Frequency modulation of neuronal theta-bursts in rabbit's septum by low-frequency repetitive stimulation of the afferent pathways.
Activity of the neurons with stable theta-bursts was recorded extracellularly in intact and hippocampectomized septum of unanesthetized chronic rabbits during low-frequency (3-17 Hz) stimulation of horizontal limb of diagonal band or lateral septal nucleus. The stimulation rarely evoked standard oligosynaptic single-spike responses in stable theta-bursting units. Instead, gradual entrainment and phase-locking of the spontaneous theta-cycles occurred. Two types of entrainment were observed: "entrainment by the pause", where interburst interval was reset by the stimuli; and "entrainment by the burst", where bursts were time-locked to the stimuli. Such reorganization of the spontaneous bursts occurred in the narrow frequency range of stimulation (from 4 Hz up to 9-12 Hz), with the best resonance following in the range of "basic" theta frequencies of the awake rabbit (5-6 Hz). With stimulation beyond the theta-range three phenomena occurred: shift of the burst frequencies to higher or lower harmonics of stimulation frequencies; complex interactions of basic background frequency with rhythm of stimulation ("beating"); return to background theta-burst frequency in spite of continuing stimulation ("escape"). The properties of the septal theta-bursting cells as presumable intrinsic bursting pacemakers are discussed.


DoubletDecon: Deconvoluting Doublets from Single-Cell RNA-Sequencing Data.
Methods for single-cell RNA sequencing (scRNA-seq) have greatly advanced in recent years. While droplet- and well-based methods have increased the capture frequency of cells for scRNA-seq, these technologies readily produce technical artifacts, such as doublet cell captures. Doublets occurring between distinct cell types can appear as hybrid scRNA-seq profiles, but do not have distinct transcriptomes from individual cell states. We introduce DoubletDecon, an approach that detects doublets with a combination of deconvolution analyses and the identification of unique cell-state gene expression. We demonstrate the ability of DoubletDecon to identify synthetic, mixed-species, genetic, and cell-hashing cell doublets from scRNA-seq datasets of varying cellular complexity with a high sensitivity relative to alternative approaches. Importantly, this algorithm prevents the prediction of valid mixed-lineage and transitional cell states as doublets by considering their unique gene expression. DoubletDecon has an easy-to-use graphical user interface and is compatible with diverse species and unsupervised population detection algorithms.


CK2 kinase activity but not its binding to CK2 promoter regions is implicated in the regulation of CK2α and CK2β gene expressions.
Protein kinase CK2, a ubiquitous serine/threonine kinase in control of a variety of crucial cellular functions, is composed of catalytic α- and α'-subunits and non-catalytic β-subunits which form holoenzymes such as CK2(αβ)2, CK2αα'β2, or CK2(α'β)2. In addition, there is ample evidence for the occurrence of the individual subunits beside the holoenzyme. While the CK2 subunits are well analyzed on the protein level, only little is known about the regulation of their transcription. The existence of multiple forms of CK2 subunits raised the question about a mutual regulation of their expression. Here we defined two 5'-upstream regions of the CK2α and the CK2β genes, respectively, as sequences with promoter activities. We found that CK2α and CK2α' stimulated the expression of the reporter constructs whereas, CK2β was inactive. Using chromatin immunoprecipitation assays, we were unable to detect binding of endogenous CK2 subunits to these promoter sequences in vivo. However, it turned out that inhibition of the kinase activity of CK2 attenuated the promoter activity indicating that CK2α and CK2α' might regulate their gene expression indirectly by phosphorylation reactions. Thus, we have shown here (i) that under normal physiological conditions CK2 does not bind to CK2 promoter regions and (ii) that the CK2 kinase activity is implicated in the regulation of its own expression.


Bees reflect better on their ecosystem health than their products.
Beehives constitute a source of environmental contaminants because forager bees explore their habitat and unintentionally accumulate them while foraging for food. Therefore, this review paper investigated different bee species and products from 55 countries to identify how they can help environmental biomonitoring by giving an overview of the past 11 years. Thereby is presented in this study the beehive's use as a bioindicator for metals, analytical techniques, data analysis, environmental compartments, common inorganic contaminants, reference thresholds for some metal concentrations in bees and honey, and other factors over more than 100 references. Most authors agree that the honey bee is a suitable bioindicator to assess toxic metal contamination, and among its products, propolis, pollen, and beeswax are more suited than honey. However, in some situations, when comparing bees with their products, bees are more efficient as potential environmental biomonitors. Some factors such as the colony location, floral sources, regional effects, and activities surrounding the apiary influence the bees, and the composition of their products is reflected by alterations in their chemical profile, making them suitable bioindicators.


What do we really know about UK paediatric dental general anaesthesia services?
Dental general anaesthesia (DGA) is only permitted within a hospital setting where critical care facilities are available. Recently, concern has been expressed about the number of hospital admissions for the dental care of children following the publication of a high profile paper which highlighted an apparent increase in children being admitted for extractions due to caries under DGA. Coincidentally new best practice standards for paediatric DGA services have been published. An evaluation of DGA services in Yorkshire and the Humber suggested that existing monitoring was inadequate and is unlikely to represent true levels of activity and that any apparent increase may reflect the method of remuneration for services. In fact, recent changes in service structure and changes to improve quality have reduced DGA activity in some areas. In addition, the evaluation revealed that many services were not meeting standards of best practice.


The diagnostic value of interleukin-6 and interleukin-8 for early prediction of bacteremia and sepsis in children with febrile neutropenia and cancer.
Early diagnosis of sepsis in children with febrile neutropenia and cancer still remains a challenge for modern medicine because of lack of specific laboratory markers and clinical signs especially at the beginning of the infection. The objective of this study was to evaluate the ability of interleukin-6 and interleukin-8 to predict bacteremia and sepsis during the first 2 days in oncohematologic patients with febrile neutropenia. A total of 61 febrile neutropenic episodes in 37 children were studied. Serum samples were collected on day 1 and day 2 from the onset of fever and analyzed using an automated random access analyzer. Neutropenic children with febrile episodes were classified into the following 2 groups: (1) fever of unknown origin group--patients with a negative blood culture--and (2) bacteremia/sepsis group--patients with a positive blood culture or clinical sepsis. High negative predictive values were found on day 1 for interleukin-6 and interleukin-8 (89% and 82%, respectively) for exclusion of bacteremia/sepsis. These interleukins could be used as a screening tool for the rejection of sepsis or bacteremia on the first day of fever in neutropenic children with cancer.


Concurrent Pansinusitis and Orbital Cellulitis Complicated by Extensive Head and Neck Venous Thrombosis in an Unvaccinated Adolescent Patient with COVID-19: A Case Report.
Orbital cellulitis is an infrequent but serious infectious complication of rhinosinusitis, most commonly seen in the pediatric population. Extension into the cavernous sinus, leading to further infection and thrombosis, is a rare but life-threatening complication. Although COVID-19 has been linked to an increased risk of venous thromboembolism, most cases involve extremity deep venous thrombosis or pulmonary embolism; reports of intracranial or jugular system thrombosis are rare. We describe a case of a 17-year-old female patient with no significant medical history or thrombotic risk factors found to have orbital cellulitis and severe pansinusitis, complicated by multiple venous thromboses in the head and neck requiring emergent surgical intervention and pediatric intensive care admission. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Extensive head and neck venous thrombosis and intracranial abscesses are rare complications of pansinusitis and orbital cellulitis, and the thrombotic complications of COVID-19 are well documented. A delay in diagnosis and treatment can lead to potentially devastating consequences.


Cystic tumors of the pancreas.
Cystic neoplasms of the pancreas are relatively uncommon lesions that should not be confused with pancreatic pseudocysts. Guidelines for this differential diagnosis, the characteristics of the more common varieties, and the authors' experience with 130 cystic tumors are described.


[Magnetic resonance imaging of the brain in neonates and infants].
Magnetic resonance imaging (MRI) is increasingly being used for infants and small children due to rapid sequence protocols, broader scanner availability and good monitoring possibilities. The sequence protocol should always be adapted to the individual clinical needs of the infant or toddler. For some clinical indications, such as control of ventricular width in children with shunted hydrocephalus, ultrafast protocols can be used with a scanning time of just a few minutes. For more complex clinical questions, more extensive sequence protocols are warranted. Particularly for neonates and using a rapid investigation protocol, MRI examinations can very often be performed without sedation. The necessity of using gadolinium-based contrast agents has to be critically deliberated in infants and neonates and has to be exactly tailored to the clinical needs. In many cases MRI examinations of the brain in infants and neonates do not require gadolinium-based contrast agents.


Suxamethonium in myasthenia gravis.
The effects of suxamethonium 1.0 and 0.5 mg/kg were studied in myasthenic patients. Resistance was not encountered at the 1.0 mg/kg dose but was seen at the lower dose. A non-depolarising type of block developed in patients in both groups. However, recovery from the non-depolarising block was not prolonged beyond the requirements of surgery. The neurophysiological basis for, and clinical implications of these findings are discussed.


Increase of paradoxical sleep (PS) by intraperitoneal injection of brain extract from PS-deprived rats.
Intraperitoneal injection of a brain extract obtained from paradoxical sleep-(PS) deprived donor rats resulted in a small but significant increase of PS in normal recipient rats. Brain extract of non-deprived control rats was without effect. The results provide further evidence for the existence of a PS-inducing factor accumulating in the brain during PS deprivation.


Isolation of adenovirus type 5 host range deletion mutants defective for transformation of rat embryo cells.
A series of adenovirus type 5 (Ad5) deletion, insertion and substitution mutants, some of which are defective for transformation of rat cells, have been isolated. The mutants were selected as variants which lack the Xba I endonuclease cleavage site at 4 map units on the viral chromosome. The deletions range in size from 150-2300 bp and are located between 1.5 and 10.5 map units. The mutants can be propagated in 293 cells (Ad5-transformed human embryonic kidney cells), but are defective for growth in HeLa or human embryonic kidney cells. No viral DNA synthesis was observed in mutant virus-infected HeLa cells. All but one of the deletion mutants tested were defective for transformation of rat embryo and rat embryo brain cells.


