism and DOM biodegradation during the heterotrophic process. In response to diverse DOM conditions, the taxonomic composition and metabolic function of the microbial community presented significant differences. Different taxa may be involved in metabolizing various DOM components. As indicative bacteria that are closely associated with DOM components, Proteobacteria (Sphingomonas) are significant for microbial utilization and were important during the DOM-degrading process. Compared with other conditions, the abundance of carbon metabolism was higher in convergences where urban rivers joined with estuary or source water. Furthermore, humic-like DOM, converging in the confluence zone, induced a more active lipid metabolism. This study applied techniques that capture the diversity and complexity of bacterial communities and DOM, and provides new insight on the basis of the interaction between bacterial communities and DOM in confluence processes of biogeochemical significance.


Sustainability transition for Indian agriculture.
Farming in India faces a sustainability challenge due to its overreliance on chemical inputs. For every US$ 1,000 investment in sustainable farming, a US$ 100,000 subsidy is allocated for chemical fertilizers. Indian farming system is far off the optimal nitrogen efficiency, calling for substantial reforms in policy towards the transition to sustainable inputs. We examine the propensity of Indian farmers to adopt biofertilizers and other sustainable inputs. While small farmers are inclined towards chemical inputs, sustainable inputs are costly. Here we show that less than 5 per cent of the farming population contributes to the 95 per cent usage of the bio-fertilizer in India. However, small and marginal farmers contribute substantially to food security. Shifting from chemical to sustainable inputs calls for autonomous investment by the state to augment the capacity and improve affordability. We illustrate the transition to sustainability through a framework that includes scale, affordability, and sustainable inputs.


Monoclonal nonspecific suppressor factor beta inhibits interleukin-4 secretion by a type-2 helper T cell clone.
Monoclonal nonspecific suppressor factor (MNSF) is a lymphokine product of a murine T cell hybridoma that inhibits the generation of lipopolysaccharide-induced immunoglobulin secreting cells in an antigen-nonspecific manner. Most recently, a cDNA clone encoding MNSF beta, a subunit of MNSF, was isolated and sequenced (Nakamura et al., Proc. Natl. Acad. Sci. USA 1995. 92: 3463). The MNSF beta cDNA encodes a 14.5-kDa ubiquitin-like protein showing several MNSF activities. We have previously observed that hybridoma-derived native MNSF can inhibit interleukin (IL)-4 secretion by bone marrow-derived mast cells. Therefore, we studied whether MNSF beta is also able to inhibit IL-4 secretion by the type-2 helper T cell clone D10. G4.1. MNSF beta inhibited both the IL-4 secretion and the proliferation of concanavalin A-activated D10 cells, although neither effect was complete.


Associations of Nut Consumption with All-Cause Mortality among Individuals with Type 2 Diabetes.
Nuts are energy-dense, high-fat foods, and whether nut consumption influences mortality risk among individuals with type 2 diabetes (T2D) remains unclear. This study aimed to investigate the associations of nut consumption with all-cause mortality among adults with T2D and to further explore the potential mediation effects of cardiometabolic biomarkers. The current analysis included 5090 US participants with T2D from the National Health and Nutrition Examination Survey (1999-2014). Cox proportional hazards models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI). After 35,632 person-y of follow-up, 1174 deaths were documented. Higher nut consumption was significantly associated with a lower risk of all-cause mortality among individuals with T2D. After multivariable adjustment including lifestyles and dietary factors, diabetes duration, and glycated hemoglobin, compared with participants who did not consume nuts, the HR (95% CI) for those who consumed nuts over 3.5 ounce equivalent (oz.eq)/wk was 0.64 (0.50, 0.82; P-trend < 0.001) for all-cause mortality. A linear dose-response relationship was observed between nut consumption and all-cause mortality among individuals with T2D (Poverall=0.004, Pnonlinearity=0.35). In substitution analyses, replacing one serving of red and processed meat, refined grains, eggs, and dairy foods with one serving of nuts was associated with a 18% to 22% lower risk of all-cause mortality. In addition, mediation analysis suggested that C-reactive protein and γ-glutamine transaminase explained 6.7% and 9.1% of the relationship between nut consumption with all-cause mortality, respectively. Higher nut consumption was significantly associated with lower all-cause mortality among individuals with T2D. These findings indicate a potential benefit of nut consumption in the prevention of premature death among individuals with T2D.


Continuous regional anaesthesia in infants.
Physiological immaturity of the respiratory musculature and central respiratory control centres leads to an increased risk of apnoea and respiratory complications following general anaesthesia in neonates. Regional anaesthetic techniques may obviate the need for general anaesthesia and lessen the risks of perioperative morbidity. Although these techniques have been described in infants, previous reports have dealt with single-shot techniques for brief surgical procedures (< 60 min). Experience with prolonged operative cases using regional anaesthesia via indwelling catheters in infants is limited. We present our experience with four infants in whom either caudal epidural or spinal anaesthesia was administered via indwelling catheters for operative procedures that lasted 90 to 180 min. We believe this technique is an alternative to general anaesthesia in these patients.


Phase I-II study of intraoperative radiation therapy (IORT) after radical prostatectomy for prostate cancer.
Recent studies have suggested an alpha/beta ratio in prostate cancer of 1.5-3 Gy, which is lower than that assumed for late-responsive normal tissues. Therefore the administration of a single, intraoperative dose of irradiation should represent a convenient irradiation modality in prostate cancer. Between February 2002 and June 2004, 34 patients with localized prostate cancer with only one risk factor (Gleason score > or =7, Clinical Stage [cT] > or =2c, or prostate-specific antigen [PSA] of 11-20 ng/mL) and without clinical evidence of lymph node metastases were treated with radical prostatectomy (RP) and intraoperative radiotherapy on the tumor bed. A dose-finding procedure based on the Fibonacci method was employed. Dose levels of 16, 18, and 20 Gy were selected, which are biologically equivalent to total doses of about 60-80 Gy administered with conventional fractionation, using an alpha/beta ratio value of 3. At a median follow-up of 41 months, 24 (71%) patients were alive with an undetectable PSA value. No patients died from disease, whereas 2 patients died from other malignancies. Locoregional failures were detected in 3 (9%) patients, 2 in the prostate bed and 1 in the common iliac node chain outside the radiation field. A PSA rise without local or distant disease was observed in 7 (21%) cases. The overall 3-year biochemical progression-free survival rate was 77.3%. Our dose-finding study demonstrated the feasibility of intraoperative radiotherapy in prostate cancer also at the highest administered dose.


