Nitric oxide and hydrogen peroxide independently act in mitigating chromium stress in Triticum aestivum L. seedlings: Regulation of cell death, chromium uptake, antioxidant system, sulfur assimilation and proline metabolism.
In this study, we have explored potential of a nitric oxide (NO) donor (SNP, sodium nitroprusside) and hydrogen peroxide (H2O2) in curtailing stress of hexavalent chromium [Cr(VI)] in wheat seedlings. Cr(VI) stress caused a significant decline in growth (30%) and photosynthesis (13%) as a result of enhanced uptake of Cr(VI) and root tips cell death. Further, Cr(VI) stress also accelerated indices of oxidative stress but differentially regulated antioxidant system. But application of either NO or H2O2 separately significantly mitigated Cr(VI) stress by reducing cell death and Cr(VI) uptake in roots, and oxidative stress markers. The application of c-PTIO [2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a scavenger of NO] and N-acetyl-L-cysteine (a scavenger of ROS) reserved alleviatory effect of NO and H2O2, respectively and thus further increased Cr(VI) toxicity. Application of diphenylene iodonium (DPI, an inhibitor of NADPH oxidases) also further increased Cr(VI) toxicity. But SNP and H2O2 significantly rescued negative effects of DPI and c-PTIO, respectively under Cr(VI) stress. Overall results suggested that NO and H2O2 both independently act in mitigating Cr(VI) stress in wheat seedlings by minimizing cell death, restricting Cr(VI) uptake in roots, and increasing antioxidant system, sulfur assimilation and proline metabolism.


Approaching mercury distribution in burial environment using PLS-R modelling.
Mercury environmental cycle and toxicology have been widely researched. Given the long history of mercury pollution, researching mercury trends in the past can help to understand its behaviour in the present. Archaeological skeletons have been found to be useful sources of information regarding mercury loads in the past. In our study we applied a soil multi-sampling approach in two burials dated to the 5th to 6th centuries AD. PLRS modelling was used to elucidate the factors controlling mercury distribution. The model explains 72% of mercury variance and suggests that mercury accumulation in the burial soils is the result of complex interactions. The decomposition of the bodies not only was the primary source of mercury to the soil but also responsible for the pedogenetic transformation of the sediments and the formation of soil components with the ability to retain mercury. The amount of soft tissues and bone mass also resulted in differences between burials, indicating that the skeletons were a primary/secondary source of mercury to the soil (i.e. temporary sink). Within burial variability seems to depend on the proximity of the soil to the thoracic area, where the main mercury target organs were located. We also conclude that, in coarse textured soils, as the ones studied in this investigation, the finer fraction (i.e. silt + clay) should be analysed, as it is the most reactive and the one with the higher potential to provide information on metal cycling and incipient soil processes. Finally, our study stresses the need to characterise the burial soil environment in order to fully understand the role of the interactions between soil and skeleton in mercury cycling in burial contexts.


Reactive oxygen species in cancer: a paradox between pro- and anti-tumour activities.
Cancer constitutes a group of heterogeneous diseases that share common features. They involve the existence of altered cellular pathways which result in uncontrolled cell proliferation. Deregulation of production and/or elimination of reactive oxygen species (ROS) appear to be a relevant issue in most of them. ROS have a dual role in cell metabolism: they are compromised in normal cellular homeostasis, but their overproduction has been reported to promote oxidative stress (OS), a process that may induce the damage of cell structures. ROS accumulation is implicated in the activation of signaling pathways that promote cell proliferation and metabolic adaptations to tumour growth. One characteristic of cancer cells is the sensitivity to OS, which often results from the combination of high anabolic needs and hypoxic growth conditions. However, there is still no clear evidence about the levels of oxidant species that promote cellular transformation or, otherwise, if OS induction could be adequate as an antitumour therapeutic tool. There is a need for novel therapeutic strategies based on the new knowledge of cancer biology. Targeting oncogenic molecular mechanisms with non-classical agents and/or natural compounds would be beneficial as chemoprevention or new adjuvant therapies. In addition, epigenetics and environment, and particularly dietary factors may influence the development and prevention of cancer. This article will present a revision of the current research about molecular aspects proposed to be involved in the anticancer features of oxidant and antioxidant-based therapies targeting cancer cells, and their participation in the balance of oxidative species and cancer cell death.


Modulation of calcium signals by fluorescent dyes in the presence of tubular endoplasmic reticulum: a modelling approach.
The complex network of Ca(2+) signals uses local events as building blocks for generating global calcium signals with different shapes. However, the nature of the large time- and space-scales of local calcium signals observed in Xenopus oocytes has remained unclear. By numeric simulations that include optical blurring of the image and the geometrical restrictions imposed by tubules of the endoplasmic reticulum or other cell structures, we investigate how the fluorescent dye affect the observed features of calcium events, such as rate of signal decay, spatial size, fluorescence amplitude, or the apparent diffusion like from a point source in a spherically symmetric space. We add more evidence that, irrespective of the dye properties, local calcium signals produced in the presence of tubular cellular structures are consistently wider than expected in a homogeneous environment. Moreover, the spatial dimension and the decay time of the event increase with the quantity of liberated Ca(2+). Our results also indicate that a fast binding Ca(2+) indicator that does not bind to cytosolic proteins yields fast signals when the event is observed in the front of the release site, and slow signals when the event is viewed from the opposite side of the tubule. We propose several ways to test our model by various experimental procedures.


Differences in estimates for 10-year risk of cardiovascular disease in Black versus White individuals with identical risk factor profiles using pooled cohort equations: an in silico cohort study.
Sex-specific and race-specific pooled cohort equations (PCEs) are recommended for estimating the 10-year risk of cardiovascular disease, with an absolute risk of more than 7·5% indicating a clinical decision threshold. We compared differences between Black and White individuals in PCE-estimated absolute cardiovascular disease risk across various plausible risk factor combinations with the aim of evaluating if using the PCE might result in different clinical decisions in Black versus White individuals with identical risk profiles. We generated in silico patient risk profiles by combining numerical risk factors (age [5-year intervals], total cholesterol [20-mg/dl intervals], HDL cholesterol [5-mg/dl intervals], systolic blood pressure [10-mm Hg intervals]) and binary risk factors (smoking, diabetes, and antihypertensive treatment). We compared PCE-estimated 10-year cardiovascular disease risk in Black versus White individuals with identical risk profiles. We did similar comparisons using eligible participants in the Framingham Heart Study (FHS) third generation cohort and the National Health and Nutrition Examination Survey (NHANES) 2017-18. For our in silico analysis, we evaluated 29 515 risk factor combinations for women and 30 565 for men, after excluding profiles that generated 10-year cardiovascular disease risk estimates below 1% or above 30%. There were 6357 risk profiles associated with 10-year cardiovascular disease risk above 7·5% for Black men but not for White men (median risk difference [RD] 6·25%, range 0·15-22·8; median relative risk [RR] 2·40, range 1·02-12·6). There were 391 profiles with 10-year cardiovascular disease risk above 7·5% for White men but not Black men (median RD 2·68%, range 0·07-16·9%; median RR 1·42, range 1·01-3·57). There were 6543 risk profiles associated with 10-year estimated cardiovascular disease risk above 7·5% for Black women but not for White women (median RD 6·14%, range 0·35-26·8%; median RR 2·29, range 1·05-12·6). There were 318 profiles with 10-year cardiovascular disease risk above 7·5% for White women but not Black women (median RD 3·71%, range 0·22-20·1%; median RR 1·66, range 1·03-5·46). For the population-based samples, we calculated the PCE-based 10-year cardiovascular disease risk for 1272 eligible participants (378 women; median age 48 years [IQR 44-52]; 100% White) in the FHS third generation cohort and 550 participants (223 women [36·8% Black] and 327 men [40·4% Black]; median age 61 years [IQR 52-67]) in the NHANES cohort. The population-based samples showed similar risk differences to that of the in silico analyses. The PCE might generate substantially divergent cardiovascular disease risk estimates for Black versus White individuals with identical risk profiles, which could introduce race-related variations in clinical recommendations for cardiovascular disease prevention. US National Institutes of Health.


Enhancement of keratinocyte performance in the production of tissue-engineered skin using a low-calcium medium.
The success of laboratory-expanded autologous keratinocytes for the treatment of severe burn injuries is often compromised by their lack of dermal remnants and failure to establish a secure dermo-epidermal junction on the wound bed. We have developed a tissue-engineered skin substitute for in vivo use, based on a sterilized donor human dermis seeded with autologous keratinocytes and fibroblasts. However, culture rates are currently too slow for clinical use in acute burns. Our aim in this study was to increase the rate of production of tissue-engineered skin. Two approaches were explored: one using a commercial low-calcium media and the other supplementing well-established media for keratinocyte culture with the calcium-chelating agent ethylene glutamine tetra-acetic acid (EGTA). Using commercial low-calcium media for both the initial cell culture and subsequent culture of tissue-engineered skin did not produce tissue suitable for clinical use. However, it was possible to enhance the initial proliferation of keratinocytes and to increase their horizontal migration in tissue-engineered skin by supplementing established culture medium with 0.04 mM EGTA without sacrificing epidermal attachment and differentiation. Enhancement of keratinocyte migration with EGTA was also maximal in the absence of fibroblasts or basement membrane.


Effective reduction of Vibrio vulnificus in the Eastern oyster (Crassostrea virginica) using high salinity depuration.
Depuration under different salinities was used to reduce the human pathogen Vibrio vulnificus from Eastern oysters (Crassostrea virginica). Individual recirculating systems were used to test the efficacy of depuration at three salinities (15, 25, and 35 psu) in four independent trials during a 14 day period. Initial loads of V. vulnificus were higher than 10,000 MPN/g of oyster meat in all trials. Data showed that 25 and 35 psu treatments were more efficient in reducing V. vulnificus numbers than 15 psu with an overall reduction of >3 logs. A significant decrease in MPN/g was observed as early as day 6 and further reductions were observed at day 10, while longer depurations did not improve efficacy. Only the highest salinity (35 psu) was capable of reducing V. vulnificus numbers to the FDA recommended level of <30 MPN/g in two of the four trials. Oysters survived well in the depuration systems with minimal mortality (<1%) but their condition index (meat quality and yield) decreased during the 14 day period in all treatments. The data presented in this study suggests that high salinity depuration is a promising method to reduce V. vulnificus in oysters.


