D₁ receptor activation improves vigilance in rats as measured by the 5-choice continuous performance test.
Impaired attention/vigilance is putatively core to schizophrenia. The dopaminergic D(1) receptor system has been reported as one of the most promising targets for improving cognition in patients with schizophrenia, with some evidence suggesting D(1) activation may improve sustained attention. The purpose of this study was twofold: firstly assessing the applicability of using rats in the 5-Choice Continuous Performance Test (5 C-CPT), recently validated in mice. Secondly, the effect of systemic administration of a D(1) partial agonist, SKF 38393, on task performance during baseline, and a challenge session consisting of a reduced event-rate was investigated. Animals were trained to perform the 5 C-CPT with performance assessed following systemic SKF 38393 (2, 4 and 6 mg/kg) vs. vehicle administration. Rats could discriminate between target (requiring a response) and non-target (requiring the inhibition of response) trials within the 5 C-CPT. Moreover, SKF 38393 treatment impaired performance during the baseline session reducing target detection, yet improved performance during the reduced event-rate challenge session, increasing target detection and improving signal discrimination indicating an SKF 38393-induced enhancement of vigilance. Thus, these data suggest that activation of the D(1) system affected 5 C-CPT performance in a baseline dependent manner. Rats can be trained to perform the 5 C-CPT, appropriately withholding from responding to non-target trials. Systemic administration of SKF 38393 impaired performance during baseline conditions. Following a task-related challenge, which reduced the event rate, activation of the dopamine (DA) D(1) system improved performance by heightening the animals' vigilance levels, quantified using signal detection theory.


Experimental and spontaneous metastasis assays can result in divergence in clonal architecture.
Intratumoural heterogeneity is associated with poor outcomes in breast cancer. To understand how malignant clones survive and grow in metastatic niches, in vivo models using cell lines and patient-derived xenografts (PDX) have become the gold standard. Injections of cancer cells in orthotopic sites (spontaneous metastasis assays) or into the vasculature (experimental metastasis assays) have been used interchangeably to study the metastatic cascade from early events or post-intravasation, respectively. However, less is known about how these different routes of injection impact heterogeneity. Herein we directly compared the clonality of spontaneous and experimental metastatic assays using the human cell line MDA-MB-231 and a PDX model. Genetic barcoding was used to study the fitness of the subclones in primary and metastatic sites. Using spontaneous assays, we found that intraductal injections resulted in less diverse tumours compared to other routes of injections. Using experimental metastasis assays via tail vein injection of barcoded MDA-MB-231 cells, we also observed an asymmetry in metastatic heterogeneity between lung and liver that was not observed using spontaneous metastasis assays. These results demonstrate that these assays can result in divergent clonal outputs in terms of metastatic heterogeneity and provide a better understanding of the biases inherent to each technique.


What Urinary Colony Count Indicates a Urinary Tract Infection in Children?
Post-hoc analysis of the Randomized Intervention for Children with Vesicoureteral Reflux study suggests that, in concordance with European guidelines, using bacteriologic criterion of ≥10 000 colony forming units/mL of a single organism does not decrease diagnostic specificity of an urinary tract infection in children aged 2 months to 6 years in a properly collected urine if symptoms/fever and pyuria are present. ClinicalTrials.gov: NCT00405704.


Quantitative and qualitative evaluations of protein intake in a geriatric subpopulations from a southern Swedish community.
The daily intake of protein and the amino acid content of food samples collected in association with a dietary survey of male and female Swedish pensioners, were determined. Duplicate portions of 1-day, mixed food samples were collected. The samples were homogenized and the fat was extracted before lyophilization. Protein content was determined by a modified Kjeldahl method. Cysteine and methionine were determined by ion-exchange chromatography after performic acid oxidation follow by acid hydrolysis, whereas tryptophan was determined by a spectrofluorometric method. All other amino acids were analyzed by gas-liquid chromatography. Median protein intake was 0.69 g per person per kilograms of body weight per day for the male pensioners and 0.67 g per person per kilograms of body weight per day for the female pensioners and 0.67 g per person per kilograms of body weight per day for the female pensioners. The quality of protein consumed by the participants, determined by amino acid analysis, showed that lysine, threonine, and tryptophan were the limiting amino acids. The chemical score, when compared with the FAO reference protein, varied between 35 and 100 (mean = 77).


Saliva oxytocin, cortisol, and testosterone levels in adolescent boys with autism spectrum disorder, oppositional defiant disorder/conduct disorder and typically developing individuals.
The aim of the current study was to compare levels of oxytocin, cortisol, and testosterone in adolescents with either autism spectrum disorder (ASD), or oppositional defiant disorder (ODD)/conduct disorder (CD), and in typically developing individuals (TDI), and relate hormone levels to severity and subtype of aggression and callous-unemotional (CU) traits. Saliva concentrations of oxytocin, cortisol, and testosterone were assessed in 114 male participants (N = 49 ASD, N = 37 ODD/CD, N = 28 TDI,) aged 12-19 years (M = 15.4 years, SD = 1.9). The ASD and the ODD/CD groups had significantly lower levels of oxytocin than the TDI group, and the ODD/CD group had significantly higher levels of testosterone than the ASD group. There were no group effects on cortisol levels. Group differences remained for oxytocin after correcting for the influence of CU traits, but were not significant after controlling for aggression. Results for testosterone became non-significant after correction for either CU traits or aggression. Across groups, higher levels of CU traits were related to higher levels of cortisol and testosterone, however, proactive and reactive aggression were unrelated to all three hormonal levels. The current findings show that, regardless of cognitive ability or comorbid disorders, the diagnostic groups (ASD, ODD/CD) differ from each other by their hormonal levels, with the ASD group characterized by relative low level of oxytocin, and the ODD/CD group by a relative low level of oxytocin and high level of testosterone. These group effects were partly driven by differences in CU traits between the groups.


The use of dextran after keratoplasty for visualizing the vitreous cavity.
Corneal edema during penetrating keratoplasty (PK) precludes the visualization of the fundus required to perform vitreoretinal surgery. In this study, the clearing of the cornea and fundus visualization with dextran 40 following PK was evaluated. Topical dextran 40 was used in 12 eyes that underwent uncomplicated PK (phase 1) and in 5 eyes that underwent combined PK with vitreoretinal surgery (phase 2). Clearing of the cornea and visualization of the fundus were observed in all eyes after dextran had been instilled for a mean of 4 and 5 minutes in eyes for phase 1 and 2, respectively. Vitreoretinal surgery could successfully be performed after PK in all eyes of phase 2. Topical use of dextran 40 following PK produces enough clearing of the cornea to enable visualization of the fundus for further vitreoretinal procedures after the graft has been sutured.


Anthropogenic and natural CO2 emission sources in an arid urban environment.
Recent research has shown the Phoenix, AZ metropolitan region to be characterized by a CO2 dome that peaks near the urban center. The CO2 levels, 50% greater than the surrounding non-urban areas, have been attributed to anthropogenic sources and the physical geography of the area. We quantified sources of CO2 emissions across the metropolitan region. Anthropogenic CO2 emission data were obtained from a variety of government and NGO sources. Soil CO2 efflux from the dominant land-use types was measured over the year. Humans and automobile activity produced more than 80% input of CO2 into the urban environment. Soil CO2 efflux from the natural desert ecosystems showed minimal emissions during hot and dry periods, but responded rapidly to moisture. Conversely, human maintained vegetation types (e.g. golf courses, lawns, irrigated agriculture) have greater efflux and are both temperature and soil moisture dependent. Landfills exhibited the most consistent rates, but were temperature and moisture independent. We estimate the annual CO2 released from the predominant land-use types in the Phoenix region and present a graphical portrayal of soil CO2 emissions and the total natural and anthropogenic CO2 emissions in the metropolitan region using a GIS-based approach. The results presented here do not mimic the spatial pattern shown in previous studies. Only, with sophisticated mixing models will we be able to address the total effect of urbanization on CO2 levels and the contribution to regional patterns.


Glucagon-like peptide-1: a potent regulator of food intake in humans.
Studies in animals suggest a physiological role for glucagon-like peptide-1-(7-36)-amide (GLP-1) in regulating satiety. The role of GLP-1 in regulating food intake in man has, however, not been investigated. Subjects-Sixteen healthy male subjects were examined in a double blind placebo controlled fashion. The effect of graded intravenous doses (0, 0.375, 0.75, and 1.5 pmol/kg/min) of synthetic human GLP-1 on food intake and feelings of hunger and satiety was tested in healthy volunteers. Graded GLP-1 infusions resulted in a dose dependent reduction in food intake (maximal inhibition 35%, p<0.001 v control) and a similar reduction in calorie intake (32%; p<0.001). Fluid ingestion was also reduced by GLP-1 (18% reduction, p<0.01). No overt side effects were produced by GLP-1, but subjects experienced less hunger and early fullness in the period before a meal during GLP-1 infusion at the highest dose (p<0.05). Intravenous infusions of GLP-1 decrease spontaneous food intake even at physiological plasma concentrations, implying an important role for GLP-1 in the regulation of the early satiety response in humans.


Manganese-mediated ammonium removal by a bacterial consortium from wastewater: Experimental proof and biochemical mechanisms.
Manganese-redox-mediated nitrogen transformation is promising for ammonium wastewater treatment. However, due to the limited contact between insoluble Mn and the microbe, extracellular electron transfer (EET) inefficiencies become a technical bottleneck in the technical practical application. To overcome this obstacle, humic acid (HA) was introduced to synthesize manganese-humic acid complex (Mn-HA) to increase Mn solubility. The TIN (Total Inorganic Nitrogen) removal rate constant k was 3.18, 1.08, 3.56, 1.13 and 1.05 times higher than CK (Control group) at 10, 15, 20, 40 and 60 mg/L influent nitrate in the MH group, respectively. Mn-HA was inferred to stimulated the nitrogen removal by providing more reaction active sites, bridging Mn-O bonds to transfer electrons and playing a redox role in the respiratory chain. A Mnammox-NDMO (manganese oxide reduction-coupled ammonium oxidation - nitrate/nitrite- dependent manganese oxidation) bacteria consortium was enriched in MH group, containing Mnammox bacteria Geothrix, Geobacter and NDMO bacteria Pseudomonas and Bacillus.


