Development of rearing and testing protocols for a new freshwater sediment test species: the gastropod Valvata piscinalis.
This paper aimed at proposing rearing and testing protocols for Valvata piscinalis, a new potential species for sediment toxicity testing. Such tests were developed since this species reliably represents the bio/ecological characteristics of other gastropods. It may thus be representative of their sensitivity to chemicals. V. piscinalis was successfully cultured in our laboratory for six generations. Cultures provided a high productivity for a low working time and low costs. The tests conditions we proposed seemed to be relevant for the development of reliable tests with this species. Indeed, hatching probability of egg-capsules, as well as embryo, newborn and juvenile survival rates, were close to 100%. Moreover, growth rates and fecundity were significantly higher than in field and in other laboratory studies. Partial life-cycle tests on clean sediments were achieved for various feeding levels to determine survival, growth and reproduction patterns, ad libitum feeding level and life cycle parameters values. Ad libitum feeding levels for newborn, juveniles and adults were 0.1, 0.4 and 0.8 mg Tetramin/individual/working day. Growth tests with zinc-spiked sediments provided a no-effect concentration and a lowest effect concentration of respectively 200 and 624 mg zinc/kg dry sediment. Other growth tests on spiked sediments we ran at our laboratory with second, third and fourth instars larvae of Chironomus riparius pointed out that V. piscinalis was more sensible to zinc than the chironomid, which is a routine test species in ecotoxicology. According to these results, V. piscinalis is a promising candidate species for sediment toxicity testing.


Analysis of biostructural changes, dynamics, and interactions - Small-angle X-ray scattering to the rescue.
Solution small angle X-ray scattering from biological macromolecules (BioSAXS) plays an increasingly important role in biostructural research. The analysis of complex protein mixtures, dynamic equilibriums, intrinsic disorder and evolving structural processes is facilitated by SAXS data, either in stand-alone applications, or with SAXS taking a prominent role in hybrid biostructural analysis. This is not the least due to the significant advances in both hardware and software that have taken place in particular at the large-scale facilities. Here, recent developments and the future potential of BioSAXS are reviewed, exemplified by numerous examples of elegant applications to challenging systems.


Detection of Fungal Jasmonates by Liquid Chromatography Paired with Mass Spectrometry.
Liquid chromatography-mass spectrometry (LC-MS) is one of the most important analytical chemistry techniques for the detection and characterization of biologically active compounds of low abundance-for example, hormones. Gas chromatography (GC) coupled with mass spectrometry has been a method of choice to detect jasmonic acid, the well-known defense hormone in plants. Recently, we identified structural and functional analogs of phytohormone jasmonic acid (JA) and its derivatives, in the rice-blast fungus Magnaporthe oryzae. Here, we describe protocols of LC-MS/MS-based identification and quantification of fungal jasmonates, especially during pathogenic development in the rice blast fungus.


[Characteristics of falls of neurological cause in the elderly].
Falls are a cause of disability and death in geriatric population. Third part of the elderly suffer at least one fall per year. Neurological illness are a very important risk factor in developing falls. To establish the differences between neurological and not neurological patients with recurrent falls. We select 113 patients over 65 years-old with two or more falls in the last six months, collecting demographic and medical data, as well as a functional, mental and social evaluation, gait and balance tests and posturography. Complementary examinations were done to clarify the diagnosis in each case. Average age was 78 years-old. We define a group A, patients in which the main cause of falls is a neurological disease and group B with a non-neurological cause. Group A shows more number of falls (p < 0.053), worse functional (p < 0.002) and mental (p < 0.001) situation and more comorbility (p = 0.05), as well as worse scores in gait tests. Neurological illness are a very important risk factor in falls due to the disturbances in gait and balance that they produce. Dementia, parkinsonism and cerebrovascular diseases are frequently found in elderly patients with recurrent falls. Patients with falls due to neurological illness tend to fall oftener and have worse mental and functional situation. Evaluating neurological risk factors in geriatric patients with recurrent falls is essential to establish appropriate prevention strategies.


Formation of eLiposomes as a drug delivery vehicle.
This paper discusses the formation of eLiposomes, defined as a liposome with internal emulsion droplets. Liposomes have been investigated as passively targeted drug carriers due to their ability to deliver drugs to a cancerous tumor via the enhanced permeability and retention (EPR) effect. The enclosed emulsion droplets in an eLiposome add the ability to further control the location and time of release from the liposome with ultrasound. Emulsion droplets were formed from perfluorohexane (PFC6) by sonication at 20 kHz and stabilized with dipalmitoyl phosphatidyl choline (DPPC). The size of the resulting droplets was reduced to approximately 100 nm or 50 nm by extrusion through polycarbonate filters of the same size at 50°C. Small unilamellar vesicles (SUVs) were prepared from DPPC by thin film hydration and extrusion through a 50 nm filter. Interdigitated DPPC sheets were prepared from the SUVs by the addition of ethanol to a concentration of 3M. Excess ethanol was removed by centrifugation washing. The sheets were mixed with emulsion and the solution was heated to 50°C, resulting in the refolding of the DPPC sheets into closed vesicles. Emulsion droplets were encapsulated inside of the newly formed eLiposomes. The size of the eLiposomes was reduced by extrusion. Cryogenic transmission electron microscopy (cryoTEM) and negative-staining TEM were used to image the emulsion droplets and the eLiposomes. Encapsulation of emulsion droplets was verified by rotating the microscope stage of cryoTEM samples.


How do patients and professionals differentiate between intra-articular joint bleeds and acute flare-ups of arthropathy in patients with haemophilia?
The overlap in symptoms between joint bleeds and flare-ups of haemophilia arthropathy (HA) creates difficulties in differentiating between the two conditions. Diagnosis of haemarthrosis is currently empirically made based upon clinical presentations. However, no standard diagnostic criteria are available. To offer appropriate treatment, rapid and accurate diagnosis is essential. Additionally, adequate differentiation can decrease health costs significantly. The aim of this study was to identify signs and symptoms to differentiate between an intra-articular joint bleed and an acute flare-up of HA in patients with haemophilia and make an initial proposal of items to include in a diagnostic criteria set. Six focus group interviews with a total of 13 patients and 15 professionals were carried out. The focus groups were structured following the Nominal Group Technique (NGT). The most important signs and symptoms used to differentiate between joint bleeds and HA were (i) course of the symptoms, (ii) cause of the complaints, (iii) joint history, (iv) type of pain and (v) degree of impairments in range of motion. This qualitative study provides insight into signs and symptoms that are currently used to differentiate between joint bleeds and flare-ups of HA. Results of this study can be used to develop a valid and standardized clinical diagnostic criteria set to differentiate between these two conditions. Further research is necessary to validate the signs and symptoms found in this study.


Biological markers of protein-energy malnutrition.
The biological markers of undernutrition fall into three categories: (a) those that measure structure; (b) those that measure function; and (c) indices of the above two. Ideally a marker of nutritional status should have the following characteristics: specific to nutritional status; sensitive to changes in nutritional status; reproducible; simple to measure; inexpensive and widely available. Unfortunately there are no such markers, and therefore individuals involved in the assessment of nutritional status should be aware of the advantages and disadvantages of the markers they use. For example, body composition can be assessed using sophisticated techniques that make fewer assumptions than simple bedside techniques (1). However, these sophisticated techniques (eg neutron activation, and combinations of techniques such as hydro-densitometry, water dilution techniques and dual-energy X-ray absorptiometry) are not widely available and some of them are labour intensive. On the other hand simple bedside techniques, such as those based on skinfold thicknesses can be applied widely because they are easy and quick to perform, but they are probably not as accurate as the classic body composition techniques (hydro-densitometry or water dilution techniques) or other sophisticated methods based on the assessment of multiple body compartments (1). Therefore the choice of method depends not only on the availability of investigative tools, but also on the practicalities of using them in individuals, a small group of individuals, or large groups of individuals, (eg national surveys during famine and non-famine conditions). In this brief review only some aspects concerned with simple bedside or laboratory methods will be discussed.


Gastric drainage procedures: effects in normal dogs. I. Introduction and description of surgical procedures.
Gastric drainage procedures are commonly used in veterinary medicine, particularly in dogs in attempts to prevent recurrence of gastric dilatation-volvulus (GDV). The following five different procedures have been most commonly described: the Fredet-Ramstedt pyloromyotomy (FRP); Heineke-Mikulicz pyloroplasty (HMP); Finney pyloroplasty (FP); Jaboulay's gastroduodenostomy (JG); and antral gastrojejunostomy (AG). These surgical procedures have not been compared in a controlled study. This first article of a series of three describes the gastric drainage procedures performed in 30 normal dogs for a comparative study. The FRP and HMP were the fastest and easiest procedures to perform. The degree of difficulty was found to be increased but similar for FP, JG, and AG. No complication occurred during or immediately after surgery.


Ethanol desensitizes cannabinoid CB1 receptors modulating monoamine synthesis in the rat brain in vivo.
The endocannabinoid system and the cannabinoid CB(1) receptors are involved in the development of ethanol tolerance and dependence. This study aimed to investigate the in vivo sensitivity of a CB(1) receptor agonist (WIN 55,212-2) modulating the synthesis of 3,4-dihydroxy-phenylalanine/dopamine/noradrenaline (DOPA/DA/NA) and that of 5-hydroxy-tryptophan/serotonin (5-HTP/5-HT) in rat brain after ethanol treatment and withdrawal. In control rats, WIN 55,212-2 (4 mg/kg, i.p., for 1h), through a mechanism sensible to the CB(1) antagonist SR 141716A, increased the synthesis of DOPA/NA in a slice of brainstem containing the locus ceruleus (250%) and in the hippocampus (64%), and it reduced DOPA/DA synthesis in the striatum (47%). WIN 55,212-2 also decreased the synthesis of 5-HTP/5-HT in the locus ceruleus (43%), hippocampus (35%) and striatum (35%). In the locus ceruleus of ethanol-treated rats, the stimulatory effect of WIN 55,212-2 on DOPA/NA synthesis was abolished (acute treatment) or markedly attenuated (53-55%, chronic treatment and withdrawal), whereas in the hippocampus this effect was reduced only in chronic ethanol-withdrawn rats (33%). In the striatum of ethanol-treated rats (acute, chronic and withdrawal), the inhibitory effect of WIN 55,212-2 on DOPA/DA synthesis was completely blunted or markedly reduced. Similarly, the inhibitory effect of WIN 55,212-2 on 5-HTP/5-HT synthesis was reduced or abolished in the three brain regions after chronic ethanol and during withdrawal. These results indicate that treatment with ethanol in rats induces a functional desensitization of CB(1) receptors modulating the synthesis of brain monoamines.