Ethical challenges of seclusion in psychiatric inpatient wards: a qualitative study of the experiences of Norwegian mental health professionals.
Seclusion is an invasive clinical intervention used in inpatient psychiatric wards as a continuation of milieu therapy with vast behavioural implications that raise many ethical challenges. Seclusion is in Norway defined as an intervention used to contain the patient, accompanied by staff, in a single room, a separate unit, or an area inside the ward. Isolation is defined as the short-term confinement of a patient behind a locked or closed door with no staff present. Few studies examine how staff experiences the ethical challenges they encounter during seclusion. By making these challenges explicit and reflecting upon them, we may be able to provide better care to patients. The aim of this study is to examine how clinical staff in psychiatric inpatient wards describes and assess the ethical challenges of seclusion. This study was based on 149 detailed written descriptions of episodes of seclusion from 57 psychiatric wards. A descriptive and exploratory approach was used. Data were analysed using qualitative content analysis. The main finding is that the relationship between treatment and control during seclusion presents several ethical challenges. This is reflected in the balance between the staff's sincere desire to provide good treatment and the patients' behaviour that makes control necessary. Particularly, the findings show how taking control of the patient can be ethically challenging and burdensome and that working under such conditions may result in psychosocial strain on the staff. The findings are discussed according to four core ethical principles: autonomy, beneficence, non-maleficence, and justice. Ethical challenges seem to be at the core of the seclusion practice. Systematic ethical reflections are one way to process the ethical challenges that staff encounters. More knowledge is needed concerning the ethical dimensions of seclusion and alternatives to seclusion, including what ethical consequences the psychosocial stress of working with seclusion have for staff.


Stage A versus stage B adenocarcinoma of the prostate: morphological comparison and biological significance.
Morphological features in radical prostatectomy specimens from 11 stage A and 73 stage B prostatic carcinomas were compared by mapping of tumor locations, and determinations of cancer volumes and histological patterns. Small stage A cancers were located anteromedially, while small stage B carcinomas were concentrated against the posterior capsule at the rectal surface. Small stage A carcinomas commonly invaded the anterior fibromuscular stroma and benign prostatic hyperplasia nodules, features that were uncommon even in large stage B tumors. Stage A cancers often appeared to arise within benign prostatic hyperplasia nodules and had a distinctive histological appearance. Even when large, stage A carcinomas tended not to spread close to the rectal surface of the gland. Stages A and B cancers spanned a roughly comparable volume range, and both showed progressive dedifferentiation with increasing volume. It is proposed that stages A and B cancers are biologically similar malignancies, distinguished only by their site of origin. Prognosis for patients with stage A carcinoma probably is closely related to tumor volume and dedifferentiation, features that are not reliably estimated in tissue samples removed at operation for benign prostatic hyperplasia.


Prevalence of depressive and anxiety symptoms and their relationship with life-threatening events, tobacco dependence and hazardous alcohol drinking: a population-based study in the Brazilian Amazon.
The burden of mental health disorders is high and may be particularly alarming in developing countries. We assessed the prevalence of depressive and anxiety symptoms and their relationship with life-threatening events, tobacco dependence, and hazardous alcohol drinking in the Brazilian Amazon. Cross-sectional population-based study conducted in Manaus in 2019 with adults selected by probabilistic sampling. Depressive symptoms were measured by the PHQ-9 instrument (cut-off ≥9) and anxiety symptoms by the GAD-7 scale (cut-off ≥10). Prevalence ratios (PRs) of depressive and anxiety symptoms were calculated by Poisson regression with robust variance with 95% confidence intervals (CI) following a hierarchical model. Partial least squares structural equation modeling was used to investigate the relationship between the outcomes and risk behaviors. Out of the 2,321 participants, 24.3% (95%CI 22.2-26.5%) had depressive and 21.6% (95%CI 19.6-23.7%) had anxiety symptoms. Depressive symptoms were more frequent in women (PR=1.32; 95%CI 1.08-1.61), lower social class (PR=1.59; 95%CI 1.11-2.27), life-threatening events (PR=2.66; 95%CI 2.00-3.54), tobacco dependence (PR=1.84; 95%CI 1.37-2.47), worse health statuses (p<0.001), and chronic diseases (PR=1.63; 95%CI 1.33-2.00), but were lower in older adults (p=0.014). Anxiety symptoms were higher in women (PR=1.74; 95%CI 1.42-2.14), lower educational levels (PR=2.19; 95%CI 1.38-3.47), evangelical individuals (PR=1.28; 95%CI 1.05-1.57), having no religion (PR=1.72; 95%CI 1.24-2.38), life-threatening events (PR=3.26; 95%CI 2.41-4.41), tobacco dependence (PR=1.53; 95%CI 1.09-2.16), worse health statuses (p<0.001), and chronic diseases (PR=1.77; 95%CI 1.40-2.25). Depressive symptoms, anxiety symptoms, and life-threatening events were directly correlated with one another, while tobacco dependence and hazardous alcohol drinking were significantly intercorrelated (p<0.05). Cross-sectional design limits the assessment of causality. Recall bias was possible as responses were self-reported. GAD-7 scale was not validated in the Brazilian population. Nearly a quarter of the population had depressive symptoms and one-fifth presented anxiety symptoms, which were associated with socioeconomic, behavioral, and health-related factors. Implementation of social well-being policies is required to minimize the burden of mental health disorders in the Amazonian population.


Long-term effects of the Dutch Schoolgruiten Project--promoting fruit and vegetable consumption among primary-school children.
To evaluate the long-term effects of the Schoolgruiten Project, a Dutch primary school-based intervention providing free fruit and vegetables (F&V). In addition, we assessed whether children's appreciation of the project mediated these intervention effects. Participating schoolchildren (mean age 9.9 years at baseline) and their parents completed parallel questionnaires at baseline, at 1-year and at 2-year follow-up, including questions on usual F&V intake of the child, potential behavioural determinants, their appreciation of the project and general demographics. Primary outcomes were usual F&V intakes as assessed by parent and child self-reported food frequency measures. Secondary outcome measures were taste preference, knowledge of daily recommendations, availability and accessibility for fruit intake. Multilevel linear regression analyses were used to assess differences at second follow-up adjusted for baseline values between control and intervention groups. Reports were available for 346 intervention children (148 parents) and 425 control children (287 parents). Both child and parent reports indicated that the intervention group had a significantly higher fruit intake at 2-year follow-up (difference, servings/d: 0.15; 95 % CI 0.004, 0.286 for child reports; 0.19; 95 % CI 0.030, 0.340 for parent reports). No significant effects on vegetable intake were observed. Significant positive intervention effects were also found for knowledge of fruit recommendations among boys. Some evidence was found for partial mediation analyses of the effects on fruit intake. The present study indicates that the Schoolgruiten scheme was effective in increasing children's fruit intake and that appreciation of the project partially mediated this effect.