The selective κ-opioid receptor antagonist JDTic attenuates the alcohol deprivation effect in rats.
The mechanisms behind relapse to ethanol intake in recovering alcoholics are still unclear. The negative reinforcing effects contributing to ethanol addiction, including relapse, are considered to be partly driven by the κ-opioidergic system. As the κ-opioidergic system interacts with the mesolimbic reward pathway, the aim of the study was to clarify the role of nucleus accumbens shell κ-opioidergic mechanisms in relapse to ethanol intake by using the alcohol deprivation effect (ADE) paradigm. The ADE is defined as a transient increase in voluntary ethanol intake after a forced period of abstinence. Male Long-Evans rats were trained to voluntarily consume 10% (v/v) ethanol solution. Ethanol access and deprivation cycles were initiated after stable ethanol intake baselines had been reached and bilateral guide cannulas had been implanted above the nucleus accumbens shell. One cycle consisted of 10 days of 90 min access to ethanol followed by 6 days of ethanol deprivation. The ADE was measured in the beginning of a new cycle. Rats received JDTic, a selective κ-antagonist, either subcutaneously (10 mg/kg) or intra-accumbally (15 µg/site) or, as a reference substance, systemic naltrexone (0.3 mg/kg) before ethanol re-access, and the effects on the ADE were evaluated. Systemic and intra-accumbal JDTic significantly attenuated the ADE on the first day of ethanol re-access, as did systemic naltrexone. Additionally, naltrexone decreased ethanol intake levels. These results suggest that nucleus accumbens shell κ-opioidergic mechanisms may have a role in mediating relapse to ethanol intake. Additionally, κ-antagonism could be a valuable adjunct in ethanol relapse prevention.


Topographic segregation and convergence of verbal, object, shape and spatial working memory in humans.
This functional magnetic resonance imaging study investigates commonalties and differences in working memory (WM) processes employing different types of stimuli. We specifically sought to characterize topographic convergence and segregation with respect to prefrontal cortex involvement using verbal, spatial, real object and shape memory items in a two-back WM task. Both the dorsolateral and ventrolateral prefrontal cortices are conjointly activated across all stimulus types. No stimulus-specific differences in the activation patterns of the prefrontal cortex could be demonstrated giving support to the view of an amodal prefrontal involvement during WM processes. However, extra-frontal regions specialized on feature processing and involved in the preprocessing of the stimuli were selectively activated by these different subtypes of WM. These selectively activated regions are assigned to parts of the ventral and dorsal stream.


A rare nonvalvular left ventricular papillary fibroelastoma: A case report.
Papillary fibroelastomas are benign cardiac tumors with high embolic potential typically found on the valvular surfaces of the heart. Nonvalvular papillary fibroelastomas are exceedingly rare. We report the case of a 66-year-old Caucasian male with acute bilateral basal ganglia infarctions found to have a mass adherent to the left ventricular septum by transesophageal echocardiography. The mass was identified as a rare nonvalvular cardiac papillary fibroelastoma based on echogenicity, pedunculated nature, and typical motion. Tissue characterization by cardiac magnetic resonance imaging demonstrated homogeneously hypo-intense signal on T2 weighted imaging and signal hyperintensity after administration of gadolinium contrast, confirming the fibroelastic nature of the mass. Surgical excision was performed via ventriculotomy and histopathologic examination was pathognomonic of a papillary fibroelastoma. We conclude that transesophageal echocardiography provides high diagnostic certainty in patients with cardiac papillary fibroelastomas and can reliably identify atypical locations of these tumors on nonvalvular surfaces. A multimodality imaging approach is not necessarily indicated in all patients with this condition. Papillary fibroelastomas are benign cardiac tumors with high embolic potential typically found on the valvular surfaces of the heart. Nonvalvular papillary fibroelastomas are exceedingly rare. Transesophageal echocardiography readily identifies nonvalvular papillary fibroelastomas based on echogenicity, pedunculated nature, and characteristic motion, and reliably differentiates them from other cardiac masses. A multimodality imaging approach is not indicated in all patients with this condition.


CTLA4-Ig Effectively Controls Clinical Deterioration and Immune Condition in a Murine Model of Foxp3 Deficiency.
FOXP3 deficiency results in severe multisystem autoimmunity in both mice and humans, driven by the absence of functional regulatory T cells. Patients typically present with early and severe autoimmune polyendocrinopathy, dermatitis, and severe inflammation of the gut, leading to villous atrophy and ultimately malabsorption, wasting, and failure to thrive. In the absence of successful treatment, FOXP3-deficient patients usually die within the first 2 years of life. Hematopoietic stem cell transplantation provides a curative option but first requires adequate control over the inflammatory condition. Due to the rarity of the condition, no clinical trials have been conducted, with widely unstandardized therapeutic approaches. We sought to compare the efficacy of lead therapeutic candidates rapamycin, anti-CD4 antibody, and CTLA4-Ig in controlling the physiological and immunological manifestations of Foxp3 deficiency in mice. We generated Foxp3-deficient mice and an appropriate clinical scoring system to enable direct comparison of lead therapeutic candidates rapamycin, nondepleting anti-CD4 antibody, and CTLA4-Ig. We found distinct immunosuppressive profiles induced by each treatment, leading to unique protective combinations over distinct clinical manifestations. CTLA4-Ig provided superior breadth of protective outcomes, including highly efficient protection during the transplantation process. These results highlight the mechanistic diversity of pathogenic pathways initiated by regulatory T cell loss and suggest CTLA4-Ig as a potentially superior therapeutic option for FOXP3-deficient patients.


No evidence of interference of hypocapnia/respiratory alkalosis with classical conditioning of electrodermal responses.
Most phobias can be traced to aversive experiences relating to the phobic cue, but most aversive experiences do not result in phobias. Why is it that only sometimes these experiences result in classical conditioning of fear? It was hypothesized that if the subject is in a state of hypocapnia/respiratory alkalosis, classical conditioning of fear is facilitated, while extinction of fear responses is inhibited. Thirty-two healthy volunteers underwent a classical conditioning procedure with slides as conditioned stimulus, electric shocks as unconditioned stimulus, and electrodermal responding as (un) conditioned response. During conditioning, half of the subjects hyperventilated and were hypocapnic/alkalotic, while the other half was not. In both groups clear conditioning occurred, but there was no effect of hypocapnia. Results are critically discussed.


Gastric infarction secondary to small bowel obstruction: a preventable complication after Nissen fundoplication.
Two infants who required a Nissen fundoplication for severe gastroesophageal reflux developed small bowel obstruction 5 and 21 months postoperatively. Their inability to belch or vomit, coupled with inappropriate airway management during resuscitation led to massive gastric dilation, and eventual infarction of their stomach, duodenum, and small intestines. These complications are preventable with appropriate management.


Oral health-related quality of life and the IOTN index as predictors of children's perceived needs and acceptance for orthodontic treatment.
To evaluate whether the index of orthodontic treatment need (IOTN) could be improved by adding an oral health-related quality of life measure to predict both the outcome of orthodontic consultation and the child's perceived need for orthodontic treatment. The sample consisted of 187 children aged 11-16 years referred to orthodontic clinics in the Bedfordshire Personal Dental Service (PDS) in the United Kingdom. The children completed a questionnaire containing the Child Perception Questionnaire (CPQ11-14), were clinically examined and completed the Child-OIDP index in face-to-face interviews. Demographic information and perceived need for orthodontic treatment were also collected. Clinical data on orthodontic treatment need was collected using the IOTN. 49.3% of children reported one or more oral impacts. Combining the IOTN index with either of the two oral health-related quality of life measures used in this study did not predict outcome of consultation, however it explained children's perceived need for braces. There were some discrepancies between need according to the orthodontist and children's perceptions. Adding an oral health-related quality of life measure to IOTN did not influence prediction of outcome of consultation but it explained the prediction of perceived need for braces. Importantly, children with an impact were denied orthodontic treatment.


Role of proline 1150 in functional interactions between the membrane spanning domains and nucleotide binding domains of the MRP1 (ABCC1) transporter.
The ATP-binding cassette multidrug resistance protein 1 (MRP1) mediates ATP-dependent cellular efflux of drugs and organic anions. We previously described a mutant, MRP1-Pro1150Ala, which exhibits selectively increased estradiol glucuronide (E217betaG) and methotrexate transport as well as altered interactions with ATP. We have now further explored the functional importance of MRP1-Pro1150 at the interface of transmembrane helix 15 and cytoplasmic loop 7 (CL7) by replacing it with Gly, Ile, Leu and Val. All four mutants exhibited a phenotype similar to MRP1-Pro1150Ala with respect to organic anion transport and [gamma32P]8N3ATP photolabeling. They also displayed very low levels of substrate-independent vanadate-induced trapping of [alpha32P]8N3ADP. To better understand the relationship between the altered nucleotide interactions and transport activity of these mutants, [alpha32P]8N3ADP trapping experiments were performed under different conditions. Unlike leukotriene C4, E217betaG decreased [alpha32P]8N3ADP trapping by both wild-type and mutant MRP1. [alpha32P]8N3ADP trapping by MRP1-Pro1150Ala could be increased by using Ni2+ instead of Mg2+, and by decreasing temperature; however, the transport properties of the mutant remained unchanged. We conclude that the reduced [alpha32P]8N3ADP trapping associated with loss of Pro1150, or the presence of E217betaG, is due to enhanced ADP release following ATP hydrolysis rather than a reduction in ATP hydrolysis itself. We hypothesize that loss of Pro1150 alters the role of CL7 as a coupling helix that mediates signaling between the nucleotide binding domains and some substrate binding sites in the membrane spanning domains of MRP1.


A possible role of inorganic phosphate as a regulator of oxidative phosphorylation in combined urea synthesis and gluconeogenesis in perfused rat liver. A phosphorus magnetic resonance spectroscopy study.
Metabolic control of oxidative metabolism was studied in perfused rat liver by means of phosphorus magnetic resonance spectroscopy. Oxygen consumption, ATP, and Pi were measured with different rates of gluconeogenesis and urea synthesis by varying concentrations of the substrates in the perfusate. Five levels of oxygen consumption (VO2) were obtained: an average control value of 1.94 +/- 0.14 and 2.93 +/- 0.25, 3.29 +/- 0.46, 3.85 +/- 0.26, and 4.18 +/- 0.56 mumol/min/g liver (mean +/- S.D., n = 6). The corresponding ATP concentrations were 2.51 +/- 0.20, 2.39 +/- 0.08, 2.24 +/- 0.09, 2.13 +/- 0.12, and 1.91 +/- 0.13 mM. Pi increased stoichiometrically with the decrease in ATP. Free Pi (Pif) was calculated as NMR-visible Pi in control plus -delta ATP (1.94 mM + (-delta ATP]. The kinetic relationship of oxidative phosphorylation as a function of Pif followed a Michaelis-Menten type of equation: VO2 = 5.55/(1 + 0.24/[( Pif] - 1.81]. The observed Km value for Pi of 0.24 mM approximates the reported Km value in isolated mitochondria of 1 mM. The free Pi concentration of 1.94 mM is in the range of the Km value, while the free ADP concentration of 200 microM exceeds the Km value of 20 microM. Therefore, it is suggested that Pi play a major role in the regulation of mitochondrial oxidative phosphorylation in combined urea synthesis and gluconeogenesis.