Imaging of rare medullary adrenal tumours in adults.
Although adrenal medullary tumours are rare, they have important clinical implications. They form a heterogeneous group of tumours, ranging from benign, non-secretory, incidental masses to hormonally active tumours presenting acutely, or malignant tumours with disseminated disease and a poor prognosis. Increasingly, benign masses are incidentally detected due to the widespread use of imaging and routine medical check-ups. This review aims to illustrate the multimodality imaging appearances of rare adrenal medullary tumours, excluding the more common phaeochromocytomas, with clues to the diagnosis and to summarise relevant epidemiological and clinical data. Careful correlation of clinical presentation, hormone profile, and various imaging techniques narrow the differential diagnosis. Image-guided percutaneous adrenal biopsy can provide a definitive diagnosis, allowing for conservative management in selected cases. A close collaboration between the radiologist, endocrinologist, and surgeon is of the utmost importance in the management of these tumours.


Interaction of intrathecally infused morphine and lidocaine in rats (part II): effects on the development of tolerance to morphine.
There has been little information regarding the effects of local anesthetics on tolerance to opioids, although chronic use of combination of opioids and local anesthetics is popular for pain control. This study was designed to examine the effects of lidocaine on morphine tolerance to somatic and visceral antinociception. Rats received a continuous intrathecal infusion of morphine (0.3-10 microg x kg(-1) x h(-1)), lidocaine (30-1000 microg x kg(-1). h(-1)), a combination of those, or saline. After 6- day infusion, intrathecal morphine challenge test (5 microg/10 microl) was performed, and time-response curve was constructed to assess the magnitude of tolerance. The tail flick (TF) test and colorectal distension (CD) test were used to measure somatic and visceral antinociceptive effects, respectively. Antinociceptive effects in the TF and CD tests caused by morphine challenge were reduced (P < 0.01) in the morphine infused groups. The magnitude of the tolerance was inversely associated with the amount of morphine infused. Lidocaine infusion induced no different change in the morphine challenge test from that seen in the saline infusion group. Development of tolerance was greater in morphine 3 microg x kg(-1) h(-1) than in morphine 0.75 microg x kg(-1) x h(-1) + lidocaine 150 microg x kg(-1) x h(-1) despite their similar antinociceptive effects during intrathecal infusion. The infusion of a low dose of morphine (0.3 microg kg(-1) x h(-1)) did not reduce the antinociceptive effects in the challenge test. Lidocaine in combination with morphine does not reduce tolerance to morphine nor develop cross-tolerance. The intrathecal infusion of morphine induced tolerance to somatic and visceral antinociception in a dose-dependent fashion.


Factors associated with suicidal ideation: role of emotional and instrumental support.
Suicidal ideation is an important phase in the suicidal process, preceding suicide attempts and completed suicide. Weak social ties and low support from friends or relatives have been significantly associated with suicidal ideation. This study investigated the relationship between social support and suicidal ideation among young and middle-aged adults in Korea. The Seoul Citizens Health and Social Indicators Survey conducted face-to-face interviews with 10,922 self-reporting adults. Questions were asked to assess suicidal ideation, and several questions focused on social support, social networks, health behaviors, and health status. The strongest association in middle-aged adults was that between suicidal ideation and lack of social support. Poor emotional support significantly influenced suicidal ideation in middle-aged men, whereas lack of instrumental support significantly affected suicidal thoughts in middle-aged women, after controlling for sociodemographic factors, health behaviors, and health status. High alcohol use, functional limitations, and stress were related to suicidal thoughts in young adults, whereas depressive feelings had the strongest association with suicidal ideation in middle-aged women. Social support is a crucial independent correlate of suicidal ideation, especially in middle-aged adults in an urban community setting. This study shows that it is essential to provide gender-specific social support to prevent suicide.


Long-term administration of the antidepressant vilazodone modulates rat brain monoaminergic systems.
Vilazodone has high affinity for the human 5-hydroxytryptamine1A (h5-HT1A) receptor and for the serotonin transporter (5-HTT). A previous in vivo microdialysis experiment showed that a single administration of vilazodone, dose-dependently increases extracellular 5-HT but not norepinephrine (NE) or dopamine (DA) levels in rat medial prefrontal cortex and ventral hippocampus. The effects of vilazodone on monoaminergic systems were assessed using single-unit extracellular recordings and microiontophoresis in the rat brain. Following depletion of 5-HT with para-chlorophenylalanine methyl-ester hydrochloride (PCPA), vilazodone still suppressed neuronal firing of dorsal raphe nucleus (DRN) 5-HT neurons to a similar extent than controls, indicating that this inhibition is via 5-HT1A receptors activation. Following 2-day intraperitoneal administration of vilazodone (5 mg/kg/day), there was a significant decrease in 5-HT neuronal firing which recovered to baseline levels by day 14 of administration, likely due to 5-HT1A autoreceptor desensitization. Two- and 14-day administration of vilazodone decreased the mean firing and bursting activities of ventral tegmental area (VTA) DA neurons, while only its repeated administration significantly dampened the mean firing rate of locus coeruleus (LC) NE neurons. Vilazodone acted as an agonist at 5-HT1A receptors, while showing a 5-HTT blocking capacity when injected acutely. After repeated vilazodone regimen, while there was no change in sensitivity of 5-HT1A receptors, the enhancement in 5-HT transmission yielded an increase in the tonic activation of these receptors located in the hippocampus.


The effect of carcinogens on the nuclear size of HeLa cells.
The size of HeLa S-3 cell nuclei was measured after 1--3 days in culture. After exposure to carcinogens, nuclear size increased and the frequency distribution pattern of nuclear size changed. The optimal conditions for these changes were the use of concentrations of chemicals which had a low order of cytotoxicity and the measurement of nuclear size 48 h after pulse treatment of the cells for 30--60 min. These effects were not seen with non-carcinogens. The results obtained suggest that changes in nuclear size may be an index of chemical carcinogenicity.


A comparison of secretory component - immunoglobulin interactions amongst different species.
1) SC from many species may be isolated by affinity chromatography to human IgA-Sepharose. 2) In some species SC may exist in two molecular forms. 3) The SC-binding sites on polymeric IgA and IgM are not identical. 4) In some species SC binds to IgM with higher affinity than to polymeric IgA while in other species SC binds best to polymeric IgA. This difference may influence the relative concentrations of these two immunoglobulin classes in the secretions of different species. 5) The SC-binding site is present on high molecular weight immunoglobulin in species as primitive as the nurse shark.


A Bayesian zero-inflated binomial regression and its application in dose-finding study.
In early phase clinical trial, finding maximum-tolerated dose (MTD) is a very important goal. Many researches show that finding a correct MTD can improve drug efficacy and safety significantly. Usually, dose-finding trials start from very low doses, so in many cases, more than 50% patients or cohorts do not have dose-limiting toxicity (DLT), but DLT may occur suddenly and increase fast along with just two or three doses. Although some fantastic models were built to find MTD, little consideration was given to those '0 DLTs' and the 'jump' of DLTs. In this paper, we developed a Bayesian zero-inflated binomial regression for dose-finding study, which analyses dose-finding data from two aspects: 1) observation of only zeros, 2) number of DLTs based on binomial distribution, so it can help us analyse if the cohorts without DLT have potential possibility to have DLT and fit the 'jump' of DLTs.


Anticipation and early detection can reduce bowel elimination complications.
Adequate bowel elimination is essential for physiologic functioning and daily comfort of older patients. A careful assessment of normal bowel elimination patterns will help to prevent unnecessary bowel problems when the older patient is hospitalized or admitted to a long-term care facility. Constipation and incontinence are the two most common bowel elimination problems affecting older adults. Many simple nursing interventions exist that will help to prevent major complications that can occur when constipation or incontinence is present.


Probucol affords neuroprotection in a 6-OHDA mouse model of Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic nigrostriatal neurons. Although the etiology of the majority of human PD cases is unknown, experimental evidence points to oxidative stress as an early and causal event. Probucol is a lipid-lowering phenolic compound with anti-inflammatory and antioxidant properties that has been recently reported as protective in neurotoxicity and neurodegeneration models. This study was designed to investigate the effects of probucol on the vulnerability of striatal dopaminergic neurons to oxidative stress in a PD in vivo model. Swiss mice were treated with probucol during 21 days (11.8 mg/kg; oral route). Two weeks after the beginning of treatment, mice received a single intracerebroventricular (i.c.v.) infusion of 6-hydroxydopamine (6-OHDA). On the 21st day, locomotor performance, striatal oxidative stress-related parameters, and striatal tyrosine hydroxylase and synaptophysin levels, were measured as outcomes of toxicity. 6-OHDA-infused mice showed hyperlocomotion and a significant decrease in striatal tyrosine hydroxylase (TH) and synaptophysin levels. In addition, 6-OHDA-infused mice showed reduced superoxide dismutase activity and increased lipid peroxidation and catalase activity in the striatum. Notably, probucol protected against 6-OHDA-induced hyperlocomotion and striatal lipid peroxidation, catalase upregulation and decrease of TH levels. Overall, the present results show that probucol protects against 6-OHDA-induced toxicity in mice. These findings may render probucol as a promising molecule for further pharmacological studies on the search for disease-modifying treatment in PD.


Sound-production mechanism in Pomatoschistus pictus.
Fish acoustic signals play a major role during agonistic and reproductive interactions. Among the sound-generating fish, Gobiidae, a large fish family with 1866 valid species, is one of the most studied groups of acoustic fishes, with sound production being documented in a number of species. Paradoxically, the sound-producing mechanism remains poorly studied in this group. The painted goby, Pomatoschistus pictus, produces two distinct sounds called drums and thumps. A combination of morphological and experimental analyses involving high-speed videos synchronized with sound recordings supports that drums are produced during lateral head movements involving at least the alternate contractions of the levator pectoralis muscles originating on the skull and inserting on the pectoral girdle. These movements are reported in many Gobiidae species, suggesting the pectoral-girdle-based mechanism is common in the family and could have evolved from locomotory movements.


Pneumocephalus and Facial Droop on an Airplane: A Case Report.
Pneumocephalus (PNC) is most commonly associated with trauma or intracranial surgery, less commonly secondary to an infectious source, and is rarely caused by barotrauma. A 32-year-old woman presented to the emergency department with complaint of resolved left-sided facial droop and a lingering paresthesia of her left upper extremity after a cross-country flight. Computed tomography demonstrated several foci of air in the subdural space consistent with PNC. For PNC to occur there must be a persistent negative intracranial pressure gradient, with or without an extracranial pressure change. In this case the pressure change occurred due to cabin pressure.