Experimental study of small intraocular lenses using an eye model.
Contrast and glare tests were performed on small intraocular lenses (IOLs) using a new eye model, which was based on and about the same size as the Gullstrand eye model. Lenses with a small optic diameter were inserted and retinal images were observed under the operating microscope. Contrast and glare disability tests were done using the MCT-8000 contrast tester and the Miller-Nadler glare tester. No effect on contrast sensitivity attributable to glare was observed, but under severe glare light conditions a faint reflection around the circumference of the optic was found. Questionnaires from patients implanted with small optic IOLs confirmed that this phenomenon was similar to their symptoms.


Impact of root hairs on microscale soil physical properties in the field.
Recent laboratory studies revealed that root hairs may alter soil physical behaviour, influencing soil porosity and water retention on the small scale. However, the results are not consistent, and it is not known if structural changes at the small-scale have impacts at larger scales. Therefore, we evaluated the potential effects of root hairs on soil hydro-mechanical properties in the field using rhizosphere-scale physical measurements. Changes in soil water retention properties as well as mechanical and hydraulic characteristics were monitored in both silt loam and sandy loam soils. Measurements were taken from plant establishment to harvesting in field trials, comparing three barley genotypes representing distinct phenotypic categories in relation to root hair length. Soil hardness and elasticity were measured using a 3-mm-diameter spherical indenter, while water sorptivity and repellency were measured using a miniaturized infiltrometer with a 0.4-mm tip radius. Over the growing season, plants induced changes in the soil water retention properties, with the plant available water increasing by 21%. Both soil hardness (P = 0.031) and elasticity (P = 0.048) decreased significantly in the presence of root hairs in silt loam soil, by 50% and 36%, respectively. Root hairs also led to significantly smaller water repellency (P = 0.007) in sandy loam soil vegetated with the hairy genotype (-49%) compared to the hairless mutant. Breeding of cash crops for improved soil conditions could be achieved by selecting root phenotypes that ameliorate soil physical properties and therefore contribute to increased soil health. The online version contains supplementary material available at 10.1007/s11104-022-05530-1.


Daily activity timing in the Anthropocene.
Animals are facing novel 'timescapes' in which the stimuli entraining their daily activity patterns no longer match historical conditions due to anthropogenic disturbance. However, the ecological effects (e.g., altered physiology, species interactions) of novel activity timing are virtually unknown. We reviewed 1328 studies and found relatively few focusing on anthropogenic effects on activity timing. We suggest three hypotheses to stimulate future research: (i) activity-timing mismatches determine ecological effects, (ii) duration and timing of timescape modification influence effects, and (iii) consequences of altered activity timing vary biogeographically due to broad-scale variation in factors compressing timescapes. The continued growth of sampling technologies promises to facilitate the study of the consequences of altered activity timing, with emerging applications for biodiversity conservation.


Anti-inflammatory effects of brucea javanica oil via inhibition of NF-κB activation.
As a traditional herbal medicine extracted from the seeds of Brucea javanica, Brucea javanica oil (BJO) has been clinically used to treat wart, chronic gastroenteritis and a variety of malignant tumors, including gastrointestinal cancer and lung cancer. We have recently reported the anti-tumor role and possible molecular mechanisms of BJO in treatment of lung cancer. However, it remains elusive whether BJO also has an anti-inflammatory effect. The pneumonia-related inflammatory factors of macrophages under LPS treatment were investigated by real-time PCR and ELISA assays. LPS-induced acute pneumonia rat model was established. Hematoxylin and eosin (HE) examination was performed to detect histopathological changes in the lung tissues. Real-time PCR and ELISA assays were also used to detect the pneumonia-related inflammatory factors in lung tissues. LPS-induced expression and secretion of pneumonia-related inflammatory factors (TNF-α, IL-1β, IL-6 and IL-8) were significantly suppressed by BJO in a concentration-dependent manner in RAW264.7 cells. However, BJO did not affect cell proliferation and survival rate. Further mechanistic studies revealed that BJO down-regulated the phosphorylation of IκB and p65, thereby inhibiting NF-κB pathway of macrophages and exerting its anti-inflammatory function. Western blot analysis showed that the phosphorylation levels of IκB and p65 were significantly up-regulated while the protein level of IκB was inhibited upon LPS stimulation in RAW264.7 cells and in lung tissue. Notably, LPS stimulation levels of IκB and p65 were effectively reversed under BJO co-treatment. The expression level of p65 was not influenced by LPS and BJO treatment. HE staining results showed that BJO can reduce the infiltration of inflammatory cells in lung. BJO can reduce the level of inflammatory factors in lung tissue, which provides a theoretical basis for BJO emulsion as an adjuvant therapy for pneumonia.


Use of the triglyceride to HDL cholesterol ratio for assessing insulin sensitivity in overweight and obese children in rural Appalachia.
Studies have suggested that triglyceride to HDL-cholesterol ratio (TRG/HDL) is a surrogate marker of insulin resistance (IR), but information regarding its use in pediatric patients is limited. This study investigated the ability of TRG/HDL ratio to assess IR in obese and overweight children. The sample consisted of de-identified electronic medical records of patients aged 10-17 years (n=223). Logistic regression was performed using TRG/HDL ratio as a predictor of hyperinsulinemia or IR defined using homeostasis model assessment score. TRG/HDL ratio had limited ability to predict hyperinsulinemia (AUROC 0.71) or IR (AUROC 0.72). Although females had higher insulin levels, male patients were significantly more likely to have hypertriglyceridemia and impaired fasting glucose. TRG/HDL ratio was not adequate for predicting IR in this population. Gender differences in the development of obesity-related metabolic abnormalities may impact the choice of screening studies in pediatric patients.