Fatal Cardiac Arrhythmias During Electronic Gaming in Patients With Genetically Mediated Heart Diseases.
Recently, electronic gaming has been reported as a precipitant of life-threatening cardiac arrhythmias in susceptible individuals. However, the prevalence of cardiac events in genetic heart diseases (GHDs) in the setting of electronic gaming has not been established. In this study, we sought to define the prevalence of cardiac events occurring in the setting of electronic gaming in GHDs. Retrospective review of all patients evaluated and treated at Mayo Clinic's genetic heart rhythm clinic from July 2000 to November 2022 was performed to identify patients with a history of playing electronic games at the time of their cardiac event. Cardiac event was used to define events occurring before diagnosis, and breakthrough cardiac event (BCE) was used for events occurring after diagnosis. Of the 3,370 patients with a GHD (mean age at first evaluation 27 ± 19 years, 55% female), 1,079 (32%) had a cardiac event before diagnosis, with 5 patients (0.5%) having an electronic gaming-associated event (3 catecholaminergic polymorphic ventricular tachycardia, 1 long QT syndrome, and 1 premature ventricular contraction-triggered ventricular fibrillation). After diagnosis and treatment, 431 patients (13%) experienced ≥1 BCE during follow-up, of which 1 electronic gaming-associated BCE (0.2%) occurred in a patient with catecholamine-sensitive right outflow tract ventricular tachycardia. Although anecdotal cases of electronic gaming-associated life-threatening arrhythmias have been reported, in this largest single-center study to date, we show that these are extremely rare occurrences. While electronic gaming can have adverse health consequences, the threat of electronic gaming-triggered sudden death should not be used to try to curb time spent gaming.


Intimal cushions in the lingual artery of neonates and children.
Focal musculo-elastic thickenings were identified in the intima. The distribution of these cushions may be related to haemodynamic stresses.


The effect of dimethylnitrosamine on host resistance and immunity.
Adult female B6C3F1 mice were injected ip with 0.2 ml phosphate-buffered saline (PBS) only or PBS containing 1.5, 3, or 5 mg dimethylnitrosamine (DMN)/kg body wt daily for 14 days. On Day 16, mice were evaluated for changes in immune status as measured by the antibody response to sheep red blood cells (SRBCs), blastogenesis to T- and B-cell mitogens, natural killer (NK) cell function, delayed hypersensitivity, and alveolar macrophage (AM) bactericidal activity; and for changes in host resistance following challenge with various microorganisms or tumor cells. DMN-exposed animals exhibited reduced humoral antibody responses, T-cell mitogenesis, and AM bactericidal activity. B-cell mitogenesis, NK cell activity, and delayed hypersensitivity were increased. Resistance to challenge with Listeria monocytogenes, Trichinella spiralis, or Herpes simplex types 1 or 2 virus (HSV-1, HSV-2) was not significantly impaired, while that to Streptococcus zooepidemicus and influenza virus was significantly reduced. Resistance to B16-F10 tumor challenge was enhanced following DMN exposure. The data show that DMN treatment altered humoral immunity and antibody-mediated host defense mechanisms. Increased NK cell activity may account for the increased resistance to challenge with Herpes virus and B16-F10 tumor cells.


Hearing assessment in Egyptian children with chronic renal failure on regular hemodialysis and renal transplantation children.
Hearing impairment is frequent in patients with end-stage renal disease (ESRD). We aimed to assess the prevalence of hearing impairment in children on regular hemodialysis and renal transplantation. Transient-evoked otoacoustic emissions (TEOAEs) has been done for 80 children on regular hemodialysis and 40 with renal transplant. In hemodialysis group, TEOAEs showed that 53.8% children had hearing affection, it was significantly related to dialysis duration, dialysis adequacy, vascular access infection, hepatitis C virus (HCV) infection, and ototoxic drugs (p = 0.001, 0.037, 0.011, 0.004, 0.030, 0.007, and 0.044, respectively). In renal transplant group hearing impairment was 25%. There was significant relation with period of dialysis before transplantation and biopsy proved rejection (p = 0.008, <0.001, respectively). Hearing impairment is a common finding in ESRD patients. Thus audiological assessment must be done in these patients.


ExPert ConsEnsus on the management of Advanced clear-cell RenaL celL carcinoma: INDIAn Perspective (PEARL-INDIA).
In advanced Renal Cell Carcinoma (aRCC), systemic therapy is the mainstay of treatment, with no or little role for surgery in these patients. Tyrosine kinase inhibitors (TKIs) and immune-oncological (IOs) therapies, either alone or in combination, are recommended in these patients depending on patient and tumour factors. The sequencing of therapies is critical in RCC because the choice of subsequent line therapy is heavily dependent on the response and duration of the previous treatment. There are additional barriers to RCC treatment in India. Immunotherapy is the cornerstone of treatment in ccRCC, but it is prohibitively expensive and not always reimbursed, effectively putting it out of reach for the vast majority of eligible patients in India. Furthermore, in advanced RCC (particularly the clear cell variety), Indian oncologists consider the disease burden of the patients, which is particularly dependent on the quantum of the disease load, clinical symptoms, and performance status of the patient, before deciding on treatment. There are no India-specific guidelines for clear cell RCC (ccRCC) treatment or the positioning and sequencing of molecules in the management of advanced ccRCC that take these country-specific issues into account. The current consensus article provides expert recommendations and treatment algorithms based on existing clinical evidence, which will be useful to specialists managing advanced ccRCC.


[Morphofunctional changes in the pineal gland during adaptation to hypothermia].
The influence of hypothermal stress (+4 degrees during 3 h) on the ways of serotonin metabolism in pineal gland and its structure has been studied in dynamics on adult male Wistar rats. It has been revealed that melatonin-producing epiphyseal function suffers from phase changes in dynamics of adaptation--significant rising during 15 min. after beginning of the experiment, rehabilitation up to normal--in 30 min, and fast suppressing--in 3 hrs. Suppressing of the functional pineal activity is not due to switched serotonin metabolism with melatonin and new indoles release, but to a partial pinealocytes breaking from their active function.


Land use change alters carbon and nitrogen dynamics mediated by fungal functional guilds within soil aggregates.
Land use change is one of the greatest threats to soil biodiversity and ecological functions; however, how such a transition affects soil carbon (C) and nitrogen (N) dynamics driven by fungal communities at the aggregate level remains unclear. Here, we explored the variation in soil C and N pools, specific enzyme activities and fungal communities and functional guilds within three aggregate sizes (megaaggregates, > 2 mm; macroaggregates, 0.25-2 mm; microaggregates, < 0.25 mm) in a natural forest, 12- and 24-year-old rubber monocultures and corresponding agroforestry systems in tropical China. Tropical forest conversion to rubber monocultures generally reduced C and N pools in all aggregates, while agroforestry systems decreased microbial biomass C and N. Carbon- and N-degrading enzyme activities responded differently to forest conversion and were enhanced in agroforestry systems. The levels of C and N pools and their related enzyme activities increased as the aggregate size decreased. Moreover, fungal compositional shifts in dominance from copiotrophic Ascomycota and Basidiomycota (r-strategists) into oligotrophic Zygomycota (K-strategists) were noted following forest conversion, resulting in more pathogenic fungi at the expense of saprotrophic and arbuscular mycorrhizal fungi. Pathogenic fungi were greatly inhibited due to abundant Mortierella after the establishment of 12-year-old agroforestry systems. The diversity of saprotrophic fungi was the highest in microaggregates. Regardless of land use type, aggregate-associated C and N pools, especially DOC, MBC, NO3--N and DON in microaggregates, were interactively mediated by functional guilds of fungi, which was primarily driven by soil pH. These results highlight the importance of fungal functional guilds in determining C and N dynamics at the aggregate level and provide insights into the sustainable management of cash tree plantations.


The effects of miniscrew-assisted rapid palatal expansion on the upper airway of adults with midpalatal suture in the last two degrees of ossification.
Transverse deficiencies of the maxillary basal bone have been treated in adult patients using miniscrew-assisted rapid palatal expansion (MARPE) therapy. However, the midpalatal suture's degree of ossification may affect the upper airway dimensions. This study compared the volumetric changes of the total upper, retropalatal, retroglossal airways, and the minimal transverse airway constriction after MARPE therapy in patients with midpalatal suture in the last stages of ossification. This controlled clinical trial included a total of 20 adult patients (mean age 24.5 ± 6.2 years) with maxillary atresia treated with MARPE. Preoperative (T0) cone-beam computed tomography scans were used to determine the degree of midpalatal suture ossification. Two groups were formed considering the last two stages of sutural ossification "D" or "E" (n = 10 per group). After 120 days of the therapy (T1), cone-beam computed tomography assessments were performed to compare the pre and post-treatment outcomes. The total upper, retropalatal, and retroglossal airways and the minimal transverse airway constriction were evaluated. The three-dimensional reconstruction was performed with OsiriX MD software. The comparisons were carried out using mixed models for repeated measures at fixed time points (α = 0.05). Groups D and E showed no significant difference for any of the analyzed parameters (P > 0.05). Both groups showed a statistically significant increase for all airway segments after the treatment with MARPE (P < 0.05). The total upper airway increased (11.6% and 16.1%) for groups D and E, respectively (P = 0.3356). MARPE therapy resulted in dimensional gains of the upper airway for adult patients, irrespective of the intermaxillary sutural degree of ossification.


Lumbosacral transitional vertebra and S1 radiculopathy: the value of coronal MR imaging.
The association of a lumbosacral transitional vertebra with accelerated degeneration of the disc above has been described. Lumbosacral transitional vertebrae have also been reported as a cause of extraforaminal entrapment of the L5 nerve root between the transverse segment of the transitional vertebra and the sacral ala optimally demonstrated by coronal MRI. The association of the lumbosacral transitional vertebra pseudoarthroses and S1 nerve root entrapment due to degenerative stenosis of the nerve root canal has never been described. We present 12 patients with lumbosacral transitional vertebrae that were referred for symptoms and signs of S1 nerve root radiculopathy in which the sagittal and axial MRI sequences failed to identify a plausible cause for the patients' S1 nerve root symptoms. A coronal T1-weighted imaging (T1WI) MRI sequence was consequently added to the investigation. The coronal T1WI MRI sequence demonstrated hypertrophic degenerative stenosis of the S1 nerve root canal at the level of the lumbosacral transitional vertebra pseudoarthrosis, with entrapment of the respective S1 nerve root in all patients. We emphasize the value of coronal T1WI MRI of the lumbosacral junction and sacrum if the cause for S1 radicular symptoms was not identified on conventional sagittal and axial MRI sequences in patients with lumbosacral transitional vertebrae.