Temperature and H2O2-operated nano-valves on mesoporous silica nanoparticles for controlled drug release and kinetics.
Temperature and H2O2 dual-responsive nanoparticles were fabricated from ferrocene modified mesoporous silica (MSN-Fc) and β-cyclodextrin-poly(N-isopropylacrylamide) (β-CD-PNIPAM) star-shaped polymer due to the host-guest interactions for controlled drug release. The formation and structure of β-CD-PNIPAM@MSN-Fc composite nanoparticles was confirmed by FTIR, TGA, TEM and N2 adsorption-desorption isotherms. The size of nanoparticles was about 100-150 nm with well-ordered mesoporous structure and PNIPAM chains coating on the surface as outer shell. The channels of MSNs and hydrophobic cavities of β-CD were all contributed to the high drug loading capacity for nanoparticles. The release of DOX from nanoparticles was enhanced with the increase of temperature above LCST or adding H2O2 in ambient O2. The release kinetics were studied using different models to explain drug release mechanism. Furthermore, the drug loaded composite nanoparticles exhibited excellent anti-cancer activity.


Roles of metabotropic glutamate receptor subtypes in modulation of pentylenetetrazole-induced seizure activity in mice.
The anticonvulsant or proconvulsant properties of ligands at metabotropic glutamate receptors (mGluRs) were examined in a chemoconvulsant model using pentylenetetrazole (PTZ). Mice received mGluR ligands by intracerebroventricular (i.c.v.) infusion prior to a subcutaneous injection of PTZ and the latency to onset of tonic convulsions was recorded. The group I mGluR antagonist 1-aminoindan-1,5-dicarboxylic acid (AIDA) dose-dependently antagonised PTZ-induced seizures with a mean ED50 value of 465 nmol. In contrast, the selective group I mGluR agonist, (S)-3,5-dihydroxyphenylglycine [(S)-DHPG], was proconvulsive and decreased the PTZ-induced seizure latency (ED50=60 nmol i.c.v.). A selective agonist of group II mGluRs, (1S,3S)-1-aminocyclopentane dicarboxylic acid [(1S,3S)-ACPD], was proconvulsive but did not affect PTZ-induced seizure latency. Moreover, the proconvulsant effect of (IS,3S)-ACPD was not blocked by the mGluR2 antagonist, alpha-methylserine-O-phosphate monophenyl ester but was blocked by AIDA suggesting the involvement of group I mGluRs. (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-IV), which is a potent mGluR2 antagonist and a group III mGluR agonist at higher doses, increased the PTZ-induced seizure latency (ED50=51 nmol) and this effect was fully reversed by the group III mGluR antagonist, (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4). Similarly, the group III mGluR agonist 1-amino-3-(phosphonomethylene)cyclobutanecarboxylate (cyclobutylene-AP5) increased the PTZ-induced seizure latency (ED50=12 nmol) in a MAP4-sensitive manner. Collectively, these data suggest that mGluR ligands modulate PTZ-induced seizure activity in mice by either antagonizing group I mGluRs or activating group III mGluRs.


Improvement of the precision of lattice parameter determination by nano-beam electron diffraction.
A highly precise determination of lattice parameters using higher-order Laue zone (HOLZ) reflections observed in nano-beam electron diffraction is presented. The introduction of more than 40 HOLZ reflections, whose positions are corrected by considering the aberration of the electron optics and are determined with an accuracy of 0.04 nm⁻¹, allows us to achieve a remarkable high precision of a 0.02% error, which is four times higher than the precision without HOLZ reflections.


Distinctive medium chain wax esters, triglycerides, and diacyl glyceryl ethers in the head fats of the Pacific beaked whale, Berardius bairdi.
Lipids were extracted from the mandibular fat body (jaw), the fatty forehead (melon), and the dorsal blubber of a Pacific beaked whale (Berardius bairdi) and separated into lipid classes by preparative thin layer chromatogrphy. The head fats were mixtures of wax esters and triglycerides with a very small amount of diacyl glyceryl ether. The blubber fat contained 97% wax ester and 3% triglyceride. Gas liquid chromatography (GLC) of the intac lipid classes indicated an unusually low C26-C30 range for most of the jaw and melon wax esters compared to the more normal C32-C40 molecules found in the blubber. Distinctive lower molecular weight C24-C40 triglycerides occurred in the head fats vs. the usual C44-C58 range in the blubber. Most diacyl glyceryl ethers were in the C35-C46 range, below the molecular weight of hexadecyldipalmitoyl glyceryl ether (C48). GLC of the derived fatty acid methyl esters showed that the lower molecular weight neutral lipids in the head fats were due to high levels of iso-10:0, n-10:0, iso-11:0, iso-12:0, N-12:0, and iso-13:0 acids. The wax ester fatty alcohols and the alkoxy chains of the glyceryl ethers were mostly the C14-C20 chain lengths commonly observed in marine organisms. The distinctive medium chain neutral lipids in the jaw and melon fats of this whale may be related to the postulated acoustical role of these tissues in echolocation.


Mustard operation for transposition of the great arteries in a 3-day-old infant, complicated by acute renal failure.
A successful operative treatment of a three day old girl with transposition of the great arteries is described. Post-operative course was complicated by furosemide resistant anuria which was treated by peritoneal dialysis. At the age of eight months, she is a pink, active baby, developing normally. This case report demonstrates the importance of aggressive treatment of severe congenital heart lesions in the first few days of life. The importance of post-operative care is emphasized.


Campylobacter-like omega intracellular antigen in proliferative colitis of ferrets.
Proliferative colitis in the ferret consistently displays, along with marked proliferation of mucosal cells, intracytoplasmic campylobacter-like organisms within the apical portion of the epithelial cells. Fluorescent antibody to "omega" campylobacter antigen present in porcine intestinal adenomatosis and hamster proliferative ileitis was demonstrated at the site of bacterial colonization within hyperplastic epithelial cells of six colons from ferrets affected with proliferative colitis.


Meta-analysis of incidence rate data in the presence of zero events.
When summary results from studies of counts of events in time contain zeros, the study-specific incidence rate ratio (IRR) and its standard error cannot be calculated because the log of zero is undefined. This poses problems for the widely used inverse-variance method that weights the study-specific IRRs to generate a pooled estimate. We conducted a simulation study to compare the inverse-variance method of conducting a meta-analysis (with and without the continuity correction) with alternative methods based on either Poisson regression with fixed interventions effects or Poisson regression with random intervention effects. We manipulated the percentage of zeros in the intervention group (from no zeros to approximately 80 percent zeros), the levels of baseline variability and heterogeneity in the intervention effect, and the number of studies that comprise each meta-analysis. We applied these methods to an example from our own work in suicide prevention and to a recent meta-analysis of the effectiveness of condoms in preventing HIV transmission. As the percentage of zeros in the data increased, the inverse-variance method of pooling data shows increased bias and reduced coverage. Estimates from Poisson regression with fixed interventions effects also display evidence of bias and poor coverage, due to their inability to account for heterogeneity. Pooled IRRs from Poisson regression with random intervention effects were unaffected by the percentage of zeros in the data or the amount of heterogeneity. Inverse-variance methods perform poorly when the data contains zeros in either the control or intervention arms. Methods based on Poisson regression with random effect terms for the variance components are very flexible offer substantial improvement.


Status of different immune cells during regression of a rat histiocytoma.
Status of CD4 and CD8 positive T-lymphocytes, natural killer cells and macrophages has been studied in animals which reject AK-5 histiocytoma. Analysis of immune cells which enter the tumour showed higher number of CD8 positive and NK cells around day 25 after tumour transplantation, suggesting their participation in tumour rejection.


Rainfall and the interaction of microclimate with larval resources in the population dynamics of checkerspot butterflies (Euphydryas editha) inhabiting serpentine grassland.
The interaction of host plant phenology and microclimatic heterogeneity was examined to determine its role in the population dynamics of checkerspot butterflies, Euphydryas editha, inhabiting serpentine grassland in California's outer Coast Range.Within the 2-3 hectares inhabited by a population of E. editha (Jasper Ridge Area H), microclimatic differences resulting from topographic heterogeneity largely determine the temporal and spatial pattern of senescence of the larval host plants, Plantago erecta and Orthocarpus densiflorus. Survival of larvae from hatching to diapause is extremely low as a result of unpredictable variation in the timing of larval development relative to the timing of host plant senescence, both of which are mediated by microclimatic patterns. During this study, population H declined to near extinction as a result of two consecutive years of record rainfall that apparently disrupted the tenuous temporal relationship between larval development and plant senescence. Retarded development of post-diapause larvae led to a late and extended flight season and delayed egg production; this in turn resulted in massive mortality of pre-diapause larvae due to starvation because host plant senescence occurred before larvae became large enough to enter diapause. Adult population size the following spring was the smallest in 25 years of study. This work emphasizes the importance of microclimatic heterogeneity for understanding population-level processes in small ectothermic animals and underlines the potential importance of such heterogeneity in the establishment of reserves designed to protect such animals.


[Cerebral infarction and migrainous attack. Angiographic and CT scan studies (author's transl)].
A lateral homonymous hemianopia appareared in a 40 years old housewife during a migrainous attack and persisted as sequella. Angiographic study was normal and CT scan showed an area of low density at the right occipital level enhancing with heterogenous aspect after the iodinate injection. The occurrence of a cerebral infarction during a migrainous attack is probably due to numerous factors.


Cloning of the L-lactate dehydrogenase gene from the ruminal bacterium Selenomonas ruminantium HD4.
A clone from a Selenomonas ruminantium HD4 Lambda ZAP II genomic library was isolated by its ability to complement the anaerobic growth deficiency of an Escherichia coli (pfl, ldh) double mutant. The 1.0-kb insert from the clone was sequenced and revealed a single open reading frame (ORF, 957-bp) which was preceded by a putative Shine-Dalgarno (SD) sequence (AGGGGG). The potential SD sequence corresponded to 3' 16S rRNA sequences of various Selenomonas strains. The ORF was predicted to encode a protein of 318 amino acids with a calculated molecular mass of 34,975 Da and an isoelectric point of 5.54. In addition, the ORF contained 51 mol % G + C and this is consistent with the average G + C content (54%) of the S. ruminantium chromosome. The cloned S. ruminantium gene exhibited 59% nucleotide identity and 61% deduced amino acid similarity with L-lactate dehydrogenases (L-LDH) of Pediococcus acidilactici and Bacillus megaterium, respectively. Incorporation of the cloned S. ruminantium gene into E. coli DC1368 (pfl, ldh) restored anaerobic growth on glucose and L-LDH activity was detected in cell extracts. Because lactate accumulation within the rumen can be detrimental to animal performance, characterizing the gene(s) involved in lactate production by predominant ruminal bacteria will lead to a better understanding of lactate metabolism within the rumen.