Presumed minor salivary gland secretion in a patient with a history of oral mucous membrane graft.
To describe presumed minor salivary gland secretion in a patient with a history of oral mucous membrane graft in conjunctival plastic surgery. Interventional case report. A 74-year-old woman who had had an oral mucous membrane graft in the left eye complained of mucous discharge. Slit-lamp examination revealed a yellowish-red mass lesion in the superior bulbar conjunctiva. The lesion was excised. Histopathologic examination of the excised tissue revealed lobules and a duct of minor salivary glands. After removal of the mass, mucous discharge decreased. Minor salivary glands within a mucous membrane graft may cause mucous discharge in the eye.


[Prevalence and characteristics of serum autoantibodies in patients followed for infertility at Grenoble University Hospital].
Fertility disorders in autoimmune diseases are well described. However, little is known about the presence of a humoral serum autoimmunity in case of infertility (antinuclear antibodies, ACAN or antiphospholipid, APL) without criteria of autoimmune disease. We studied the prevalence, associated factors, and efficacy of immunomodulatory therapy in patients with unexplained infertility. Two groups were created retrospectively among patients followed in medically assisted procreation (PMA) for infertility: a group with serum autoimmunity (AI+) (ACAN, APL or anti-thyroperoxidase antibodies) and a group without serum autoimmunity (HAVE-). Clinical, biological, and therapeutic data were collected. The prevalence of autoimmunity was 33% among consultant patients. One hundred patients were seen in internal medicine consultation, 70 were included in the AI+ group and 30 in the AI- group. In the AI+ group, 76% had ACANs, 29% had anti-TPOs and 23% had APLs. There was a significant correlation between ACAN level and the presence of endometriosis (P=0.048). Immunomodulatory therapy was introduced for 68 of the 70 women in the AI+ group; pregnancy occurred in 28 patients (40%) during the treatment period, compared with 7 in the "AI-" group (23%), with a tendency to significance (P=0.09). In conclusion, there is an increased prevalence of serum autoimmunity in patients with fertility disorders, possibly with the efficacy of an immunomodulatory treatment to confront prospective therapeutic studies.


Electrophysiological effect of beta-N-methylamino-L-alanine on retzius nerve cells of the leech Haemopis sanguisuga.
We investigated the effect of beta-N-methylamino-L-alanine (L-BMAA) on input membrane resistance of leech Retzius nerve cells and the effect of the same substance on the membrane potential in the presence of 20 mM bicarbonate. Results of our experiments show that L-BMAA significantly reduces input membrane resistance on our model. This leads to the conclusion that L-BMAA depolarizes the cell by increasing membrane permeability and conductance. The effect of L-BMAA in 20 mM bicarbonate is significantly higher than in standard Ringer solution. These results indicate that bicarbonate increases the excitatory effect of L-BMAA in our model.


The association between high-arched feet, plantar pressure distribution and body posture in young women.
The aim of this study was to examine the effect of excessive feet arching (symmetrical and asymmetrical) on plantar pressure distribution and on the alignment of pelvis, spine and shoulder girdle. Eighty-one women (20-40 years old, 61 +/- 12 kg, 165 +/- 5 cm) were divided into 3 groups based on the foot arch index (Group 1 - with normally arched feet, Group 2 with one foot properly arched and the other high-arched, Group 3 with both feet high-arched). Plantar pressure distribution between the right and left foot for the forefoot, midfoot and rearfoot, respectively and body posture were assessed. A slight increase in longitudinal arch of the foot caused changes in the distribution of feet loads both between limbs and between the forefoot and rearfoot and also influenced the whole body. Asymmetrical high-arching of the feet resulted in asymmetry of lower limb load and in the height of the shoulder girdle. We have suggested that any alteration of the foot arch may be harmful to body tissues and should not be considered as correct. Due to the fact that slight increases in longitudinal arch of the foot are very common, they should be considered as a foot defect, and appropriate corrective exercises should be used to prevent forefoot overload and alterations in body posture.


Two neolignans from Perilla frutescens and their inhibition of nitric oxide synthase and tumor necrosis factor-alpha expression in murine macrophage cell line RAW 264.7.
Two neolignans were isolated from leaves of Perilla frutescens (Labiatae) as inhibitors of nitric oxide syntheses (IC50 5.9 microM and 53.5 microM, respectively) and tumor necrosis factor-alpha in lipopolysaccharide-activated RAW 264.7 cells. Their structures were identified as 1beta,2alpha,3beta,4alpha-1,2-dimethyl-3,4-bis-(2,4,5-trimethoxyphenyl)-cyclobutane (magnosalin), and 1alpha,2beta,3beta,4alpha-1,2-dimethyl-3,4-bis-(2,4,5-trimethoxyphenyl)-cyclobutane (andamanicin), and their activities were confirmed as resulted from the suppressed expression of inducible nitric oxide synthase enzyme and from the secretion of tumor necrosis factor-alpha from activated macrophages.


Self-determination theory: its application to health behavior and complementarity with motivational interviewing.
Mounting evidence implicates health behaviors (e.g., nutrition, physical activity, tobacco abstinence) in various health outcomes. As the science of behavior change has emerged, increasing emphasis has been placed on the use of theory in developing and testing interventions. Self-determination theory (SDT)-a theoretical perspective-and motivational interviewing (MI)-a set of clinical techniques-have both been used in health behavior intervention contexts. Although developed for somewhat different purposes and in relatively different domains, there is a good deal of conceptual overlap between SDT and MI. Accordingly, SDT may offer the theoretical backing that historically has been missing from MI, and MI may offer SDT some specific direction with respect to particular clinical techniques that have not been fully borne out within the confines of health related applications of SDT. Research is needed to empirically test the overlap and distinctions between SDT and MI and to determine the extent to which these two perspectives can be combined or co-exist as somewhat distinct approaches.


Posterior cruciate ligament reconstruction for chronic lesions: clinical experience with hamstring versus ligament advanced reinforcement system as graft.
The aim of this study was to compare clinical and laximetric results in chronic, isolated posterior cruciate ligament (PCL) rupture repairs, using either a hamstring graft or an artificial ligament (ligament advanced reinforcement system (LARS®)). Sixteen patients presenting with an isolated unilateral PCL rupture were included in this retrospective study. Initially, eight underwent a PCL reconstruction using a hamstring tendon autograft (hamstring group), and over a later period, eight further patients underwent a reconstruction using an artificial ligament with a new procedure. Fifteen patients were male and one female, with an average age of 29.3 years. All patients were operated on within an average time of 18 months post-injury. Pre-operative posterior laxity was equivalent (p = 0.309), 18.25 mm on average for the hamstring group and 18.75 mm for the LARS group. With an average follow-up of 24 months, residual posterior laxity was significantly improved, decreasing from 18.25 to 7.37 mm for the hamstring group (p < 0.05) with a median at 7.5 mm and from 18.75 to 5.25 mm for the LARS group (p < 0.05) with a median at 5 mm. The improvement in laxity for the hamstring group was 60% and 71.5% for the LARS group. The LARS group compares favourably (p = 0.003 and 0.01). Tegner activity level improved significantly following ligamentoplasty, with no difference between the two groups (p = 0.4). Likewise, there was no significant difference in the Lysholm and IKDC scores between the two groups (p = 0.4). The initial hypothesis of this study was proven correct. Nevertheless, a longer term study is necessary to assess the consequences of residual laxity in hamstring grafts and the long-term behaviour and tolerance of the LARS artificial ligament.


Comparison of the plasminogen activator activity of superficial hand and foot veins.
The plasminogen activator (PA) activity in superficial hand and foot veins was determined with a fibrin slide technique in 68 patients (46 with and 22 without thrombosis). The activity in the hand veins was identical to that of the foot veins in 57% of the patients and higher in 38%. There was a correlation between activity in hand and foot veins in patients with and without thrombosis. Thus, biopsy specimens from superficial hand veins can be used for assessing the PA activity in patients with leg thrombosis.


How Changing Tick-Borne Disease Prevalence in Dogs Affects Diagnostic Testing.
Ixodes scapularis (the deer tick), Amblyomma americanum (the lone star tick) and Rhipicephalus sanguineus (the brown dog tick) are ticks that commonly parasitize dogs in the United States. In the first part of this article, we will examine their changing epidemiology to illustrate how being aware of their distribution and adapting diagnostic testing to include a broad range of pathogens may improve our ability to identify and help infected patients, especially those with suspected idiopathic immune-mediated disease. We will then discuss how to optimize testing for these pathogens using available panels.


Retrolabyrinthine craniectomy: the unsung hero of skull base surgery.
Despite being the foundation of, or supplement to, many skull base exposures, the retrolabyrinthine approach has not been adequately illustrated in the skull base literature. As an aid to skull base surgeons in training, this article provides a step-by-step description of the microsurgical anatomy and operative nuances of this important technique.


Improved prognosis with additional medium-dose VP16 to CY/TBI in allogeneic transplantation for high risk ALL in adults.
Allogeneic hematopoietic stem cell transplantation (HSCT) with the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen is an essential therapeutic strategy for acute lymphoblastic leukemia (ALL) in adults. Medium-dose etoposide (VP16, 30-40 mg/kg) can be added to intensify this CY/TBI regimen and reduce relapse; however, differences in prognosis between the VP16/CY/TBI and CY/TBI regimens have not yet been fully analyzed. We conducted a retrospective cohort study using a Japanese transplant registry database to compare the prognosis between the VP16/CY/TBI (VP16, total 30-40 mg/kg) (N = 376) and CY/TBI (N = 1178) regimens in adult patients with ALL transplanted at complete remission (CR) between January 1, 2000 and December 31, 2014. Our analyses indicated that VP16/CY/TBI significantly reduced relapse compared with CY/TBI (risk ratio, 0.75; 95% confidence interval [CI], 0.56-1.00; P = .05) with a corresponding improvement in leukemia-free survival (hazard ratio [HR], 0.76; 95%CI, 0.62-0.93; P = .01), particularly in patients transplanted at CR1 with advanced-risk (positive minimal residual disease, presence of poor-risk cytogenetics, or an initial elevated leukocyte count) (HR, 0.75; 95%CI, 0.56-1.00; P = .05) or those transplanted beyond CR2 (HR, 0.58; 95%CI, 0.39-0.88; P = .01). The addition of VP16 did not increase post-transplant complications or nonrelapse mortality (HR, 0.88; 95%CI, 0.65-1.18; P = .38). This study is the first to reveal the efficacy of the addition of medium-dose VP16 to CY/TBI in high-risk ALL. To establish new myeloablative conditioning regimens including VP16, a large-scale prospective study is necessary.