Effects of halothane and methoxyflurane on the hypothalamic-pituitary-adrenal axis in rat.
Effects of acute exposure (2 h) to either 1.5% halothane or 0.5% methoxyflurane on chemical mediators of the hypothalamic-pituitary-adrenal (HPA) axis were evaluated in male Sprague-Dawley rats immediately after exposure, after the righting reflex (4 h), or 24 h postexposure. Effects of these anesthetics on hippocampal corticotropin releasing factor (CRF) were also evaluated. Methoxyflurane caused significant elevations in pituitary adrenocorticotropin hormone (ACTH)-like immunoreactivities in all three of the experiment's time groups, yet halothane failed to cause the same response immediately after exposure. Serum ACTH-like immunoreactivities were significantly elevated immediately after exposure to both anesthetics, but were not elevated at 4 and 24 h postexposure. Corticosterone (CORT)-like immunoreactivities were significantly elevated by halothane in all experimental groups, and in the 2- and 24-h groups following methoxyflurane exposure. Hippocampal CRF-like immunoreactivities remained unaffected by either anesthetic. Results indicate that a 2-h exposure to either halothane or methoxyflurane results in significant activation of the rat hypothalamic-pituitary-adrenal axis, and that the activation appears to be sustained over a 24-h period.


Plasma alcohol, smoking, hormone concentrations and self-reported aggression. A study in a social-drinking situation.
Plasma alcohol concentrations and the number of cigarettes smoked by men during social-drinking situations were significantly related to change in testosterone levels. Age, height, plasma alcohol and smoking were related to self-reports of prior assault and verbal aggression. Agression was not related to testosterone concentration.


Novel approach to idursulfase and laronidase desensitization in type 2 and type 1 S mucopolysaccharidosis (MPS).
Idursulfase and laronidase are drugs used to treat Hunter syndrome (mucopolysaccharidosis type 2) and Scheie syndrome (mucopolysaccharidosis type 1 S), respectively. These are rare lysosomal storage disorders, leading to accumulation of glycosaminoglycans within lysosomes. Failure of early recognition of the disease and/or delay in starting the appropriate treatment result in severe clinical impairment and death. For almost 20 years, enzyme replacement therapy with recombinant proteins has represented the first line therapeutic option. However, administration of idursulfase and laronidase is associated with infusion-related hypersensitivity reactions, in approx. 20% of patients. In these patients, rapid desensitization by intravenous administration protocols has been used in order to avoid treatment discontinuation. This approach proved effective and safe. However, long-term tolerance could not be achieved. Thus, we decided to combine rapid desensitization with allergen immunotherapy-like desensitization. Two patients with Hunter syndrome and one patient with Scheie syndrome developed severe allergy to idursulfase and laronidase, respectively, preventing them from continuing the otherwise indispensable therapy. In all three patients, the possible IgE-mediated nature of the reactions suffered was suggested by positive skin tests with the two enzymes, respectively. By devising 12-step, 3-dilution rapid desensitization protocols, we resumed the enzyme replacement therapy. However, the prolonged time required for administration (a not negligible pitfall, since therapy should be given weekly for life) and the persistent occurrence of reactions (mild but still requiring anti-allergic medication at full dosage) led us to combine rapid desensitization with a compact 11-step, 24-day allergen immunotherapy-like desensitization protocol. Thus, idursulfase and laronidase were injected subcutaneously, with a 500-fold increase from step 1 to step 11 for idursulfase and a 222-fold increase for laronidase. This strategy led to restoration of long-term tolerance, allowing weekly intravenous therapy administration under standard conditions, according to the manufacturer instructions, in the absence of side effects and with only precautionary low-dose premedication. Rapid desensitization is a suitable and safe option in the case of idursulfase and laronidase allergy. Combination with subcutaneous allergen immunotherapy-like desensitization afforded restoration of enzyme replacement therapy given by the normal administration schedule, by inducing sustained tolerance.


Schistosoma japonicum: Tsunagi/Y14 protein plays a critical role in the development of the reproductive organs and eggs.
Tsunagi/Y14 is an evolutionarily conserved RNA-binding protein that is required for the maintenance of oogenesis and the masculinization of the germ-line in many animal models. We speculated that Tsunagi/Y14 might also regulate reproductive organ development in Schistosoma japonicum (S. japonicum, Sj). Sj Tsunagi/Y14 and control double-stranded RNAs were introduced into schistosomula by electroporation respectively. These transfected schistosomula were cultured in vitro for 1, 3 or 5 days. The mRNA and protein levels of the target gene in the cultured schistosomula were significantly suppressed compared with those of the control group. Furthermore, BALB/c mice were infected with the transfected schistosomula for 6 weeks and were sacrificed to harvest the adult worms. We found that the silencing of Sj Tsunagi/Y14 led to defects in reproductive organs development in both male and female worms. Moreover, it also affected the size, quantity and activity of the eggs in the mice liver. Our findings indicated that Tsunagi/Y14 plays a critical role in the development of reproductive organs and eggs in S. japonicum.


Striatal lesions in delusional parasitosis revealed by magnetic resonance imaging.
Delusional parasitosis (DP) is a syndrome characterized by the firm conviction that small living beings infest the skin. The etiology can be primary and secondary. Structural brain abnormalities in DP have only been reported in case reports often subcortical vascular encephalopathy and right-hemisphere strokes in the temporo-parietal cortex. Systematic brain imaging studies are lacking. We aimed to identify a brain region with structural lesions in patients with DP in order to better understand the pathophysiology of DP. Nine consecutive patients with DP in a psychiatric outpatient department were assessed clinically and by means of cranial magnetic resonance imaging (MRI). Five of the nine cases were diagnosed as having DP as psychotic disorders due to a general medical condition while three had DP arising from pre-existing psychiatric illness and one suffered from a delusional disorder, somatic type (primary form). Four of the five DP cases secondary to a general medical condition (one case could not be analyzed) had striatal lesions predominantly in the putamen. Thalamic or cortical lesions were found in one case, respectively. In the primary DP case and all cases secondary to another psychiatric disorder basal ganglia and subcortical gray matter lesions were absent. In all medical (secondary) DP cases subcortical white matter lesions were found mainly in the centrum semiovale. Three of the five medical DP cases showed severe generalized brain atrophy which was absent in the primary DP case and in the cases secondary to other psychiatric disorders. We present the findings of the first structural MRI study in DP. Our results suggest a possible relevance of structural lesions in the striatum, predominantly the putamen, in the medical (secondary) DP-subgroup. Our findings are in line with other studies demonstrating that the putamen, in addition to its role in motor regulation, represents a brain area that mediates visuo-tactile perception. Disturbed functioning of the putamen and associated brain areas of the somatic/dorsal striato-thalamo-cortical loop might therefore play an important role in the pathophysiology of DP, which is characterized by somatic delusions, tactile misperceptions and sometimes also visual hallucinations. The involvement of the striatum and the efficacy of antidopaminergic antipsychotics indicate dopaminergic dysfunction in DP. Evidence from DP in intoxication with substances influencing the dopamine transporter (DAT) (e.g. cocaine, methylphenidate, bupropion) further supports this observation. Further neuroimaging studies in larger samples are needed to expand our preliminary knowledge obtained from this case-series study.


The predictive value of abbreviated migraine diagnostic criteria.
To determine the operating characteristics and predictive value of abbreviated criteria for the diagnosis of migraine headache. The International Headache Society (IHS) diagnostic criteria for migraine have been adopted in limited fashion in clinical practice. Primary care physicians in particular deal with innumerable conditions and diagnostic algorithms. Unless the IHS criteria are simplified the recognition of migraine headache in primary care settings will not be apt to improve. This study was a retrospective analysis of four discrete research databases: headache clinic patients (N = 390), private practice neurology patients (N = 290), college students (N = 99), and community-based patients (N = 784). Physicians and psychologists expert in the diagnostic criteria for migraine headache syndromes conducted a standardized diagnostic interview in all patients (N = 1524). Each was later assigned an IHS headache diagnosis by a previously validated computer-based algorithm. The sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for single- and multiple-variable models of migraine predictors. Optimal models were defined as those with positive likelihood ratios (+LRs) of >4.5 and negative likelihood ratios (-LRs) of <0.25 for the combined population. The only optimal single-variable model was nausea, which had an overall +LR of 4.8 and -LR of 0.23. None of the two-variable models met criteria for an optimal model. The best of the optimal three-variable models were nausea/photophobia/pulsating (+LR 6.7, -LR 0.23) and nausea/photophobia/worsening with physical activity (+LR 5.9, -LR 0.21). These three models maintained positive predictive values >0.80 in all 4 patient populations and negative predictive values >0.70 in the majority of populations. The single-variable model of nausea and the three-variable models of nausea/photophobia/worse with exertion and nausea/phonophobia/pulsating can effectively predict migraine in diverse clinical settings. These models however, should only be applied after a careful exclusion of secondary headache disorders.


Near-infrared spectroscopy combined with pattern recognition algorithms to quickly classify raisins.
With the development of commodity economy, the emergence of fake and shoddy raisin has seriously harmed the interests of consumers and enterprises. To deal with this problem, a classification method combining near-infrared spectroscopy and pattern recognition algorithms were proposed for adulterated raisins. In this study, the experiment was performed by three kinds of raisins in Xinjiang (Hongxiangfei, Manaiti, Munage). After collecting and normalizing the spectral data, we compared the spectra of three kinds of raisins. Next the principal component analysis (PCA) was preformed to compress the dimension of the spectral data, and then classification models including support vector machine (SVM), multiscale fusion convolutional neural network (MCNN) and improved AlexNet were established to identify raisins. The accuracy of SVM, MCNN, and improved AlexNet is 100%, 92.83%, and 97.78% respectively. This study proves that near-infrared spectroscopy combined with pattern recognition is feasible for the raisin inspection.