Crystal structures of a Formin Homology-2 domain reveal a tethered dimer architecture.
Formin proteins participate in a wide range of cytoskeletal processes in all eukaryotes. The defining feature of formins is a highly conserved approximately 400 residue region, the Formin Homology-2 (FH2) domain, which has recently been found to nucleate actin filaments. Here we report crystal structures of the S. cerevesiae Bni1p FH2 domain. The mostly alpha-helical FH2 domain forms a unique "tethered dimer" in which two elongated actin binding heads are tied together at either end by an unusual lasso and linker structure. Biochemical and crystallographic observations indicate that the dimer is stable but flexible, with flexibility between the two halves of the dimer conferred by the linker segments. Although each half of the dimer is competent to interact with filament ends, the intact dimer is required for actin nucleation and processive capping. The tethered dimer architecture may allow formins to stair-step on the barbed end of an elongating nascent filament.


Genome sequencing: and then there were six.
The genome of the fission yeast Schizosaccharomyces pombe has been sequenced, bringing the number of sequenced eukaryotic genomes to six. Analysis of the sequence predicts only 4824 protein coding genes, the smallest number yet recorded for a free-living eukaryote.


Mechanisms for community prevention of violence against women in low- and middle-income countries: A realist approach to a comparative analysis of qualitative data.
Growing evidence suggests that community-based interventions in low- and middle-income countries (LMICs) can effectively address harmful social norms that promote or sustain gender inequality and drive violence against women (VAW). However, understanding what actions communities are already taking to address harmful social norms and prevent VAW is an essential first step for intervention development. Towards this goal, drawing on collective action theory, we conducted a realist analysis of secondary qualitative data collected with communities in India, Afghanistan, Peru and Rwanda. We coded interview and focus-group data from 232 participants to identify the contexts, mechanisms and outcomes (CMO) relevant for community action. We synthesized CMO configurations from each dataset into a conceptual framework composed of three middle-range theories of mechanisms driving community action to prevent VAW in LMICs. Our results highlight the importance of dedicated spaces for discussing VAW, VAW leaders as positive role models, and community perceptions of VAW as a problem worthy of intervention. In Rwanda and Peru, there was strong evidence to support the operation of these mechanisms. Contextual factors, including national and local policy and programmes targeting VAW, activated mechanisms that led to community action. In India and Afghanistan, evidence for the presence of these mechanisms was weaker, with social norms about women's position and violence being a private family matter preventing communities from addressing violence. Despite contextual differences, our data demonstrated communities in all four settings were somewhere along a pathway of change towards VAW prevention. This supports the need to build future prevention interventions on pre-existing mechanisms that trigger community action, rather than implementing existing interventions without local adaptation. Our conceptual framework serves as a tool for assessing these mechanisms of community action as part of intervention development research, centring community knowledge and fostering local ownership for more relevant and sustainable VAW prevention interventions.


Outcomes of pediatric inguinal hernia repair with or without opening the external oblique muscle fascia.
Considering that complications and outcome of each method of pediatric inguinal hernia repair are one of the determinants for pediatric surgeons for selection of the appropriate surgical technique, we compared the early and late complications of two inguinal repair techniques, with and without opening the external oblique muscle fascia. In this double-blind clinical trial study, boy children aged 1-month to 6 years with diagnosed inguinal hernia were included and randomly allocated into two groups for undergoing two types of hernia repair techniques, with and without opening the external oblique muscle fascia. Surgical complications such as fever, scrotal edema and hematoma, and wound infections classified as early complication and recurrence, testis atrophy and sensory impairment of inguinal area classified as late complications. The rates of mentioned early and late complications were compared in the two interventional groups. In this study, 66 patients were selected and allocated to the two interventional groups. The prevalence of early and late complications in two studied groups were not different significantly in two interventional groups (P > 0.05). Operation time was significantly shorter in inguinal repair techniques without opening the external oblique muscle fascia than the other studied technique (P = 0.001). The findings of our study indicated that though early and late complications of the two repair methods were similar, but the time of procedure was shorter in herniotomy without opening the external oblique muscle, which considered the superiority of this method than inguinal hernia repair with opening the external oblique muscle.


Differential induction, purification and characterization of cold active lipase from Yarrowia lipolytica NCIM 3639.
The production, purification and characterization of cold active lipases by Yarrowia lipolytica NCIM 3639 is described. The study presents a new finding of production of cell bound and extracellular lipase activities depending upon the substrate used for growth. The strain produced cell bound and extracellular lipase activity when grown on olive oil and Tween 80, respectively. The organism grew profusely at 20 °C and at initial pH of 5.5, producing maximum extracellular lipase. The purified lipase has a molecular mass of 400 kDa having 20 subunits forming a multimeric native protein. Further the enzyme displayed an optimum pH of 5.0 and optimum temperature of 25 °C. Peptide mass finger printing reveled that some peptides showed homologues sequence (42%) to Yarrowia lipolytica LIP8p. The studies on hydrolysis of racemic lavandulyl acetate revealed that extracellular and cell bound lipases show preference over the opposite antipodes of irregular monoterpene, lavandulyl acetate.


Correlations between humor styles and loneliness.
In a previous study, a significant negative correlation between shyness with affiliative humor and a significant positive one with self-defeating humor were reported. Since shyness and loneliness share many of the same characteristics, poor social skills and negative affect, for example, significant negative correlations of loneliness with affiliative and self-enhancing humor and a significant positive one with self-defeating humor were hypothesized. 106 community college students (34 men, 72 women) ranging in age from 17 to 52 years (M=23.5, SD=7.7) were tested. The hypotheses were supported. Interrelationships among humor, shyness, and loneliness should be examined within one study.


The clinical significance of gadolinium enhancement of lumbar disc herniations and nerve roots on preoperative MRI.
The clinical significance of preoperative gadolinium DPTA enhancement around disc herniations and in the epidural space on MRI is not clear. The relation of nerve root enhancement to dysfunction also remains controversial. To investigate the clinical significance of contrast enhancement we looked at the symptoms and signs and gadolinium DPTA-enhanced images of 71 consecutive surgical candidates in a standardised fashion. Annular rupture and disc enhancement were found to be closely related, and correlated with sensory loss and paresis, respectively. Nerve root enhancement was found to be related to neurological deficits in general and sensory impairment in particular.


Effects of Injectable Trace Minerals (ITMs) on Th1/Th2 Cytokine Balance of Newborn Calves with Tropical Theileriosis.
Injectable trace minerals (ITMs) could provide a potential alternative way of trace mineral delivery for sick animals. Therefore, evaluation of ameliorative potentials of ITMs (copper, manganese, selenium, and zinc) on the circulating Th1/Th2 cytokine misbalance in Theileria annulata-infected calves was aimed. Forty-three T. annulata-infected newborn calves were randomly allocated into four groups: buparvaquone alone-treated group (BUPA), buparvaquone + oxytetracycline (BUPA + OXY)-treated group, buparvaquone + injectable trace minerals (BUPA + ITMs)-treated group, and BUPA + OXY + ITM-treated group. Blood samples were collected from each of the calves before the start of therapy (day 0) and on day 14 post-therapy. Serum contents of pro- and anti-inflammatory cytokines were estimated by bovine specific ELISA kits. On day 14 post-therapy, significant amelioration in the circulating levels of the studied cytokines was not observed in the calves treated with BUPA, while the calves treated with BUPA + OXY revealed significant (P ≤ 0.04) amelioration in the circulating tumour necrosis factor-α (TNF-α) level. The calves treated with BUPA + ITMs revealed significant (P ≤ 0.041) elevation in the circulating interferon-γ (IFN-γ) and significant (P ≤ 0.011) reduction in the interleukin-10 (IL-10) levels. Moreover, the calves treated with BUPA + OXY + ITMs revealed significant reduction in TNF-α (P ≤ 0.0001) and IL-10 (P ≤ 0.012) contents, and significant elevation in IFN-γ (P ≤ 0.0002) content on day 14 post-therapy. None of the treated calve group revealed significant alteration in the circulating level of transforming growth factor-β (TGF-β) on day 14 post-therapy. In conclusion, administration of ITMs to the therapeutic regimen of newborn calves with tropical theileriosis could be a promising therapeutic strategy. ITMs can be recommended for the amelioration of immunological misbalance due to tropical theileriosis in newborn calves.


Erratum: Author Correction: Cost-effectiveness Analysis of Hypoallergenic Milk Formulas for the Management of Cow's Milk Protein Allergy in the United Kingdom.
[This corrects the article DOI: 10.36469/jheor.2021.26010.].


Implementation of interprofessional learning in hospital practice.
Some universities of applied science struggle with implementing interprofessional learning due to a lack of diversity in professions. The aim of this study was to investigate whether an interprofessional learning model with an informational letter describing interprofessional learning opportunities can provide nursing students in rural areas with sufficient interprofessional learning during internships. This qualitative study utilized a hermeneutical approach. A total of 17 individuals participated in focus groups, group interviews and written responses. The data collection: January 2019. Four categories were observed: (a) assumptions about interprofessional learning, (b) available interprofessional learning opportunities, (c) hindrances to interprofessional learning and (d) stimulation of interprofessional learning. The conclusion was that interprofessional learning can be implemented to some extent in areas where different professions work, even when only one student is present. A focus on interprofessional collaboration, patient safety and patient flow are valuable interprofessional learning objectives. An informational letter with suggestions for interprofessional learning, such as shadowing, was considered valuable by the participants.


Neuronal depletion of the amygdala resembles the learning deficits induced by low level lead exposure in rats.
The behavioral deficits observed after lead exposure have been related to limbic system dysfunction. In a previous study it was shown that the neurotoxicity of lead could not be explained by the damage of the hippocampus alone. The purpose of the present investigation was to use behavioral comparisons to test the hypothesis that the intrinsic neurons of several nuclei of the amygdala, where lead has been found to accumulate, can be a target of the effects of the metal as well. A group of rats were maternally and permanently exposed to lead (750 ppm in the diet as lead acetate). Another group of equally aged and housed rats, never experimentally exposed to lead, were injected ibotenic acid into the amygdala. All groups plus sham-operated and unoperated controls were tested in the open field, the radial arm maze, and a passive avoidance task. The results showed that lead exposure (both permanent and maternal) and amygdalectomy produced a) no effect on locomotor activity, b) impairments in the acquisition phase of the radial maze, and c) impairments in passive avoidance. These results suggest an involvement of the amygdala in the neurotoxic action of lead, but not as the only brain structure. The deficits in permanently lead-exposed rats are more pronounced than in only maternally-exposed animals suggesting a longlasting, but not totally irreversible effect of early lead exposure.