A novel electrochemical sensor based on double-walled carbon nanotubes and graphene hybrid thin film for arsenic(V) detection.
In this work, we demonstrate the preparation of hybrid thin films based on double-walled carbon nanotubes and graphene for electrochemical sensing applications. The hybrid films were synthesized on polycrystalline copper foil by thermal chemical vapor deposition under low pressure. This carbonaceous hybrid film has exhibited high transparency with a transmittance of 94.3 %. The occurrence of this hybrid material on the electrode surface of screen-printed electrodes was found to increase electroactive surface area by 1.4 times, whereas electrochemical current was enhanced by 2.4 times. Such a highly transparent and conductive hybrid film was utilized as a transducing platform of enzymatic electrochemical arsenic(V) sensor. The as-prepared sensor shows the linear detection of arsenic(V) in the range from 1 to 10 ppb, with a limit of detection as low as 0.287 ppb. These findings provide a promising approach to develop new multifunctional electrochemical sensing systems for environmental monitoring and biomedical diagnostics.


China's practice to prevent and control COVID-19 in the context of large population movement.
The emerging infectious disease, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a serious threat in China and worldwide. Challenged by this serious situation, China has taken many measures to contain its transmission. This study aims to systematically review and record these special and effective practices, in hope of benefiting for fighting against the ongoing worldwide pandemic. The measures taken by the governments was tracked and sorted on a daily basis from the websites of governmental authorities (e.g. National Health Commission of the People's Republic of China). And the measures were reviewed and summarized by categorizations, figures and tables, showing an ever-changing process of combating with an emerging infectious disease. The population shift levels, daily local new diagnosed cases, daily mortality and daily local new cured cases were used for measuring the effect of the measures. The practices could be categorized into active case surveillance, rapid case diagnosis and management, strict follow-up and quarantine of persons with close contacts, and issuance of guidance to help the public understand and adhere to control measures, plus prompt and effective high-level policy decision, complete activation of the public health system, and full involvement of the society. Along with the measures, the population shift levels, daily local new diagnosed cases, and mortality were decreased, and the daily local new cured cases were increased in China. China's practices are effective in controlling transmission of SARS-CoV-2. Considering newly occurred situations (e.g. imported cases, work resumption), the control measures may be adjusted.


Near-infrared and short-wavelength autofluorescence in resolved central serous chorioretinopathy: association with outer retinal layer abnormalities.
To evaluate the correlation between changes in fundus autofluorescence (AF) measured using 2 different sources (near-infrared fundus autofluorescence from melanin and short-wavelength fundus autofluorescence from lipofuscin) with changes in spectral-domain optical coherence tomography (SD OCT) and fluorescein angiography in resolved central serous chorioretinopathy (CSC). Retrospective, observational case study. A total of 91 eyes from 86 patients with a history of resolved CSC and abnormal AF imaging findings were included. In addition to AF, patients were assessed by means of SD OCT and fluorescein angiography. Outer retinal layer alterations in OCT images and abnormalities in fluorescein angiography were analyzed and correlated with the corresponding AF data. All eyes with abnormal near-infrared AF showed a hyperfluorescent angiography window defect in the corresponding area. There was a significant association between the OCT and short-wavelength AF findings. An abnormal short-wavelength AF signal was significantly associated with loss of the ellipsoid portion of the inner segments (EPIS, previously known as the junction between the inner and outer segments of the photoreceptors) on SD OCT (χ(2) test; P < .0001). Near-infrared AF could not predict the status of EPIS without the short-wavelength AF image. Outer retinal layer changes in OCT images can be predicted by analyzing both short-wavelength AF and near-infrared AF images. Abnormal changes in the short-wavelength AF image were predictive of EPIS damage.


Effect of DNA supercoiling on in vitro transcription from the adenovirus early region 4.
The effect of DNA supercoiling on in vitro transcription from the early region 4 (E4) promoter of adenovirus type 5 (Ad5) has been investigated by using a cell-free transcription system that maintains supercoiled DNA templates. The supercoiled DNAs yield several-fold higher levels of E4 transcripts and more faithfully reflect the regulation of in vivo transcription than the linear DNAs.


The role of appearance and motion in action prediction.
We used a novel stimulus set of human and robot actions to explore the role of humanlike appearance and motion in action prediction. Participants viewed videos of familiar actions performed by three agents: human, android and robot, the former two sharing human appearance, the latter two nonhuman motion. In each trial, the video was occluded for 400 ms. Participants were asked to determine whether the action continued coherently (in-time) after occlusion. The timing at which the action continued was early, late, or in-time (100, 700 or 400 ms after the start of occlusion). Task performance interacted with the observed agent. For early continuations, accuracy was highest for human, lowest for robot actions. For late continuations, the pattern was reversed. Both android and human conditions differed significantly from the robot condition. Given the robot and android conditions had the same kinematics, the visual form of the actor appears to affect action prediction. We suggest that the selection of the internal sensorimotor model used for action prediction is influenced by the observed agent's appearance.


Simulation study on radiation fields around targets to apply CR-39 for photo-neutron measurement in electron accelerator near the threshold energy.
Photo-neutron production in electron accelerator near the threshold energy has been studied by Monte Carlo simulation using the FLUKA code. A pencil beam of 10 MeV electron was incident normally on W, Ta, Pb and Bi targets and a CR-39 detector attached to the target was used as scoring region. In the simulation, photon and neutron spectra, yield and their spatial distribution, fast neutron fluence above 100 keV, total dose and neutron dose deposition were estimated for these metallic targets. The photon emission was found to be forward peaked whereas the neutron emission was isotropic in nature. The photon yield was found to be 5 to 6 orders of magnitude higher than that of neutrons. In W and Ta, the photon yield is maximum for 1.5 mm thickness whereas for Pb and Bi, the photon yield is highest at 2 and 2.5 mm respectively. The total neutron yield was highest for W and lowest for Pb whereas highest number of fast neutrons above 100 keV was for W followed by Bi, Pb and Ta. Production of significant number of fast neutrons above 100 keV suggests the possibility of the use of CR-39 detector for measurement of these neutrons. The total dose deposition was found to be highest for Bi followed by Pb, Ta and W whereas the neutron dose equivalent was highest for W followed by Pb, Bi and Ta. This simulation study will be useful for neutron dosimetry, estimation of source term, implementation of CR-39 for measurement and other radiation protection aspects in the vicinity of an electron accelerator.


Correlation of continuous-wave Doppler assessment of chronic aortic regurgitation with hemodynamics and angiography.
Fifteen patients with chronic aortic regurgitation (AR) were studied by cardiac catheterization and continuous-wave (CW) Doppler echocardiography. The slope of the AR CW Doppler signal was higher in patients with severe AR (5.7 +/- 2.1 m/s2) than in those with moderate (2.5 +/- 1.3 m/s2) or mild (1.8 +/- 0.7 m/s2) AR (p less than 0.05). The slopes in patients with mild (less than or equal to 18 mm Hg), moderate (19 to 24 mm Hg) and severe (greater than 24 mm Hg) elevation of left ventricular end-diastolic pressure were significantly different (1.9 +/- 0.6, 3.3 +/- 1.2 and 7.1 +/- 0.4 m/s2, respectively, p less than 0.05). Patients with severe AR had shorter pressure half-times than those with mild AR (283 +/- 141 vs 820 +/- 393 ms, p less than 0.05). There was a significant correlation between the slope and left ventricular end-diastolic pressure (r = 0.80, p less than 0.001) and a weaker inverse correlation between pressure half-time and left ventricular end-diastolic pressure (r = -0.59, p less than 0.05). The end-diastolic pressure gradient estimated from CW Doppler using a simplified Bernoulli equation correlated poorly with the catheter measured gradient (r = 0.59, p less than 0.02). The slope of the CW Doppler signal is a better predictor of severity than pressure half-time and is affected by left ventricular end-diastolic pressure in addition to angiographic severity of AR.


Ecological genetics of Bromus tectorum : II. Intraspecific variation in phenotypic plasticity.
For Bromus tectorum, an alien annual grass now widespread in western North America, we assessed the sensitivity of the phenotypic expression of populational differences in phenology and demography to variation in plant density. Plants were grown in an unheated glasshouse from seeds collected from six habitat types located along a moisture-temperature gradient. Survival to flowering was high with a mean overall survival of 91%. Survival was highest among plants from the coolest, most mesic site. Time to first flowering decreased at the higher sowing density and was dependent on seed source. Plant dry weight and average seed production was lowest within high density plots; the magnitude of this reduction was significantly dependent on seed source. Individual seed weight was also dependent on the interaction of seed source and sowing density. Seed weight did not vary as much as seed number or plant weight in response to density. Differences among sources in hierarchies of plant size and seed production were detected at low sowing densities. The degree of inequality in the distributions of plant size and seed number increased at high density.


Diterpenoids from the Chinese herb Caryopteris terniflora and their antibacterial and antitumor activity.
Two ent-kaurene type diterpenoids, diterpenoids A (1) and B (2) were isolated from the Chinese herb Caryopteris terniflora and defined as ent-7beta, 11alpha,14-trihydroxy-18-aldehyde-11beta-20-epoxy-kaur-16-en15-one and ent-7beta,14-dihydroxy-11alpha-methoxy-18-aldehyde-11beta-20-epoxy-kaur-16-en-15-one respectively. Compounds 1 and 2 showed significant antibacterial and antitumour activity.


Alterations in hepatocytes of mice fed a gallstone-inducing diet: occurrence of nuclear and cytoplasmic lipids.
Mice fed a high cholesterol-cholic acid (lithogenic) diet for one year develop fatty livers in addition to gallstones. Light and electron micrographs demonstrate large amounts of lipids in liver parenchymal cells, often to the exclusion of most other cytoplasmic organelles. In addition, some hepatocytes exhibit nuclear lipid pseudo- and true inclusions. Other prominent features of hepatocytes after lithogenic diet include segregation of nucleolar granular and fibrillar material. Accumulation of considerable collagen in extracellular spaces is also noted. Observations suggest changes induced by the cholesterol diet are comparable to cytologic alterations seen in spontaneous and drug induced hepatic tumors, as well as to more general "fatty metamorphosis" of the liver.