Geographic variation in habitat structure for the wood warblers in Maine and Minnesota.
The habitats occupied by species of wood warblers (Emberizidae) were compared at two study areas, Itasca State Park, Minnesota and Mount Blue State Park, Maine. Univariate comparisons of each variable of habitat structure show geographic differences for each species of warbler. Habitats available were also different because small trees were always more dense in Maine than in Minnesota. The Black-throated Green Warbler had the most dissimilar habitat with 9 of 11 variables different at the two sites.Cluster analysis identified four generalized habitat groups containing (1) species occupying territories with high percent shrub cover, (2) forest species from Maine, (3) forest species from Minnesota and (4) open country species. Reciprocal averaging ordination was used to identify habitat gradients at each site. The first axis of the Maine and Minnesota ordinations was a gradient from open country with dense ground cover to forest vegetation. The second axes differed, however. In Minnesota, the gradient separated medium deciduous trees from large conifers, whereas in Maine, vegetation graded from medium and large deciduous trees to coniferous habitats. Spearman rank correlation indicated that the warblers were similarly arranged along both habitat axes at each site despite differences in axis loadings of habitat variables.A combined reciprocal averaging ordination separated forest and shrub-forest edge species in Maine from the same two species groups in Minnesota along a smaller to larger tree axis. The results clearly demonstrate that habitat structure is not consistent throughout the range of many widely distributed species. It is suggested that the similar arrangement of species along the habitat axes probably results from an individualistic distribution of opportunistic bird species. Variation is probably induced at a site level by intraspecific competition for territories, small-scale vegetation dynamics, and resource fluctuation that occurs both within and between seasons.


Risk Factors and Comorbidities Associated With the Allergic Rhinitis Phenotype in Children According to the ARIA Classification.
Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77-15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40-40.74). Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.


Disturbed lipid metabolism in diabetic coronary vessels.
The aim of this study was to clarify whether or not arachidonic acid metabolic disorders are caused by a substrate inavailability and whether such disorders might contribute to circulatory disturbances in the diabetic myocardium. Norepinephrine induced a decrease in the conductivity of both coronary arterial bed and myocardial microcirculation in alloxan-diabetic dogs. It was markedly (p less than 0.05) attenuated both by indomethacin and acetylsalicylic acid pretreatments indicating an imbalance among the vasoactive prostanoids in diabetes. TXA2 release from the diabetic coronary rings was found to be elevated and could be normalized after the blockade of vascular adrenoceptors by phentolamine (p less than 0.05). PGI2 synthesis was also enhanced by adrenergic blockade in the diabetic arterial rings. After pretreatment with 14C arachidonic acid, in order to measure substrate availability, the arachidonic acid metabolic rate was less in the diabetic coronary arteries than in healty vessels (p less than 0.05). Ten mumol/l norepinephrine decreased arachidonic acid metabolism in the presence of prelabelled substrate in the diabetic animals, compared to an increase observed in metabolically healthy dogs. Therefore diabetes appears to diminish arachidonic acid metabolism and uptake independent of adrenoceptors and to induce an imbalance between vasoconstrictor and vasodilator cyclooxygenase products, resulting in elevated TXA2 release controlled by adrenergic mechanisms which may contribute to an impairment in myocardial microcirculation.


1H-NMR spectroscopy metabonomics of reactive, ovarian carcinoma and hepatocellular carcinoma ascites.
Metabolomic profiling of human malignant effusion remain a field poorly investigated. Proton nuclear magnetic resonance (1H-NMR) spectroscopy is a rapid relatively low cost technique, and effusion is an optimal biospecimen suitable for metabonomic investigations. With this study we addressed metabolomic profiling of malignant ascitic effusion (mAE) from patients with high grade serous ovarian carcinoma (HGSOC), Hepatocellular carcinoma (HCC), and benign AEs (bAEs) from patients with reactive peritonitis. Metabolic profiling with 1H-NMR was performed on 72 AEs (31 HGSOC, 16 HCC and 25 bAE) prospectively collected in our cytology service. Histological confirmation was requested for all malignant case. Multivariate analysis comprising PCA and PLS-DA was applied to discover metabolites suitable to differentiate effusions among the investigated groups. 1H-NMR metabonomic analysis showed clearly different spectra for malignant and benign AEs, as well as for HGSOC vs. HCC effusion. When compared with HCC effusions, the HGSOC effusion were enriched, among all, in alanine, lipids, N-acetyl groups and phenylalanine and depleted in glutamine. Subject to validation in further larger studies, 1H-NMR metabonomics could be an effective and reliable ancillary tool for AE investigations and diagnosis particularly in acellular effusions.


Structure-function relationship of the eukaryotic DNA replication factor, proliferating cell nuclear antigen.
Proliferating cell nuclear antigen (PCNA) is essential for eukaryotic DNA replication and functions as a processivity factor of DNA polymerase delta (pol delta). Due to the functional and structural similarity with the beta-subunit of Escherichia coli DNA polymerase III, it has been proposed that PCNA would act as a molecular clamp during DNA synthesis. By site-directed mutagenesis and biochemical analyses, we have studied the functional domains of human PCNA required for stimulation of replication factor C (RF-C) ATPase and DNA synthesis by pol delta. Short deletions from either the N or C termini caused drastic changes in extraction and chromatographic behaviors, suggesting that both of these terminal regions are crucial to fold the tertiary structure of PCNA. The short C-terminal stretch from Lys254 to Glu256 is necessary for stimulation of RF-C ATPase activity, but not for stimulation of DNA synthesis by pol delta. Nine basic amino acids that are essential for activating DNA synthesis by pol delta are positioned at the internal alpha-helices of PCNA. This result is in good agreement with the observation that PCNA has a ring structure similar to the beta-subunit and clamps a template DNA through this positively charged internal surface. Several other charged amino acids are also required to stimulate either RF-C ATPase or pol delta DNA synthesis. Some of them are positioned at loops which are exposed on one of the side surface of PCNA adjacent to the C-terminal loop. In addition, the beta-sheets composing the intermolecular interface of the trimeric PCNA are important for interaction with pol delta. Therefore, the outer surface of PCNA has multiple functional surfaces which are responsible for the interaction with multiple factors. Furthermore, the two side surfaces seem to be functionally distinguishable, and this may determine the orientation of tracking PCNA along the DNA.


Cell membrane-camouflaged DOX-loaded β-glucan nanoparticles for highly efficient cancer immunochemotherapy.
Biomimetics plays an important role in cancer treatment since it can prolong the circulation of nanoparticles, enhance their delivery and retention in target tissues, and reduce the systemic toxicity of drugs and their carriers. In this study, we developed a biomimetic nanosystem consisting of chemotherapeutic and immunotherapeutic agents wrapped in cell membranes. Specifically, the anti-tumor drug doxorubicin (DOX) was loaded into a bacterial-derived immunomodulatory agent (low molecular weight curdlan, lCUR), and the lCUR-DOX was further wrapped in the red blood cell membrane for camouflage and prolonged circulation. The successful preparation of the lCUR-DOX@RBC nanosystem was supported by various optical and morphological characterizations. In vitro studies indicated that the nanosystem can escape uptake by macrophages, inhibit the invasion of tumor cells, and reprogram M2 macrophages with an immunosuppressive phenotype into M1 macrophages with an immunopromoting phenotype via the MAPK signaling pathway while promoting the phagocytosis of macrophages. In vivo studies showed that the nanosystem effectively inhibits tumor growth in the A-375 tumor-bearing mouse model. Taken together, the above results support further development of the lCUR-DOX@RBC platform for cancer immunochemotherapy in clinical applications.


Early and late complications of endoscopic oesophageal varices sclerotherapy.
We report the complications of perendoscopic sclerotherapy observed during treatment of oesophageal varices in 104 patients and 409 sclerotherapy sessions. Complications were related to each individual session and to the aim of the treatment (therapeutic or prophylactic). Major complications occurred in 17.3% of the patients treated: 13 cases of severe bleeding and 5 of oesophageal stricture. Conservative therapy stopped haemorrhage in all but 4 patients, who died of uncontrolled bleeding (3.8%). Three oesophageal strictures recovered spontaneously, while the remaining two required endoscopic dilations. Minor complications occurred after 102/409 sessions (24.9%). Epigastric and/or retrosternal pain developed after 17.6% of the sessions, oesophageal ulcerations after 12.5%, fever after 11.7% and transient dysphagia after 3.7%. Bleeding was observed only in Child's category C patients who underwent therapeutic treatment. The risk of bleeding remained unchanged until complete eradication of varices was achieved. The incidence of minor complications did not correlate with the progression or the aim of the treatment.


Fgf-R3 is expressed in a subset of chicken spinal motorneurons.
The expression pattern of the fibroblast growth factor receptor Fgf-R1, R2 and R3 genes was studied in the chicken spinal cord using in situ hybridization (ISH). Unlike Fgf-R1 which is widely expressed in motoneurons, Fgf-R3 is expressed in a subset of motoneurons in the medial subdivision of the median motor column (MMCm) that also express Islet-1 and Lim-3. The motoneuron identity of the labelled cells was confirmed by double ISH and by single cell RT-PCR. Interestingly, E3.5 spinal cord motoneurons do not express Fgf-R3, suggesting the expression of Fgf-R3 in motoneurons begins with axonal growth.


Trans-activation by HIV-1 Tat via a heterologous RNA binding protein.
The HIV-1 trans-activator Tat increases levels of viral gene expression and replication. The target for Tat is an RNA stem-loop called TAR, located at the 5' end of all viral transcripts. To study the mechanism of action and map functional domains of Tat, we fused Tat to the coat protein of bacteriophage MS2, an RNA binding protein. TAR in the HIV-1 LTR was replaced by the operator, the RNA target of the coat protein. The hybrid Tat-coat protein trans-activated HIV-1 LTRs containing either TAR or operator sequences. Mutations in the operator that weaken binding of the coat protein in vitro led to decreased levels of trans-activation in vivo. Deletions in Tat within the hybrid Tat-coat protein identified activation and RNA binding domains of Tat. These experiments suggest that trans-activation by Tat can occur independently of TAR RNA and DNA binding proteins and that Tat exerts its effects on HIV-1 transcription by directly interacting with the TAR RNA stem-loop.


Vibrio harveyi sepsis in a child with cancer.
A paediatric oncology patient presented with central line sepsis caused by Vibrio harveyi, a gram negative bioluminescent marine bacterium known to be pathogenic to fish and marine invertebrates, after swimming in the sea.