[Use of immunoenzyme analysis on nitrocellulose membranes for assessing different methods of purifying the yellow mosaic virus of beans].
The comparative study of different methods for the purification of bean yellow mosaic virus isolated from lupine has been made. To evaluate the method of purification, electron-microscopic, spectrophotometric and ELISA techniques have been used. The possibility of using ELISA on nitrocellulose filters with the utilization of a peroxidase-antiperoxidase complex, manufactured in the USSR, for the determination of viral carriership in plants has been shown.


Elp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress responses through tRNALysUUU modifications.
Efficient protein synthesis in eukaryotes requires diphthamide modification of translation elongation factor eEF2 and wobble uridine modifications of tRNAs. In higher eukaryotes, these processes are important for preventing neurological and developmental defects and cancer. In this study, we used Schizosaccharomyces pombe as a model to analyse mutants defective in eEF2 modification (dph1Δ), in tRNA modifications (elp3Δ), or both (dph3Δ) for sensitivity to cytotoxic agents and thermal stress. The dph3Δ and elp3Δ mutants were sensitive to a range of drugs and had growth defects at low temperature. dph3Δ was epistatic with dph1Δ for sensitivity to hydroxyurea and methyl methanesulfonate, and with elp3Δ for methyl methanesulfonate and growth at 16 °C. The dph1Δ and dph3Δ deletions rescued growth defects of elp3Δ in response to thiabendazole and at 37 °C. Elevated tRNALysUUU levels suppressed the elp3Δ phenotypes and some of the dph3Δ phenotypes, indicating that lack of tRNALysUUU modifications were responsible. Furthermore, we found positive genetic interactions of elp3Δ and dph3Δ with sty1Δ and atf1Δ, indicating that Elp3/Dph3-dependent tRNA modifications are important for efficient biosynthesis of key factors required for accurate responses to cytotoxic stress conditions.


Premetamorphic changes in the ultrastructure of Calliphora fat cells.
In the fat body of Calliphora a drastic reorganization of the cell structure, which is related to premetamorphic functional changes, can be observed during the 3rd larval stage of development. These changes include an accumulation of protein storage granules, a decrease in the relative volume of the mitochondria and the surface area of endoplasmic reticulum membrane, and the disappearance of vacuoles. "Absolute" values obtained for organelle areas and membrane perimeters confirm the assumption that large numbers of organelles are eliminated by autophagic activity prior to the pupation period. A temporary restoration of the endoplasmic reticulum is found immediately before pupariation. Large variations in organelle density were found between individual fat cells and between the nuclear, mid- and peripheral regions of the cytoplasm.


Inflammatory biomarker detection in milk using label-free porous SiO2 interferometer.
N-acetyl-β-d-glucosaminidase (NAGase) is an established indicative biomarker released upon damage or necrosis of tubular epithelial cells in both humans and animals, indicating severe nephrological disorders and bovine mastitis (BM), respectively. The latter is the most common and costly disease in dairy cattle associated with production losses, elevated somatic cell counts and deteriorated health status. Herein, we report on a reflective based assay for early diagnosis of BM through the analysis of NAGase inherent content found in whole milk samples using a miniaturized optical transducer. Gelatin functionalized porous Si Fabry-Pérot interferometers are employed for monitoring the lysosomal activity in various stages of the inflammation (healthy, subclinical and clinical). The enzymatic reaction products precipitate and accumulate within the porous nanostructure, thus alter the average refractive index monitored using reflectometric interference spectroscopy. The optical assay is calibrated within the clinically relevant concentrations of BM while presenting a dynamic range of 1.04-16.7 μM min-1 and the detection limit of 0.49 μM min-1. The specific optical performance of the biosensor correlates with a gold standard laboratory-based approach, in which escalated somatic cell counts reveal augmented NAGase levels and thus severe pathogenesis. Overall, our study provides new opportunities to develop a convenient bio-diagnostic sensing system for BM detection and classification by addressing the limitations of conventional practices.


Utilizing an artificial intelligence system to build the digital structural proteome of reef-building corals.
Reef-building corals play an important role in the marine ecosystem, and analyzing their proteomes from a structural perspective will exert positive effects on exploring their biology. Here we integrated mass spectrometry with newly published ColabFold to obtain digital structural proteomes of dominant reef-building corals. Of the 8,382 homologous proteins in Acropora muricata, Montipora foliosa, and Pocillopora verrucosa identified, 8,166 received predicted structures after about 4,060 GPU hours of computation. The resulting dataset covers 83.6% of residues with a confident prediction, while 25.9% have very high confidence. Our work provides insight-worthy predictions for coral research, confirms the reliability of ColabFold in practice, and is expected to be a reference case in the impending high-throughput era of structural proteomics.


Radiative Recombination Processes in Halide Perovskites Observed by Light Emission Voltage Modulated Spectroscopy.
The kinetics of light emission in halide perovskite light-emitting diodes (LEDs) and solar cells is composed of a radiative recombination of voltage-injected carriers mediated by additional steps such as carrier trapping, redistribution of injected carriers, and photon recycling that affect the observed luminescence decays. These processes are investigated in high-performance halide perovskite LEDs, with external quantum efficiency (EQE) and luminance values higher than 20% and 80 000 Cd m-2 , by measuring the frequency-resolved emitted light with respect to modulated voltage through a new methodology termed light emission voltage modulated spectroscopy (LEVS). The spectra are shown to provide detailed information on at least three different characteristic times. Essentially, new information is obtained with respect to the electrical method of impedance spectroscopy (IS), and overall, LEVS shows promise to capture internal kinetics that are difficult to be discerned by other techniques.


Calcium requirement for the inhibition by theophylline of histamine release from mast cells.
When added to Ca2+-free Hanks' solution, Ca2+ (0.1-2.5 mM) had no significant effect on antigen-induced histamine release from rat mast cells, but Sr2+ (1.0-3.0 mM) dose-dependently increased the release. Ba2+ (1.0 and 2.0 mM) also enhanced the release. Ca2+ and Ba2+ inhibited compound 40/80-induced histamine release, in a dose-dependent manner. In ordinary Hanks' medium, theophylline and 3-isobutyl-1-methylxanthine (IBMX) dose-dependently inhibited the antigen-induced histamine release but these drugs were ineffective in Ca2+-free medium. Theophylline (1.0 mM) also inhibited compound 48/80-induced histamine release in the presence but not absence of Ca2+. There was an optimal Ca2+ concentration for the theophylline effect. Sr2+ but not Ba2+ could substitute for Ca2+ in supporting the theophylline effect. Theophylline (1.0 mM) and IBMX (1.0 mM) increased mast cell cyclic AMP levels both in the presence and absence of Ca2+. These results suggest that Ca2+ is required in the interaction of theophylline and specific sites on mast cells or in the mast cell response to theophylline which probably does not involve the cyclic AMP increase and is linked to the inhibition of histamine release.


Cesarean delivery is rising: implications for care for the perianesthesia Nurse.
Cesarean deliveries are on the rise, a fact that is impacting perianesthesia nurses across the country. Although many factors have contributed to this phenomenon, the end result is the need for perianesthesia nurses to update their knowledge base and skill sets to include standard care during the immediate postpartum period. In addition, the perianesthesia nurse will need to consider the normal physiological changes of pregnancy and delivery to assess for postoperative complications unique to obstetrical patients that can significantly affect mortality and morbidity in the surgical postpartum patient.


Somatotopic organization of the facial nucleus is disrupted after lesioning and regeneration of the facial nerve: the histological representation of synkinesis.
After facial nerve repair, involuntary movement of part of the face during voluntary movement of another part of the face is common. We describe an animal model of facial nerve lesion, repair, and regeneration that demonstrates abnormal organization of the facial nucleus; this model may be used to study synkinesis. In 18 rats, the facial nerve was cut completely, proximal to the parotid gland, and immediately sutured end-to-end. After a period of regeneration of 1 to 10 months, retrograde fluorescence labeling of the distal branches of the facial nerve was performed. The distribution of the tracers in the facial nucleus was assessed in both the lesioned animals and in a nonlesioned group (n = 20). In the control animals, muscle groups were somatotopically represented in the facial nucleus. After lesioning, repair, and regeneration, the somatotopy of the facial nucleus was disrupted. Axons projected from the facial nucleus to incorrect peripheral muscle groups, and aberrant branches were observed to simultaneously innervate different subdivisions of the facial nerve. The numbers of aberrant axons and branches did not change significantly during periods of regeneration ranging from 1 to 10 months. Our model provides a clear demonstration of the failure of adult facial nerve axons to make correct connections with their distal targets during regeneration. This model may be used to assess strategies aimed at minimizing synkinesis and, by assessing histology together with behavior, provides a more robust model than those previously described.


Birth characteristics and risk of Ewing sarcoma.
The incidence of Ewing sarcoma varies according to race and ethnicity, and genetic susceptibility is known to affect disease risk. Apart from these factors, the etiology of Ewing sarcoma is largely unknown. We compared the birth characteristics of a population-based series of 556 Ewing sarcoma cases born in California in 1978-2015 and diagnosed in 1988-2015 with those of 27,800 controls selected from statewide birth records and frequency-matched to cases on the year of birth, using multivariable logistic regression models. We also assessed whether Ewing sarcoma clustered within families. Compared to non-Hispanic White subjects, Black (odds ratio [OR] = 0.07, 95% confidence interval [CI] 0.03-0.18), Asian (OR = 0.57, 95% CI 0.41-0.80), and Hispanic (OR = 0.73, 95% CI 0.62-0.88) individuals had a significantly lower risk of Ewing sarcoma. Race and ethnicity differences were more profound for metastatic Ewing sarcoma. Birthweight was also identified as a significant risk factor (OR = 1.09, 95% CI 1.00-1.18 for each 500 g increase in birthweight). A separate family-based cancer clustering analysis did not suggest any strong role for familial predisposition alleles. This population-based study with minimal selection bias provides support for a role of accelerated fetal growth in the etiology of Ewing sarcoma in addition to more precise estimates of racial and ethnic variations in disease risk. This comparatively large analysis of birth characteristics and Ewing sarcoma in a multiethnic population should stimulate further investigations into genetic and environmental causes.