SHAPE to Probe RNA Structure and RNA-Protein Interactions In Vitro.
Selective 2' hydroxyl acylation analyzed by primer extension (SHAPE) is used to distinguish between the levels of flexibility of nucleotides regulated by base pairing or protein binding. In this method, a reagent reacts with the 2' hydroxyl group to form an adduct, which is then detected by reverse transcription reaction. The number of RNA molecules with an adduct at a specific nucleotide position indicates the SHAPE reactivity of that nucleotide. Here, we describe the method for probing the structure of an RNA in a protein-free or a protein-bound state by in vitro SHAPE.


Cyclophilin-A is a zinc-dependent DNA binding protein in macrophages.
The association of cyclosporin A (CsA) immunosuppression with inhibition of transcription factor-dependent lymphokine gene activation formed the basis of our decision to investigate nuclear-associated Cyp isoforms. Immunofluorescence microscopy of mouse macrophages cell line with a monoclonal antibody mAb7F1 raised against CypA shows a co-localisation of CypA in the nucleus and in the cytosol. Nuclear CypA binds to DNA in a zinc ion-dependent manner, in contrast to recombinant CypB. Peptidyl-prolyl cisltrans isomerase (PPIase) activity of nuclear CypA is inhibited by zinc ions. The zinc inhibited CypA does not bind cyclosporin A (CsA). We suggest that nuclear Cyp in complex with zinc ions recognizes DNA sequences and is involved in transcription modulating processes.


Children with a history of both maternal immune activation and prematurity are not at increased risk of ADHD symptoms.
Maternal autoimmune diseases (AID) are risk factors for Attention Deficit Hyperactivity Disorder (ADHD). Animal studies suggest that maternal immune activation (MIA) is a disease primer for ADHD, with second environmental factor precipitating the onset of the disease. Prematurity is also a major risk factor for ADHD. In this study, we sought to explore the interaction between parental AID and prematurity on ADHD risk in a community sample. Children of AID parents born prematurely appeared at increased odds of ADHD but these two risk factors do not appear to be additive (OR 1.39 [95 CI 0.75; 2.46]). Longitudinal studies with larger numbers of participants are needed.


Incompatibility between lasalocid and chloramphenicol in broiler chicks after a long-term simultaneous administration.
Two growth experiments were conducted to evaluate in broiler chicks the compatibility between lasalocid medication in the feed (at 90 or 125 ppm) and a long-term administration of chloramphenicol either via the feed (500 ppm) or via the drinking water (500 mg/liter). The simultaneous administration of lasalocid and chloramphenicol generally caused severe growth depression, decreased feed intake and impaired feed conversion. Several chicks showed evident symptoms of intoxication, such as ataxia, leg weakness and paralysis. The development and frequency of these symptoms were dependent on the dosage of lasalocid and on the duration of the simultaneous administration. Biochemical examinations (Experiment 2) revealed in the affected chicks significant changes in several parameters, in particular a markedly increased activity of creatine kinase and GOT in the plasma. It confirmed that the observed leg weakness and paralysis were caused by myodegeneration.


Characterization of the gene encoding component C3 of the complement system from the spider Loxosceles laeta venom glands: Phylogenetic implications.
A transcriptome analysis of the venom glands of the spider Loxosceles laeta, performed by our group, in a previous study (Fernandes-Pedrosa et al., 2008), revealed a transcript with a sequence similar to the human complement component C3. Here we present the analysis of this transcript. cDNA fragments encoding the C3 homologue (Lox-C3) were amplified from total RNA isolated from the venom glands of L. laeta by RACE-PCR. Lox-C3 is a 5178 bps cDNA sequence encoding a 190kDa protein, with a domain configuration similar to human C3. Multiple alignments of C3-like proteins revealed two processing sites, suggesting that Lox-C3 is composed of three chains. Furthermore, the amino acids consensus sequences for the thioester was found, in addition to putative sequences responsible for FB binding. The phylogenetic analysis showed that Lox-C3 belongs to the same group as two C3 isoforms from the spider Hasarius adansoni (Family Salcitidae), showing 53% homology with these. This is the first characterization of a Loxosceles cDNA sequence encoding a human C3 homologue, and this finding, together with our previous finding of the expression of a FB-like molecule, suggests that this spider species also has a complement system. This work will help to improve our understanding of the innate immune system in these spiders and the ancestral structure of C3.


Differential inhibition of polymerase and strand-transfer activities of HIV-1 reverse transcriptase.
A new class of inhibitors of HIV-1 reverse transcriptase obtained by the systematic structural simplification of epicatechin and epigallocatechin gallates are also shown here to inhibit DNA-strand-transfer, a process critical to the completion of the HIV-1-RT reproduction and to recombination-associated mutation of the virus. Up to 80-fold selectivity for DNA-strand-transfer inhibition over polymerase inhibition was observed for a defined subset of these agents. Such specific DNA-strand-transfer inhibitors may have important therapeutic potential.


Small bowel obstruction caused by a congenital intestinal web with an enteric bezoar in an adult: report of a case.
An intestinal web is a rare congenital anomaly, typically reported in childhood, but often remaining asymptomatic throughout the entire life span of the individual. We report the case of a symptomatic intestinal web associated with an enteric bezoar in an adult, which to the best of our knowledge has never been documented before. A 25-year-old man presented with acute small bowel obstruction, and laparotomy revealed a stenotic area of the ileum as well as impaction of an enteric bezoar. We resected this segment of ileum and an intestinal web was subsequently found in the stenotic area. The patient recovered well and has remained asymptomatic for 3 years. Although rare, a congenital intestinal web may be a cause of adult small bowel obstruction requiring surgical resection.


Feruloylation and structure of arabinoxylan in wheat endosperm cell walls from RNAi lines with suppression of genes responsible for backbone synthesis and decoration.
Arabinoxylan (AX) is the major component of the cell walls of wheat grain (70% in starchy endosperm), is an important determinant of end-use qualities affecting food processing, use for animal feed and distilling and is a major source of dietary fibre in the human diet. AX is a heterogeneous polysaccharide composed of fractions which can be sequentially extracted by water (WE-AX), then xylanase action (XE-AX) leaving an unextractable (XU-AX) fraction. We determined arabinosylation and feruloylation of AX in these fractions in both wild-type wheat and RNAi lines with decreased AX content (TaGT43_2 RNAi, TaGT47_2 RNAi) or decreased arabinose 3-linked to mono-substituted xylose (TaXAT1 RNAi). We show that these fractions are characterized by the degree of feruloylation of AX, <5, 5-7 and 13-19 mg bound ferulate (g-1 AX), and their content of diferulates (diFA), <0.3, 1-1.7 and 4-5 mg (g-1 AX), for the WE, XE and XU fractions, respectively, in all RNAi lines and their control lines. The amount of AX and its degree of arabinosylation and feruloylation were less affected by RNAi transgenes in the XE-AX fraction than in the WE-AX fraction and largely unaffected in the XU-AX fraction. As the majority of diFA is associated with the XU-AX fraction, there was only a small effect (TaGT43_2 RNAi, TaGT47_2 RNAi) or no effect (TaXAT1 RNAi) on total diFA content. Our results are compatible with a model where, to maintain cell wall function, diFA is maintained at stable levels when other AX properties are altered.


Root-Secreted Spermine Binds to Bacillus amyloliquefaciens SQR9 Histidine Kinase KinD and Modulates Biofilm Formation.
The signal molecules in root exudates that are sensed by plant growth-promoting rhizobacteria (PGPR) are critical to regulate their root colonization. Phosphorylated Spo0A is an important global transcriptional regulator that controls colonization and sporulation in Bacillus species. In this study, we found that deletion of kinD from PGPR strain Bacillus amyloliquefaciens SQR9, encoding an original phosphate donor of Spo0A, resulted in reduced biofilm formation in root exudates compared with the wild-type strain, indicating that KinD is responsible for sensing root exudates. Ligands of B. amyloliquefaciens SQR9 KinD in cucumber root exudates were determined by both the nontargeted ligand fishing method and the targeted surface plasmon resonance detection method. In total, we screened 80 compounds in root exudates for binding to KinD and found that spermine and guanosine could bind to KinD with dissociation constant values of 213 and 51 μΜ, respectively. In addition, calcium l-threonate, N-acetyl-l-aspartic acid, sodium decanoic acid, and parabanic acid could also bind weakly to KinD. The three-dimensional binding models were then constructed to demonstrate the interactions between the root-secreted signals and KinD. It was observed that exogenous spermine reduced the wrinkles of biofilm when kinD was deleted, indicating that KinD might be involved in sensing root-secreted spermine and stabilizing biofilm in response to this negative effector. This study provided a new insight of interaction between a rhizobacterial sensor and root-secreted signals.


Novel selenoorganic compounds as modulators of oxidative stress in blood platelets.
Many selenoorganic compounds play an important role in biochemical processes and act as antioxidants, enzyme inhibitors, or drugs. The effects of five new synthesized selenoorganic compounds (2-(5-chloro-2-pyridyl)-7-azabenzisoselenazol-3(2H)-one; 2-phenyl-7-azabenzisoselenazol-3(2H)-one; 2-(pyridyl)-7-azabenzisoselenazol-3(2H)-one; 7-azabenzisoselenazol-3(2H)-one; bis(2-aminophenyl) diselenide) on oxidative changes in human blood platelets and in plasma were studied in vitro and compared with those of ebselen, a well known antioxidant. Our studies demonstrated that bis(2-aminophenyl) diselenide has distinctly protective effects against oxidative stress in blood platelets and in plasma. It might have greater biological relevance and stronger pharmacological effects than ebselen.


Molecular mechanism of apoptosis: prediction of three-dimensional structure of caspase-6 and its interactions by homology modeling.
Caspases, the intracellular cysteine proteinases, play a central role in the process of programmed cell death. Caspases induce apoptosis through a highly integrated and regulated biological, biochemical, and genetic mechanism. Although proper execution of apoptosis is fundamental for cell growth artificial caspase inhibition can be considered in certain degenerative diseases. This realization has attracted attention towards caspases as likely targets for pharmaceutical intervention. Here we analyze the structure of caspase-6 and also predict the possible glycosylation, phosphorylation, and myristoylation sites as very little is known about the functional role of these post translational modifications in the caspase family. These studies are expected to improve our understanding of associations of caspases with other molecules and the possible role played in apoptosis. The predicted tertiary structure of caspase-6 as well as the enzyme complexed with its inhibitor (tetra-peptide aldehyde Ac-IETD-CHO) shows similar binding feature as seen in other caspases. Cys/His catalytic dyad for caspase-6 and -8 show possible involvement of a third component, i.e., Pro29 and Arg258 in caspase-6 and caspase-8, respectively. Changes in the length and nature of loop between alpha5 and beta9, involved in defining the S4 subsite, result in modification of P4 (Ile) site. These interactions provide detail of inhibitor binding on structural level and also help in designing mutants for structure-function studies of these enzymes.