István Mészáros, the unconscious, and false consciousness.
Hungarian philosopher István Mészáros' more recent work expands our understanding of consciousness in a way that is particularly relevant to psychoanalysis. He underscores the tragedy of consciousness, increasingly alienated from the totality of our social and individual being, and replaced by its false analog. To make sustainable an anachronistic type of vertical social structure, ideologists of false consciousness join arms with those who control society's historically developed means to reproduce itself and its members. This results in the social phenomenon of alienation, whereby actively produced false consciousness creates a correlate individual unconscious. Mészáros' theory seems compatible with the psychoanalytic paradigms developed by Karen Horney and the Neo-Freudians.


Application of a new type of moving bio-film in aerobic sequencing batch reactor (aerobic-SBR).
A moving bio-film (MB), made from the inner tube of used tyres was applied in a conventional-aerobic-SBR for increasing the system efficiency and quality of bio-sludge due to good sedimentation (the density of 1.925+/-0.21 g/cm(3)), non-biodegradability and re-usability of the media without any regeneration. The total bio-sludge mass of the MB-aerobic-SBR was about 30% higher than that of the conventional-aerobic-SBR resulting in a reduction of the F/M value of the system and amount of suspended bio-sludge waste. The amount of suspended bio-sludge waste, SVI and SRT of the MB-aerobic-SBR under a low organic loading of 80+/-9.3g BOD(5)/m(3)-d were 1,485+/-146 mg/d, 51+/-3.7 ml/g and 10.1+/-5.1 days, respectively while they were 1,800+/-152 mg/d, 69+/-4.0 ml/g and 8.3+/-5.3 days, respectively in the conventional-aerobic-SBR. The BOD(5), TKN and TP removal efficiencies of the MB-aerobic-SBR were about 1-2, 2-3 and 10-12% higher, respectively, than that of the conventional-aerobic-SBR. Also, the BOD(5) and COD removal efficiencies of the MB-aerobic-SBR were higher than 95% even when the system was operated with synthetic wastewater containing 800 mg/l BOD(5) under a very low HRT of 1.5 days (organic loading of 528+/-50.8 g BOD(5)/m(3)-d). The effluent BOD(5), COD, total kjeldahl nitrogen, total phosphorus and suspended solids of the MB-aerobic-SBR under a high organic loading of 528+/-50.8 g BOD(5)/m(3)-d were 45+/-5.1, 37+/-3.6, 4.1+/-1.0, 1.5+/-0.80 and 41+/-2mg/l, respectively.


Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): current understanding and challenges.
New diagnostic criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have recently been proposed, distinguishing this syndrome from other inflammatory diseases of the central nervous system. Seropositivity status for MOG-IgG autoantibodies is important for diagnosing MOGAD, but only in the context of robust clinical characterization and cautious interpretation of neuroimaging. Over the last several years, access to cell-based assay (CBA) techniques has improved diagnostic accuracy, yet the positive predictive value of serum MOG-IgG values varies with the prevalence of MOGAD in any given patient population. For this reason, possible alternative diagnoses need to be considered, and low MOG-IgG titers need to be carefully weighted. In this review, cardinal clinical features of MOGAD are discussed. Key challenges to the current understanding of MOGAD are also highlighted, including uncertainty regarding the specificity and pathogenicity of MOG autoantibodies, the need to identify immunopathologic targets for future therapies, the quest to validate biomarkers that facilitate diagnosis and detect disease activity, and the importance of deciphering which patients with MOGAD require long-term immunotherapy.


The Workplace Support for Health Scale: Reliability and Validity of a Brief Scale to Measure Employee Perceptions of Wellness.
To examine the reliability and validity of a brief measure (the Workplace Support for Health [WSH] scale) to assess employees' perceived support for a healthy lifestyle. Repeated cross-sectional surveys. We collected employer- and employee-level survey data from small, low-wage workplaces in King County, WA enrolled in a randomized controlled trial. We analyzed data from 68 workplaces that had 2,820 and 2,640 employees complete surveys at baseline and 15 months, respectively. The WSH scale consisted of five items. To assess validity, we examined associations between the WSH scale and employer implementation of evidence-based interventions for health promotion, employee self-rated health, and job satisfaction. We performed an exploratory factor analysis to assess the unidimensionality of the WSH scale items, and produced Cronbach's alpha coefficients to examine scale reliability. We ran regression models using generalized estimating equations to examine validity. The factor analysis indicated one factor, which accounted for 59% of the total variance in the workplace support for health items. The scale had good reliability at baseline (α = 0.82) and 15 months (α = 0.83). Employer evidence-based intervention implementation was positively associated with WSH. WSH was also associated with higher self-rated health and job satisfaction. These associations indicate good concurrent validity. The WSH scale is a reliable and valid measure of perceived workplace support for health. Employers can use the scale to identify gaps in support and create a plan for improvement.


Regulation of cancer-related gene expression by galectin-3 and the molecular mechanism of its nuclear import pathway.
Galectin-3 (Gal-3), a member of the beta-galactoside-binding gene family, distributes inside and outside the cell and has pleiotropic biological functions such as cell growth, cell adhesion, cell-cell interaction, and mRNA processing in a specific situation. In particular, Gal-3 in the nucleus plays a pivotal role in the regulation of cancer-related gene expression, including cyclin D1, TTF-1 and MUC2, presumably associated with tumor progression. Therefore, to understand the mechanism of nuclear import of Gal-3 is very significant and might be developed to the new approach for the cancer treatment. In this review, we focus on the role of Gal-3 in the nucleus and the molecular mechanism of nuclear import pathways of Gal-3, providing the hints for the inhibition of Gal-3 function.


Ichthyosis follicularis syndromes in patients with mutations in GJB2.
Ichthyosis follicularis (IF) manifests as generalized spiny follicular projections found in syndromic diseases secondary to SREBF1 and MBTPS2 mutations. We sought the genetic cause of IF in two distinct families from a cohort of 180 patients with ichthyosis. In Family 1, the proband (Patient 1) presented with IF, bilateral sensorineural hearing loss and punctate palmoplantar keratoderma. Using DNA from peripheral blood lymphocytes, two compound heterozygous mutations, c.526A>G and c.35delG, were discovered in GJB2. In Family 2, the proband (Patient 2) presented with a previously unreported IF phenotype in the context of keratitis-ichthyosis-deafness syndrome, and whole-exome sequencing found a de novo heterozygous mutation, c.148G>A in GJB2. Histopathology was consistent with porokeratotic eccrine ostial and dermal duct naevus (PEODDN) and IF in Patients 1 and 2, respectively. Our findings add to the clinical and histopathological spectrum of IF and emphasize the association of PEODDN-like entities with GJB2 variants.


Effects of conditioning polarization on the membrane ionic currents in rat myometrium.
Membrane ionic currents were measured in pregnant rat uterine smooth muscle under voltage clamp conditions by utilizing the double sucrose gap method, and the effects of conditioning pre-pulses on these currents were investigated. With depolarizing pulses, the early inward current was followed by a late outward current. Cobalt (1 mM) abolished the inward current and did not affect the late outward current per se, but produced changes in the current pattern, suggesting that the inward current overlaps with the initial part of the late outward current. After correction for this overlap, the inward current reached is maximum at about +10 mV and its reversal potential was estimated to be +62 mV. Tetraethylammonium (TEA) suppressed the outward currents and increased the apparent inward current. The increase in the inward current by TEA thus could be due to a suppression of the outward current. The reversal potential for the outward current was estimated to be -87 mV. Conditioning depolarization and hyperpolarization both produced a decrease in the inward current. Complete depolarization block occurred at membrane potential of -20 mV. Conditioning hyperpolarization experiments in the presence of cobalt and/or TEA revealed that the decrease in the inward current caused by conditioning hyperpolarization was a result of an increase in the outward current overlaping with the inward current. It appears that a part of the potassium channel population is inactivated at the resting membrane potential and that this inactivation is removed by hyperpolarization.


C-doped ZnO nanocomposites molecularly imprinted photoelectrochemical sensor for ultrasensitive and selective detection of oxytetracycline in milk.
Antibiotic monitoring remains vital to ensure human health and safety in the environment and foods. As the most popular detection method, photoelectrochemical (PEC) sensor can achieve rapid and accurate detection of antibiotics with the advantages of high sensitivity, easy-to-preparation process, as well as high selectivity. Herein, an extremely-efficient visible-light responsible ZnO/C nanocomposite was prepared and combined with acetylene black (as an enhanced conductive matrix), and the electron migration efficiency was greatly accelerated. Meanwhile, a molecularly imprinted polymer obtained by electrical agglomeration was conjugated as a specific recognizing site for target. Furthermore, the as-prepared rMIP-PEC sensor showed a low detection limit (8.75 pmol L-1, S/N = 3) in a wide linear detection range of 0.01-1000 nmol L-1 for oxytetracycline (OTC), with excellent selectivity and long-term stability. Our work shed light on applying C-doped ZnO semiconductor and molecularly imprinted polymer as photoelectric active sensing materials for rapid and accurate analysis of antibiotics in foods and environment.


Marking systems for multiple choice examinations.
This article discusses the advantages and disadvantages of no penalty and penalty marking systems. It also reviews ways in which examiners have attempted to correct for guessing by candidates, and the use of 'don't know' options and confidence-weighting for attempting to assess the degree of certainty that candidates attach to their answers.


IgM secretory tailpiece drives multimerisation of bivalent scFv fragments in eukaryotic cells.
The monoclonal antibody (mAb) TP-3 binds selectively to human and canine osteosarcoma (OS) cells and is therefore a potential candidate for use as a targeting agent in radioimmunoimaging and therapy of OS metastases. However, intact murine mAbs have several drawbacks such as large size, delayed blood clearance and high immunogenicity, all of which can be overcome by genetic engineering. To construct and express bivalent and multivalent TP-3 scFv fragments from the mammalian expression vector, pLNO. This vector has unique restriction sites for simple cassette cloning of any individual variable (V) and constant (C) genes and has previously been used for expression of intact chimeric TP-3 mAbs and Fab fragments. Furthermore, it is also suitable for expression of any modified V region, such as a scFv fragment, fused to any modified C region or to non-immunoglobulin protein sequences. Six different constructs were made; three scFv-CH3 fragments that differed in the design of linker between the scFv fragment and the IgG CH3 domain. These constructs were also made with the IgM secretory tailpiece (microtp) attached to the C terminus. All constructs were secreted as bivalent antibody fragments with a molecular weight of about 100 kDa. A band corresponding to a dimer appeared in all the supernatants from TP-3 scFv-CH3 producing cells, whether microtp was present or not, whereas higher orders of multimers were not seen. However, pulse chase analyses of the cells revealed that a small fraction of higher order polymers was formed from genes including the fragment encoding microtp and that microtp conferred retention both to monomers and intermediate polymers. The recombinant TP-3 antibody fragments were shown to bind human OS cells. Recombinant mAb fragments can be designed and cloned into the mammalian expression vector, pLNO. This vector is flexible in the sense that the genes encoding such fragments can be expressed from either cDNA or from genomic DNA. A microtp attached to the CH3 domain in these fragments was sufficient to drive polymerization, however inefficiently and intracellular retention of both monomers and intermediate polymers was observed.