Health promotion and the older population: expanding our theoretical horizons.
As the year 2000 approaches (and beyond) more health educators will be involved in the implementation of health promotion programs and related activities specifically designed for the older population. Most health educators draw upon a variety of theoretical frameworks as they design programs. Traditionally, health education has been grounded in behavior change theories such as the Health Belief Model, the Theory of Reasoned Action, and Bandura's Social Learning/Cognitive Theories. When the focus is gerontological, however, an opportunity exits to expand health education's theoretical horizons by incorporating features drawn from gerontology itself. Principles of adult cognitive development, social gerontology and person-environment fit can potentially complement and supplement those models already in use as more programs are targeted for a growing older population.


Detection and analysis of DNA methylation by pyrosequencing.
Pyrosequencing is a "sequencing by synthesis" technique which can be used to quantify DNA methylation at specific CpG sites within the target region of interest. Biotin labelled polymerase chain reaction (PCR) products form the template for base-pair nucleotide incorporation causing a light emitting cascade reaction resulting in the formation of a pyrogram and the calculation of the percentage methylation for each site. Prior to pyrosequencing, it is essential to bisulphite-convert the DNA sample and then perform locus-specific PCR for the region of interest. One of the PCR primers needs to be biotinylated and a separate sequencing primer is required for the pyrosequencing itself.


Transgenic zebrafish expressing mutant human RETGC-1 exhibit aberrant cone and rod morphology.
Cone-rod dystrophy 6 (CORD6) is an inherited blindness that presents with defective cone photoreceptor function in childhood, followed by loss of rod function. CORD6 results from mutations in GUCY2D, the human gene encoding retinal guanylate cyclase 1 (RETGC-1). RETGC-1 functions in phototransduction, synthesising cGMP to open ion channels in photoreceptor outer segments. As there is limited histopathological data on the CORD6 retina, our goal was to generate a CORD6 model by expressing mutant human RETGC-1 in zebrafish cone photoreceptors and to investigate effects on retinal morphology and function. cDNAs encoding wildtype and mutant (E837D R838S) RETGC-1 were cloned under the control of the cone-specific gnat2 promoter and microinjected into zebrafish embryos to generate transgenic lines. RETGC-1 mRNA expression in zebrafish eyes was confirmed by RT-PCR. Fluorescent microscopy analysed retinal morphology and visual behaviour was quantified by the optokinetic response (OKR). Stable transgenic lines expressing mutant or wildtype human RETGC-1 in zebrafish eyes were generated. OKR assays of 5-day-old larvae did not uncover any deficits in visual behaviour. However, transgenic (E837D R838S) RETGC-1 expression results in aberrant cone morphology and a reduced cone density. A reduction in the number of photoreceptor nuclei, the thickness of the outer nuclear layer and the labelling of rod outer segments, particularly in the central retina, was evident. Expression of mutant human RETGC-1 leads to a retinal phenotype that includes aberrant photoreceptor morphology and a reduced number of photoreceptors. This phenotype likely explains the compromised visual function, characteristic of CORD6.


Molecular Epidemiology of Ralstonia pseudosolanacearum Phylotype I Strains in the Southwest Indian Ocean Region and Their Relatedness to African Strains.
The increasing requirement for developing tools enabling fine strain traceability responsible for epidemics is tightly linked with the need to understand factors shaping pathogen populations and their environmental interactions. Bacterial wilt caused by the Ralstonia solanacearum species complex (RSSC) is one of the most important plant diseases in tropical and subtropical regions. Sadly, little, outdated, or no information on its epidemiology is reported in the literature, although alarming outbreaks are regularly reported as disasters. A large set of phylotype I isolates (n = 2,608) was retrieved from diseased plants in fields across the Southwest Indian Ocean (SWIO) and Africa. This collection enabled further assessment of the epidemiological discriminating power of the previously published RS1-MLVA14 scheme. Thirteen markers were validated and characterized as not equally informative. Most had little infra-sequevar polymorphism, and their performance depended on the sequevar. Strong correlation was found with a previous multilocus sequence typing scheme. However, 2 to 3% of sequevars were not correctly assigned through endoglucanase gene sequence. Discriminant analysis of principal components (DAPC) revealed four groups with strong phylogenetic relatedness to sequevars 31, 33, and 18. Phylotype I-31 isolates were highly prevalent in the SWIO and Africa, but their dissemination pathways remain unclear. Tanzania and Mauritius showed the greatest diversity of RSSC strains, as the four DAPC groups were retrieved. Mauritius was the sole territory harboring a vast phylogenetic diversity and all DAPC groups. More research is still needed to understand the high prevalence of phylotype I-31 at such a large geographic scale.


Psychosocial Factors Affecting Parental Report of Symptoms in Children: A Systematic Review.
Parents make important treatment decisions for their children based on symptoms they perceive their child to be experiencing. Multiple psychological factors are associated with subjective symptom perception, but factors affecting perception of symptoms in others have been explored less. We systematically reviewed the literature to identify parent and child psychological factors associated with parental report of physical symptoms in their child. We searched Embase, Ovid, PsycINFO, and Scopus for studies that investigated associations between psychological factors and parental report of symptoms in their child. Thirty-six citations reporting on 34 studies that assessed the association between parent or child psychological factors and parental report of physical symptoms in the child were included in the review. Three main factors were identified as being associated with parental symptom report. First, there was evidence for an association between parental symptom report and affect, in particular parent and child anxiety. Second, child behavioral and conduct problems, and temperament-related challenges (problems with feeding and sleeping) were associated with parental symptom report. Third, parental expectations and beliefs that symptoms would occur were associated with parental symptom report, although few studies investigated these associations. Parent and child affect, and parental expectations and beliefs may influence parents' cognition, causing them to pay more attention to their child, interpret their child's behavior as symptomatic, and recall symptoms in the child. Given the importance of parental perception of symptoms in driving decisions around care, additional research in this field is needed.


Glibenclamide mitigates cognitive impairment and hippocampal neuroinflammation in rats with type 2 diabetes and sporadic Alzheimer-like disease.
A growing body of evidence suggests that type 2 diabetes (T2D) is a risk factor for cognitive impairment and dementia. Both preclinical and clinical studies have provided evidence that brain insulin resistance is associated with cognitive decline in patients with T2D and sporadic Alzheimer disease (AD). Accordingly, antidiabetic medications have been suggested as potential drugs for the treatment of cognitive impairments in patients with sporadic AD. This study set out to determine whether glibenclamide (GBC), an antidiabetic agent, can ameliorate cognitive impairments in rats with T2D and sporadic AD. Both animal models were treated with GBC for 23 consecutive days. To assess working and spatial memory, animals were subjected to the Y-maze and Morris water-maze tests. We measured glucose and insulin levels in the blood, and inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the hippocampus of animals. Our findings indicated that T2D and sporadic AD impaired memory and elevated TNF-α and IL-6 in the hippocampus. We found increased glucose and insulin levels in the blood of T2D-induced rats but not of sporadic AD rats. In contrast, GBC treatment improved memory impairment, increased insulin, and reduced glucose and hippocampal inflammation in rats with T2D and sporadic AD. This study suggests that GBC could be considered as a potential treatment for cognitive deficits in patients with T2D and sporadic AD. Taken together, this study highlights the need for further studies in humans to test whether GBC treatment is associated with cognitive improvement in sporadic AD patients.


Overexpression of phosphatidylethanolamine-binding protein 4 (PEBP4) associates with recurrence of meningiomas.
Abnormal expression of phosphatidylethanolamine-binding protein 4 (PEBP4) has been identified in various types of malignant tumors. In the present study, we investigated the expression of PEBP4 in meningioma cases and examined whether PEBP4 expression was correlated with outcomes among these patients. The expression levels of PEBP4 and Ki-67 in human meningioma tissues from 65 patients were evaluated by immunohistochemical staining. The correlation between PEBP4 immunoreactivity in meningioma samples and patients' clinical outcomes was examined using the Kruskal-Wallis correlation test. The prognostic value of PEBP4 expression in meningiomas patients also was investigated. Immunohistochemical analysis revealed up-regulated PEBP4 expression in both atypical and anaplastic meningiomas compared with classical meningiomas (13.38 ± 4.19% vs. 3.64 ± 2.04%, P < 0.001). PEBP4 immunoreactivity in meningioma samples was closely correlated with that for Ki-67 (Spearman r = 0.7922, P < 0.0001). PEBP4 expression was also associated with tumor differentiation grade and clinical recurrence (P < 0.05). Multivariate regression analysis showed with high PEBP4 expression was associated with a longer recurrence-free survival (hazard ratio=0.252, 95% confidence interval: 0.067-0.940, P = 0.040). PEBP4 may play an important role in the progression of meningioma, as high PEBP4 expression was associated with a higher pathological grade of meningioma. Moreover, PEBP4 expression may be a meaningful prognostic biomarker in meningioma.


Pathologic features of extraosseous Ewing's sarcoma: a report from the Intergroup Rhabdomyosarcoma Study.
Eighty-four cases of extraosseous Ewing's sarcoma (EOE) were found during the pathology review of the Intergroup Rhabdomyosarcoma Study I and II. Patients commonly presented during or after adolescence with the most common primary sites including the trunk, extremities, and retroperitoneum. Males were slightly more affected. Histologic sections of 74 tumors in the pathology repository were re-reviewed with attention to rosette formation (positive in 18 cases) and glycogen deposition (++ in 21, + in 36, +/- in 11, and - in 2 of 70 cases examined). Fourteen tumors (7 with rosettes and 7 without) were selected for immunohistochemical and ultrastructural studies, and 13 showed single or multiple neural markers (neuron-specific enolase in 8, S-100 protein in 6, and neurosecretory-type granules in 9). These possible cases of neural EOE could be divided into three subgroups: tumor with bidirectional neuroblastic and schwannian differentiation (5 cases), tumor with monodirectional neuroblastic differentiation (7 cases), and tumor with monodirectional schwannian differentiation (1 case). EOE with a neural nature may be categorized into a spectrum of peripheral primitive neuroectodermal tumors. Clinical, histopathologic, and biologic differences between this disease and conventional sympathetic neuroblastoma are discussed.