Long-term antibody persistence induced by a combined hepatitis A and B vaccine in children and adolescents.
Two cohorts, comprising of subjects aged 1-6 years and 6-15 years were vaccinated with Twinrix according to a 0-, 1- and 6-month schedule. The 1-6 years cohort was followed up for 7.5 years and the 6-15 years cohort for 10 years. At the latest follow-up time point, all subjects were seropositive for anti-HAV antibodies, while 86.5% (32/37) and 95.5% (21/22) had anti-HBs >or= 10 mIU/ml in the 1-6 years and in the 6-15 years cohort. The geometric mean concentrations (GMCs; mIU/ml) were 233 and 680 for anti-HAV antibodies, and 147 and 165 for anti-HBs antibodies, in the 1-6 years and 6-15 years cohorts, respectively. The high persistence of circulating anti-HAV and anti-HBs antibodies in children and adolescents demonstrates the long-term protection offered by Twinrix in these age groups.


Cinacalcet for the treatment of primary hyperparathyroidism.
Primary hyperparathyroidism (HPT) is the leading cause of hypercalcemia in the outpatient setting, and it is treated primarily by parathyroidectomy. There are few nonsurgical treatment options for patients who do not wish to have surgery, who have failed surgery, or who have contraindications to surgery. Cinacalcet increases the sensitivity of parathyroid calcium-sensing receptors to extracellular calcium, thereby reducing serum calcium levels. We conducted a retrospective chart review from 2004 to 2006 to investigate the efficacy of cinacalcet in reducing serum total calcium, ionized calcium, and parathyroid hormone (PTH) in patients with primary HPT. Patients were started on cinacalcet if they met at least one indication for parathyroidectomy, which includes T score less than -2.5 standard deviations from the mean, serum calcium 1 mg/dL above the upper limit of normal, 24-hour urine calcium above 400 mg/dL, age less than 50 years, or a creatinine clearance that is 30% below age- and sex-matched controls. The primary outcome was normalization of serum calcium. A total of 18 patients with primary HPT were started on cinacalcet: 16 men and 2 women with a mean age of 70 years. Mean baseline serum calcium was 10.60 +/- .53 mg/dL; ionized serum calcium, 1.45 +/- .07 mmol/L; and serum PTH, 141 +/- 78 pg/mL. After treatment with cinacalcet, the mean serum calcium decreased to 9.46 +/- .34 mg/dL, ionized calcium decreased to 1.26 +/- .06 mmol/L, and PTH decreased to 108 +/- 64.5 pg/mL. Ninety-four percent of the patients on cinacalcet had normal total serum calcium, 81% had normal serum ionized calcium, whereas only 25% had a normal serum PTH level. Cinacalcet normalizes serum calcium in most patients while only modestly reducing serum PTH levels.


Cerebral venous angioma: computerized tomography and angiographic diagnosis.
Four cases of cerebral venous angioma were studied by both CT and angiography. All cases showed similar angiographic findings: a normal arterial phase and a local network of small veins that converged centrally into a single large draining vein. However, CT showed nodular areas of high density in three cases, and a curvilinear enhanced lesion representing the draining vein in the other. CT findings are nonspecific but very useful for detecting the lesion and demonstrating the associated hematoma. Angiographic findings are not so obvious as in AVM, but are necessary for the final diagnosis of the venous angioma.


Soy intake and chronic disease risk: findings from prospective cohort studies in Japan.
There has been much interest in the potential role of soy in reducing the risk of chronic diseases. Soy foods are uniquely rich in isoflavones, a fact that has triggered much research including intervention studies. However, there have been few long-term prospective observational studies that include disease itself as an outcome. High intake of soy foods is intrinsic to the Japanese diet, which can be advantageous for conducting such studies in Japan. The present report reviews the findings from Japanese prospective cohort studies on soy intake and the risk of cardiovascular diseases, cancer, type 2 diabetes, osteoporosis, menopausal symptoms, and dementia. The results suggest a beneficial role of soy in several chronic diseases, but they are not without controversy. Discrepancies have been observed in the findings of studies of Japanese or other Asians as compared to those of non Asians. This review discusses the issues to be explored in future studies.


Left main bronchus foreign body masquerading as diaphragmatic hernia in an adult patient.
Foreign body aspiration is quite uncommon in the adults. It can be a life-threatening situation and it often requires a high index of suspicion, because the diagnosis can be obscure. We present a case of food aspiration by a 31-year old female patient, masquerading as diaphragmatic hernia, for the first time in the literature. Foreign body aspiration may escape diagnosis, especially if there is no recollection of the episode. The thoracic surgeon may be suspicious of this condition, even if the patient history and imaging obscure the clinical picture.


Protective effect of geranylgeranylacetone against hydrogen peroxide-induced oxidative stress in human neuroblastoma cells.
Heat shock protein 70 (HSP70), one of the major HSPs, has been reported to suppress apoptosis and formation of pathogenic proteins in neurodegenerative disorders. Geranylgeranylacetone (GGA), an anti-ulcer drug, induces HSP70 and thereby protects against cellular damage in various diseases. We investigated the effect of GGA on hydrogen peroxide (H2O2)-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. H2O2-induced neuronal toxicity was measured by a CCK-8 assay and Hoechst 33342 staining. We also assessed oxidative stress and apoptosis by measuring reactive oxygen species (ROS) generation with 2′,7′-dichlorofluorescein diacetate (DCFH-DA), caspase-3 activity, and mitogen-activated protein kinase (MAPK) pathway. GGA showed a concentration-dependent inhibition on H2O2-induced apoptotic cell death. H2O2-induced induction of HSP70 was enhanced by GGA pretreatment. GGA effectively suppressed the up-regulation of Bax and down-regulation of Bcl-2. GGA also blocked the H2O2-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). In addition, GGA attenuated H2O2-induced ROS generation and caspase-3 activity. These results demonstrate that GGA protects SH-SY5Y cells from H2O2-induced apoptosis, at least in part by enhancing HSP70 production. Neuroprotective properties of GGA indicate that this compound may be a potential therapeutic agent for the treatment and prevention of neurodegenerative diseases.


High cooperativity, specificity, and multiplicity in the protein kinase C-lipid interaction.
The number of phosphatidylserine molecules involved in activating protein kinase C was determined in a mixed micelle system where one monomer of protein kinase C binds to one detergent:lipid micelle of fixed composition. Unusually high cooperativity, specificity, and multiplicity in the protein kinase C-phospholipid interaction are demonstrated by examining the lipid dependence of enzymatic activity. The rates of autophosphorylation and substrate (histone) phosphorylation are specifically regulated by the phosphatidylserine content of the micelles. Hill coefficients of 8-11 were calculated for phosphatidylserine-dependent stimulation of enzyme activity, with a maximum occurring in micelles containing greater than or equal to 12 phosphatidylserine molecules. The high specificity that exists is illustrated by the fact that phosphatidylethanolamine and phosphatidylglycerol, but not phosphatidylcholine or phosphatidic acid, can replace only some of the phosphatidylserine molecules. We propose that Ca2+ and acidic phospholipids cause the protein to undergo a conformation change revealing multiple phosphatidylserine binding sites and resulting in the highly cooperative and specific interaction of protein kinase C with phosphatidylserine. Consistent with this, the proteolytic sensitivity of protein kinase C increases approximately 10-fold in the presence of phosphatidylserine and Ca2+ compared to Ca2+ alone. The high degree of cooperativity and specificity may provide a sensitive method for the physiological regulation of protein kinase C by phospholipid.


Anti-CD3 and phorbol ester induce distinct phosphorylated sites in the SH2 domain of p56lck.
P56lck is a protein tyrosine kinase of the Src family specifically expressed in T lymphocytes. Triggering of T cells with anti-CD3 or with phorbol 12-myristate 13-acetate (PMA) results in the appearance of slower migrating forms (shift) of p56lck. To investigate the phosphorylation sites on the shifted forms of p56lck and to assess the role of protein kinase C in this phosphorylation, Jurkat cells were treated with a selective inhibitor of this kinase (GF 109203X). This inhibitor completely reversed the shift induced by PMA but only partially reversed the one induced after triggering with anti-CD3. To analyze the shift further, p56lck was immunoprecipitated from in vivo labeled cells treated either with anti-CD3 or with PMA. Tryptic phosphopeptides were generated and analyzed by using a combination of thin layer chromatography, high reticulation polyacrylamide gel electrophoresis, reverse phase chromatography, and phosphopeptide sequencing. We identified serine 158 as a newly phosphorylated site after PMA treatment and tyrosine 192 and serine 194 in the major tryptic phosphopeptide obtained after anti-CD3 triggering. The three sites identified are located in the SH2 domain of p56lck; this suggests that their phosphorylation may regulate the interaction with other proteins or with other internal domains in p56lck.


Bacterial enzymes: powerful tools for protein labeling, cell signaling, and therapeutic discovery.
Bacteria have evolved a diverse set of enzymes that enable them to subvert host defense mechanisms as well as to form part of the prokaryotic immune system. Due to their unique and varied biochemical activities, these bacterial enzymes have emerged as key tools for understanding and investigating biological systems. In this review, we summarize and discuss some of the most prominent bacterial enzymes used for the site-specific modification of proteins, in vivo protein labeling, proximity labeling, interactome mapping, signaling pathway manipulation, and therapeutic discovery. Finally, we provide a perspective on the complementary advantages and limitations of using bacterial enzymes compared with chemical probes for exploring biological systems.


Maternal urine for prenatal diagnosis--an analysis of cell-free fetal DNA in maternal urine and plasma in the third trimester.
The aim of the study was the detection, quantification and correlation of cell-free fetal (cff) DNA in maternal urine and plasma in normal and complicated pregnancies during the third trimester. One hundred and fifty-one urine and plasma samples obtained from 96 women carrying male fetuses, and 55 carrying female fetuses were collected and analyzed for cff-DNA using fluorescent PCR and quantitative real-time PCR. DNA was extracted from 1 mL maternal urine and analyzed with two different primer sets (SRY and DYS-14). The concentrations of cff and total DNA in maternal plasma were correlated with maternal and obstetric parameters using appropriate correlation analyses. Y-chromosome-specific sequences were detected in 31 of 96 (32.3%) urine samples collected from women pregnant with male fetuses using DYS-14 and in 6 of 96 (6.3%) urine samples using SRY as primers using real-time PCR. All 96 plasma samples obtained from women carrying male fetuses were positive for cff-DNA using real-time PCR. Cff-DNA exhibited a correlation with gestational age (R = 0.244; P = 0.018) and an inverse correlation with the latency between blood collection and birth (R = - 0.218; P = 0.036). Total DNA showed a correlation with placental weight (R = 0.182; P = 0.034) and pregnancy-associated complications (R = 0.280; P < 0.001). Our data confirm that cff-DNA is cleared by the kidneys in detectable amounts, but due to its low concentration or problematic detection in maternal urine this source seems inappropriate for noninvasive prenatal diagnosis.