Signalling through phospholipase C interferes with clathrin-mediated endocytosis.
We investigated if phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P2) hydrolysis by phospholipase C activation through cell surface receptors would interfere with clathrin-mediated endocytosis as recruitment of clathrin assembly proteins is PtdIns(4,5)P2-dependent. In the WKPT renal epithelial cell line, endocytosed insulin and beta2-glycoprotein I (beta2gpI) were observed in separate compartments, although endocytosis of both ligands was clathrin-dependent as demonstrated by expression of the clathrin-binding C-terminal domain of AP180 (AP180-C). The two uptake mechanisms were different as only insulin uptake was reduced when the mu2-subunit of the adaptor complex AP-2 was silenced by RNA interference. ATP receptors are expressed at the apical surface of renal cells and, thus, we examined the effect of extracellular ATP on insulin and beta2gpI uptake. ATP stimulated phospholipase C activity, and also suppressed uptake of insulin, but not beta2gpI. This effect was reversed by the PLC inhibitor U-73122. In polarized cell cultures, insulin uptake was apical, whereas beta2gpI uptake was through the basolateral membrane, thus providing an explanation for selective inhibition of insulin endocytosis by ATP. Taken together, these results demonstrate that stimulation of apical G-protein-coupled P2Y receptors, which are coupled to phospholipase C activation diminishes clathrin-mediated endocytosis without interfering with basolateral endocytic mechanisms.


Surgical outcomes of elderly patients with cervical spondylotic myelopathy.
Cervical spondylotic myelopathy is a potentially serious neurologic disorder that commonly presents with gait difficulty and hand dysfunction. Because the development of CSM is in large part related to advanced spondylosis and degenerative disk disease, elderly patients appear to be at an increased risk to develop this condition. The surgical outcomes of this patient population have been understudied; the authors seek to report their clinical results in a series of patients with CSM older than 75 years who underwent surgical treatment. This report is composed of a cohort of 36 elderly patients (older than 75 years) and 34 younger patients (younger than 65 years) who underwent decompressive surgery for CSM at one institution between 2001 and 2005. The patients' functional status was evaluated preoperatively and postoperatively using the mJOA disability scale. The mean follow-up time in the elderly group was 24 months, with a range from 12 to 48 months. There was a statistically significant improvement between mean preoperative (11.3) and postoperative (14.4) mJOA scores (P< .0001). The younger group had a higher neurologic recovery rate (71%) than the elderly group (59%); however, this was not statistically significant (P= .29). The postoperative complication rate in the elderly population (38%) was higher than in the younger group (6%; P= .002). Elderly patients with CSM are likely to obtain neurologic improvement after decompressive surgery. Their postoperative complication rate is higher than that of younger patients, yet most complications appear to be self limiting and do not adversely affect neurologic outcome.


Highly Stable Red-Emissive Ratiometric Probe for Monitoring β-Galactosidase Activity Using Fluorescence Microscopy and Flow Cytometry.
β-Galactosidase (β-gal), well known as a useful reporter enzyme, is a potent biomarker for various diseases such as colorectal and ovarian cancers. We have developed a highly stable red-emissive ratiometric fluorescent probe (CCGal1) for quantitatively monitoring the β-gal enzyme activity in live cells and tissues. This ratiometric probe showed a fast emission color change (620-662 nm) in response to β-gal selectively, which was accompanied by high enzyme reaction efficacy, cell-staining ability, and outstanding stability with minimized cytotoxicity. Confocal fluorescence microscopy ratiometric images, combined with fluorescence-activated cell sorting flow cytometry, demonstrated that CCGal1 could provide useful information for the diagnosis, prognosis, and treatment of β-gal enzyme activity-related diseases such as colorectal and ovarian cancers. Further, it may yield meaningful strategies for designing and modifying multifunctional bioprobes with different biomedical applications.


[Medical anthropology].
The title should be understood as a world play--since, obviously, Medicine is not bound to be considered a new branch of Anthropology. The author comments the different historical approaches which focused on the problem of disease as such. I.E., in times past, medical thinkers considered disease as a self-existing entity absolutely unrelated to the individual who, however, was suffering from it. Quite contrary, disease should be envisioned as the response the living system sets against physiological, psychological, and/or social stimuli which severely affect its equilibrium. So, 'feeling well' means more than being free of illness. It means Man ought to enjoy his vital gifts fully within a twofold relationship, with himself and the environment as well. Hence, in future, Medicine is to comprehend Man as a whole. In other words, healing is no longer to be the sole duty of Medicine to come. Aiming at bringing health up to perfection will be its major commitment.


A neuropathologic study of Werdnig-Hoffmann disease with special reference to the thalamus and posterior roots.
The brains of five cases of severe infantile form of Werdnig-Hoffmann (W-H) disease were studied to observe the pathologic changes of sensory neurons and the thalamus. The present study disclosed severe cell loss, chromatolytic degeneration, and empty cell beds of the spinal anterior horn and cranial motoneurons (V, VII, X, XII). Glial bundles were also noted in the anterior roots. In the sensory systems, glial bundles in the posterior roots (2/5), ghost cells in Clarke's column (2/5), and degeneration of the thalamus, mainly in the lateral formation (4/4) were noted. It was demonstrated that not only degeneration of lower motor neurons and glial bundles in the anterior roots, but also degeneration of sensory neurons and thalamus were present in W-H disease. These findings suggested the possibility that W-H disease is a multisystemic disease involving both the anterior and posterior root systems. No sensory involvement was found clinically. Characteristic wrist drop was observed in four cases, two of which also having motor nerve conduction velocity (MCV) delay. On the other hand, MCV of another case without wrist drop was normal. The possibility that wrist drop might be one of the clinical features of peripheral nerve dysfunction was discussed, but further pathologic evaluation of peripheral nerves is needed.


Osteoporosis: A role for lipids.
An inverse relationship between bone marrow (BM) adiposity and bone mass has been described in different physiological and pathological conditions, including osteoporosis (OP). In osteoporotic patients, lower bone mass density is indeed associated with higher BM fat content, suggesting a potential role for bone lipids in the OP pathogenesis. Nevertheless, some questions remain. Is that BM adiposity a cause or a consequence of the bone loss? What kinds of lipids are involved? Human data are somehow contradictories regarding bone lipid signature related to OP, and animal data are needed to support on one or another way the human observations. Bone lipid signature associated to OP needs to be clarified if we want to understand better their roles in OP. In that context, by using an ovariectomy-induced OP murine model and looking at lipids in two bone compartments: BM and mineralized tissue (MT), our first challenge was to identify local lipid changes in relation to OP, in view to explore later the mechanisms by which those compounds could alter bone quality, particularly during the mineralization process. As the most striking data, long-term OP resulted in an accumulation of triglycerides, reduced levels of arachidonic and docosahexaenoic acids, an increase of stearoyl-CoA desaturase indices and a reduction of sphingomyelin in the MT, and potential consequences on bone properties and cell activities are discussed. The reader will appreciate that we are at an early stage of understanding the roles of lipids in the OP development and more investigations will be necessary.


Non-UV based germicidal activity of metal-doped TiO2 coating on solid surfaces.
A stain-based screening method was developed to screen different catalyst coatings for their germicidal activity. A Baclight dead/live bacteria viability kit (invitrogen, molecular probes) was used for staining the cell. The screening was carried out following a standard procedure. This included loading cell suspension to solid surface and maintaining contact for 30 min, then staining with a mixture containing dyes. The stained cells were observed using an epifluorescent microscope and photographed with a CCD camera under UV. Metal-doped TiO2 coatings on Al plates were prepared and tested for non-UV germicidal activity without using UV. It was tested using model microorganisms such as Bakers Yeast (Saccharomyces cerevisiae), Bacillus subtilis, Pseudomonas putida, and Escherichia coli. On the basis of the germicidal activity of catalyst and the degree of damage caused to the cells, the stained cells may appear green (viable), green with red or yellow nuclei and yellow (compromised) or red (nonviable). According to their stained color, cells were counted to calculate the percentage of dead, live, and compromised cells. Compromised cells are cells that grow very slowly after reculturing indicating a degree of reversible cell damage. Screening the germicidal activity using this staining method is accurate and efficient, and requires less time than the culture-based method. A modification to the procedure for measuring germicidal activity of rough surfaces or fibrous coatings was developed. Both TiO2 and metal-doped TiO2 (Ag, Pt, Au, Cu) possess non-UV based germicidal activity. The germicidal activity of TiO2 was found to be related with its wetting property and can be improved by UV irradiation before testing. It is not greatly affected by contact time, indicating a fast acting germicidal activity.


Functional calcium imaging in zebrafish lateral-line hair cells.
Sensory hair-cell development, function, and regeneration are fundamental processes that are challenging to study in mammalian systems. Zebrafish are an excellent alternative model to study hair cells because they have an external auxiliary organ called the lateral line. The hair cells of the lateral line are easily accessible, which makes them suitable for live, function-based fluorescence imaging. In this chapter, we describe methods to perform functional calcium imaging in zebrafish lateral-line hair cells. We compare genetically encoded calcium indicators that have been used previously to measure calcium in lateral-line hair cells. We also outline equipment required for calcium imaging and compare different imaging systems. Lastly, we discuss how to set up optimal imaging parameters and how to process and visualize calcium signals. Overall, using these methods, in vivo calcium imaging is a powerful tool to examine sensory hair-cell function in an intact organism.


Implementing self-directed teams.
The "self-directed team" concept is an innovative approach in the healthcare setting. Long-term benefits of customer satisfaction and quality improvement are consistent with concepts of total quality improvement and patient-focused care. Initial investment of time and money pays off in low turnover and marked employee and patient satisfaction.