The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate enhances the long-term maintenance of pancreatic islet B cell differentiated function in tissue culture.
A study was undertaken to examine the effects of the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, on pancreatic islet B cell differentiated function and number. Islets from 3-day-old rats were maintained in tissue culture for up to 30 days with or without the addition of the phorbol ester. Changes in the insulin content of the media and tissue were determined at 48 hr and weekly intervals, respectively, using radioimmunoassay. The 30-day cumulative output of insulin into the medium was increased almost 2-fold and the tissue insulin content was increased 4-fold by the phorbol ester. Counts of cell smears processed for the immunocytochemical localization of insulin indicated no effect on the total numbers of B cells or non-B cells in either control or treated cultures. This enhanced maintenance of islet B cell differentiated function by 12-O-tetradecanoylphorbol-13-acetate suggests that pancreatic islets may be a useful model with which to study the mechanisms of action of this and other tumor-promoters.


Nanofluid Development Using Silver Nanoparticles and Organic-Luminescent Molecules for Solar-Thermal and Hybrid Photovoltaic-Thermal Applications.
Exploiting solar energy using photo-thermal (PT) and/or hybridised photovoltaic/thermal (PVT) systems can represent a viable alternative to the growing demand for renewable energy. For large-scale implementation, such systems require thermal fluids able to enhance the combined conversion efficiency achievable by controlling the 'thermal' and 'electrical' components of the solar spectrum. Nanofluids are typically employed for these purposes and they should exhibit high heat-transfer capabilities and optical properties tuned towards the peak performance spectral window of the photovoltaic (PV) component. In this work, novel nanofluids, composed of highly luminescent organic molecules and Ag nanoparticles dispersed within a base fluid, were tested for PT and PVT applications. These nanofluids were designed to mimic the behaviour of luminescent down-shifting molecules while offering enhanced thermo-physical characteristics over the host base fluid. The nanofluids' conversion efficiency was evaluated under a standard AM1.5G weighted solar spectrum. The results revealed that the Ag nanoparticles' inclusion in the composite fluid has the potential to improve the total solar energy conversion. The nanoparticles' presence minimizes the losses in the electrical power component of the PVT systems as the thermal conversion increases. The enhanced performances recorded suggest that these nanofluids could represent suitable candidates for solar energy conversion applications.


Mechanism of resistance to thiostrepton in the producing-organism Streptomyces azureus.
An antibiotic-producing organism, Streptomyces azureus, defends itself against its own toxic product by methylating the RNA of its ribosomes.


Differential Natural Selection of Human Zinc Transporter Genes between African and Non-African Populations.
Zinc transporters play important roles in all eukaryotes by maintaining the rational zinc concentration in cells. However, the diversity of zinc transporter genes (ZTGs) remains poorly studied. Here, we investigated the genetic diversity of 24 human ZTGs based on the 1000 Genomes data. Some ZTGs show small population differences, such as SLC30A6 with a weighted-average FST (WA-FST = 0.015), while other ZTGs exhibit considerably large population differences, such as SLC30A9 (WA-FST = 0.284). Overall, ZTGs harbor many more highly population-differentiated variants compared with random genes. Intriguingly, we found that SLC30A9 was underlying natural selection in both East Asians (EAS) and Africans (AFR) but in different directions. Notably, a non-synonymous variant (rs1047626) in SLC30A9 is almost fixed with 96.4% A in EAS and 92% G in AFR, respectively. Consequently, there are two different functional haplotypes exhibiting dominant abundance in AFR and EAS, respectively. Furthermore, a strong correlation was observed between the haplotype frequencies of SLC30A9 and distributions of zinc contents in soils or crops. We speculate that the genetic differentiation of ZTGs could directly contribute to population heterogeneity in zinc transporting capabilities and local adaptations of human populations in regard to the local zinc state or diets, which have both evolutionary and medical implications.


Duplex scanning of neck vessels: need for extending the consensus on indications.
We studied the percentage and distribution of appropriate indications for duplex scanning of neck vessels in an outpatient population. A total of 650 consecutive outpatients sent by their general practitioner (GP) or a specialist for duplex scanning of epi-aortic arterial vessels were studied. The aim was to verify the percentage of appropriate (APR) an inappropriate (INAPR) indications for the examination, according to the current literature. After analysis of indications as reported by GPs or specialists and a brief anamnestic examination, 77% of patients were found to have had one or more APR and 23% of patients had none. Analysis of severity of atheromasic lesions between the two groups showed that patients with APR had significantly ( p<0.001, chi-square test) more severe lesions than patients with INAPR. In more detail, no patient with INAPR had severe (>60%) stenosis while 6.4% of patients with APR had severe stenosis. Moreover, the percentage of normal examinations or intima-media thickness only was 32.5% in patients with INAPR but fell to 17.2% in patients with APR. In the entire group, women were more represented than men even after consideration of the natural prevalence of female gender in the local population. Among inappropriate indications for the examination, isolated dizziness or vertigo, syncope and tinnitus were the most frequent. Continuous medical education is needed to reduce inappropriate indications and thus to find solutions, although partial, to shorten the waiting lists that have become an urgent problem for the public health systems of several Western countries. However, this appears to be difficult challenge, as experiments conducted on this issue by other researchers only gave transient positive results.


Guided soft tissue healing in implant dentistry.
Frustrations with creating subgingival implant restorations that are aesthetic and maintainable can be alleviated by using surgical indexing; provisionals as implant copings; or corresponding healing abutments and impression copings. Advantages and disadvantages of each are presented.


A103 immunostaining in the diagnosis of adrenal cortical tumors: an immunohistochemical study of 316 cases.
The monoclonal antibody A103 recognizes an antigen on melanoma cells known as Melan-A or MART-1. Recent studies have shown that A103 also reacts with adrenal cortical cells and may be useful in the diagnosis of adrenal cortical tumors. However, only small numbers of some of the tumors in the differential diagnosis of adrenal cortical neoplasms have been studied. To study the specificity of A103 immunohistochemistry in a large number of tumors in the differential diagnosis of adrenal cortical neoplasms. Formalin-fixed, paraffin-embedded tissue from 21 adrenal cortical tumors, 16 cases of metastatic carcinoma to the adrenal, 10 pheochromocytomas, and 269 extra-adrenal carcinomas was evaluated for A103 immunoreactivity using a commercially available antibody (Novocastra, Newcastle, UK). Positive staining was seen in all of the adrenal cortical tumors but in none of the adrenal metastases or pheochromocytomas. In the 269 extra-adrenal carcinomas, A103 immunoreactivity was limited to a single ovarian serous carcinoma. A103 immunostaining is useful in distinguishing adrenal cortical neoplasms from other carcinomas and pheochromocytoma.


A call for implementation of the Law 2120 against junk food during pandemic times in Colombia
Durante dos años y medio, tanto en Colombia como en el resto del mundo, hemos enfrentado la pandemia generada por el SARS-CoV-2, agudizando los múltiples problemas de salud pública que venían cursando a manera de sindemias. Tal es el caso de las enfermedades crónicas no transmisibles asociadas, entre otros factores, a los malos hábitos alimenticios, especialmente por el gran consumo de alimentos ultraprocesados y bebidas azucaradas. En julio del 2021, se aprobó la Ley 2120, por medio de la cual se adoptaron medidas para fomentar entornos alimentarios saludables. Entre estas medidas, también se promueve que los alimentos empacados, procesados y que afectan negativamente la salud humana, tengan un sello que identifique sus componentes y valor nutricional para informar a los consumidores sobre el producto que están comprando o consumiendo. Entre las enfermedades más prevalentes en Colombia que afectan la salud bucal, se encuentran las caries y las periodontitis, ambas con factores de riesgo comunes con las enfermedades crónicas no transmisibles. Dados sus costos y prevalencia, dichas enfermedades crónicas no transmisibles resultan primordiales desde un enfoque de gestión del riesgo en salud pública, siendo, quizá, su gravedad mayor durante la pandemia generada por el SARS CoV-2. Asimismo, se especula que la población confinada pudo llegar a consumir más comida chatarra durante la pandemia del COVID-19 en comparación con otros períodos, además, porque en aquellos con enfermedades crónicas no transmisibles, el confinamiento obligado se asocia con mayor sedentarismo y con un menor número de controles médicos regulares, asuntos que se han reportado previamente. La promulgación de la ley de comida chatarra no va a cambiar los hábitos de alimentación de los colombianos "de la noche a la mañana" y, por esto, se necesita con urgencia implementar procesos de educación y sensibilización frente a los efectos adversos de los alimentos procesados y ultraprocesados en la salud.


Plasma Proteomic Kinetics in Response to Acute Exercise.
Regular exercise has many favorable effects on human health, which may be mediated in part by the release of circulating bioactive factors during each bout of exercise. Limited data exist regarding the kinetic responses of plasma proteins during and after acute exercise. Proteomic profiling of 4163 proteins was performed using a large-scale, affinity-based platform in 75 middle-aged adults who were referred for treadmill exercise stress testing. Plasma proteins were quantified at baseline, peak exercise, and 1-h postexercise, and those with significant changes at both exercise timepoints were further examined for their associations with cardiometabolic traits and change with aerobic exercise training in the Health, Risk Factors, Exercise Training and Genetics Family Study, a 20-week exercise intervention study. A total of 765 proteins changed (false discovery rate < 0.05) at peak exercise compared to baseline, and 128 proteins changed (false discovery rate < 0.05) at 1-h postexercise. The 56 proteins that changed at both timepoints included midkine, brain-derived neurotrophic factor, metalloproteinase inhibitor 4, and coiled-coil domain-containing protein 126 and were enriched for secreted proteins. The majority had concordant direction of change at both timepoints. Across all proteins assayed, gene set enrichment analysis showed increased abundance of coagulation-related proteins at 1-h postexercise. Forty-five proteins were associated with at least one measure of adiposity, lipids, glucose homeostasis, or cardiorespiratory fitness in Health, Risk Factors, Exercise Training and Genetics Family Study, and 20 proteins changed with aerobic exercise training. We identified hundreds of novel proteins that change during acute exercise, most of which resolved by 1 h into recovery. Proteins with sustained changes during exercise and recovery may be of particular interest as circulating biomarkers and pathways for further investigation in cardiometabolic diseases. These data will contribute to a biochemical roadmap of acute exercise that will be publicly available for the entire scientific community.