Genomic insights into the distribution, genetic diversity and evolution of polyketide synthases and nonribosomal peptide synthetases.
Polyketides and nonribosomal peptides are important secondary metabolites that exhibit enormous structural diversity, have many pharmaceutical applications, and include a number of clinically important drugs. These complex metabolites are most commonly synthesized on enzymatic assembly lines of polyketide synthases and nonribosomal peptide synthetases. Genome-mining studies making use of the recent explosion in the number of genome sequences have demonstrated unexpected enzymatic diversity and greatly expanded the known distribution of these enzyme systems across the three domains of life. The wealth of data now available suggests that genome-mining efforts will uncover new natural products, novel biosynthetic mechanisms, and shed light on the origin and evolution of these important enzymes.


Effect of chronic stress on gastric emptying and plasma ghrelin levels in rats.
Chronic stress is associated with gastrointestinal functional diseases. Although the pathophysiology seems to be associated with gastrointestinal motility, their mechanisms remain unclear. We investigated gastric emptying and chemical mediators under conditions of continuous stress, which were produced using 8-week-old male Wistar rats kept in a cage filled with water to 2 cm height for 5 days. We examined gastric emptying by the phenol red method and chemical mediators at 4, 8, and 24 h and 3 and 5 days after initiation of stress restraint. Plasma ACTH level was significantly higher in the stress throughout the period of measurement. Continuous stress delayed gastric emptying until 24 h: peak delay was observed at 8 h, whereas gastric emptying was accelerated on days 3 and 5. Plasma noradrenalin level was significantly elevated at every time point until 24 h. Guanethidine pretreatment eliminated the delay in gastric emptying at 8 h. Active ghrelin was significantly increased on days 3 and 5 after peak (at 24 h) plasma total and desacyl ghrelin in the stress group. Number of ghrelin-immunoreactive cells and level of preproghrelin mRNA expression in the gastric body increased in parallel with plasma active ghrelin level. Pretreatment with growth hormone secretagogue receptor antagonist at 5 days partially inhibited the stress-induced acceleration of gastric emptying. Delayed gastric emptying at acute phase of continuous stress was mediated via sympathetic pathway, while acceleration at chronic phase was mediated via increased active ghrelin release from the stomach.


Pathogenesis and management of the lens-iris diaphragm retropulsion syndrome during phacoemulsification.
After the ultrasonic tip is introduced into the highly myopic eye and inflow is activated, the anterior chamber deepens, the lens-iris diaphragm is displaced posteriorly, the iris becomes concave, and the pupil dilates from the weight of the water column above the eye. We define a known but undescribed syndrome--the lens-iris diaphragm retropulsion syndrome (LIDRS)--which is thought to be caused by abnormally loose zonules. The surgeon's reflexive action, lowering the infusion bottle height, reduces the weight of the water column but also reduces the infusion limit. We managed this situation with an inflow-splitting technique in which the infusion bottle height was lowered significantly and a Lewicky chamber maintainer connected to a second infusion bottle at the same height as the first bottle was introduced into the anterior chamber. Pressure monitoring that enabled simultaneous, synchronized recording of phacoemulsification and intraocular pressure fluctuations was used.


Enrichment and aggression in primates.
There is considerable evidence that primates housed under impoverished conditions develop behavioural abnormalities, including, in the most extreme example, self-harming behaviour. This has implications for all contexts in which primates are maintained in captivity from laboratories to zoos since by compromising the animals' psychological well-being and allowing them to develop behavioural abnormalities their value as appropriate educational and research models is diminished. This review examines the extensive body of literature documenting attempts to improve living conditions with a view to correcting behavioural abnormalities and housing primates in such a way that they are encouraged to exhibit a more natural range and proportion of behaviours, including less self-directed and social aggression. The results of housing, feeding, physical, sensory and social enrichment efforts are examined with specific focus on their effect on aggressive behaviour and variation in their use and efficacy. It is concluded that while inappropriate or poorly distributed enrichment may encourage aggressive competition, enrichment that is species, sex, age and background appropriate can dramatically reduce aggression, can eliminate abnormal behaviour and substantially improve the welfare of primates maintained in captivity.


The frequency of human platelet antigen (HPA) genotypes in the Polish population.
The human platelet antigens (HPA1-5) in the Polish population were investigated using the PCR with sequence specific primers (SSP). The HPA gene frequency was: 1a--0.874, 1b--0.126; 2a--0.898, 2b--0.102; 3a--0.592, 3b--0.408; 4a--1.00, 4b--0.00; 5a--0.937, 5b--0.063. The HPA2 and HPA5 differed from those observed in some other European populations-German and both German and Austrian, respectively. The HPA5 alleles frequency was most similar to those observed in the Finnish population. The modification of SSP described allowed the genotyping of HPA1-4 under the same PCR conditions.


β-Caryophyllene attenuates dextran sulfate sodium-induced colitis in mice via modulation of gene expression associated mainly with colon inflammation.
We examined the modulatory activity of β-caryophyllene (CA) and gene expression in colitic colon tissues in a dextran sulfate sodium (DSS)-induced colitis model. Experimental colitis was induced by exposing male BALB/c mice to 5% DSS in drinking water for 7 days. CA (30 or 300 mg/kg) was administered orally once a day together with DSS. CA administration attenuated the increases in the disease activity index, colon weight/length ratio, inflammation score, and myeloperoxidase activity in DSS-treated mice. Microarray analysis showed that CA administration regulated the expression in colon tissue of inflammation-related genes including those for cytokines and chemokines (Ccl2, Ccl7, Ccl11, Ifitm3, IL-1β, IL-28, Tnfrsf1b, Tnfrsf12a); acute-phase proteins (S100a8, Saa3, Hp); adhesion molecules (Cd14, Cd55, Cd68, Mmp3, Mmp10, Sema6b, Sema7a, Anax13); and signal regulatory proteins induced by DSS. CA significantly suppressed NF-κB activity, which mediates the expression of a different set of genes. These results suggest that CA attenuates DSS-induced colitis, possibly by modulating the expression of genes associated mainly with colon inflammation through inhibition of DSS-induced NF-κB activity.


In vitro and ex vivo autoradiography studies on peripheral-type benzodiazepine receptor binding using [11C]AC-5216 in normal and kainic acid-lesioned rats.
AC-5216 was reported as a novel ligand for peripheral-type benzodiazepine receptor (PBR) with a different chemical structure from DAA1106 analogues. This ligand had potent affinity for PBR and selectivity for PBR over other neurotransmitters. We have previously labeled AC-5216 using positron-emitter (11)C. The aim of this study was to evaluate [(11)C]AC-5216 in a rat brain model with neuroinflammation using an autoradiography (ARG) technique. In vitro ARG of normal rat brain showed that [(11)C]AC-5216 accumulated highly in the olfactory bulb, choroid plexus and cerebellum. The distribution pattern agreed with the localization of PBR in the rodent brain. Infusion of kainic acid (KA: 1, 2.5 and 5 nmol) into the rat striatum resulted in neuroinflammation. In vitro and ex vivo ARG revealed that the radioactivity level of [(11)C]AC-5216 was increased significantly in the KA-lesioned striatum compared to the non-lesioned striatum. Increasing the amount of KA infused into the striatum augmented radioactivity in the striatum as well as the cerebral cortex and hippocampus of the lesioned side. Treatment with a large amount of non-radioactive AC-5216 or PK11195 inhibited the binding of [(11)C]AC-5216 and diminished the difference of radioactivity levels between the lesion and non-lesioned sides. These results demonstrated that [(11)C]AC-5216 had high specific binding to PBR in the KA-lesioned rat brain. Thus, [(11)C]AC-5216 is a promising PET ligand for imaging PBR in a brain with neuroinflammation.


Neurology of Tourette's syndrome (TS) TS as a developmental dopamine disorder: a hypothesis.
The favorable effect of dopamine (DA) depletors or DA receptor blockers suggested the state of increased transmission of DA system as the pathophysiology of Tourette's syndrome (TS). We have analysed the neurological signs of TS and evaluated the role of levodopa on the symptoms of TS. The data were compared with age-matched patients with Hereditary Progressive Dystonia (HPD) with marked diurnal fluctuation. Neurological examination of 81 drug naive TS patients revealed the clumsiness of rapid alternating pronation-supination movements of the arms and induced rigidity in the contralateral arm, which responded to the oral levodopa, and suggested hypofunction of the nigrostriatal (NS)-DA system. Postural asymmetry or scoliosis and abnormal tilting response suggested the asymmetric involvement of DA. The rotation to the side of less affected DA neuron on stepping with closed eyes suggested DA receptor supersensitivity. The favourable effects of a small dose of levodopa on these signs suggest the existence of DA receptor supersensitivity, because a small dose of levodopa is considered to alleviate the supersensitized DA receptors.


Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study.
5'-Methyltetrahydrofolic acid (5'-MTHF) in addition to standard psychotropic medication significantly improved clinical recovery in depressed patients with borderline or definite folate deficiency, and significantly reduced depressive symptoms in elderly normofolatemic patients after 3 weeks of treatment. In this equivalence study the effect of 5'-MTHF on depressive symptoms and cognitive status was compared to Trazodone (TRZ) in normofolatemic elderly patients with mild to moderate dementia and depression. Ninety-six patients with dementia, scoring 12-23 at the Mini Mental State Examination (MMSE) and > or = 18 at the Hamilton Depression Rating Scale (HDRS) after a 2-week placebo run-in, were randomized to receive either 5'-MTHF (50 mg/day p.o.) (47 patients) or TRZ (100 mg/day p.o.) (49 patients) in a double-blind design for 8 weeks. HDRS was assessed before, after 4 weeks and at the end of treatment; Rey's Verbal Memory (RVM) test for immediate and delayed recall was evaluated before and after treatment. After 4 weeks of treatment HDRS score was reduced from 23 +/- 5 to 20 +/- 6 in the 5'-MTHF (p < 0.05 vs baseline), and from 23 +/- 3 to 21 +/- 4 in the TRZ group (p < 0.05 vs baseline). A further significant decrease to 18 +/- 6 and 19 +/- 5 respectively was obtained at the end of the treatment period (p < 0.05 vs week 4) with 5'-MTHF and TRZ.(ABSTRACT TRUNCATED AT 250 WORDS)


Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, and COVID-19, beyond the lungs: a review article.
In the past 20 years four major viral infectious diseases outbreaks caused hundreds of thousands of deaths worldwide: SARS, Influenza H1N1, MERS, and COVID-19. They all present clinically initially as upper and lower respiratory tract infections and may progress to multi-organ failure. This study was a systematic review of literature conducted in September 2020 to study extra-pulmonary complications of SARS, FLU, MERS, and current COVID-19. We carried out a systematic search using the keywords in online databases of PubMed, EMBASE, and Google Scholar until June 2020. This article aims to review the most common extra-pulmonary manifestations of SARS, Influenza, MERS, and COVID-19. Several studies have reported extra-pulmonary conditions in patients diagnosed with SARS, Influenza, MERS, and COVID-19, either by direct viral injury or from the systemic response to the initial infection. SARS, Influenza, MERS, and COVID-19 have all been associated with dysfunction of kidneys, endocrine system, neuromuscular symptoms, perinatal complications, and myocardial injury. Progression from pulmonary disease to a systemic condition has a poor outcome and can result in multi-organ failure.


Determining the role of richness and evenness in alpine grassland productivity across climatic and edaphic gradients.
Spatial heterogeneity of climatic and edaphic gradients can substantially affect the grassland productivity function. However, few studies have tested the importance of species richness and evenness on regulating grassland productivity across spatial-scale climatic and edaphic changes. This study examines the complex mechanisms by which species richness and evenness regulate productivity in alpine meadow and steppe. We used field survey data to explore above-ground productivity formation and sensitivity to spatial-scale climatic and edaphic response of alpine grassland based on species richness and evenness. Results showed that the growing season solar radiation was the main driving factor of above-ground biomass and was strongly negatively correlated with above-ground biomass. Furthermore, compared with alpine steppe, above-ground biomass in alpine meadow was more responsive to climatic variables, but less responsive to soil variables. Unexpectedly, we found that the regulation patterns of species richness and evenness on above-ground biomass were different in both habitats by a structural equation model analysis. Our study demonstrated that species evenness and richness were both important in co-regulating above-ground biomass in alpine meadow, whereas species richness mattered more than species evenness in regulating above-ground biomass in alpine steppe. Our results offer further support for species richness and evenness co-regulating grassland productivity across spatial-scale climatic and edaphic gradients, which helps maintain the benefits of plant diversity and alpine grassland ecosystems.


Physiological responses and metal distributions of different organs of Phragmites australis shoots under acid mine drainage stress.
Phragmites australis, which is widely distributed throughout the world, is often used in the phytoremediation of acid mine drainage (AMD) due to its various mechanisms for survival under extremely harsh conditions. To explore the different responses of different aerial organs of P. australis to stress, soil and plant samples were collected from the AMD-polluted area of the Tongling mining area. The contents of manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), and lead (Pb) in the soil and the leaf blades, leaf sheaths, and stems of P. australis as well as the contents/activities of cysteine synthase (CSase), superoxide dismutase (SOD), peroxidase (POD), glutathione (GSH), malondialdehyde (MDA), and proline (Pro) in the organs were determined. Our results revealed that the leaf sheath had the highest potential to store metals of all the organs. The highest translocation factor (TF) for Fe was observed from the stems to the leaf sheaths. A higher bioconcentration factor (BCF) for Mn was found in the leaf blades and leaf sheaths, while higher BCFs for Cd and Zn were observed in the stems. The content/activity of enzymatic and non-enzymatic stress-resistance substances varied from organ to organ. In general, the leaf sheaths remained almost as or slightly less stress-resistant than the leaf blades. It can be concluded that different plant organs play different roles in stress resistance, and understanding the tolerance mechanism of leaf sheaths to metals is essential for the application of phytoremediation procedures.


Thrombelastography of blood from subjects with chronic renal failure.
Blood samples from 23 subjects with chronic renal failure and 19 controls were tested using thrombelastography and other hematologic tests. The uremic subjects were divided into two groups, those who had not yet begun maintenance hemodialysis treatments (12 subjects) and those who had (11 subjects). Compared to those from control subjects, the thrombelastograms from the uremic subjects consistently indicate normal clotting times but significantly elevated amplitudes. The increased amplitudes correlate positively in the dialyzed uremic group with both platelet count and fibrinogen concentration and correlate negatively in both uremic groups with hematocrit. Thrombelastography demonstrates a hypercoagulability in these samples in vitro, despite the prolonged bleeding time that commonly occurs in uremic subjects.


[Use of serum haptoglobin concentration as an indicator in animal health monitoring of dairy cows].
To investigate the association between haptoglobin concentration in the blood and the occurrence of ketosis, selected clinical parameters as well as lameness in dairy cows. The data was collected on 39 dairy farms in Bavaria over a period of 8 months. In 712 Simmental and Brown Swiss cows, clinical examinations as well as milk and blood samplings were performed between 10 and 30 days after calving. In these blood samples, the concentrations of non-esterified fatty acids (NEFA), β-hydroxybutyric acid (BHBA) and haptoglobin (Hp) were determined. Analysis of the milk included milk constituents (fat, protein, urea, lactose and acetone), BHBA, NEFA and the somatic cell count (SCC). Significant correlations were found between increased Hp-concentration on the one hand and increased NEFA levels in blood and milk (p < 0.001), increased somatic cell count (p < 0.001), lameness (p < 0.001), as well as reduced lactose content (p < 0.001) and protein content in the milk (p = 0.001) on the other hand. Animals sampled during the warmer summer months showed significantly higher serum Hp-concentrations (p < 0,001). Heifers exhibited significantly higher Hp-values than multiparous individuals (p < 0.001). By dividing the examined cows into 4 clusters, a Hp-threshold value could be determined at 0.18 mg/ml. Combined with a SCC threshold of 40 500 cells/ml milk, the majority of animals with subclinical and clinical abnormalities could be identified. Measurement of the Hp-concentration in blood is a pertinent approach in animal health monitoring during the postpartum period. In combination with evaluations of milk amount and contents, deviations from the physiological status may be recognized and affected individuals treated early on. Haptoglobin may be used to assess the health status of the individual animal as well as an indicator of herd health in the context of animal health monitoring.


Modulation of motor and premotor cortices by actions, action words and action sentences.
Recent research has indicated that processing different kinds of action verbs, such as those related to arm or leg movements (e.g. grab, kick), engages regions along the motor strip responsible for the execution of the corresponding actions. It has been proposed that this activation reflects action-related meaning and that these regions are automatically triggered whenever action words are encountered. However, this view is not universally shared by cognitive studies that have shown that the representation of verbs is highly dependent on the interactions with the semantic context. We investigated these views in a set of fMRI studies, in which participants performed a movement localiser task and listened to arm- and leg-related verbs that were presented in isolation (e.g. kick), in literal sentences (as in kick the ball) and idiomatic sentences (as in kick the bucket). We found significant activation in motor regions when action verbs were presented in isolation, and, to a lesser extent, in literal sentential contexts. When the same verbs were presented in idiomatic contexts, activation was found in fronto-temporal regions, associated with language processing, but not in motor and premotor cortices. These results suggest that motor responses were context-dependent, rather than automatic and invariable. These findings lend support to cognitive theories of semantic flexibility, by showing that the nature of the semantic context determines the degree to which alternative senses and particularly relevant features are processed when a word is heard.


Sulphonamide residues in eggs following drug administration via the drinking water.
The aim was to determine concentrations of sulphadimidine (SDM) and sulphadimethoxine (SDT) in eggs following oral administration through drinking water for 5 days (0.5 g l(-1) for SDT, 1 and 2 g l(-1) for SDM). Residues of sulphonamides in albumen and yolk were monitored by high-performance liquid chromatography with UV detection. The limit of quantification was 0.005 microg g(-1) for the two egg components. The results indicate that 0.9-1.4% of the dose administered was deposited in eggs. Maximum concentrations in albumen were much higher than those in yolk. More than 75% of the overall sulphonamides detected in eggs was concentrated in the albumen. The residue levels declined below the limit of quantification within 12-20 days for albumen and 14-15 days for yolk after treatment was discontinued.


Affine image registration of arterial spin labeling MRI using deep learning networks.
Convolutional neural networks (CNN) have demonstrated good accuracy and speed in spatially registering high signal-to-noise ratio (SNR) structural magnetic resonance imaging (sMRI) images. However, some functional magnetic resonance imaging (fMRI) images, e.g., those acquired from arterial spin labeling (ASL) perfusion fMRI, are of intrinsically low SNR and therefore the quality of registering ASL images using CNN is not clear. In this work, we aimed to explore the feasibility of a CNN-based affine registration network (ARN) for registration of low-SNR three-dimensional ASL perfusion image time series and compare its performance with that from the state-of-the-art statistical parametric mapping (SPM) algorithm. The six affine parameters were learned from the ARN using both simulated motion and real acquisitions from ASL perfusion fMRI data and the registered images were generated by applying the transformation derived from the affine parameters. The speed and registration accuracy were compared between ARN and SPM. Several independent datasets, including meditation study (10 subjects × 2), bipolar disorder study (26 controls, 19 bipolar disorder subjects), and aging study (27 young subjects, 33 older subjects), were used to validate the generality of the trained ARN model. The ARN method achieves superior image affine registration accuracy (total translation/total rotation errors of ARN vs. SPM: 1.17 mm/1.23° vs. 6.09 mm/12.90° for simulated images and reduced MSE/L1/DSSIM/Total errors of 18.07% / 19.02% / 0.04% / 29.59% for real ASL test images) and 4.4 times (ARN vs. SPM: 0.50 s vs. 2.21 s) faster speed compared to SPM. The trained ARN can be generalized to align ASL perfusion image time series acquired with different scanners, and from different image resolutions, and from healthy or diseased populations. The results demonstrated that our ARN markedly outperforms the iteration-based SPM both for simulated motion and real acquisitions in terms of registration accuracy, speed, and generalization.