B-MYB, a transcription factor implicated in regulating cell cycle, apoptosis and cancer.
B-MYB belongs to the MYB family of transcription factors that include A-MYB and c-MYB. While A-MYB and c-MYB are tissue-specific, B-MYB is broadly expressed in rapidly dividing cells of developing or adult mammals. B-MYBs liaisons with important players of the cell cycle and transcription machinery, such as E2F and retinoblastoma proteins, suggest that its essential function in stem cell formation and mammalian development could be related to its ability to directly or indirectly impinge on gene expression. Besides its role in the cell cycle, B-MYB has been shown to promote cell survival by activating antiapoptotic genes such as ApoJ/clusterin and BCL2. Here, we discuss how B-MYB could be implicated in tumourigenesis by regulating gene expression.


A quantitative analysis of the effect of bilateral subthalamic nucleus-deep brain stimulation on subjective and objective sleep parameters in Parkinson's disease.
To explore how subjective and objective sleep parameters respond to bilateral subthalamic nucleus-deep brain stimulation (STN-DBS) in patients with Parkinson's disease (PD). Thirty DBS sleep studies were included by searching PubMed, Embase, and the Cochrane Library, and only 21 prospectively designed studies, including 541 patients, were eligible for the main analysis. We evaluated sleep disturbance using 1 objective measurement, polysomnography (PSG), and 4 subjective scales, including PD Sleep Scale (PDSS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and restless legs syndrome (RLS). We pooled data using the standard mean difference (SMD). The primary outcome was a change in sleep parameters 6 months postoperatively. Outcomes from <12 months to ≥12 months follow-up were compared in the subgroup analysis. Meta-regression was further conducted. STN-DBS significantly improved all 4 subjective sleep scales in the 6-month follow-up: ESS (SMD = 0.234), PDSS (SMD = 0.724), PSQI (SMD = 1.374) and RLS (SMD = 1.086), while most PSG parameters remained unchanged, except for shortened rapid eye movement sleep latency (RSL) (SMD = 0.520). In the over-12-month follow-up, improvement persisted in PDSS but not in ESS. Dopamine drug reduction (p = 0.009) and motor improvement (p = 0.036) were correlated with ESS improvement and PDSS improvement, respectively. Bilateral STN-DBS continuously improved subjective nocturnal sleep, while its effect on ESS lasted for only 1 year. Medication reduction and motor improvement may contribute to improved daytime sleepiness and better subjective nocturnal sleep, respectively. Except for a shortened RSL, STN-DBS did not change PSG parameters, including sleep efficiency and sleep architecture. Open Science Framework: DOI 10.17605/OSF.IO/3EGRC.


Randomized, controlled trial of Behavioral Family Systems Therapy for Diabetes: maintenance and generalization of effects on parent-adolescent communication.
We report a randomized trial of a revised Behavioral Family Systems Therapy for Diabetes (BFST-D) intervention. Families of 104 adolescents with diabetes were randomized to standard care (SC) or to 6 months of an educational support group (ES) or BFST-D. Family communication and problem-solving skills were assessed at 0, 6, 12, and 18 months by independent rating of videotaped family problem-solving discussions. BFST-D improved individual communication of adolescents and mothers, but not fathers. BFST-D significantly improved quality of family interaction compared to SC (10 of 12 comparisons) and ES (6 of 12 comparisons). Changes in family communication were differentially associated with changes in glycemic control, adherence, and family conflict. BFST-D improved family communication and problem solving relative to SC and modestly relative to ES.


Serum brain-derived neurotrophic factor level in relation to illness severity and episode duration in patients with major depression.
Since there are few data on the possible association between BDNF levels and characteristics of major depression, the present study assesses brain-derived neurotrophic factor (BDNF) levels in three drug-free patient samples, and explores whether episode duration, and severity correlate with serum BDNF levels. Serum BDNF levels were measured in 42 drug-free patients with major depression. The duration of the index episode and the presence of psychotic features were assessed with the Schedule for Affective Disorders and Schizophrenia, and the severity of depression was measured with the 17-item Hamilton Rating Scale for Depression. The sample was divided into three groups: severely depressed inpatients without psychotic features, severely depressed inpatients with psychotic features, and moderately depressed outpatients. Mean serum BDNF level in the total sample was 18.0 ± 2.8 ng/ml, with no significant difference between the three patient samples (F = 1.80, df = 2, p = 0.18). Mean serum BDNF level was significantly lower in patients with an index episode over one year, compared with patients who had a shorter index episode (F = 4.90, df = 1, p = 0.033). These data show that patients with a long index episode have significantly lower serum BDNF levels. We found no influence of the presence of psychotic features and severity of depression on serum BDNF levels.


Influence of pistachios on force production, subjective ratings of pain, and oxidative stress following exercise-induced muscle damage in moderately trained athletes: A randomized, crossover trial.
Although previous studies have focused on the role of pistachios on metabolic health, the ergogenic effects of the nut must be elucidated. This study evaluated the impact of ingesting raw, shelled, unsalted pistachios on subjective pain ratings, force production, vertical jump, and biochemical indices of recovery from eccentrically biased exercise. Using a crossover design, 27 moderately trained, male athletes completed 3 trials in a randomized counterbalanced fashion. Control received water only, low dose (1.5 oz/d; PL) and high dose (3.0 oz/d; PH) consumed pistachios for 2 weeks with a 3-4-week washout between trials. PH had lower pain ratings in most muscles after 72 h of recovery (p < 0.05). PH prevented a decrease in force production at 120°/s of knee flexion (p > 0.05); whereas force was diminished in the other trials. Creatine kinase, myoglobin, and C-reactive protein increased over time following exercise (p < 0.05); however, there were no advantages following pistachio consumption. No significant changes in vertical jump or superoxide dismutase were elicited during any trial. This study demonstrates that 3.0 oz/d of pistachios can reduce delayed onset of muscle soreness and maintain muscle strength, potentially promoting exercise tolerance and training adaptations. NCT03698032.


Implementation of virtual reality in healthcare: a scoping review on the implementation process of virtual reality in various healthcare settings.
Virtual reality (VR) is increasingly used in healthcare settings as recent technological advancements create possibilities for diagnosis and treatment. VR is a technology that uses a headset to simulate a reality in which the user is immersed in a virtual environment, creating the impression that the user is physically present in this virtual space. Despite the potential added value of virtual reality technology in healthcare, its uptake in clinical practice is still in its infancy and challenges arise in the implementation of VR. Effective implementation could improve the adoption, uptake, and impact of VR. However, these implementation procedures still seem to be understudied in practice. This scoping review aimed to examine the current state of affairs in the implementation of VR technology in healthcare settings and to provide an overview of factors related to the implementation of VR. To give an overview of relevant literature, a scoping review was undertaken of articles published up until February 2022, guided by the methodological framework of Arksey and O'Malley (2005). The databases Scopus, PsycINFO, and Web of Science were systematically searched to identify records that highlighted the current state of affairs regarding the implementation of VR in healthcare settings. Information about each study was extracted using a structured data extraction form. Of the 5523 records identified, 29 were included in this study. Most studies focused on barriers and facilitators to implementation, highlighting similar factors related to the behavior of adopters of VR and the practical resources the organization should arrange for. However, few studies focus on systematic implementation and on using a theoretical framework to guide implementation. Despite the recommendation of using a structured, multi-level implementation intervention to support the needs of all involved stakeholders, there was no link between the identified barriers and facilitators, and specific implementation objectives or suitable strategies to overcome these barriers in the included articles. To take the implementation of VR in healthcare to the next level, it is important to ensure that implementation is not studied in separate studies focusing on one element, e.g., healthcare provider-related barriers, as is common in current literature. Based on the results of this study, we recommend that the implementation of VR entails the entire process, from identifying barriers to developing and employing a coherent, multi-level implementation intervention with suitable strategies. This implementation process could be supported by implementation frameworks and ideally focus on behavior change of stakeholders such as healthcare providers, patients, and managers. This in turn might result in increased uptake and use of VR technologies that are of added value for healthcare practice.


DNA read count calibration for single-molecule, long-read sequencing.
There are many applications in which quantitative information about DNA mixtures with different molecular lengths is important. Gene therapy vectors are much longer than can be sequenced individually via short-read NGS. However, vector preparations may contain smaller DNAs that behave differently during sequencing. We have used two library preparations each for Pacific Biosystems (PacBio) and Oxford Nanopore Technologies NGS to determine their suitability for quantitative assessment of varying sized DNAs. Equimolar length standards were generated from E. coli genomic DNA. Both PacBio library preparations provided a consistent length dependence though with a complex pattern. This method is sufficiently sensitive that differences in genomic copy number between DNA from E. coli grown in exponential and stationary phase conditions could be detected. The transposase-based Oxford Nanopore library preparation provided a predictable length dependence, but the random sequence starts caused the loss of original length information. The ligation-based approach retained length information but read frequency was more variable. Modeling of E. coli versus lambda read frequency via cubic spline smoothing showed that the shorter genome could be used as a suitable internal spike-in for DNAs in the 200 bp to 10 kb range, allowing meaningful QC to be carried out with AAV preparations.


Improved bovine in vitro embryo production with sexed and unsexed sperm selected by chemotaxis.
Assisted reproductive techniques (ART) have been widely used in farm animals in the last decades. Sexed cryopreserved spermatozoa, ovum pick up, in vitro embryo production and transfer constitute the ART that have revolutionized the dairy industry. However, the efficiency of some of these techniques is still low due in part to sperm quality, which influences fertilization, embryo development and implantation. The Sperm Selection Assay (SSA), based on sperm chemotaxis towards progesterone, provides a sperm subpopulation enriched with spermatozoa that are capacitated, with intact DNA and low level of oxidative stress. Since the SSA selects a sperm subpopulation at optimum physiological state, the application of the SSA may improve the efficiency of the current ART. The aim of this study was to adapt the SSA for unsexed and sexed bovine frozen-thawed semen samples, and then to test whether sperm selection by the SSA improves the cleavage rate of bovine embryos in vitro. The optimal SSA conditions to obtain the higher sperm accumulation percentage given by chemotaxis were the same for both unsexed and sexed semen samples. Thus, sperm accumulation in W2 was significantly higher when: 2 million sperm per mL were placed in W1 (unsexed samples: 12 ± 1%, p = 0.002; sexed samples: 14 ± 3%, p = 0.02); 1 pM progesterone was placed in W2 (unsexed sample: 9 ± 1%, p = 0.009; sexed samples: 11 ± 2%, p = 0.02); and to incubate the SSA device for 10 min (unsexed samples: 17 ± 2%, p = 0.007; sexed samples: 10 ± 1%, p = 0.004). We found that the quality of spermatozoa recovered from W2 in unsexed and sexed semen was enhanced. Thus, the capacitation index was significantly increased (unsexed samples: 1.75 ± 0.1, p = 0.0001; sexed samples: 1.76 ± 0.2, p = 0.004), while DNA fragmentation index was significantly decreased (unsexed samples: 0.33 ± 0.07, p = 0.0003; sexed samples: 0.32 ± 0.04, p = 0.002). Moreover, the cleavage index of oocytes fertilized with either unsexed or sexed SSA-selected sperm was significantly improved (unsexed samples: 3.2 ± 0.4, p = 0.0001; sexed samples: 2.3 ± 0.33, p = 0.03). Thus, we show that the SSA can be used to recruit a bovine sperm subpopulation at optimal functional state regardless of whether the sample is previously sexed, and that this optimal state improves bovine embryo cleavage rate.