The clustering of Cardiovascular, Renal, Adipo-Metabolic Eye and Liver disease with type 2 diabetes.
Type 2 diabetes is associated with an increased risk of cardiovascular disease, heart failure, chronic kidney disease, fatty liver disease, eye and foot disease. But equally, these conditions are associated with an increased risk of type 2 diabetes. Rather than being simply considered complications of diabetes, as exists within a 'pure' type 1 diabetes paradigm, both type 2 diabetes and its comorbidities are primarily caused by a failure to efficiently sequester excess energy leading to the accumulation of sick fat (adiposopathy). Type 2 diabetes is a symptom of a chronic disease complex, just as cardiovascular, renal, eye, foot and/or liver disease, are. In addition, each of these conditions feed forward so that dysfunction in one system accelerates dysfunction in another, partly through their shared pathogenesis and partly due dysfunction that follows in their wake. This review will explore the sticky, brittle conglomeration of CArdiac, Renal, Adipo-Metabolic, Eye and Liver disease (hereafter collectively known as CARAMEL disease) that is coincident in most patients with type 2 diabetes and contextualise the recent changes in diabetes guidelines that now specifically focus on identifying and aggressively managing these high-risk individuals with it.


Impervious surface area is a key predictor for urban plant diversity in a city undergone rapid urbanization.
Urban biodiversity has increasingly been recognized by the scientific community and environmental policymakers as a part of conservation efforts worldwide. However, most studies on urban biodiversity focus on cities in developed countries. An information gap exists for urban biodiversity of cities in developing countries. Here we focused on variability in plant diversity, a major component of biodiversity, in a Chinese city that has undergone rapid urbanization in recent time. The influence of urbanization was determined by comparing plant diversity and proportion of exotic/endemic plant species with the intensity of urbanization across the study area. We used percentage of total impervious surface area (PTIA) as an indicator of urbanization intensity, ranging from 5% to 95% across the study area. In the study area, a total of 321 plant species was recorded, totaling 83 trees, 113 shrubs and 125 herbs. Plant diversity, measured by number of plant taxa and other indices, was driven by PTIA; an increase in PTIA reduced plant diversity. In addition, the ratio of exotic to endemic plant species increased as PTIA increased. Among the exotic species, most of the tree and shrub species were purposely introduced. Above 40% PTIA, plant diversity decreased sharply and the proportion of exotic species rose. As a valuable predictor of urban biodiversity, PTIA can thus be used as a key criterion for urban planning to ameliorate urban biodiversity. Further, our findings extend current understanding of urban biodiversity for cities in developing countries.


Percutaneous Tibial Nerve Stimulation Improves Lower Urinary Tract Dysfunction and Infection Rate in a Kidney Transplant Recipient With Augmentation Cystoplasty: A Case Report and Literature Review.
Almost 20% of patients with congenital posterior urethral valves (PUV) reach end-stage kidney disease requiring kidney transplantation (KT). An augmentation cystoplasty (AC) is performed to treat significant lower urinary tract dysfunction (LUTD) which can persist afterwards due to residual valve bladder and lead to recurrent urinary tract infections (UTIs) and a worse graft survival. Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive second-line neuromodulation therapy approved for the treatment of non-neurogenic LUTD performed in the outpatient setting. Herein, we reported the case of significant improvement of bladder voiding pattern and yearly UTI rates through PTNS in a 32-year-old male KT recipient with a history of congenital PUV and AC. The patient was referred to our institution at the beginning of 2019 for urgency, high post-void residual volume (PVR) and recurrent clinically significant UTIs (3 to 4/y). After assessment, the patient attended once-weekly 30-minute sessions of PTNS for 12 consecutive weeks. A significant improvement of urodynamic and infectious outcomes was observed through 3-day bladder diaries, questionnaires, and laboratory exams during the subsequent 3 years of regular follow-up. The present results might be significant for the prevention of antibiotic resistance and for better graft survival in KT recipients. We successfully treated a patient with AC, implying that the technique may be appliable also in this case. Neuromodulation in KT is still an unexplored field of research, we advocate for prospective assessment of the efficacy of PTNS in these patients, as reproducible results might lead to life-changing improvements.


Deep sequencing of hepatitis B surface antigen gene in the preserved umbilical cords in immunoprophylaxis failure against mother-to-child HBV transmission.
Vaccine escape mutants (VEMs) are one of the causes of breakthrough infections in the mother-to-child transmission of hepatitis B virus (HBV). We hypothesized that VEMs existing as minor populations in the maternal blood are associated with breakthrough infections in children. We sought to determine whether VEMs exist as minor populations in the preserved umbilical cords of children with breakthrough infections. Two families (Family 1: three children, Family 2: two children) were enrolled. Despite immunoprophylaxis, a breakthrough infection occurred in two Family 1 children and two Family 2 children. Preserved umbilical cords, serum, and nails were used for the HBV DNA analysis. To detect VEMs, we performed direct and deep sequencing of hepatitis B surface antigen gene. The direct sequencing showed that there were no VEMs in the serum of the children or mother of Family 1 and family 2, but it identified a G145A mutant in the nails of the mother of Family 2. In Family 1, deep sequencing detected a T143S mutant as a minor population (1.7-2.0%) in the umbilical cords and serum of all three children and in the serum of the mother. A T126A mutant was also detected in the umbilical cord (9.2%) and serum (7.0%) of the first-born child of Family 1. In Family 2, the deep sequencing showed no VEMs in the umbilical cords, but it detected D144A (2.5%) and G145A (11.2%) mutants in the serum of the 2nd-born child. VEMs were present as minor populations in the preserved umbilical cords of children with breakthrough infections. The VEMs did not become major populations after the breakthrough infections. The evolution of VEMs from a minor form to a major form might not be a prerequisite for breakthrough infections in mother-to-child transmission.


Expression and purification of recombinant cytoplasmic domain of human erythrocyte band 3 with hexahistidine tag or chitin-binding tag in Escherichia coli.
The cytoplasmic domain of erythrocyte band 3 (cdb3) serves as a center of membrane organization in the erythrocytes by its interaction with multiple proteins including ankyrin, protein 4.1, protein 4.2, hemoglobin, and several glycolytic enzymes. In this paper, human cdb3 was cloned into three different expression vectors controlled by T7 polymerase promoter and induced with isopropyl beta-D-thiogalactopyranoside in Escherichia coli. Two of the fusion proteins containing hexahistidine tag in the N-terminal or C-terminal were purified by immobilized metal affinity column chromatography. The third recombinant cdb3 containing the affinity chitin-binding tag was purified using chitin beads followed by specific self-cleavage, which released cdb3 according to the mechanism of protein splicing. The molecular weights of purified recombinant proteins were verified by mass spectrometry. The pH-dependent properties of the intrinsic tryptophan fluorescence of the three kinds of recombinant cdb3 were compared with that of the cdb3 extracted from the erythrocytes, showing that there were no significant differences between them. Using pull-down assay combined with Western blot analysis, the interaction between recombinant cdb3 and protein 4.2 C3 fragment was verified. These demonstrated that the recombinant proteins were both structurally and functionally active. The typical yields of cdb3 purified with hexahistidine tag in the N-terminal, C-terminal, and cleaved from chitin bead were 10.6, 9.6, and 1.5 mg from 1L culture medium, respectively.


Assessment of Bisphenol A (BPA) neurotoxicity in vitro with mouse embryonic stem cells.
The adverse effects of environmental pollution on our well-being have been intensively studied with many in vitro and in vivo systems. In our group, we focus on stem cell toxicology due to the multitude of embryonic stem cell (ESC) properties which can be exerted in toxicity assays. In fact, ESCs can differentiate in culture to mimic embryonic development in vivo, or specifically to virtually any kind of somatic cells. Here, we used the toxicant Bisphenol A (BPA), a chemical known as a hazard to infants and children, and showed that our stem cell toxicology system was able to efficiently recapitulate most of the toxic effects of BPA previously detected by in vitro system or animal tests. More precisely, we demonstrated that BPA affected the proper specification of germ layers during our in vitro mimicking of the embryonic development, as well as the establishment of neural ectoderm and neural progenitor cells.


Early detection of biliary pancreatitis.
Biochemical tests (serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, gammaglutamyltranspeptidase, bilirubin, and serum amylase) were performed upon admission in 84 patients with suspected (36) or proven (48) acute pancreatitis at the time of the first episode of acute abdominal pain suspected clinically as acute pancreatitis. These parameters all increased significantly more in patients with gallstone pancreatitis. Among them, the SGPT was the most discriminant test between biliary and nonbiliary pancreatitis. The positive predictive value of SGPT was 92%, when the cutoff point was chosen at twice the upper limit of normal. In patients with increased SGPT, a SGOT-SGPT ratio less than 1 is the rule (88%) for those with gallstone pancreatitis. This enzymatic determination allowed us to select more accurately the patients suitable for morphological procedures to confirm the biliary origin of the pancreatitis.


Efficacy of DC-CIK-based immunotherapy combined with chemotherapy in the treatment of intermediate to advanced non-small cell lung cancer.
To evaluate the efficacy of dendritic cell-cytokine-induced killer cell (DC-CIK)-based immunotherapy combined with chemotherapy in the treatment of intermediate to advanced non-small cell lung cancer (NSCLC) and its effect on the levels of serum carbohydrate antigen 199 (CA199), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Sixty patients with intermediate to advanced NSCLC who were treated in the Department of Oncology of Jiangxi Cancer Hospital from January to June 2016 were grouped according to a randomized double-blind method, including the control group (CG, n=30) receiving a routine chemotherapy regimen and the experimental group (EG, n=30) receiving DC-CIK immunotherapy plus a routine chemotherapy regimen. The treatment efficacy, major adverse reactions, immune function, level of cytokines in peripheral blood, serum tumor markers and CA-199, MMP-9, TIMP-1 and vascular endothelial growth factor (VEGF) levels were compared between the two groups. The overall cancer control rate of treatment in the EG (70.00%) was slightly higher than that in the CG (56.67%) (P > 0.05). The peripheral blood CD4+ and natural killer (NK) cell levels in the EG after treatment were higher than those in the CG, while interleukin-4 (IL-4), interferon-γ (IFN-γ), transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), CA199, carbohydrate antigen 125 (CA125), CYFRA211, carcinoembryonic antigen (CEA), MMP-9, TIMP-1, and VEGF levels in the EG were lower than those in the CG (P < 0.05). DC-CIK immunotherapy combined with routine chemotherapy in the treatment of intermediate to advanced NSCLC had significant efficacy in enhancing patients' cellular immune function, reducing the inflammatory response, regulating tumor marker levels, and inhibiting tumor invasion and metastasis, without increasing adverse reactions.


Targeting the ICOS/ICOS-L pathway in a mouse model of established allergic asthma disrupts T follicular helper cell responses and ameliorates disease.
Allergic asthma is characterized by chronic inflammation and remodelling of the airways, associated with dysregulated type 2 immune responses and allergen-specific IgE. T follicular helper cells (TFH ) are crucial in T-dependent B-cell responses and have been implicated in allergic airway disease (AAD). TFH , unlike other CD4+ T cells, are uniquely reliant on continuous ICOS signalling to maintain their phenotype after T-cell priming; therefore, disrupting this signal can impair TFH responses. However, the contribution of TFH to disease during chronic aero-allergen exposure and the therapeutic potential of targeting these cells have not been evaluated. To establish AAD, female BALB/c mice were repeatedly exposed to house dust mite or Alternaria alternata three times a week for up to 5 weeks. To examine the impact of TFH on AAD, mice were allergen exposed for 5 weeks and co-administered anti-ICOS Ligand-targeted antibodies, three times a week for the last 2 weeks. TFH were first observed in the lung-draining lymph nodes and with further exposure were also found locally within the lungs. TFH accumulated with sustained allergen exposure, alongside germinal centre (GC) B cells. Blockade of ICOS signalling after AAD establishment successfully depleted TFH but did not affect the differentiation of other CD4+ T-cell subsets. This reduced GC responses, allergen-specific IgE, inflammation, pulmonary IL-13 and airway hyper-responsiveness. TFH are crucial in the regulation of AAD and the ICOS/ICOS-L pathway could represent a novel therapeutic target in allergic asthma.


Effect of Mass Azithromycin Distributions on Childhood Growth in Niger: A Cluster-Randomized Trial.
Mass azithromycin distributions may decrease childhood mortality, although the causal pathway is unclear. The potential for antibiotics to function as growth promoters may explain some of the mortality benefit. To investigate whether biannual mass azithromycin distributions are associated with increased childhood growth. This cluster-randomized trial was performed from December 2014 until March 2020 among 30 rural communities in Boboye and Loga departments in Niger, Africa, with populations from 200 to 2000 individuals. Communities were randomized in a 1:1 ratio to biannual mass distributions of azithromycin or placebo for children ages 1 to 59 months. Participants, field-workers, and study personnel were masked to treatment allocation. Height and weight changes from baseline to follow-up at 4 years were compared between groups. Data were analyzed from June through November 2021. Participants received azithromycin at 20 mg/kg using height-based approximation or by weight for children unable to stand every 6 months at the participants' households. Placebo contained the vehicle of the azithromycin suspension. Longitudinal anthropometric assessments were performed on a random sample of children before the first treatment and then annually for 5 years. Height and weight were the prespecified primary outcomes. Among 3936 children enrolled from 30 communities, baseline characteristics were similar between 1299 children in the azithromycin group and 2637 children in the placebo group (mean 48.2% [95% CI, 45.5% to 50.8%] girls vs 48.0% [95% CI, 45.7% to 50.3%] girls; mean age, 30.8 months [95% CI, 29.5 to 32.0 months] vs 30.6 months [95% CI, 29.2 to 31.6 months]). Baseline anthropometric assessments were performed among 2230 children, including 985 children in the azithromycin group and 1245 children in the placebo group, of whom follow-up measurements were available for 789 children (80.1%) and 1063 children (85.4%), respectively. At the prespecified 4-year follow-up visit, children in the azithromycin group gained a mean 6.7 cm (95% CI, 6.5 to 6.8 cm) in height and 1.7 kg (95% CI, 1.7 to 1.8 kg) in weight per year and children in the placebo group gained a mean 6.6 cm (95% CI, 6.4 to 6.7 cm) in height and 1.7 kg (95% CI, 1.7 to 1.8 kg) in weight per year. Height at 4 years was not statistically significantly different between groups when adjusted for baseline height (0.08 cm [95% CI, -0.12 to 0.28 cm] greater in the azithromycin group; P = .45), and neither was weight when adjusted for height and baseline weight (0.02 kg [95% CI, -0.10 to 0.06 kg] less in the azithromycin group; P = .64). However, among children in the shortest quartile of baseline height, azithromycin was associated with a 0.4 cm (95% CI, 0.1 to 0.7 cm) increase in height compared with placebo. This study did not find evidence of an association between mass azithromycin distributions and childhood growth, although subgroup analysis suggested some benefit for the shortest children. These findings suggest that the mortality benefit of mass azithromycin distributions is unlikely to be due solely to growth promotion. ClinicalTrials.gov Identifier: NCT02048007.


Integrated Counts of Carbohydrate-Active Protein Domains as Metabolic Readouts to Distinguish Probiotic Biology and Human Fecal Metagenomes.
Bowel microbiota is a "metaorgan" of metabolisms on which quantitative readouts must be performed before interventions can be introduced and evaluated. The study of the effects of probiotic Clostridium butyricum MIYAIRI 588 (CBM588) on intestine transplantees indicated an increased percentage of the "other glycan degradation" pathway in 16S-rRNA-inferred metagenomes. To verify the prediction, a scoring system of carbohydrate metabolisms derived from shotgun metagenomes was developed using hidden Markov models. A significant correlation (R = 0.9, p < 0.015) between both modalities was demonstrated. An independent validation revealed a strong complementarity (R = -0.97, p < 0.002) between the scores and the abundance of "glycogen degradation" in bacteria communities. On applying the system to bacteria genomes, CBM588 had only 1 match and ranked higher than the other 8 bacteria evaluated. The gram-stain properties were significantly correlated to the scores (p < 5 × 10-4). The distributions of the scored protein domains indicated that CBM588 had a considerably higher (p < 10-5) proportion of carbohydrate-binding modules than other bacteria, which suggested the superior ability of CBM588 to access carbohydrates as a metabolic driver to the bowel microbiome. These results demonstrated the use of integrated counts of protein domains as a feasible readout for metabolic potential within bacteria genomes and human metagenomes.


Anterior alveolar dimensions among different classifications of sagittal jaw relationship in Saudi subjects.
Sound orthodontic movement of anterior teeth is delineated by the biological dimensions of the anterior alveolus. To establish and compare the anterior alveolar dimensions among normal and abnormal sagittal maxillomandibular relationships in a Saudi sample. The lateral cephalometric radiographs of 81 Saudi subjects (42 males and 39 females) were used to determine the anteroposterior and vertical dimensions of the anterior alveolus in Class I (N = 30), Class II (N = 24), and Class III (N = 27) cases. The anterior alveolar dimensions were then compared among males and females belonging to the same sagittal classification and between the different sagittal classifications of the same gender. Significant differences (P < 0.05) in the anterior alveolar dimensions between males and females were demonstrated for the same sagittal jaw classification. Also, significant differences (P < 0.05) were detected between the anterior alveolar dimensions among the different sagittal maxillomandibular classifications of the same gender. Both the gender and the sagittal maxillomandibular relationship can affect the anteroposterior and vertical dimensions of the anterior alveolus.


Uveal melanomas near the optic disc or fovea. Visual results after proton beam irradiation.
Proximity to the disc and fovea is a risk factor for visual loss after proton beam irradiation of uveal melanomas. Of 562 eyes treated over a 10-year period with pretreatment visual acuity of 20/200 or better, 363 (64.6%) contained tumors within 2 disc diameters (DD) of the disc or fovea. Rates of visual loss after treatment to worse than 20/200 and causes of visual decline were evaluated using Kaplan-Meier analysis. Cumulative rates of visual loss among subjects with tumors near the disc or fovea were 33 and 47% 1 and 2 years after treatment compared to 17 and 28%, respectively, for subjects with tumors located farther from both structures. The leading cause of visual loss in the first year among eyes with tumors near the disc or fovea was retinal detachment. Controlling for other predictors of visual loss to worse than 20/200, location near the disc or fovea was independently related to visual loss primarily due to retinal detachment, cataract, and radiation retinopathy. Despite the unfavorable location of these tumors, over half of patients with 20/200 or better pretreatment visual acuity had useful vision 2 years after treatment.


Effects of HIS-based intervention on patient education process and patient satisfaction with nurses' education.
This quasi-experimental study (before and after intervention) was designed to determine the impact of hospital information system-based intervention on the patient education process and patient satisfaction in cardiac and cardiac intensive care units. Each nurse was observed at the time of patient education on average on eight shifts (total of 256 shifts), and at last 1350 computerized reports before and after the intervention were analyzed and 150 patient satisfaction with nurses' education questionnaires were completed before and after the intervention. After the intervention, the patient education scores were significantly improved (p < 0.001). In addition, the results of a survey of patients about the level of satisfaction with the quality of patient education showed a significant increase compared to before the intervention (p < 0.001). The ability to easily, completely, and quickly edit and record the provided education, eased the process of patient education and documentation.


Transforming growth factor-beta1 regulates the fate of cultured spinal cord-derived neural progenitor cells.
We have evaluated the physiological roles of transforming growth factor-beta1 (TGF-beta1) on differentiation, migration, proliferation and anti-apoptosis characteristics of cultured spinal cord-derived neural progenitor cells. We have used neural progenitor cells that had been isolated and cultured from mouse spinal cord tissue, and we also assessed the relevant reaction mechanisms using an activin-like kinase (ALK)-specific inhibitory system including an inhibitory RNA, and found that it involved potential signalling molecules such as phosphatidylinositol-3-OH kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK1/2). Transforming growth factor-beta1-mediated cell population growth was activated after treatment and was also effectively blocked by an ALK41517-synthetic inhibitor (4-(5-benzo(1,3) dioxol-5-yl-4-pyridine-2-yl-1H-imidazole-2-yl) benzamide (SB431542) and ALK siRNA, thereby indicating the involvement of SMAD2 in the TGF-beta1-mediated growth and migration of these neural progenitors cells (NPC). In the present study, TGF-beta1 actively induced NPC migration in vitro. Furthermore, TGF-beta1 demonstrated extreme anti-apoptotic behaviour against hydrogen peroxide-mediated apoptotic cell death. At low dosages, TGF-beta1 enhanced (by approximately 76%) cell survival against hydrogen peroxide treatment via inactivation of caspase-3 and -9. TGF-beta1-treated NPCs down-regulated Bax expression and cytochrome c release; in addition, the cells showed up-regulated Bcl-2 and thioredoxin reductase 1. They also had increased p38, Akt and ERK1/2 phosphorylation, showing the involvement of both the PI3K/Akt and MAPK/ERK1/2 pathways in the neuroprotective effects of TGF-beta1. Interestingly, these effects operate on specific subtypes of cells, including neurones, neural progenitor cells and astrocytes in cultured spinal cord tissue-derived cells. Lesion sites of spinal cord-overexpressing TGF-beta1-mediated prevention of cell death, cell growth and migration enhancement activity have been introduced as a possible new basis for therapeutic strategy in treatment of neurodegenerative disorders, including spinal cord injuries.


Sociality is a key driver of foraging ranges in bees.
Bees are important pollinators of wild and agricultural plants1,2,3,4,5 and there is increasing evidence that many bee populations decline due to a combination of habitat loss, climate change, pesticides, and other anthropogenic effects.6,7,8,9,10,11 One trait that shapes both their role in plant reproduction12,13 and their exposure to anthropogenic stressors is the distance at which bees forage. It has been suggested that bee sociality14 and diet15 affect bee foraging ranges, but how these traits and their potential interactions drive foraging ranges remains unclear. We analyzed flight distance data from 90 bee species and developed an agent-based model to test how social, dietary, and environmental factors affect foraging ranges. We confirm that bee sociality is positively associated with foraging range, with average-sized social bees foraging up to 3 times farther from the nest than size-matched solitary bees. A comparative analysis of social bees and computer simulations shows that foraging distances increase with colony size, supporting the hypothesis that greater foraging distances are an emergent property of increasing colony sizes in a food-limited environment. Flower constancy and communication, two traits often found in social bees, synergistically increase foraging distances further in many simulated environments. Diet breadth (oligolectic versus polylectic diet), on the other hand, does not appear to affect foraging ranges in solitary bees. Our findings suggest that multiple traits linked to bee sociality explain why social bees have greater foraging ranges. This has implications for predicting pollination services and for developing effective conservation strategies for bees and isolated plant populations.15,16,17,18,19.


A correlation between selenium and carnitine levels with hypo-osmotic swelling test for sperm membrane in low-grade varicocele patients.
The hypo-osmotic swelling (HOS) test predicts membrane integrity by determining the ability of the sperm membrane to maintain equilibrium between the sperm cell and its environment. The aim of our study was to determine the correlation between selenium and carnitine levels in the seminal fluid with HOS test for sperm membrane in low-grade varicocele patients. Study numbered 64 examinees who suffered from low-grade varicocele and were divided into two groups, according to fertility potential and HOS test outcome. The study also included a control group of 64 healthy subjects, with no varicocele. From the Shapiro-Wilk's test, it is clear that carnitine distribution differs significantly from normal (0.938, p = 0.03). In distribution of selenium, Kolmogorov-Smirnov test clearly shows statistically significant deviation from the normal curve (z = 0.225, p < 0.000), likewise Shapiro-Wilk's statistic (0.787, p < 0.000). According to the results, the second group had significantly higher levels of carnitine and selenium than the first group of examinees (p < 0.05); therefore, when we compared epididymal markers with HOS tests outcomes, we found significant differences between the two groups. There were no significant differences between second group and healthy subjects (p > 0.05). HOS test outcome in varicocele patients is directly proportional to the carnitine and selenium levels, which could play a major role in both determining fertility parameters and in the treatment of its impairment. This result is important for sub-clinical varicocele in infertile patients with normal semen analysis, since there is no evidence of benefit from any treatment so far.


Vulnerability assessment of urban agglomerations to the risk of heat waves in China since the 21st century.
In the context of global warming, frequent heat wave disasters have seriously threatened the safety of human life and property. The urban agglomeration, as the main region with a high concentration of population and economy, is susceptible to heat weaves due to the existing urban heat island effect. In this study, we investigated the temporal and spatial characteristics of heat waves (heat index, HI) in China from 2000 to 2020 and assess the vulnerability of 19 urban agglomerations to heat waves from the perspective of exposure, sensitivity and adaptability. The results show that: (1) In the past 20 years, the frequency and intensity of HI (greater than 26.67 °C) both showed an upward trend. (2) Shandong Peninsula, Central Henan, Yangtze River Delta, Middle Reaches of Yangtze River, and Mid-southern Liaoning urban agglomerations always maintain a high vulnerability. (3) From 2000 to 2020, the vulnerability of Beijing-Tianjin-Hebei, Yangtze River Delta, Chengdu-Chongqing, Middle reaches of Yangtze River, Guangdong-Fujian-Zhejiang, Harbin-Changchun and Mid-southern Liaoning urban agglomerations were always dominated by exposure. The vulnerability of Shandong Peninsula, Beibu Gulf and Central Henan urban agglomeration has always been dominated by sensitivity. The vulnerability of North Tianshan Mountain, Lanzhou-Xining, Guanzhong and Hu-Bao-E-Yu urban agglomeration has always been dominated by inadequate adaptability. (4) Recently, the factors that contributed most to exposure, sensitivity and adaptability were population density, the proportion of outdoor workers and water supply, with contribution rates of 38%, 55% and 26%, respectively. This study can provide a scientific basis for the rational allocation of resources among urban agglomerations, effectively formulating policies and guiding population migration from high temperature disasters.


Circulatory adaptive reactions under hypergravity in normal and cold environments.
Rats subjected to various levels of +Gz acceleration exhibited an increased blood concentration of noradrenalin and adrenalin, indicative of a sympatho-adrenergic reaction. Under the same conditions, from plasma determinations, and by histochemical examination of the supra-optic nucleus, an increased antidiuretic response was noted. This response was reduced in cold environment.


Ratcheting behavior of articular cartilage under cyclic unconfined compression.
The ratcheting deformation of articular cartilage can produce due to the repeated accumulations of compressive strain in cartilage. The aim of this study was to investigate the ratcheting behavior of articular cartilage under cyclic compression. A series of uniaxial cyclic compression tests were conducted for online soaked and unsoaked cartilage samples and the effects of stress variation and stress rate on ratcheting behavior of cartilage were investigated. It is found that the ratcheting strains of online soaked and unsoaked cartilage samples increase rapidly at initial stage and then show the slower increase with cyclic compression going on. On the contrary, the ratcheting strain rate decreases quickly at first and then exhibits a relatively stable and small value. Both the ratcheting strain and ratcheting strain rate increase with stress variation increasing or with stress rate decreasing. Simultaneously, the optimized digital image correlation (DIC) technique was applied to study the ratcheting behavior and Young's modulus of different layers for cartilage under cyclic compression. It is found that the ratcheting behavior of cartilage is dependent on its depth. The ratcheting strain and its rate decrease through the depth of cartilage from surface to deep, whereas the Young's modulus increases.


Aphallia associated with urethro-rectal fistula and stones in the bladder and urethra.
Aphallia is a rare urogenital anomaly. It usually coexists with other serious anomalies, which are incompatible with normal life. We present herewith a 18-month-old child who presented with aphallia and urethro-scrotal fistula along with stones in the bladder and urethra. The stones were removed and the fistula was surgically corrected.


Apolipoprotein E genotype and physical function among older people with mild cognitive impairment.
Mild cognitive impairment (MCI) is conceptualized as prodromal of Alzheimer's disease (AD). Declined physical function is one of the risk factors for progression to AD, whereas genetic factors, especially the apolipoprotein E ε4 allele (APOE4), also contribute to the risk of AD and affect the risk factors. However, the association between APOE4 and physical function in MCI is still unclear. To elucidate the association, we carried out the present study to compare physical function between APOE4 carriers and non-carriers in MCI. The study included 386 MCI patients (mean age 71.6 years) who were classified into APOE4 carrier and non-carrier groups. The participants' characteristics were assessed by face-to-face interviews. Grip strength, five chair stand test, walking speed and 6-min walking test were measured as physical functions. In univariate analysis, the APOE4 carrier group had decreased walking speed compared with the non-carrier group (P < 0.05), but other measures of physical function were not significantly different between the groups. The linear regression model showed a significant association between walking speed and APOE4 after adjusting for covariates (P < 0.05). The present study showed that APOE4 carrier participants with MCI had decreased walking speed compared with non-carrier participants. Thus, APOE4 genotypes should be considered as a potential mediator when the measure of walking speed is used as a risk factor of dementia in older adults with MCI. Further studies using prospective data are required to clarify the relationship between physical function and genetic factors in MCI.


Prolonged oxygen uptake kinetics during low-intensity exercise are related to poor prognosis in patients with mild-to-moderate congestive heart failure.
To investigate the prognostic value of oxygen uptake (O(2)) kinetics during low-intensity exercise in patients with congestive heart failure. Prospective cohort study. Tertiary care center. One hundred forty-six consecutive patients (128 men) with chronic heart failure, followed up for a mean (+/- SD) duration of 25 +/- 15 months. A treadmill exercise test was performed with "breath by breath" gas-exchange monitoring. VO(2) kinetics were defined as the VO(2) deficit (ie, Delta VO(2) x time[rest to steady state] - Sigma VO(2)[rest to steady state]) and mean response time (MRT) [ie, VO(2) deficit/Delta VO(2)]. Cardiac death, urgent cardiac transplantation, and hospitalization due to worsening heart failure were considered as the end points. Thirty patients (21%) died, 11 patients (8%) underwent urgent transplantation, and 32 patients (22%) were hospitalized. In univariate analysis, MRT was the most powerful predictor of survival, survival free of urgent transplantation, and survival free of hospitalization (hazard ratios [HRs] per 10 s, 1.65, 1.72, and 1.61, respectively; all p < 0.0001). The predictive value of MRT exceeded that of peak VO(2) (HR per mL/kg/min, 0.90; p = 0.02, 0.91; p = 0.007, and 0.95; p = 0.08, respectively). In multivariate analysis, MRT (HR per 10 s, 1.73; p = 0.0002), resting systolic BP (HR per 10 mm Hg, 0.65; p = 0.003), and the slope of the ventilatory response to exercise (HR per 10 U, 1.68; p = 0.02) were independent predictors of survival. Our results suggest that VO(2) kinetics are strongly related to outcome in heart failure patients. Since it has several additional advantages over peak exercise testing (eg, less time-consuming, less demanding for the patients, less dependent on motivation, and applicable in patients with limitations other than cardiopulmonary disease), it has the potential to become a prognostic test for the assessment of heart failure patients.


Action-based distractor effects on the manual response times of chimpanzees during discrimination tasks.
Two chimpanzees performed visual search and simple discrimination tasks in which manual pointing to the target stimulus was required. To clarify the action-based interference effects of the distractors, response time data were analyzed on the basis of the relationship among the positions of the target, distractors, and hand. In both tasks, clear action-based interference effects were observed. Firstly, distractors along the path of the manual response to the target caused greater interference (the response-path effect). Secondly, when distractors were located ipsilateral to the responding hand, response times were longer (the ipsilateral effect). These results are consistent with previous studies on selective reaching in humans, and they suggest that manual responses in chimpanzees are controlled by action-centered attention as is the case for humans.