Decolonizing global health: an agenda for research.
This editorial outlines the background to the BMC Health Services Research collection on decolonizing global health. The discourse on decolonizing global health is gaining increasing momentum. These persistent 'voices' have coalesced into a 'movement'. Several commentators have critiqued the way global health continues to be structured and practiced. The colonial roots of global health dominance have come under an unprecedentedly intense spotlight amid pressure for reform.


Purification of a putative Na+/D-glucose cotransporter from pig kidney brush border membranes on a phlorizin affinity column.
Phlorizin, a potent inhibitor of the Na+/D-glucose cotransporter, was derivatised to 3-aminophlorizin and subsequently coupled to Affi-Gel 15. Affinity chromatography of pig kidney brush border membranes solubilised in Triton X-100 allowed the purification of a 60 kDa protein on this resin. We consider this protein to be the Na+/D-glucose cotransporter, or part of it, for the following reasons: (i) binding of this protein to Affi-Gel 15 specifically requires phlorizin covalently attached to the resin and is lowered when phlorizin is replaced by phloretin; (ii) binding of the 60 kDa protein to a phlorizin affinity column requires the presence of Na+; (iii) polyclonal as well as monoclonal antibodies against the 60 kDa protein inhibit binding of phlorizin to brush border membranes from rabbit and pig kidney.


In vitro profiling of pesticides within the Tox21 10K compound library for bioactivity and potential toxicity.
Pesticides include a diverse class of toxic chemicals, often having numerous modes of actions when used in agriculture against targeted organisms to control insect infestation, halt unwanted vegetation, and prevent the spread of disease. In this study, the in vitro assay activity of pesticides within the Tox21 10K compound library were examined. The assays in which pesticides showed significantly more activities than non-pesticide chemicals revealed potential targets and mechanisms of action for pesticides. Furthermore, pesticides that showed promiscuous activity against many targets and cytotoxicity were identified, which warrant further toxicological evaluation. Several pesticides were shown to require metabolic activation, demonstrating the importance of introducing metabolic capacity to in vitro assays. Overall, the activity profiles of pesticides highlighted in this study can contribute to the knowledge gaps surrounding pesticide mechanisms and to the better understanding of the on- and off-target organismal effects of pesticides.


Efficient in vitro translocation into Escherichia coli membrane vesicles of a protein carrying an uncleavable signal peptide. Characterization of the translocation process.
The translocation into Escherichia coli cytoplasmic membrane vesicles of a protein containing an uncleavable signal peptide was studied. The signal peptide cleavage site of the ompF-lpp chimeric protein, a model secretory protein, was changed from Ala-Ala to Phe-Pro through oligonucleotide-directed site-specific mutagenesis of the ompF-lpp gene on a plasmid. The mutant protein was no longer processed by the signal peptidase. When proteinase K treatment was adopted as a probe for protein translocation into inverted membrane vesicles, the mutant protein exhibited rapid and almost complete translocation, most likely due to the lack of premature cleavage of the signal peptide before the translocation. This result also indicates that cleavage of the signal peptide is not required for translocation of the mature domain of the protein. The establishment of an efficient system made it possible to perform precise and quantitative analysis of the translocation process. The translocation was time-dependent, vesicle-dependent, and required ATP and NADH. Translocation into membrane vesicles was also observed with the uncleavable precursor protein purified by means of immunoaffinity chromatography, although the efficiency was appreciably low. The translocation required only ATP and NADH. Addition of the cytosolic fraction did not enhance the translocation.


Cytokine, chemokine and growth factor gene profiling of cultured human astrocytes after exposure to proinflammatory stimuli.
Astrocytes play key roles in CNS development, inflammation, and repair by producing a wide variety of cytokines, chemokines, and growth factors. Understanding the regulation of this network is important for a full understanding of astrocyte functioning. In this study, expression levels of 268 genes encoding cytokines, chemokines, growth factors, and their receptors were established in cultured human adult astrocytes using cDNA arrays. Also, changes in this gene profile were determined following stimulation with TNFalpha, IL-1beta, and IFNgamma. The data obtained reveal a highly reproducible pattern of gene expression not only between different astrocyte cultures from a single source, but also between astrocytes from different donors. They also identify several gene products not previously described for human astrocytes, including a.o. IL-17, CD70, CD147, and BIGH3. When stimulated with TNFalpha astrocytes respond with increased expression of several genes, notably including those encoding the chemokines CCL2 (MCP-1), CCL5 (RANTES), and CXCL8 (IL-8), growth factors including BMP-2A, BMP-3, neuromodulin (GAP43), BDNF, and G-CSF, and receptors such as the CRF receptor, the calcitonin receptor (CTR), and TKT. The response to IL-1beta involves largely the same range of genes, but responses were blunted in comparison to the TNFalpha response. Treatment with IFNgamma had no or only marginal effects on expression of any of the 268 genes analyzed. Astrocytes treated with a mixture of all three stimuli together displayed responses that are largely similar to those found in response to TNFalpha or IL-1beta alone, with only few additional synergistic effects.


Trends in and factors associated with the adoption of digital aids for smoking cessation and alcohol reduction: A population survey in England.
Digital smoking cessation and alcohol reduction aids are widely available in England. To estimate their public health impact, researchers need to consider their adoption in the target population. We assessed adoption rates, and characteristics of adopters, of digital smoking cessation and alcohol reduction aids in England. 3655 smokers and 2998 high-risk drinkers (defined as a score of >4 on the Alcohol Use Disorders Identification Test-Consumption; AUDIT-C) who had made a past-year quit/reduction attempt were surveyed as part of the Smoking and Alcohol Toolkit Studies between January 2015-October 2018. Respondents provided information on socio-demographic characteristics and whether they had used a digital aid in a recent quit/reduction attempt. 2.7 % (95 % CI 2.2%-3.0%) of smokers and 3.6 % (95 % CI 2.9%-4.0%) of drinkers who had made a past-year quit/reduction attempt (26.9 % and 15.3 %, respectively) had used a digital aid. Survey year was not significantly associated with use in smokers or drinkers. None of the baseline characteristics were significantly associated with the use of a digital aid in smokers. Drinkers with high motivation to reduce alcohol consumption (ORadj = 2.49, 95 % CI 1.63-3.77, p < .001) and higher AUDIT scores (ORadj = 1.07, 95 % CI 1.03-1.11, p < .001) had greater odds of adoption. Digital smoking cessation and alcohol reduction aids are rarely used by smokers or high-risk drinkers attempting to quit/cut down in England, indicating that most of the target population is not being reached. Despite overall digital access improving, adoption rates remained similarly low between 2015-2018.


Complete topographical distribution of both the in vivo and in vitro phosphorylation sites of bone sialoprotein and their biological implications.
Bone sialoprotein (BSP) is a multifunctional, highly phosphorylated, and glycosylated protein with key roles in biomineralization and tissue remodeling. This work identifies the complete topographical distribution and precise location of both the in vitro and in vivo phosphorylation sites of bovine BSP by a combination of state-of-the-art techniques and approaches. In vitro phosphorylation of native and deglycosylated BSPs by casein kinase II identified seven phosphorylation sites by solid-phase N-terminal peptide sequencing that were within peptides 12-22 (LEDS(P)EENGVFK), 42-62 (FAVQSSSDSS(P)EENGNGDS(P)S(P)EE), 80-91 (EDS(P)DENEDEES(P)E), and 135-145 (EDES(P)DEEEEEE). The in vivo phosphorylation regions and sites were identified by use of a novel thiol reagent, 1-S-mono[(14)C]carboxymethyldithiothreitol. This approach identified all of the phosphopeptides defined by in vitro phosphorylation, but two additional phosphopeptides were defined at residues, 250-264 (DNGYEIYES(P)ENGDPR), and 282-289 (GYDS(P)YDGQ). Furthermore, use of native BSP and matrix-assisted laser desorption ionization time-of-flight mass spectrometry identified several of the above peptides, including an additional phosphopeptide at residues 125-130 (AGAT(P)GK) that was not defined in either of the in vitro and in vivo studies described above. Overall, 7 in vitro and 11 in vivo phosphorylation sites were identified unequivocally, with natural variation in the quantitative extent of phosphorylation at each in vivo phosphorylation site.


Alteration of long-distance functional connectivity and network topology in patients with supratentorial gliomas.
The need for information regarding functional alterations in patients with brain gliomas is increasing, but little is known about the functional consequences of focal brain tumors throughout the entire brain. Using resting-state functional MR imaging (rs-fMRI), this study assessed functional connectivity in patients with supratentorial brain gliomas with possible alterations in long-distance connectivity and network topology. Data from 36 patients with supratentorial brain gliomas and 12 healthy subjects were acquired using rs-fMRI. The functional connectivity matrix (FCM) was created using 32 pairs of cortical seeds on Talairach coordinates in each individual subject. Local and distant connectivity were calculated using z-scores in the individual patient's FCM, and the averaged FCM of patients was compared with that of healthy subjects. Weighted network analysis was performed by calculating local efficiency, global efficiency, clustering coefficient, and small-world topology, and compared between patients and healthy controls. When comparing the averaged FCM of patients with that of healthy controls, the patients showed decreased long-distance, inter-hemispheric connectivity (0.32 ± 0.16 in patients vs. 0. 42 ± 0.15 in healthy controls, p = 0.04). In network analysis, patients showed increased local efficiency (p < 0.05), but global efficiency, clustering coefficient, and small-world topology were relatively preserved compared to healthy subjects. Patients with supratentorial brain gliomas showed decreased long-distance connectivity while increased local efficiency and preserved small-world topology. The results of this small case series may provide a better understanding of the alterations of functional connectivity in patients with brain gliomas across the whole brain scale.