Development and validation of an analytical method for the separation and determination of major bioactive curcuminoids in Curcuma longa rhizomes and herbal products using non-aqueous capillary electrophoresis.
A simple, fast and efficient non-aqueous capillary electrophoresis method (NACE) was developed for the simultaneous determination of three major bioactive curcuminoids (CMNs) in Curcuma longa rhizomes and its herbal products. Good separation, resolution and reproducibility were achieved with the background electrolyte (BGE) consisting a mixture of 15.0 mM sodium tetraborate and 7.4 mM sodium hydroxide (NaOH) in 2:10:15 (v/v/v) of water, 1-propanol, and methanol. The influences of background electrolyte, sodium hydroxide, water, sodium dodecyl sulfate and hydroxylpropyl-β-cyclodextrin on separations were investigated. The separation was carried out in a fused-silica capillary tube with reverse polarity. Hydrodynamic injection of 25mbar for 12s was used for injecting samples and a voltage of 28 kV was applied for separation. The ultrasonication method was used for the extraction of CMNs from the turmeric herbal products and the extract was filtered and directly injected without any further treatments. The limits of detection and quantification were less than 5.0 and 14.6 µg/ml respectively for all CMNs. The percentage recoveries for CMNs were >97.2% (%RSD, <2.62). The results obtained by the method were compared with existing spectrophotometric and HPLC methods. The related compounds in the extract did not interfere in the determination of CMNs. The proposed NACE method is better than existing chromatographic and electrophoretic methods in terms of simple electrophoretic medium, fast analysis and good resolution.


Relationship between plasma clozapine/N-desmethylclozapine and changes in basal forebrain-dorsolateral prefrontal cortex coupling in treatment-resistant schizophrenia.
Clozapine (CLZ) demonstrates a unique clinical efficacy relative to other antipsychotic drugs. Previous work has linked the plasma ratio of CLZ and its major metabolite, N-desmethylclozapine (NDMC), to an inverse relationship with cognition via putative action on the cholinergic system. However, neuroimaging correlates of CLZ/NDMC remain unknown. Here, we examined changes in basal forebrain functional connectivity with the dorsolateral prefrontal cortex, and secondly, cognition in relation to the CLZ/NDMC ratio. A cohort of nineteen chronically ill participants with treatment-resistant schizophrenia (TRS) undergoing 12 weeks of CLZ treatment were included. Measures of cognition and plasma CLZ/NDMC ratios were obtained in addition to resting-state functional neuroimaging scans, captured at baseline and after 12 weeks of CLZ treatment. We observed a significant correlation between basal forebrain-DLPFC connectivity and CLZ/NDMC ratios across CLZ treatment (p = 0.02). Consistent with previous findings, we also demonstrate a positive relationship between CLZ/NDMC ratio and working memory (p = 0.03). These findings may reflect the action of CLZ and NDMC on the muscarinic cholinergic system, highlighting a possible neural correlate of cognition across treatment.


Survival and process outgrowth of human iPSC-derived cells expressing Purkinje cell markers in a mouse model for spinocerebellar degenerative disease.
Purkinje cells are the sole output neurons of the cerebellar cortex and play central roles in the integration of cerebellum-related motor coordination and memory. The loss or dysfunction of Purkinje cells due to cerebellar atrophy leads to severe ataxia. Here we used in vivo transplantation to examine the function of human iPS cell-derived cerebellar progenitors in adult transgenic mice in which Purkinje-specific cell death occurs due to cytotoxicity of polyglutamines. Transplantation using cerebellar organoids (42-48 days in culture), which are rich in neural progenitors, showed a viability of >50% 4 weeks after transplantation. STEM121+ grafted cells extended their processes toward the deep cerebellar nuclei, superior cerebellar peduncle, and vestibulocerebellar nuclei. The transplanted cells were mostly located in the white matter, and they were not found in the Purkinje cell layer. MAP2-positive fibers seen in the molecular layer of cerebellar cortex received VGluT2 inputs from climbing fibers. Transplanted neural progenitors overgrew in the host cerebellum but were suppressed by pretreatment with the γ-secretase inhibitor DAPT. Hyperproliferation was also suppressed by transplantation with more differentiated organoids (86 days in culture) or KIRREL2-positive cells purified by FACS sorting. Transplanted cells expressed Purkinje cell markers, GABA, CALB1 and L7, though they did not show fan-shaped morphology. We attempted to improve neuronal integration of stem cell-derived cerebellar progenitors by transplantation into the adult mouse, but this was not successfully achieved. Our findings in the present study contribute to regenerative medical application for cerebellar degeneration and provide new insights into cerebellar development in future.


Environment-oriented low-cost porous mullite ceramic membrane supports fabricated from coal gangue and bauxite.
Porous mullite ceramic supports for filtration membrane were successfully fabricated via recycling of coal gangue and bauxite at sintering temperatures from 1100 to 1500°C with corn starch as pore-forming agent. The dynamic sintering behaviors, phase evolution, shrinkage, porosity and pore size, gas permeation flux, microstructure and mechanical property were systematically studied. A unique volume-expansion stage was observed at increased temperatures from 1276 to 1481°C caused by a mullitization-crystal-growth process. During this stage, open porosity increases and pore size distributions broaden, which result in a maximum of nitrogen gas flux at 1400°C. The X-ray diffraction results reveal that secondary mullitization took place from 1100°C and the major phase is mullite with a content of ∼84.7wt.% at 1400°C. SEM images show that the as-fabricated mullite supports have a porous microstructure composed of sintered glassy particles embedded with inter-locked mullite crystals, which grew gradually with increasing temperature from rod-like into blocky-like morphologies. To obtain mullite membrane supports with sufficient porosity and acceptable mechanical strength, the relationship between porosity and mechanical strength was investigated, which was fitted using a parabolic equation.


The purification and preliminary X-ray diffraction studies of recombinant Synechococcus ribulose-1,5-bisphosphate carboxylase/oxygenase from Escherichia coli.
X-ray crystallographic diffraction data has been collected for recombinant hexadecameric ribulose-P2 carboxylase from the cyanobacterium Synechococcus PCC6301 expressed in Escherichia coli. The enzyme has been purified and then crystallized in a number of crystal forms from polyethylene glycol solutions. The best crystals were obtained with enzyme that was first activated with the cofactors CO2 and Mg2+ in the presence of the tight-binding intermediate analogue, 2'-carboxyarabinitol 1,5-bisphosphate. One crystal form with plate-like morphology diffracts beyond 2.5 A but has one axis greater than 350 A. A second crystal form that diffracts to similar resolution grows with space group P212121 and unit cell dimensions of a = 223.9 A, b = 111.9 A, and c = 199.7 A. The crystal forms used to collect the diffraction data have been redissolved to determine that the recombinant ribulose-P2 carboxylase L8S8 molecule is indeed composed of equal numbers of large and small subunits and also that a quaternary complex between activated ribulose-P2 carboxylase E.CO2.Mg2+, and the analogue was present in the crystals. Denaturation of the redissolved enzyme in the absence of thiol-reducing agents established that the L-subunits of the L8 core are substantially dimeric, cross-linked by a disulfide bridge. Crystals of spinach ribulose-P2 carboxylase were likewise analyzed to show that dimers of the L-subunit were also predominant. This report identifies a single cysteine residue in the L-subunit that forms a bridge between those L-monomers that compose the four putative functional dimers of the L8 core.


Monodisperse conducting colloidal dipoles with symmetric dimer structure for enhancing electrorheology properties.
This study introduces an electrorheological (ER) approach that allows us to obtain remarkably enhanced ER properties by using monodisperse colloidal dimer particles. Two sets of colloidal particles, which are spheres and symmetric dimers, were synthesized employing the seeded polymerization technique. The aspect ratio of dimer particles was ~1.43. Then, the surface of the particles was coated with polyaniline by using the chemically oxidative polymerization method. After preparation of the particle suspensions having the same particle volume and concentration, their ER behavior was investigated with changing the electric field strength. At the same experimental condition, both shear stress and shear yield stress of the dimer particle suspension remarkably increased, compared with those of the spherical particle suspension. This attributes to the fact that the shape anisotropy of suspending particles effectively led to increase in the dipole moment under the electric field, thus resulting in formation of a well-structured colloidal chains between the electrodes.


Retraction.
Zhao Y, Liu C, Zhang X, Yan X. Angelica polysaccharide alleviates TNF-α-induced MIN6 cell damage a through the up-regulation microRNA-143. BioFactors. 2022;49:200. https://doi.org/10.1002/biof.1588 This article, published online on 20 November 2019 in Wiley Online Library, has been retracted by agreement between the International Union of Biochemistry and Molecular Biology, the Editor in Chief (Dr. Angelo Azzi), and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Evidence for image manipulation was found in figures 1, 2, 4, and 5. As a result, the conclusions of this article are considered to be invalid.


Community Engagement: How to Form Authentic Partnerships for Lasting Change.
Pediatricians play a critical role in promoting child health through community engagement, yet the skills required to be effective leaders and advocates alongside the community are often not the focus of traditional medical training. The American Academy of Pediatrics Community Pediatrics Training Initiative provides faculty and resident training, curricula, and collaboratives to teach the core skills needed for upstream interventions that can affect the entire population of a community. Core skills include community assessment and competence, composed of data, observational, and experiential components. The work of community action begins to effect system-level change for sustainable, impactful improvements in child health.


Structure and characterization of the gene cluster of the O-antigen of Escherichia coli O49 containing 4,6-dideoxy-4-[(S)-3-hydroxybutanoylamino]-D-glucose.
An O-polysaccharide was isolated by mild acid degradation of the lipopolysaccharide of enteropathogenic Escherichia coli O49 and studied by sugar analysis along with one- and two-dimensional 1H- and 13C-NMR spectroscopy. The following structure of the linear tetrasaccharide repeating unit of the O-polysaccharide was established: [formula], where D-Qui4N(S3HOBut) stands for 4,6-dideoxy-4-[(S)-3-hydroxybutanoylamino]-D-glucose and O-acetylation of GlcNAc is partial (~30%). To our knowledge, no N-(3-hydroxybutanoyl) derivative of Qui4N has been hitherto found in bacterial polysaccharides. Gene functions of the O-antigen gene cluster of E. coli O49 were assigned by bioinformatics analysis and found to correspond to the O-polysaccharide structure. Two new genes were revealed and suggested to be responsible for synthesis and transfer of the 3-hydroxybutanoyl group.


The effect of cyclosporine on immunization with tetanus and keyhole limpet hemocyanin (KLH) in humans.
Eleven patients with chronic uveitis treated with Cyclosporine were immunized with keyhole limpet hemocyanin (KLH) and tetanus toxoid. Delayed cutaneous hypersensitivity responses, lymphocyte blastogenic responses, and antibody production were compared with those of similarly immunized control individuals. A significant decrease in delayed cutaneous hypersensitivity (P less than 0.001 for KLH and P less than 0.01 for tetanus toxoid) was observed. No significant differences in blastogenic or antibody responses were noted. These findings demonstrate that the majority of the Cyclosporine-treated patients had intact T cell-dependent antigen responses as measured by both proliferative response and antibody production to primary and secondary antigenic challenges but that other immune functions such as delayed cutaneous hypersensitivity are affected by therapeutic doses of systemic Cyclosporine.


Association of a transcobalamin II genetic variant with falsely low results for the holotranscobalamin immunoassay.
The clinical use of holotranscobalamin (holoTC) testing to evaluate vitamin B12 status has increased in recent years. We present two patients (African Caribbean and Indian heritage), in which the holoTC assay indicated severe B12 deficiency (< 5 pmol/L). Additional clinical tests revealed that these patients had normal levels of total vitamin B12 in blood and unremarkable levels of two other markers of vitamin B12 status, homocysteine and methylmalonic acid. We hypothesized that these patients carry a variant in the transcobalamin gene (TCN2) that influences the most widely commercially available holoTC test - Active-B12 (Axis-Shield Diagnostics Ltd). Exon sequencing of the TCN2 gene was carried out. Protein characterization included total transcobalamin (TCN2) detection by Western blot, and holoTC by (57) Co-labelled B12 binding followed by size fractionation. Exon sequencing of TCN2 revealed both patients were homozygous for the minor allele of rs35838082 (p.R215W). Western blot and chromatographic analyses revealed that the serum of these patients contains intact transcobalamin and that this variant-containing protein binds vitamin B12 . The variant is rare in Caucasians (minor allele frequency (MAF) < 0·01) but more common in South Asians (MAF ~ 0·02) and those of African origin (MAF ~ 0·25). The impeded ability to detect normal levels of holoTC in these two patients may be due to this variant interfering with the detection of holoTC by one or both of the monoclonal antibodies currently employed in the Active-B12 test. Laboratories should be aware of this variant and use confirmatory tests when applicable.


Sleep-related respiratory disorders.
Sleep-induced narrowing of the upper airways underlies the widespread and supposedly trivial complaint of snoring, which may not only constitute a risk factor for the cardiocirculatory system, but in predisposed individuals may lead to the OSAS. The latter is a life-threatening condition characterized by repeated episodes of cessation of respiration at night with an associated drop in SaO2. Patients frequently present with hypersomnia, systemic and pulmonary hypertension, and even heart failure. HSD is the term we use to describe the evolutive stages from snoring to OSAS. ICAH, or Ondine's curse, is the clinical syndrome of sleep-related respiratory insufficiency in the absence of airway stenosis. We do not consider central sleep apnea to be an independent disorder. For the treatment of HSD, weight reduction should be attempted first. Also, if there are malformations in the upper airway, they should be surgically corrected. The use of various medications has been rather discouraging, and CPAP and other devices that are intended to overcome the obstruction are poorly tolerated by patients. The most effective surgical treatment for OSAS, even in progressed stages of the disease, is tracheostomy.


Computed tomography of thorotrastosis.
Two cases of thorotrastosis examined by computed tomography are reported. The appearance of the liver, spleen, and lymph nodes is diagnostic. This technique is probably the procedure of choice for detection of Thorotrast-induced liver neoplasm.


Development of the house secreting epithelium, a major innovation of tunicate larvaceans, involves multiple homeodomain transcription factors.
The mechanisms driving innovations that distinguish large taxons are poorly known and essentially accessible via a candidate gene approach. A spectacular acquisition by tunicate larvaceans is the house, a complex extracellular filtration device. Its components are secreted by the oikoplastic epithelium which covers the animal trunk. Here we describe the development of this epithelium in larvae through the formation of specific cellular territories known to produce distinct sets of house proteins (Oikosins). It involves cell divisions and morphological differentiation but very limited cell migration. A diverse set of homeobox genes, most often duplicated in the genome, are transiently and site-specifically expressed in the trunk epithelium at early larval stages. Using RNA interference, we show that two prop duplicates are involved in the differentiation of a region on and around the dorsal midline, regulating morphology and the production of a specific oikosin. Our observations favor a scenario in which multiple homeobox genes and most likely other developmental transcription factors were recruited for this innovation. Their frequent duplications probably predated, but were not required for the emergence of the house.


Prognostic prediction of thrombolytic therapy with rt-PA in acute ischemic stroke patients using an artificial intelligence model.
Through the comparison of different prediction models, we hope to find a promising statistical method to evaluate the prognosis of patients with acute ischemic stroke (AIS) after thrombolytic therapy. Data of 518 patients who received thrombolytic therapy were retrospectively collected in this study. Among them, 362 patients met the eligibility criteria, so their data such as age, sex, smoking history, previous medical history, clinical and laboratory indicators were analyzed. According to the 3 month follow-up results, 266 patients were included in a good prognosis group (modified Rankin Scale (mRS) score ≤2) and 96 in a poor prognosis group (3≤mRS≤6). All variables with P<0.05 in univariant and multivariant analyses were assigned in logistic regression model and artificial neural network (ANN) model to predict neurological prognosis, and the performance of the two models were compared. Age, NIHSS scores, the serum concentration of immediate glucose, APTT and MBP at admission were found to be the predictive factors through ANN and logistic regression analysis. The binary logistic regression model revealed that the percentage correction, the precision, recall and F1 score of the regression model were 79%, 69.23%, 37.50% and 48.65%, respectively. While those of ANN were 79.98%, 69.70%, 37.25%, and 49.66%, correspondingly. ANN model is as effective as a logistic regression model in predicting the prognosis of AIS after thrombolytic therapy with rt-PA. Moreover, ANN is slightly superior to logistic regression in accuracy, precision and F1 score.


Synthesis and characterization of lead-based metal-organic framework nano-needles for effective water splitting application.
Metal organic frameworks (MOFs) are a class of porous materials characterized by robust linkages between organic ligands and metal ions. Metal-organic frameworks (MOFs) exhibit significant characteristics such as high porosity, extensive surface area, and exceptional chemical stability, provided the constituent components are meticulously selected. A metal-organic framework (MOF) containing lead and ligands derived from 4-aminobenzoic acid and 2-carboxybenzaldehyde has been synthesized using the sonochemical methodology. The crystals produced were subjected to various analytical techniques such as Fourier-transform infrared spectroscopy (FT-IR), Powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), Brunauer-Emmett-Teller (BET), and thermal analysis. The BET analysis yielded results indicating a surface area was found to be 1304.27 m2 g-1. The total pore volume was estimated as 2.13 cm3 g-1 with an average pore size of 4.61 nm., rendering them highly advantageous for a diverse range of practical applications. The activity of the modified Pb-MOF electrode was employed toward water-splitting applications. The electrode reached the current density of 50 mA cm-2 at an overpotential of - 0.6 V (vs. RHE) for hydrogen evolution, and 50 mA cm-2 at an overpotential of 1.7 V (vs. RHE) for oxygen evolution.


Electron spin relaxations of phosphorus donors in bulk silicon under large electric field.
Modulation of donor electron wavefunction via electric fields is vital to quantum computing architectures based on donor spins in silicon. For practical and scalable applications, the donor-based qubits must retain sufficiently long coherence times in any realistic experimental conditions. Here, we present pulsed electron spin resonance studies on the longitudinal (T1) and transverse (T2) relaxation times of phosphorus donors in bulk silicon with various electric field strengths up to near avalanche breakdown in high magnetic fields of about 1.2 T and low temperatures of about 8 K. We find that the T1 relaxation time is significantly reduced under large electric fields due to electric current, and T2 is affected as the T1 process can dominate decoherence. Furthermore, we show that the magnetoresistance effect in silicon can be exploited as a means to combat the reduction in the coherence times. While qubit coherence times must be much longer than quantum gate times, electrically accelerated T1 can be found useful when qubit state initialization relies on thermal equilibration.


Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification.
Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.


AANA23 Confirms There is Still a Place for Face-To-Face Meetings.
AANA23, or the AANA Annual Meeting, set a high-water mark for our society and its members. Congratulations to all who planned and executed an exceptional educational meeting. Demonstrating that diversity continues to be front of mind, one of the first events of the meeting was the Diversity Session. Recognizing the topic's importance, next month in Arthroscopy, Sports Medicine, and Rehabilitation (ASMAR), Arthroscopy's companion online journal, we will publish our second annual special issue devoted to rehabilitation and return to sport, also with a focus on diversity as it relates to sports medicine. The Biologic Association held a comprehensive and clinically relevant 2-day meeting in conjunction with and following AANA23. AANA23 set the stage for a greatly anticipated AANA24 to be held in Boston from May 9 to 11, 2024.


N-terminal pro-brain natriuretic peptide levels had an independent and added ability in the evaluation of all-cause mortality in older Chinese patients with atrial fibrillation.
Atrial fibrillation (AF) is the most common arrhythmia and has increased prevalence in older patients, leading to poor prognosis for these patients. There is a need for a biomarker or a model of prognostic evaluation in older patients with AF, especially in China. CHADS2 and CHA2DS2VASc scores have been applied to evaluate their prognosis in patients with AF. This analysis was designed to examine whether N-terminal pro-brain natriuretic peptide (NT-proBNP) levels significantly improved the evaluation of all-cause mortality in older Chinese patients with AF when added to CHADS2 and CHA2DS2VASc scores. There were 219 older patients with AF, and follow-up was 100% complete over an average of 1.11 years. Cox regression analysis was applied to determine the variables independently associated with all-cause mortality. Median age was 85 years, and all-cause mortality was 24.2% (53 patients). Plasma NT-proBNP levels were significantly associated with all-cause mortality in univariate [hazard ratio (HR): 1.842; 95% confidence interval (CI): 1.530-2.218] and multivariate (HR: 1.377; 95% CI: 1.063-1.785) Cox regression analyses and had significantly higher c-statistic (0.771; 95% CI: 0.698-0.845) than CHADS2 (0.639; 95% CI: 0.552-0.726) and CHA2DS2VASc (0.633; 95% CI: 0.546-0.720) scores (P < 0.05 for all). The addition of NT-proBNP levels to CHADS2 (0.783; 95% CI: 0.713-0.854) and CHA2DS2VASc (0.775; 95% CI: 0.704-0.846) scores significantly increased their c-statistics (P < 0.001 for all). Model based on NT-proBNP levels including age, hemoglobin, fasting blood glucose, glomerular filtration rate and NT-proBNP levels had a significantly higher c-statistic (0.890; 95% CI: 0.841-0.938) than CHADS2 and CHA2DS2VASc scores (P < 0.001 for all). Model based on NT-proBNP levels had significantly higher c-statistic than the addition of NT-proBNP levels to CHADS2 and CHA2DS2VASc scores (P < 0.05). NT-proBNP levels were an independent biomarker associated with an increased all-cause mortality in older Chinese patients with AF, and had an independent and added ability to evaluate their all-cause mortality compared with CHADS2 and CHA2DS2VASc scores.


Lysophospholipase activity in rat brain subcellular fractions.
Lysophospholipase activity in brain subcellular fractions was measured by the release of myristic acid from 1-myristoylglycerophosphocholine or through the formation of [32P]glycerophosphocholine from [32P]lysophosphatidylcholine. Although the lysophospholipase activity was highest in microsomes, considerable enzyme activity was also found in other subcellular membrane fractions. The pH optimum for the microsomal enzyme was around 7, whereas the synaptosomes and non-synaptic plasma membranes exhibited a pH maximum around 8. Although the enzyme did not require divalent cations for activity, divalent cations (1 mM) such as Hg2+, Cu2+, and Zn2+ inhibited potently the enzyme activity. Enzyme activity was also partially inhibited by both saturated and polyunsaturated fatty acids (25-200 microM), and the inhibition seemed to be greater in the membrane than in the cytosolic fractions. Ionic detergents such as deoxycholate and taurocholate inhibited the lysophospholipase. On the other hand, the effect of Triton X-100 was biphasic, i.e., stimulation at concentrations below 100 micrograms/mg protein and inhibition at higher concentrations. Addition of cholesterol (50-250 micrograms/ml), but not cholesteryl esters, also potently inhibited enzyme activity. The presence of active lysophospholipase(s) in brain is probably an important mechanism for preventing unnecessary accumulation of lysophospholipids which may exert a deleterious effect on the membranes because of their detergent properties.


A rare case of sebaceous lymphadenoma: Cytohistological correlation of preoperative cytomorphologic findings.
We are presenting a case of a 74-year-old female with a parotid gland mass. Fine-needle aspiration (FNA) of the mass demonstrated cohesive groups of epithelial cells with overall bland-appearing nuclei and abundant vacuolated cytoplasm, consistent with sebaceous cells, in a background of polymorphous lymphocytes, scattered histiocytes, and adipose tissue. Immunostains showed that the epithelial cells stain positive for p63, but negative for CD117 and DOG-1. CD3 and CD20 showed a mixture of T- and B-cells. On the PAP-stained slides, there were numerous sac-like structures, consistent with myospherules. These findings were suggestive of neoplasm with sebaceous differentiation. The main differential diagnosis included sebaceous adenoma, sebaceous lymphadenoma, and other benign lesions with sebaceous differentiation. The parotid mass was resected. Histology sections demonstrated a well-circumscribed neoplasm with multicystic epithelial component and surrounding lymphoid infiltrate, consistent with sebaceous lymphadenoma. Sebaceous lymphadenoma (SLA) is a rare benign salivary gland neoplasm that is most commonly seen in the parotid gland. Preoperative FNA diagnosis of sebaceous neoplasms is challenging. To the best of our knowledge, this is the third case of sebaceous lymphadenoma diagnosed preoperatively. In this manuscript, we detail the epidemiological characteristics and histogenesis of sebaceous salivary gland neoplasms, and the cytomorphologic differential diagnosis of SLA with key diagnostic features of each entity.


Comparative Effectiveness of Influenza Vaccines Among US Medicare Beneficiaries Ages 65 Years and Older During the 2019-2020 Season.
Approximately 50 000 influenza-associated deaths occur annually in the United States, overwhelmingly among individuals aged ≥65 years. Although vaccination is the primary prevention tool, investigations have shown low vaccine effectiveness (VE) in recent years, particularly among the elderly. We analyzed the relative VE (RVE) of all influenza vaccines among Medicare beneficiaries aged ≥65 years to prevent influenza hospital encounters during the 2019-2020 season. Retrospective cohort study using Poisson regression and inverse probability of treatment weighting (IPTW). Exposures included egg-based high-dose trivalent (HD-IIV3), egg-based adjuvanted trivalent (aIIV3), egg-based standard dose (SD) quadrivalent (IIV4), cell-based SD quadrivalent (cIIV4), and recombinant quadrivalent (RIV4) influenza vaccines. We studied 12.7 million vaccinated beneficiaries. Following IPTW, cohorts were well balanced for all covariates and health-seeking behavior indicators. In the adjusted analysis, RIV4 (RVE, 13.3%; 95% CI, 7.4-18.9%), aIIV3 (RVE, 8.2%; 95% CI, 4.2-12.0%), and HD-IIV3 (RVE, 6.8%; 95% CI, 3.3-10.1%) were significantly more effective in preventing hospital encounters than the reference egg-based SD IIV4, while cIIV4 was not significantly more effective than IIV4 (RVE, 2.8%; 95% CI, -2.8%, 8.2%). Our results were consistent across all analyses. In this influenza B-Victoria and A(H1N1)-dominated season, RIV4 was moderately more effective than other vaccines, while HD-IIV3 and aIIV3 were more effective than the IIV4 vaccines, highlighting the contributions of antigen amount and adjuvant use to VE. Egg adaptation likely did not substantially affect our RVE evaluation. Our findings, specific to the 2019-2020 season, should be evaluated in other studies using virological case confirmation.