{4,4'-Di-bromo-2,2'-[cyclo-hexane-1,2-diylbis(nitrilo-methanylyl-idene)]diphenolato-κ4 O,N,N',O'}nickel(II).
In the title compound, [Ni(C20H18Br2N2O2)], the NiII ion is four-coordinated in a slightly distorted square-planar coordination geometry defined by two N atoms and two O atoms of the tetra-dentate dianionic 4,4'-di-bromo-2,2'-[cyclo-hexane-1,2-diylbis(nitrilo-methanylyl-idene)]diphenolato ligand. Pairs of complex mol-ecules are assembled by inter-molecular C-H⋯O hydrogen bonds with d(C⋯O) = 3.247 (4) Å.


Acetyl-α-boswellic acid and Acetyl-β-boswellic acid protects against caerulein-induced pancreatitis via down-regulating MAPKs in mice.
This study is to investigate the protective effect of Acetyl-α-boswellic acid and Acetyl-β-boswellic mixture(α/β-ABA), which is the active ingredients isolated from Frankincense, on actue pancreatitis and its mechanism. Our experimental results showed that 2 μM α/β-ABA reduced production of NO, TNF-α, IL-6, IL-10 and IL-1β in RAW264.7 cells that were stimulated with lipopolysaccharide (LPS) which indicates its anti-inflammatory role. In pancreatitis model induced by caerulein, intra-gastrical administration of 100 mg/kg α/β-ABA relieved inflammatory cells infiltration significantly and attenuated the serum elevation of amylase TNF-α and IL-6 remarkably in mice. Furthermore, α/β-ABA down-regulated mitogen-activated protein kinase (MAPK) family phosphorylated proteins in pancreas, including phosphorylated p38, ERK1/2 and JNK, to reduce the serum inflammatory factors. Finally, α/β-ABA alleviated the pancreatic edema and inflammatory cell infiltration in pancreatitis mice model. This study suggests that α/β-ABA may be targeted for drug development against pancreatitis via modulating MAPKs pathway.


Sjögren-Larsson syndrome. Impaired fatty alcohol oxidation in cultured fibroblasts due to deficient fatty alcohol:nicotinamide adenine dinucleotide oxidoreductase activity.
Lipid metabolism was studied in cultured skin fibroblasts from patients with the inherited disorder, Sjögren-Larsson syndrome (SLS). Intact SLS fibroblasts incubated in the presence of [1-14C]palmitate accumulated more radioactive hexadecanol than did normal cells, whereas incorporation of radioactivity into other cellular lipids was unaltered. The hexadecanol content of SLS fibroblasts was abnormally elevated. Hexadecanol accumulation was not due to increased fatty alcohol synthesis nor its deficient utilization for glycerol ether synthesis. The half-life of intracellular hexadecanol loaded into SLS fibroblasts was increased (70 min) compared with normal (15 min), and intact SLS fibroblasts showed impaired oxidation of [14C]-hexadecanol to fatty acid. Fatty alcohol:NAD+ oxidoreductase, the enzyme catalyzing this reaction, was deficient in SLS fibroblasts. Mean total activity in SLS fibroblasts (n = 5) was 13% of that in normal fibroblasts, and palmitoyl CoA-inhibitable activity was 1% of normal. Fibroblasts from two obligate SLS heterozygotes had enzyme activities intermediate between that in normal fibroblasts and individuals with SLS. These results suggest that the primary defect in SLS is deficiency of fatty alcohol:NAD+ oxidoreductase. SLS represents the first inherited disorder in man associated with an isolated abnormality in fatty alcohol metabolism.


Pregnancy Loss and Cardiovascular Diseases in Women: Recent Findings and Potential Mechanisms.
Pregnancy loss (PL) has been acknowledged by the American Heart Association as a risk factor for cardiovascular diseases (CVD) later in life. This review aims to sum up recent findings (< ~ 5 years), concerning the link between PL and CVD. The association between PL and risk of CVD increased with increasing number of PLs and is inversely correlated to maternal age, indicating that the association concerns euploid PLs. Likely mechanisms leading to PL and an increased risk of CVD include endothelial dysfunction, a pro-inflammatory state, antiphospholipid syndrome, autoimmunity, and genetic predisposition. PL as an independent risk factor for CVD constitutes an obvious gateway for a more targeted approach to future research, prevention, and treatment. Future research should clarify the following questions to which the answers are still unknown: whether PL is (a) directly causing the increased risk of CVD or (b) sharing pathophysiological mechanisms also leading to CVD.


Persisting leprosy transmission despite increased control measures in an endemic cluster in Brazil: the unfinished agenda.
To provide an evidence base for improvement of leprosy control in Brazil's high transmission areas. We obtained data from municipalities in a major disease cluster from databases for notifiable diseases of four states (Maranhão, Parâ, Tocantins, Piauí), including notifications from 2001 to 2009. Indicators for monitoring and evaluation of leprosy according to the World Health Organization were evaluated with emphasis on the rates of new cases presenting grade-2 disabilities and among children < 15 years of age, indicating late diagnosis and active transmission, respectively. A total of 82,463 leprosy cases were detected in the area (mean annual case detection rate: 95.9/100,000; RR = 4.56 as compared to the rest of Brazil; 95% CI: 4.45-4.66, P < 0.0001). There was a steady decrease of detection rates in the study period, from 100.8 to 75.6/100,000 inhabitants. In children <15 years of age, 9,009 cases of leprosy were detected (28.40/100,000), significantly more than in the rest of Brazil (RR = 5.80; 95% CI: 5.39-6.25, P < 0.0001). New cases with grade-2 disabilities/100,000 population maintained a stable trend at a high level (4.43 cluster vs. 1.28 rest of country; RR = 3.46; 95% CI: 3.11-3.84, P < 0.0001), whereas the proportion of new cases with grade-2 was slightly lower than the country's average (5.51% vs. 6.75%; RR = 0.84; 95% CI: 0.81-0.86, P < 0.0001). Despite recently improved leprosy control measures, there is still major active transmission and late diagnosis in the cluster. Further specific actions are needed to improve early case detection and prompt treatment with the aim to reduce disease burden in the population, considering social inequities.


Retrovirus-mediated gene transfer of transthyretin and transthyretin-methionine 30: a potential tool for the study of amyloidogenesis.
Familial amyloidotic polyneuropathy (FAP) is a genetic disease characterized by systemic amyloid deposition particularly in the peripheral nervous system. These deposits are composed mainly of a mutant form of the serum protein transthyretin (TTR) having a methionine for valine substitution at position 30-TTR Met 30. The factors involved in the formation of these deposits are unknown. The existence of animal models for FAP should allow elucidation of these factors. As one approach to the development of animal models for amyloidogenesis in FAP, we have constructed recombinant retrovirus vectors, carrying the full length human cDNA for either TTR or TTR Met 30 under the control of the Moloney murine leukemia virus (MoMLV) LTR element. After transfection of the packaging cell line, psi 2, viral stocks were used to infect a rat hepatoma cell line, H56, mouse fibroblast cell line, NIH3T3, and mouse primary fibroblasts. H56 cells efficiently secreted both TTR and TTR Met 30 as assessed by immunoprecipitation and ELISA, whereas NIH3T3 fibroblasts appeared not to release these proteins under the conditions tested. Primary fibroblasts secreted the mutant protein as assessed by ELISA. These genetically modified cells can be grafted into animals for in vivo study of amyloidogenesis, as well as be used in culture to investigate factors that might regulate the rate of amyloid deposition.


Regional vascular responses to an acute stressor in spontaneously hypertensive and Wistar-Kyoto rats.
The regional vascular responses to an acute intermittent footshock stressor were examined in Wistar-Kyoto and spontaneously hypertensive rats using the pulsed Doppler flow probe method. While both strains exhibited vascular resistance changes, which were typical of the 'defense response', the changes in regional vascular resistance were exaggerated in the spontaneously hypertensive rats compared to the Wistar-Kyoto. Despite these alterations in vascular resistance, and greater increases in heart rate in the spontaneously hypertensive rats, there were no differences in the pressor responses footshock between the Wistar-Kyoto and spontaneously hypertensive rats. These findings indicate that very specific regional hemodynamic changes accompany the characteristic sympathetic nervous system hyperresponsiveness of spontaneously hypertensive rats to environmental stress.


MiR-30a inhibits silica dust-induced epithelial-mesenchymal transition by targeting Snail.
The mechanism of action of MicroRNA-30a(miR-30a) and Snail, a transcription factor, in silica(SiO2) dust-induced pulmonary EMT and secondary pulmonary fibrosis remains elusive. In this study, the cellular EMT model induced by the stimulation of A549 cells with SiO2 was established. A549 cells were transfected with miR-30a mimic and miR-30a inhibitor and the SNAIL gene was silenced to examine the mechanism of miR-30a targeting Snail to regulate silica dust-induced EMT. The results showed that 50 μg/mL SiO2 stained A549 cells for 24 h could induce EMT in A549 cells. Exposure of A549 cells to SiO2 dust decreased miR-30a expression, as well as mRNA and protein expression levels of E-cad. Conversely, SiO2 exposure increased mRNA and protein expression levels of α-SMA, vimentin, and Snail. The miR-30a mimic upregulated mRNA and protein expression levels of E-cadherin in SiO2-induced A549 cells, while downregulating mRNA and protein expression levels of α-SMA, vimentin and Snail. MiR-30a inhibitors have the opposite effect. Silencing the SNAIL gene, followed by SiO2 dust-induced stimulation of A549 cells, could enhance mRNA and protein expression levels of E-cad, whereas those of α-SMA and vimentin were reduced. Altogether, we found that miR-30a directly targeted Snail and inhibited its expression, thereby delaying silica induced pulmonary EMT.