Assessment of quality and interpretation of panoramic radiographs obtained in the Lao People's Democratic Republic as part of a teleradiology collaboration with Japan.
As part of quality assessment of a teleradiology program we evaluated the validity of patient information received, the quality of panoramic radiography imaging in Laos, and the ability of a Laotian radiologist to detect temporomandibular joint abnormalities. The amount of patient information gathered from 2,021 scans of panoramic radiographs was evaluated by triage before image diagnosis. Among the radiographs from 2,021 patients, primary triage indicated that there was insufficient information for 794 (39.3%) patients. Secondary triage to assess imaging failure included 1,227 radiographs, four of which were excluded from imaging diagnosis because of unacceptable image flaws. In total, 2,446 joints from 1,223 radiographs were evaluated for temporomandibular joint abnormalities in order to compare the image interpretation abilities of Laotian and Japanese radiologists. The kappa coefficient was 0.836 (P < 0.01) for the agreement between the two observers in detecting temporomandibular joint abnormalities on radiographs. We conclude that additional efforts are needed in order to overcome the challenges of maintaining quality in imaging techniques and diagnoses in Laos.


Pharmacokinetic characterization of hydroxylpropyl-beta-cyclodextrin-included complex of cryptotanshinone, an investigational cardiovascular drug purified from Danshen (Salvia miltiorrhiza).
1. The study aimed to investigate the pharmacokinetics of cryptotanshinone in a hydroxylpropyl-beta-cyclodextrin-included complex in dogs and rats. 2. Animals were administrated the inclusion complex of cryptotanshinone and the concentrations of cryptotanshinone and its major metabolite tanshinone IIA were determined by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. 3. Cryptotanshinone in inclusion complex was absorbed slowly after an oral dose, and the C(max) and AUC(0-)(t) were dose-proportional. The bioavailability of cryptotanshinone in rats was (6.9% +/- 1.9%) at 60 mg kg(-1) and (11.1% +/- 1.8%) in dogs at 53.4 mg kg(-1). The t(1/2) of the compound in rats and dogs was 5.3-7.4 and 6.0-10.0 h, respectively. Cryptotanshinone showed a high accumulation in the intestine, lung and liver after oral administration, while the lung, liver and heart had the highest level following intravenous dose. Excretion data in rats showed that cryptotanshinone and its metabolites were mainly eliminated from faeces and bile, and the dose recovery rate was 0.02, 2.2, and 14.9% in urine, bile, and faeces, respectively. 4. The disposition of cryptotanshinone in an inclusion complex was dose-independent and the bioavailability was increased compared with that without cyclodextrin used to formulate the drug. Cryptotanshinone was distributed extensively into different organs. Excretion of cryptotanshinone and its metabolites into urine was extremely low, and they were mainly excreted into faeces and bile.


Axillary Reverse Mapping in the Prevention of Lymphoedema: A Systematic Review and Pooled Analysis.
This is a systematic review of randomized controlled trials (RCT) comparing the use of axillary reverse mapping (ARM) with conventional technique for axillary dissection (AD) in breast cancer surgery. This review was written in line with the PRISMA protocol. Articles were retrieved from PubMed, EMBASE, CINAHL and Cochrane databases, using keywords ..úaxillary reverse mapping..Ñ and "axillary lymph node dissection". Non-RCT were excluded. Abstracts were screened independently by 2 reviewers. Data from eligible studies were retrieved for qualitative synthesis and pooled analysis. 73 publications were identified for initial screening. 68 articles were excluded from analysis according to the pre-defined systematic review protocol. 5 RCTS with 1696 subjects were included for analysis. 802 patients received ARM, 894 patients received AD. Pooled ARM node detection rate was 84.9% (Range 79.2 - 94.9%). There was a lower rate of post-operative lymphedema in ARM group patients across all 5 RCTs. The pooled lymphedema incidence in the ARM group was 4.8% (37/766) when compared to 18.8% (164/873) in the AD group (P < .0001). Axillary recurrence rate with median followof 37 months was 1.03% (8/778) in the ARM group, which was identical to 1.03% (9/870) in the AD group (P = 1). ARM resulted in decreased incidence of lymphedema. There was no significant increase in axillary recurrence at 37 months post-operation.


Impact of a hospital improvement initiative in Bangladesh on patient experiences and satisfaction with services: two cross-sectional studies.
The Bangladesh government implemented a pilot Hospital Improvement Initiative (HII) in five hospitals in Sylhet division between 1998 and 2003. This included management and behaviour change training for staff, waste disposal and procurement, and referral arrangements. Two linked cross-sectional surveys in 2000 and 2003 assessed the impact of the HII, assessing both patients' experience and satisfaction and public views and use of the hospitals. In each survey we asked 300 consecutive outpatients and a stratified random sample of 300 inpatients in the five hospitals about waiting and consultation time, use of an agent for admission, and satisfaction with privacy, cleanliness, and staff behaviour. The field teams observed cleanliness and privacy arrangements, and visited a sample of households in communities near the hospitals to ask about their opinions and use of the hospital services. Analysis examined changes over time in patients' experience and views. Multivariate analysis took account of other variables potentially associated with the outcomes. Survey managers discussed the survey findings with gender stratified focus groups in each sample community. Compared with 2000, an outpatient in three of the hospitals in 2003 was more likely to be seen within 10 minutes and for at least five minutes by the doctor, but outpatients were less likely to report receiving all the prescribed medicines from the hospital. In 2003, inpatients were more likely to have secured admission without using an agent. Although patients' satisfaction with several aspects of care improved, most changes were not statistically significant. Households in 2003 were significantly more likely to rate the hospitals as good than in 2000. Use of the hospitals did not change, except that more households used the medical college hospital for inpatient care in 2003. Focus groups confirmed criticisms of services and suggested improvements. Improvements in some aspects of patients' experience may have been due to the programme, but the decreased availability of medicines in government facilities across the country over the period also occurred in these hospitals. Monitoring patients' experience and satisfaction as well as public views and use of hospital services is feasible and useful for assessing service interventions.


Prosthetic component relationship of the reverse Delta III total shoulder prosthesis in the transverse plane of the body.
The Delta III (DePuy International Ltd, Leeds, UK) reverse total shoulder prosthesis has provided a successful functional outcome in cuff tear arthropathy (CTA); however, internal and external rotation remain compromised. Positioning of the prosthetic components in the transverse plane has theoretically been suggested to affect rotation. Twenty-seven patients who received a Delta III reversed total shoulder prosthesis for CTA were analyzed (mean follow-up, 43 months) using standard radiographs and computed tomography. The position of the prosthetic components and the possible influence of scapular rotation was analyzed using a uniform spatial reference system using axes in reference to the sagittal or coronal plane. We assessed impingement of the humeral component on the glenoid neck in neutral and internal rotation. An increase in the anterior divergence of the glenoid and humeral prosthetic components correlates with an increase in radiologically measured internal rotation (r = 0.932, P < .001). The uniformity of the reference system used seems to allow accurate positioning of the components intraoperatively and can be useful for analysis of the prosthetic component relationship postoperatively.


Pilot Study of Attitudes of Taiwanese Veterinarians and Undergraduate Veterinary Students toward Animal Abuse and Interpersonal Violence.
There is a strong association between animal abuse and interpersonal violence; therefore, veterinarians may encounter both. Dealing with animal abuse cases is beneficial for advancing animal welfare and the overall public health. Veterinarians play an important role in identifying and responding to this relationship. This study estimated the incidence of animal abuse encountered by veterinarians, examined veterinarians' awareness of the relationship between animal abuse and human abuse, examined veterinarians' attitudes towards how they deal with abuse cases, and related demographic characteristics to their attitudes of intervention and the frequency of encountering abuse cases. An anonymous self-administered questionnaire was designed and distributed through social media. Our results show that respondents' motivation to interfere for animal abuse cases was positively related to their moral or legal responsibility, willingness to assist, and agreement of mandatory reporting. Our results indicated that respondents who believed they had been provided with adequate training were more willing to deal with animal abuse, more capable of distinguishing abuse cases, and did not believe that dealing with abuse cases was beyond their ability. However, more than 60% of our respondents self-evaluated that the animal cruelty awareness training courses were insufficient. Hence, in addition to the traditional role of veterinarians, identifying and responding to animal cruelty should be enhanced through education.


[Lymphocyte aggregation in the intermediate part of the human pituitary gland as an expression of H. Bautzmann's lympho-glandular unit].
The lymphocytic aggregates in the pars intermedia of the human pituitary are preferentially situated among the mucous glands and colloid cysts. This localization gives rise to interpret them as expression of a functional unit which was pointed out by H. Bautzmann as a rule within all exocrine glands.


Food habits and the basal rate of metabolism in birds.
The correlation of basal rate of metabolism with various factors is examined in birds. Chief among these is body mass. As in mammals, much of the remaining variation in basal rate among birds is associated with food habits. Birds other than passerines that feed on grass, nectar, flying insects, or vertebrates generally have basal rates that are similar to mammals of the same mass and food habits. In contrast, most invertebrate-eating birds that weigh over 100 g have higher basal rates than equally-sized, invertebrate-eating mammals. The high basal rates of small passerines equal those of small mammals that do not enter torpor and represent the minimal cost of continuous endothermy. Large passerines and small procellariiforms, charadriiforms, and psittaciforms generally have higher basal rates than mammals with the same mass and food habits. The high basal rates of passerines (in combination with altricial habits) may have significance in permitting high post-natal growth rates and the exploitation of seasonally abundant resources. These interrelations may contribute to the predominance of passerines in temperate land environments.


The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily.
PCAF histone acetylase is found in a complex with more than 20 associated polypeptides. Here we report cloning and characterization of the 400 kDa PCAF-associated factor referred to as PAF400. PAF400 is almost identical to TRRAP, which binds to c-Myc and E2F, and has significant sequence similarities to the ATM superfamily including FRAP, ATM, ATR, and the catalytic subunit of DNA-PK. Remarkably, PAF400 and FRAP share sequence similarity in broad regions that cover 80% of the entire PAF400 sequence. However, unlike the other members of the ATM superfamily, PAF400 is not a protein kinase as judged from the lack of kinase motif and autophosphorylation activity. We discuss the possibility that PAF400 may play a role in signaling of DNA damage to p53 by stimulation of p53 acetylation.


Value of plasma neutrophil gelatinase-associated lipocalin in predicting the mortality of patients with sepsis at the emergency department.
Sepsis is a major cause of morbidity and mortality in the emergency department. This study aimed to evaluate the assessment of severity of sepsis by and prognostic value of plasma neutrophil gelatinase-associated lipocalin (NGAL) compared with other widely used biological markers of inflammation in patients with sepsis. NGAL, procalcitonin, and C-reactive protein values were measured in 470 patients with suspected sepsis, and the Mortality in Emergency Department Sepsis (MEDS) score was obtained for all enrolled subjects, who were followed for up to 28days. The median plasma NGAL value was increased with sepsis severity according to the MEDS score. The plasma NGAL value was higher in nonsurvivors than in survivors. The area under the receiver operating characteristic curve of NGAL (0.797) was greater than that of procalcitonin (0.599) and MEDS score (0.774) in predicting 28-day hospital mortality. Multivariable logistic regression found that the plasma NGAL value was an independent predictor for hospital mortality in patients with sepsis. The plasma NGAL values were positively correlated with C-reactive protein and procalcitonin levels, and MEDS scores. Plasma NGAL is a valuable biological marker in the assessment of severity and prediction of prognosis of patients with sepsis in the emergency department.


Ecological tannin assays : Evaluation of proanthocyanidins, protein binding assays and protein precipitating potential.
Estimations of condensed tannin content are generally based on calibration standard curves from Quebracho condensed tannins. We generated calibration standard curves from eight Sonoran Desert species for comparison with estimates of tannin concentrations derived from the Quebracho standard curve. Estimates of leaf tannin concentrations of each of the eight species using each species standard curve differed significantly with the estimates given by the Quebracho standard curve. Standard curves constructed from tannins from different individuals of three of the species varied significantly between, but not within, species. The efficiency of precipitation of protein bovine serum albumin (BSA) by each different tannin varied up to a factor of fifty for tannins of different species. Ordering species from highest to lowest based on tannin concentrations or binding efficiencies gave two different ranks. We argue that concentration or efficiency alone do not describe adequately tannin ecological activity. Instead, we suggest combining tannin concentrations and binding efficiencies to measure the protein precipitating potential of a leaf. Leaf protein precipitating potential is a more ecologically realistic parameter, we feel, for between-species comparisons than tannin content or binding efficiencies alone.


The design and construction of a multiple proportional counter used to study axonal transport.
The design and construction of a multiple proportional counter, a position-sensitive detector of ionizing radiation, are described. Both the mechanical and electronic aspects are discussed. Testing procedures are outlined, and test values are cited.


[Orbital tumor in Goodpasture's syndrome (author's transl)].
Diplopia and unilateral exophthalmus of a female patient, aged 34, with Goodpasture's syndrome were the indication for echographic examination. A- and B-scan echography revealed a diffuse retrobulbar tumor carrying the characteristics of the sarcoma/lymphoma/pseudotumor group.


The effect of augmentation with resorbable or conventional bone cement on the holding strength for femoral neck fracture devices.
To compare maximum extraction torque and pull-out load for femoral neck fracture implants inserted with standard technique or after augmentation with polymethylmethacrylate (PMMA) or calcium phosphate cement (Norian SRS). Biomechanical study using synthetic bone. Implants were inserted in foam blocks with three different densities for simulation of normal bone or slight or severe osteoporosis. Tested implants included three screws (AO, Olmed, Hansson), one screw with both threads and a barb (Hybrid), and one pin with a hook (LIH hook-pin). Implants were inserted by standard technique and after augmentation with PMMA or Norian SRS. The effect of (a) density of the synthetic bone (low, medium, high), (b) augmentation (none, PMMA, SRS), and (c) type of implant (AO, Olmed, Hansson, Hybrid, LIH) on the maximum extraction torque and pull-out load was determined using a material testing machine. Analysis of variance with Fisher's PLSD post hoc test was used to determine statistical differences. PMMA significantly increased maximum torque and pull-out load for all implants and block densities when compared without cement (p < 0.0001), whereas enhancement with SRS was far less pronounced and most obvious in low density blocks. For screws normally inserted without predrilling (Olmed and Hansson) the use of SRS in high density blocks caused a significant reduction in maximum torque (p < 0.0001) and pull-out load (p < 0.0001). SRS-augmented specimens failed through the cement at the periphery of the threads, whereas PMMA-augmented specimens failed between the cement and the synthetic bone. This study suggests that augmentation with PMMA around femoral neck fracture implants will increase the holding power significantly when compared with standard insertion technique as well as augmentation with calcium phosphate cement. Augmentation with calcium phosphate cement like SRS will increase the holding characteristics mainly in low density bone, whereas in high density bone it might even reduce the maximum torque because of the need for predrilling when using the cement for augmentation.


Insights into the functional role of grass carp IL-8 in head kidney leukocytes: pro-inflammatory effects and signalling mechanisms.
Interleukin-8 (IL-8) is a critical chemokine regulating immune cells' chemotaxis as well as their physiological or pathological activations. In fish cells, recombinant IL-8 proteins induced transcriptions of pro-inflammatory cytokines. Nonetheless, the exact mechanisms underlying the function of fish IL-8 as a pro-inflammatory cytokine are still unclear. In this paper, the authors first prepared recombinant grass carp IL-8 (rgcIL-8) using an Escherichia coli expression system, and later confirmed rgcIL-8 increased gene expression of il8, il1β and tumour necrosis factor alpha (tnfα) in grass carp head kidney leukocytes (HKLs). Using signalling pathway inhibitors, the authors showed that rgcIL-8 regulated transcriptions of pro-inflammatory cytokines via MAPK and/or NF-κB signalling pathways. They cloned gcIL-8-specific receptor CXCR1 and subsequently discovered that gcIL-8 could increase the activity of NF-κB and the transcription of IL-1β via CXCR1. Simultaneously, antibody neutralization assay showed that endogenous IL-8 is partially relevant to the self-regulation of IL-1β. Moreover, rgcIL-8 led to the expression of inducible nitric oxide synthase gene, causing an accumulation of nitric oxide in the culture medium of HKLs, suggesting the potential of gcIL-8 to mediate inflammatory response. This study not only enriched the function of IL-8 in teleost but also revealed it as a potential target for the inflammatory control in grass carp.


A galactose specific agglutinin from the hemolymph of the snail Achatina fulica: purification and characterization.
A galactose specific agglutinin has been detected in the hemolymph of the snail Achatina fulica fulica Bowdich. The agglutinin, which agglutinates rabbit erythrocytes, has been purified by affinity chromatography on crosslinked guargum followed by gel filtration on a Biogel P-200 column. The purified agglutinin has a native molecular weight of 210,000 and comprises of non covalently linked identical subunits of molecular weight 15,000. The pI of the agglutinin was found to be 8.1. The activity of the agglutinin is independent of divalent cations. The inhibition of hemagglutination data reveals that 2-deoxy-D-galactose is the most potent inhibitor of the agglutinin followed by galactose and lactose.


Is impaired dopaminergic function associated with mobility capacity in older adults?
The capacity to move is essential for independence and declines with age. Slow movement speed, in particular, is strongly associated with negative health outcomes. Prior research on mobility (herein defined as movement slowness) and aging has largely focused on musculoskeletal mechanisms and processes. More recent work has provided growing evidence for a significant role of the nervous system in contributing to reduced mobility in older adults. In this article, we report four pieces of complementary evidence from behavioral, genetic, and neuroimaging experiments that, we believe, provide theoretical support for the assertion that the basal ganglia and its dopaminergic function are responsible, in part, for age-related reductions in mobility. We report four a posteriori findings from an existing dataset: (1) slower central activation of ballistic force development is associated with worse mobility among older adults; (2) older adults with the Val/Met intermediate catecholamine-O-methyl-transferase (COMT) genotype involved in dopamine degradation exhibit greater mobility than their homozygous counterparts; (3) there are moderate relationships between performance times from a series of lower and upper extremity tasks supporting the notion that movement speed in older adults is a trait-like attribute; and (4) there is a relationship of functional connectivity within the medial orbofrontal (mOFC) cortico-striatal network and measures of mobility, suggesting that a potential neural mechanism for impaired mobility with aging is the deterioration of the integrity of key regions within the mOFC cortico-striatal network. These findings align with recent basic and clinical science work suggesting that the basal ganglia and its dopaminergic function are mechanistically linked to age-related reductions in mobility capacity.


Ab initio and DFT studies on vibrational spectra of some halides of group IIIB elements.
The vibrational spectra of some group IIIB elements halides MX(3) and their dimmers, M(2)X(6) (M=Sc(III), Y(III), La(III); X=F, Cl, Br, I), have been systematically investigated by ab initio restricted Hartree-Fock (RHF) and density functional B3LYP methods with LanL2DZ and SDD basis sets. The optimized geometries and calculated vibrational frequencies are evaluated via comparison with experimental values. The vibrational frequencies, calculated by two methods with different basis sets, are compared to each other. The effect of the methods and the basis sets used on the calculated vibrational frequencies are discussed. Some vibrational frequencies of these complexes are also predicted.


Idax and Rinf facilitate expression of Tet enzymes to promote neural and suppress trophectodermal programs during differentiation of embryonic stem cells.
The Inhibitor of disheveled and axin (Idax) and its ortholog the Retinoid inducible nuclear factor (Rinf) are DNA binding proteins with nuclear and cytoplasmic functions. Rinf is expressed in embryonic stem cells (ESCs) where it regulates transcription of the Ten-eleven translocation (Tet) enzymes, promoting neural and suppressing mesendoderm/trophectoderm differentiation. Here, we find that Idax, which is not expressed in ESCs, is induced upon differentiation. Like Rinf, Idax facilitates neural and silences trophectodermal programs. Individual or combined loss of Idax and Rinf led to downregulation of neural and upregulation of trophectoderm markers during differentiation of ESCs to embryoid bodies as well as during directed differentiation of ESCs to neural progenitor cells (NPCs) and trophoblast-like cells. These defects resemble those of Tet-deficient ESCs. Consistently, Tet genes are direct targets of Idax and Rinf, and loss of Idax and Rinf led to downregulation of Tet enzymes during ESC differentiation to NPCs and trophoblast-like cells. While Idax and Rinf single and double knockout (DKO) mice were viable and overtly normal, DKO embryos had reduced expression of several NPC markers in embryonic forebrains and deregulated expression of selected trophoblast markers in placentas. NPCs derived from DKO forebrains had reduced self-renewal while DKO placentas had increased junctional zone and reduced labyrinth layers. Together, our findings establish Idax and Rinf as regulators of Tet enzymes for proper differentiation of ESCs.