CD3delta couples T-cell receptor signalling to ERK activation and thymocyte positive selection.
Thymocytes from mice lacking the CD3delta chain of the T-cell receptor (TCR), unlike those of other CD3-deficient mice, progress from a CD4- CD8- double-negative to a CD4+ CD8+ double-positive stage. However, CD3delta-/- double-positive cells fail to undergo positive selection, by which double-positive cells differentiate into more mature thymocytes. Positive selection is also impaired in mice expressing inactive components of the Ras/mitogen activated protein (MAP) kinase signalling pathway. Here we show that CD3delta-/- thymocytes are defective in the induction of extracellular signal-regulated protein kinase (ERK) MAP kinases upon TCR engagement, whereas activation of other MAP kinases is unaffected. The requirement for CD3delta maps to its extracellular or transmembrane domains, or both, as expression of a tail-less CD3delta rescues both ERK activation and positive selection in CD3delta-/- mice. Furthermore, the defect correlates with severely impaired tyrosine phosphorylation of the linker protein LAT, and of the CD3zeta chain that is localized to membrane lipid rafts upon TCR engagement. Our data indicate that the blockade of positive selection of CD3delta-/- thymocytes may derive from defective tyrosine phosphorylation of CD3zeta in lipid rafts, resulting in impaired activation of the LAT/Ras/ERK pathway.


[Idiopathic edema, capillaropathy, pericardial and pleural effusions with high protein content (author's transl)].
Clinical and electron microscopic studies of two female patients are reported who, in addition to the symptoms and signs of idiopathic edema, had pericardial (and pleural) effusions. In one patient pericardiectomy had to be performed, in the other patient pharmacotherapy with spironolactone was effective. In these patients the protein-concentrations of edema fluid (25 and 12 g/l) and pericardial fluid (55-61 and 48 g/l) were relatively high; the distribution space of labelled protein was increased; blood volumes were low-normal or decreased. Electronmicroscopy of the microvasculature showed identical alterations in both cases. In the cutaneous vessels the endothelium developed numerous abnormal cytoplasmic processes and intercellular "gaps". In the capillaries of skeletal muscle our findings indicate an increase in vesicular transport. We suggest the electron microscopic alterations to be the morphologic correlate for the increased transport and extravascular accumulation of protein. Changes as they are described here in humans with idiopathic edema have been documented before in animals with experimental edema.


Susceptibility testing of Nocardia species for the clinical laboratory.
Not all patients are able to tolerate or show a favorable response to the treatment of choice for Nocardia, the sulfonamides. Many new drugs are available with good activity against N. asteroides, the most common pathogenic species, although susceptibility to these agents, including amikacin, amoxicillin/clavulanic acid, and the third generation cephalosporins, is variable. For these and other reasons, we recommend routine susceptibility testing of Nocardia. Disk diffusion testing on Mueller Hinton agar is the best currently available clinical method. A suggested control strain and tentative susceptible and resistant breakpoints for 12 antimicrobial agents are provided. This includes agents not previously evaluated, including cefotaxime, amikacin, ciprofloxacin, and doxycycline. The zones of inhibition were all larger than those currently used by the NCCLS for rapidly growing bacteria, and the disk breakpoints generally fit best with the MIC breakpoints used with the dilution susceptibility method (M7-T). A broth microdilution MIC method is described that showed good correlation with disk diffusion results, but need additional study. Because of limited experience in most laboratories with this species, reliance on a good reference laboratory for confirmatory susceptibility testing is recommended. Beta-lactamase testing is not helpful, as almost all Nocardia produce beta-lactamase, although many isolates retain susceptibility to selected beta-lactams.


[A report of 31 cases of asthenospermia treated by jujing granulation].
To evaluate the therapeutic effects of Jujing granulation on asthenospermia. Thirty-six patients aged from 24 to 39 years with asthenospermia were received at our clinic of andrology from July 2004 to April 2005, and they were given Jujing granulation 120 ml twice a day for 3 months. The sperm parameters of the patients were analyzed by computer assisted sperm analysis system before and after Jujing granulation treatment. Of the 31 patients who accomplished 3-month Jujing granulation therapy, only 3 remained unimproved in sperm parameters, while the other 28 were significantly improved in rapid sperm motility, forward sperm motility and total sperm motility, except in sperm density. Five of the patients' wives got pregnant and one had a child. Oral Jujing granulation therapy is efficacious for asthenospermia.


Is total-body MRI useful as a screening tool to rule out malignant progression in patients with multiple osteochondromas? Results in a single-center cohort of 319 adult patients.
To evaluate the results of total-body (TB) MRI used as a screening tool for assessment or exclusion of malignant transformation in patients with hereditary multiple osteochondromas (HMO). In a single-institute cohort of MO patients, 366 TB-MRI examinations, including T1-weighted and STIR images, were performed for screening and follow-up purposes to rule out the malignant transformation, and retrospectively analyzed. In each patient, the presence and location of osteochondromas in the axial and appendicular bones were recorded. Forty-seven patients underwent a second TB surveillance in this period. STIR sequences were used to identify sites of increased signal intensity that could represent suspicious thickened cartilage caps or indeterminate reactive changes related to osteochondromas. In 82% of patients, one or more OC locations were determined in one or more flat bones. In 366 exams, nine OC (2,5 %) with suspicious imaging features were identified. These proved to be peripheral chondrosarcomas after targeted MRI and resection were performed. All nine malignant lesions were in flat bones (pelvis 5, ribs 3, scapula 1). Three of these patients were 19 years of age. In 12 patients who had peripheral or intraosseous low-grade chondrosarcoma in their history, before their first TB-MRI, no new lesions were identified. Twenty-three additional TB-MRI exams, demonstrating focal high T2 signal intensity, also gave rise to performing additional targeted MRI. One OC of the distal femur was excised and appeared benign. No suspicious cartilage caps were depicted on the remaining 22 targeted MRI exams but instead increased T2 signal was clarified by reactive changes (frictional bursitis, soft tissue edema) in close relation with benign osteochondromas. No malignant lesions were found in 47 patients who had a second TB surveillance (mean interval between exams 3.2 years, range 2-5 years). TB-MRI can identify malignant transformation of osteochondromas in HMO patients. All peripheral chondrosarcomas occurred in flat bones (ribs, scapula, pelvis) in our study. TB-MRI might assist in triage between higher risk patients with a high burden of OC, including the location of OC in main flat bones vs lower risk patients without OC of the flat bones.


Nectar intake rate is modulated by changes in sucking pump activity according to colony starvation in carpenter ants.
Dynamics of fluid feeding has been deeply studied in insects. However, the ability to vary the nectar-intake rate depending only on the carbohydrate deprivation has been clearly demonstrated only in Camponotus mus ants. When insect morphometry and fluid properties remain constant, changes in intake rate could only be attributed to variations in sucking pump activity. Previous records of the electrical activity generated during feeding in C. mus have revealed two different signal patterns: the regular (RP, frequencies: 2-5 Hz) and the irregular (IP, frequencies: 7-12 Hz). This work studies the mechanism underlying food intake-rate modulation in ants by analysing whether these patterns are involved. Behaviour and electrical activity generated by ants at different starvation levels were analysed during feeding on sucrose solutions. Ants were able to modulate the intake rate for a variety of sucrose concentrations (10, 40 and 60%w/w). The IP only occurred for 60% of solutions and its presence did not affect the intake rate. However, during the RP generated under the starved state, we found frequencies up to 7.5 Hz. RP frequencies positively correlated with the intake-rate for all sucrose concentrations. Hence, intake-rate modulation according to sugar deprivation is mainly achieved by the ant's ability to vary the pumping frequency.


Single ventricle palliation of truncus arteriosus with mitral atresia, interrupted aortic arch, and aberrant right subclavian artery.
The association of truncus arteriosus communis with interrupted aortic arch and mitral atresia is an exceptionally rare congenital defect. We describe the initial decision-making and management of this lesion, which eventually achieved a Fontan palliation.


Enzymatic resolution of homoallyllic alcohols using various Rhizopus species.
The asymmetric resolution of various 1-aryl-3-buten-1-ols via microbial hydrolysis of the corresponding acetates has been investigated using different Rhizopus species. The chosen species, R. arrhizus (wild type), efficiently hydrolyzed 1-phenyl- and 1-para-substituted phenyl-3-buten-1-ol acetates, producing the enantiomerically pure (R)-alcohols with 53-65% yields. Although the antipode acetates were obtained with 9-52% enantiomeric excess, the (S)-alcohols were amenable in >99% enantiomeric excess via a R. arrhizus mediated asymmetric reduction of the corresponding ketones.


Antimicrobial resistance in Klebsiella species from milk specimens submitted for bovine mastitis testing at the Wisconsin Veterinary Diagnostic Laboratory, 2008-2019.
The purpose of this retrospective study was to describe antimicrobial resistance trends in Klebsiella isolates cultured from milk samples submitted to the Wisconsin Veterinary Diagnostic Laboratory for bovine mastitis testing. In vitro antimicrobial susceptibility testing was conducted in 483 Klebsiella isolates cultured from 63,841 milk samples submitted from January 1, 2008, through December 31, 2019. The Wisconsin Veterinary Diagnostic Laboratory conducted antimicrobial susceptibility testing according to the Clinical and Laboratory Standards Institute by using a broth microdilution panel. Ten antimicrobials were tested in the panel: ampicillin, penicillin, erythromycin, oxacillin + 2% NaCl, pirlimycin, penicillin/novobiocin, tetracycline, ceftiofur, cephalothin, and sulfadimethoxine. Isolates were considered resistant to specific antimicrobials based on minimum inhibitory concentrations described in Clinical and Laboratory Standards Institute guidelines. No guidelines were available for sulfadimethoxine; isolates were categorized as resistant when bacterial growth was not inhibited. The proportion of isolates resistant to ceftiofur, cephalothin, or tetracycline did not increase over time. For sulfadimethoxine, the proportion of resistant isolates decreased over time. These results do not demonstrate a trend toward increasing antimicrobial resistance among Klebsiella isolates. Despite that, antimicrobial resistance should continue to be monitored.


Physico-chemical and genotoxicity analysis of Guaribas river water in the Northeast Brazil.
River pollution in Brazil is significant. This study aimed to evaluate the physico-chemical and genotoxic profiles of the Guaribas river water, located in Northeast Brazil (State of Piauí, Brazil). The study conducted during the dry and wet seasons to understand the frequency of pollution throughout the year. Genotoxicity analysis was done with the blood of Oreochromis niloticus by using the comet assay. Water samples were collected from upstream, within and downstream the city Picos. The results suggest a significant (p < 0.05) genotoxic effect of the Guaribas river water when compared to the control group. In comparison to the control group, in the river water we found a significant increase in metals such as - Fe, Zn, Cr, Cu and Al. In conclusion, Guaribas river carries polluted water, especially a large quantity of toxic metals, which may impart the genotoxic effect.