Ocular fluorometry: standardization and instrumentation development. A Concerted Action in the European Community (EUROEYE).
A Concerted Action on Ocular Fluorometry, stressing standardization and instrumentation development has been funded by the European Community. Agreement was reached on harmonization of protocols. The results obtained show that the protocols proposed for Clinical Ocular Fluorometry were generally appropriate and may be followed closely, with reproducible and meaningful results. In each group, areas for improvement could, however, be detected, particularly regarding facility of use of the newly developed softwares. The success of the ECNOF was very rewarding and every effort is being made to consolidate this success in the publication and dissemination of the agreed guidelines and results. The field of Ocular Fluorometry appears to have even more potential than was apparent at the beginning of this Concerted Action. The needs for instrumentation development have been clarified and four main directions where progress has been achieved are identifiable: spectral fluorescence analysis of naturally occurring ocular fluorophores, light scattering analysis of ocular structures and fluids, improved axial resolution for better quantification of ocular permeabilities and, finally, development of simple routine clinical instrumentation. Corneal and lens natural fluorescence appear extremely promising as indicators of disease status, particularly in diabetes. Blood-retinal barrier permeability has the potential to become a screening test isolating the eyes at risk for developing diabetic blindness and, therefore needing closer follow-up and earlier treatment. Light scattering methodologies particularly in association with ocular fluorometry, may allow improved monitorization of chronic inflammation, better therapeutical management of a variety a sight-threatening diseases.


Isozymic differentiation of two sibling species of Squatina (chondrichthyes) in South Brazil.
Two sympatric morphotypes of the nominal species Squatina argentina from South Brazil are compared by the frequencies of 25 isozymes distributed over 14 presumptive loci. The Nei's Genetic Identity index obtained in a comparison of the populations is of 0.71. The loci EST-2 and EST-4 are fixed at different isozymes for each population, indicating a reproductive isolation between them. The most significant morphological and meristical differences between the morphotypes are the presence or absence of dorsal spines and the dental formula. The agreement between these characteristics and the genetical data indicates that the two morphotypes belong to different species.


Expanding the limits of nephron-sparing surgery: Surgical technique and mid-term outcomes of purely off-clamp robotic partial nephrectomy for totally endophytic renal tumors.
To report surgical technique, perioperative, oncological, and mid-term functional outcomes in a single-center purely off-clamp robotic partial nephrectomy series for totally endophytic masses. A retrospective analysis of a prospectively collected, institutional review board-approved renal cancer database was carried out to include patients with a totally endophytic renal tumor treated with off-clamp robotic partial nephrectomy between January 2013 and December 2020 at our center. Our database was queried to identify cases that had been assigned 3 points for the "E" domain of the R.E.N.A.L. nephrometry score and 3 points for the "exophytic rate" domain of the PADUA (Preoperative Aspects and Dimensions Used for an Anatomical) nephrometry score. Preoperative indocyanine green renal mass marking was performed in 33 patients, in whom the tumor was vascularized by a specific feeding artery. Surgical steps, perioperative, oncological and functional data were reported. Fifty-six consecutive patients with totally endophytic renal masses were treated. The median tumor diameter was 3 cm, and median PADUA and R.E.N.A.L. scores were both 10. The median operative time was 82 min. Low-grade Clavien complications occurred in two patients (3.6%) and high-grade Clavien complications were observed in four patients (7.1%). Positive surgical margins were detected in one patient; 2-year recurrence-free, cancer-specific, and overall survival rates were 100%, 100%, and 98.2%, respectively. At a median follow-up of 24 months, new onset of chronic kidney disease stage 3b occurred in one patient. At last follow-up, the median estimated glomerular filtration rate was 77 mL/min, with a median estimated glomerular filtration rate percent decrease of 5.5%. Trifecta was achieved in 91% of patients. Purely off-clamp robotic partial nephrectomy is a feasible and safe surgical approach, even in totally endophytic renal tumors, providing a favorable perioperative complications rate, excellent oncological outcomes, and negligible impact on renal function at mid-term follow-up. Indocyanine green preoperative marking of endophytic renal tumors represents a useful tool for rapid intraoperative identification of the mass, real-time control of resection margins, and a more precise dissection.


Hkakabo Razi landscape as one of the last exemplar of large contiguous forests.
Deforestation and forest degradation around the world endanger the functioning of ecosystems, climate stability, and conservation of biodiversity. We assessed the spatial and temporal dynamics of forest cover in Myanmar's Hkakabo Razi Landscape (HRL) to determine its integrity based on forest change and fragmentation patterns from 1989 to 2016. Over 80% of the HRL was covered by natural areas, from which forest was the most prevalent (around 60%). Between 1989 and 2016, forest cover declined at an annual rate of 0.225%. Forest degradation occurred mainly around the larger plains of Putao and Naung Mung, areas with relatively high human activity. Although the rate of forest interior loss was approximately 2 to 3 times larger than the rate of total forest loss, forest interior was prevalent with little fragmentation. Physical and environmental variables were the main predictors of either remaining in the current land-cover class or transitioning to another class, although remaining in the current land cover was more likely than land conversion. The forests of the HRL have experienced low human impact and still constitute large tracts of contiguous forest interior. To ensure the protection of these large tracts of forest, sustainable forest policies and management should be implemented.


Coordination engineering of single zinc atoms on hierarchical dual-carbon for high-performance potassium-ion capacitors.
Dual-carbon engineering combines the advantages of graphite and hard carbon, thereby optimizing the potassium storage performance of carbon materials. However, dual-carbon engineering faces challenges balancing specific capacity, capability, and stability. In this study, we present a coordination engineering of Zn-N4 moieties on dual-carbon through additional P doping, which effectively modulates the symmetric charge distribution around the Zn center. Experimental results and theoretical calculations unveil that additional P doping induces an optimized electronic structure of the Zn-N4 moieties, thus enhancing K+ adsorption. A single-atom Zn metal coordinated with nitrogen and phosphorus reduces the K+ diffusion barrier and improves fast K+ migration kinetics. Consequently, Zn-NPC@rGO exhibits high reversible specific capacities, excellent rate capability, and impressive cycling stability, and remarkable power and energy densities for potassium-ion capacitors (PICs). This study provides insights into crucial factors for enhancing potassium storage performance.


[Internet: a fundamental tool for the retrieval of the information useful for medical research and health care in oncology].
Internet represents an essential aid for the professional updating of physicians and researches. Also for the research and therapy in oncology, Internet provides important such as bibliographic data, trials and guidelines with full text, as well as epidemiologic and statistical data. Some of the most authoritative sites are indicated.