Pupil dynamics after in-the-bag versus anterior and retropupillary iris-fixated intraocular lens implantation.
An Intraocular Lens (IOL) fixated on the iris either anteriorly, as a phakic IOL, or posteriorly, as an aphakic IOL, can influence pupil motility. In this interventional case series study, we evaluated pupil size under different levels of illumination (scotopic = 0.04 lx, low-mesopic = 0.4 lx and high-mesopic = 4 lx) for anterior iris-claw IOL fixation for correcting myopia or hyperopia (IFPH), retropupillary iris-claw IOL fixation to correct aphakia or as treatment for late in-the-bag IOL dislocation/subluxation (IFRP), and capsular-fixation IOL in-the-bag implantation (IB). Pupil size was measured preoperatively for the IFPH- and IB-group as well as 6 months after surgery for all groups. We analyzed a total of 70 eyes: 22 eyes of 11 patients with phakic IOLs, 22 eyes of 20 patients in the IFRP group and 26 eyes of 13 patients in the IB group. Both IFPH and IB showed a smaller postoperative scotopic pupil size, compared with the preoperative values. When compared to postoperative values of IB and IFPH, IFRP showed a significantly smaller postoperative scotopic pupil size (IFPH: 5.89 ± 0.83 mm, IFRP: 4.37 ± 0.83 mm, IB: 5.34 ± 0.98 mm, p < 0.001) while no differences were seen at high-mesopic lighting. Neither of the surgical techniques seems to impair the constriction of the pupil.


Targeted mechanical stimulation via magnetic nanoparticles guides in vitro tissue development.
Tissues take shape through a series of morphogenetic movements guided by local cell-scale mechanical forces. Current in vitro approaches to recapitulate tissue mechanics rely on uncontrolled self-organization or on the imposition of extrinsic and homogenous forces using matrix or instrument-driven stimulation, thereby failing to recapitulate highly localized and spatially varying forces. Here we develop a method for targeted mechanical stimulation of organoids using embedded magnetic nanoparticles. We show that magnetic clusters within organoids can be produced by sequential aggregation of magnetically labeled and non-labeled human pluripotent stem cells. These clusters impose local mechanical forces on the surrounding cells in response to applied magnetic fields. We show that precise, spatially defined actuation provides short-term mechanical tissue perturbations as well as long-term cytoskeleton remodeling in these organoids, which we term "magnetoids". We demonstrate that targeted magnetic nanoparticle-driven actuation guides asymmetric tissue growth and proliferation, leading to enhanced patterning in human neural magnetoids. This approach, enabled by nanoparticle technology, allows for precise and locally controllable mechanical actuation in human neural tube organoids, and could be widely applicable to interrogate the role of local mechanotransduction in developmental and disease model systems.


Low-cost modified-atmosphere hermetic storage structures to reduce storage losses of maize (Zea mays L.) cobs and sorghum (Sorghum bicolor L.) heads.
Production and marketing of cereal grains are some of the main activities in developing countries to ensure food security. However, the food gap is complicated further by high postharvest loss of grains during storage. This study aimed to compare low-cost modified-atmosphere hermetic storage structures with traditional practice to minimize quantitative and qualitative losses of grains during storage. The study was conducted in two phases: in the first phase, seven hermetic storage structures with or without smoke infusion were compared, and one selected structure was further validated at scaled-up capacity in the second phase. Grains stored in PVC bag-supported structures (with or without smoke infusion) resulted in low live weevil population, low percentage of damaged grains and reduced weight loss with better retention of crude protein and fat contents. Results from validation study also demonstrated that maize and sorghum stored in improved storage structures experienced, respectively, 9.8% and 10.4% weevil damage as compared with 47.3% and 42.3% when stored in traditional storage structures. The same was true in terms of crude protein and fat contents. The study demonstrated that storage structures supported with PVC bags are efficient and low-cost structures for reducing storage-related losses and supporting food security efforts as compared to traditional methods. Furthermore, the bags can be made locally and with various storage capacities to store either shelled or unshelled products. © 2019 Society of Chemical Industry.


Immune hemolytic anemia associated with tolmetin and suprofen.
This article reports the first case of immune hemolytic anemia possibly associated with the ingestion of suprofen. The patient suffered from massive hemoglobinuria and acute renal failure. Serologic studies of the patient's serum revealed suprofen-dependent red cell antibodies. However, tolmetin-dependent antibodies were also found in the serum, showing the same properties as the suprofen antibodies and an even higher titer. The patient not only had drug-dependent antibodies in the serum, but also had developed autoantibodies, a phenomenon that has been described for several other drugs. The working mechanism by which suprofen and tolmetin caused immune hemolysis had properties of both the immune complex model and the induction of autoimmunity. Although it was unclear whether the immune hemolytic anemia was the result of suprofen, tolmetin, or cross-reacting antibodies, we feel that suprofen should be added to the list of nonsteroidal anti-inflammatory drugs associated with a positive direct antiglobulin test.


Schwangerschaftsprotein 1 (SP1) in serum and cerebrospinal fluid of patients with gestational trophoblastic disease.
The beta subunit of human chorionic gonadotrophin (beta-hCG) and Schwangerschaftsprotein 1 (SP1) were measured by radioimmunoassay in the serum and cerebrospinal fluid (CSF) of 46 postmolar and postpartum patients who developed gestational trophoblastic disease. There was a significant correlation between beta-hCG and SP1 serum levels. The mean serum SP1 level in high-risk patients was significantly higher than that in low-risk patients. There was a significant correlation between serum and CSF beta-hCG levels. The ratio of serum to CSF beta-hCG levels was low in the three patients with clinical evidence of intracranial metastasis. SP1 was present in the CSF of only one of these three patients, but it could be detected in the CSF of another four patients without clinical evidence of metastases in the central nervous system. The two low-risk patients with SP1 present in the CSF showed poor response to intramuscular methotrexate.


Exponential consensus of discrete-time non-linear multi-agent systems via relative state-dependent impulsive protocols.
In this paper, we discuss the exponential consensus problem of discrete-time multi-agent systems with non-linear dynamics via relative state-dependent impulsive protocols. Impulsive protocols of which the impulsive instants are dependent on the weighted relative states of any two agents are introduced for general discrete-time multi-agent systems. The analysis of such impulsive protocols is transformed into an investigation on reduced fixed-time impulsive protocols by constructing a map, which is achieved mainly by a derived B-equivalence method in discrete-time domain. Our main results indicate that the exponential consensus of the multi-agent systems via relative state-dependent impulsive protocols can be achieved if the reduced systems via fixed-time impulsive protocols can achieve exponential consensus, which need to satisfy suitable sufficient conditions. Numerical simulations are presented to support the theoretical results.


Cloning and characterization of thermostable esterase from Archaeoglobus fulgidus.
Thermostable esterase gene was cloned (Est-AF) from extremophilic microorganisms, Archaeoglobus fulgidus DSM 4304. The protein analysis result showed that Est-AF is monomer with total 247 amino acids and molecular weight of estimated 27.5 kDa. It also showed repeating units G-X-S-X-G (GHSLG) (residues 86 approximately 90) which is reported as active site of known esterases, and the putative catalytic triad composed of Ser88, Asp198 and His226. The esterase activity test with various acyl chain length of rho-nitrophenol resulted that Est-AF showed highest specific activity with rho-nitrophenylbutyrate (pNPC4) and rapidly decrease with rho-nitrophenyl ester contain more than 8 carbon chain. These results represent that cloned enzyme is verified as a carboxylesterase but not a lipase because esterase activity is decreased with rho-nitrophenyl ester contains more than 8 carbon chains but lipase activity does not affected with carbon chain length. Optimum temperature of esterase reaction with rho-nitrophenylbutyrate (pNPC4) was 80 degrees C. When ketoprofen ethyl ester was used as a substrate, activity of Est-AF showed the highest value at 70 degrees C, and 10% of activity still remains after 3 h of incubation at 90 degrees C. This result represents Est-AF has high thermostability with comparison of other esterases that have been reported. However, Est-AF showed low enantioselectivity with ketoprofen ethyl ester. Optimum pH of Est-AF is between pH 7.0 and pH 8.0. Km value of ketoprofen ethyl ester is 1.6 mM and, Vmax is 1.7 micromole/mg protein/min. Est-AF showed similar substrate affinity but slower reaction with ketoprofen ethyl ester compare with esterase from mesophilic strain P. fluorescens.


Preparation and evaluation of amphipathic lipopeptide-loaded PLGA microspheres as sustained-release system for AIDS prevention.
At present, AIDS drugs are typical inhibitors that cannot achieve permanent effects. Therefore, the research of blocking HIV infection is essential. Especially for people in the high-risk environment, long-term prevention is important, because HIV can easily infect cells once the drug is interrupted. However, there is still no long-acting AIDS prevention drug approved. Hence, the purpose of this study is to prepare a fusion inhibitor loaded poly(d, l-lactic-co-glycolic acid) (PLGA) microspheres as a sustained-release system for long-term AIDS prevention. As the HIV membrane fusion inhibitor (LP-98) used in this research is amphiphilic lipopeptide, W1/O/W2 double-emulsion method was chosen, and premix membrane emulsification technique was used for controlling the uniformity of particle size. Several process parameters that can impact drug loading efficiency were summarized: the concentration of LP-98 and PLGA, and the preparation condition of primary emulsion. Finally, the microspheres with high loading efficiency (>8%) and encapsulation efficiency (>90%) were successfully prepared under optimum conditions. Pharmacokinetic studies showed that LP-98-loaded microspheres were capable to continuously release for 24 days in rats. This research can promote the application of sustained-release microspheres in AIDS prevention, and the embedding technique used in this study can also provide references for the loading of other amphipathic drugs.


The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes.
The T cell surface glycoproteins T4 and T8 are thought to mediate efficient cell-cell interactions in the immune system and in this way may be responsible for the appropriate targeting of subpopulations of T cells. We have used gene transfer combined with subtractive hybridization to isolate both cDNA and functional genomic clones encoding the T8 protein. The sequence of the cDNA reveals that T8 is a transmembrane protein with an N-terminal domain which shares significant homology to immunoglobulin variable region light chains. This immunoglobulin-like structure is likely to be important in the function of T8 during differentiation and in the course of the immune response.


Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens.
Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine.