Lateralization in male rats and dopaminergic system: evidence of right-side population bias.
Recent studies have reported population right-biased lateralization in rats, although with low percentages (between 54-59%). The present study investigated the spatial preference of rats in an electrified T-maze during successive days and the influence of ascending dopaminergic systems using apomorphine, a dopamine agonist, as well as ipsilateral and contralateral lesions on the side preference. Results showed a marked right-biased lateralization at both individual and population levels (85.71% of the rats presented a behavioral asymmetry, being 80% right-biased and 20% left-biased within the lateralized group). Also, the results suggest that there is a presynaptic dominance in the contralateral dopaminergic system to the spatial preference in the T-maze and postsynaptic dominance in the ipsilateral side.


NADPH oxidases regulate endothelial inflammatory injury induced by PM2.5 via AKT/eNOS/NO axis.
Fine particulate matter (PM2.5 )-induced detrimental cardiovascular effects have been widely concerned, especially for endothelial cells, which is the first barrier of the cardiovascular system. Among potential mechanisms involved, reactive oxidative species take up a crucial part. However, source of oxidative stress and its relationship with inflammatory response have been rarely studied in PM2.5 -induced endothelial injury. Here, as a key oxidase that catalyzes redox reactions, NADPH oxidase (NOX) was investigated. Human umbilical vein endothelial cells (EA.hy926) were exposed to Standard Reference Material 1648a of urban PM2.5 for 24 h, which resulted in NOX-sourced oxidative stress, endothelial dysfunction, and inflammation induction. These are manifested by the up-regulation of NOX, increase of superoxide anion and hydrogen peroxide, elevated endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA) level, reduced nitric oxide (NO) production, and down-regulation of phosphorylation of endothelial NO synthase (eNOS) with increased levels of inducible NO synthase, as well as the imbalance between tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1), and changes in the levels of pro-inflammatory and anti-inflammatory factors. However, administration of NOX1/4 inhibitor GKT137831 alleviated PM2.5 -induced elevated endothelial dysfunction biomarkers (NO, ET-1, ADMA, iNOS, and tPA/PAI-1), inflammatory factors (IL-1β, IL-10, and IL-18), and adhesion molecules (ICAM-1, VCAM-1, and P-selectin) and also passivated NOX-dependent AKT and eNOS phosphorylation that involved in endothelial activation. In summary, PM2.5 -induced NOX up-regulation is the source of ROS in EA.hy926, which activated AKT/eNOS/NO signal response leading to endothelial dysfunction and inflammatory damage in EA.hy926 cells.


Biosynthetic approach for functional protein microarrays.
Protein microarrays have emerged as an indispensable research tool for providing information about protein functions and interactions through high-throughput screening. Traditional methods for immobilizing biomolecules onto solid surfaces have been based on covalent and noncovalent binding, entrapment in semipermeable membranes, microencapsulation, sol gel, and hydrogel methods. Each of these techniques has its own strengths but fails to combine the most important tenets of a functional protein microarray such as covalent attachment, native protein conformation, homogeneity of the protein monolayer, control over active site orientation, and retention of protein activity. Here we present a selective and site-directed covalent immobilization technique for proteins via a benzoxazine ring formation through a Diels-Alder reaction in water and a genetically encoded 3-amino-L-tyrosine (3-NH(2)Tyr) amino acid. Fully functional protein microarrays, with monolayer arrangements and complete control over their orientations, were generated using this strategy.


Disinfection technology and strategies for COVID-19 hospital and bio-medical waste management.
The isolation wards, institutional quarantine centers, and home quarantine are generating a huge amount of bio-medical waste (BMW) worldwide since the outbreak of novel coronavirus disease-2019 (COVID-19). The personal protective equipment, testing kits, surgical facemasks, and nitrile gloves are the major contributors to waste volume. Discharge of a new category of BMW (COVID-waste) is of great global concern to public health and environmental sustainability if handled inappropriately. It may cause exponential spreading of this fatal disease as waste acts as a vector for SARS-CoV-2, which survives up to 7 days on COVID-waste (like facemasks). Proper disposal of COVID-waste is therefore immediately requires to lower the threat of pandemic spread and for sustainable management of the environmental hazards. Henceforth, in the present article, disinfection technologies for handling COVID-waste from its separate collection to various physical and chemical treatment steps have been reviewed. Furthermore, policy briefs on the global initiatives for COVID-waste management including the applications of different disinfection techniques have also been discussed with some potential examples effectively applied to reduce both health and environmental risks. This article can be of great significance to the strategy development for preventing/controlling the pandemic of similar episodes in the future.


Effect of high-intensity sound on cochlear microphonics and activity of inferior colliculus neurons in the guinea pig.
The input-output functions of cochlear microphonics (recorded from the round window) in guinea pigs exposed briefly to high-intensity sound (2 kHz, 130 dB, 30 min) were shifted toward higher intensities by about 15 dB in comparison with normal animals. 2-4 h after the exposure this shift decreases to 10 dB. The response characteristics of the inferior colliculus neurons were compared under similar conditions. Thresholds at the characteristc frequencies (CF) measured 2-4 h after exposure, were raised by 30-50 dB, a higher threshold increase was observed at frequencies from 5-7 kHz. 48 h after exposure the thresholds approached those obtained in normal animals. There was no pronounced hair cell loss after exposure. It is assumed that in addition to the impairment of sound transduction in hair cells there may be a specific effect of high-intensity sound exposure on neuronal transmission in the auditory pathway.


[Isolation and properties of the initiation of DNA replication in the sea urchin embryo].
Using the instability of replication loops as a method for the isolation of double-stranded nascent DNA from embryos of the sea urchin Strongylocentrotus intermedius, extruded DNA enriched for replication origins was obtained. The average length of the fragments of the DNA of this fraction was estimated to be about 800 base pairs. The origin-enriched nascent DNA strands were assayed for the presence of inverted repeats. The results show that the origin-enriched DNA is also enriched in inverted repeats. The bulk of palindromes in the total nuclear DNA was estimated to be 200 base pairs in length and from the origin-enriched DNA-150 base pairs.


Structural basis of HIV-1 resistance to AZT by excision.
Human immunodeficiency virus (HIV-1) develops resistance to 3'-azido-2',3'-deoxythymidine (AZT, zidovudine) by acquiring mutations in reverse transcriptase that enhance the ATP-mediated excision of AZT monophosphate from the 3' end of the primer. The excision reaction occurs at the dNTP-binding site, uses ATP as a pyrophosphate donor, unblocks the primer terminus and allows reverse transcriptase to continue viral DNA synthesis. The excision product is AZT adenosine dinucleoside tetraphosphate (AZTppppA). We determined five crystal structures: wild-type reverse transcriptase-double-stranded DNA (RT-dsDNA)-AZTppppA; AZT-resistant (AZTr; M41L D67N K70R T215Y K219Q) RT-dsDNA-AZTppppA; AZTr RT-dsDNA terminated with AZT at dNTP- and primer-binding sites; and AZTr apo reverse transcriptase. The AMP part of AZTppppA bound differently to wild-type and AZTr reverse transcriptases, whereas the AZT triphosphate part bound the two enzymes similarly. Thus, the resistance mutations create a high-affinity ATP-binding site. The structure of the site provides an opportunity to design inhibitors of AZT-monophosphate excision.


Retroelements in human disease.
Retroelements are an abundant class of noncoding DNAs present in about half of the human genome. Among them, L1, Alu and SVA are currently active. They "jump" by retrotransposition, shuffle genomic regions by 5' and 3' transduction, and promote or inhibit gene transcription by providing alternative promoters or generating antisense and/or regulatory noncoding RNAs. Recent data also suggest that retroelement insertions into exons and introns of genes induce different types of genetic disease, including cancer. Retroelements interfere with the expression of genes by inducing alternative splicing via exon skipping and exonization using cryptic splice sites, and by providing polyadenylation signals. Here we summarize our current understanding of the molecular mechanisms of retroelement-induced mutagenesis which causes fifty different types of human disease. We categorize these mutagenic effects according to eleven different mechanisms and show that most of them may be explained either by traditional exon definition or transcriptional interference, a previously unrecognized molecular mechanism. In summary, this review gives an overview of retroelement insertions in genes that cause significant changes in their transcription and cotranscriptional splicing and show a remarkable level of complexity.


Biological Subtype Predicts Risk of Locoregional Recurrence After Mastectomy and Impact of Postmastectomy Radiation in a Large National Database.
To evaluate locoregional recurrence (LRR) after mastectomy and impact of postmastectomy radiation (PMRT) by breast cancer subtype. Between 2000 and 2009, 5673 patients with stage I to III breast carcinoma underwent mastectomy and nodal evaluation; 30% received PMRT. Isolated LRR (iLRR) and LRR were compared across groups defined by biological subtype and receipt of trastuzumab: luminal A (estrogen [ER]/progesterone [PR]+, HER2-, low/intermediate grade), luminal B (ER/PR+, HER2-, high grade), HER2 with trastuzumab, HER2 without trastuzumab, and triple negative (TN; ER-, PR-, HER2-). LRR hazard ratios (HR) were estimated with multivariable Fine and Gray models. The effect of PMRT on LRR was evaluated with Fine and Gray models stratified by propensity for PMRT. With a median follow-up time of 50.1 months, there were 19 iLRR and 109 LRR events. HER2 patients with trastuzumab had no iLRR and only a single LRR. Compared with luminal A patients, TN patients had significantly greater adjusted risk of iLRR (HR 14.10; 95% CI 2.97%-66.90%), with a similar trend among luminal B (HR 4.94; 95% CI 0.94%-25.82%) and HER2 patients without trastuzumab (HR 4.41; 95% CI 0.61%-32.11%). Although PMRT reduced LRR, the effect of PMRT varied by subgroup, with the greatest and smallest effects seen among luminal A (HR 0.17; 95% CI 0.05%-0.62%) and TN patients (HR 0.59; 95% CI 0.25%-1.35%), respectively. TN patients had the highest risk of LRR and the least benefit from PMRT; these patients may benefit from alternative treatment strategies. In contrast, in the era of HER2-directed therapy, the role of local therapy may need to be reassessed among HER2 patients.


Deficits in LTP and recognition memory in the genetically hypertensive rat are associated with decreased expression of neurotrophic factors and their receptors in the dentate gyrus.
We have previously reported that a genetically hypertensive strain of Wistar rat (GH), is deficient in nerve growth factor (NGF) and Trk receptors in dentate gyrus and that these deficits are accompanied by impaired expression of long-term potentiation (LTP) in perforant path-granule cell synapses. Here we confirm this deficit in LTP and report that this strain of rat also displays impairments in long-term recognition memory when compared with normotensive controls. Further analysis of neurotrophin expression in dentate gyrus confirmed the previously-reported deficit in NGF and revealed a decrease in expression of brain-derived neurotrophic factor (BDNF), but not neurotrophin 3 (NT3) or neurotrophin 4 (NT4), in GH rats. These alterations in ligand expression were accompanied by changes in Trk receptor expression; specifically, a decrease in expression of TrkA and TrkB, but not TrkC, in the dentate gyrus of GH, compared with normotensive, rats. We conclude that the impairments in LTP and learning and memory observed in the GH strain are associated with aberrant expression of specific neurotrophic factors and their receptors in the dentate gyrus, adding weight to the evidence indicating a role for these proteins in several forms of synaptic plasticity.


Whole-Genome Sequence of Streptococcus pyogenes Strain 591, Belonging to the Genotype emm49.
Streptococcus pyogenes strain 591 is a clinical isolate belonging to the genotype emm49. It has been intensively studied for its pathogenicity traits. In this study, the complete genome of strain 591 was sequenced. It consists of a chromosome of 1,762,765 bp with a G+C content of 38.5%.


TATA box binding protein and ribosomal protein 4 are suitable reference genes for normalization during quantitative polymerase chain reaction study in bovine mesenchymal stem cells.
Quantitative polymerase chain reaction (qPCR) has been extensively used in the field of mesenchymal stem cell (MSC) research to elucidate their characteristics and clinical potential by normalization of target genes against reference genes (RGs), which are believed to be stably expressed irrespective of various experimental conditions. However, the expression of RGs is also variable depending on the experimental conditions, which may lead to false or contradictory conclusions upon normalization. Due to the current lack of information for a clear list of stable RGs in bovine MSCs, we conducted this study to identify suitable RGs in bovine MSCs. The cycle threshold values of ten traditionally used RGs (18S ribosomal RNA [18S], beta-2-microglobulin [B2M], H2A histone family, member Z [H2A], peptidylprolyl isomerase A [PPIA], ribosomal protein 4 [RPL4], succinate dehydrogenase complex, subunit A [SDHA], beta actin [ACTB], glyceraldehyde-3-phosphate dehydrogenase [GAPDH], TATA box binding protein [TBP], and hypoxanthine phosphoribosyltrasnfrase1 [HPRT1]) in bovine bone marrow-derived MSCs (bBMMSCs) were validated for their stabilities using three types of RG evaluation algorithms (geNorm, Normfinder, and Bestkeeper). The effect of validated RGs was then verified by normalization of lineage-specific genes (fatty acid binding protein 4 [FABP4] and osteonectin [ON]) expressions during differentiations of bBMMSCs or POU class 5 homeobox 1 (OCT4) expression between bBMMSCs and dermal skins. Based on the results obtained for the three most stable RGs from geNorm (TBP, RPL4, and H2A), Normfinder (TBP, RPL4, and SDHA), and Bestkeeper (TBP, RPL4, and SDHA), it was comprehensively determined that TBP and RPL4 were the most stable RGs in bBMMSCs. However, traditional RGs were suggested to be the least stable (18S) or moderately stable (GAPDH and ACTB) in bBMMSCs. Normalization of FABP4 or ON against TBP, RPL4, and 18S presented significant differences during differentiation of bBMMSCs. However, although significantly low expression of OCT4 was detected in dermal skins compared to that in bBMMSCs when TBP and RPL4 were used in normalization, normalization against 18S exhibited no significance. This study proposes that TBP and RPL4 were suitable as stable RGs for qPCR study in bovine MSCs.


Single gold nanoclusters: Formation and sensing application for isonicotinic acid hydrazide detection.
Nano-sized electrodes have their special advantages for sensing applications, such as small overall dimension, fast response and low background current. In this work, single gold nanoclusters (AuNCs) were controllably prepared on single Pt nanoelectrode surface by electrodeposition method. The AuNCs covered Pt nanoelectrode (AuNCs/PtNE) had steady-state voltammetric response in redox species solution, which was similar to micro-/nano-sized electrodes. It was interesting to find isonicotinic acid hydrazide (INH, also known as isoniazid) showed good electrochemical response on AuNCs/PtNE surface, which had investigated carefully by square wave voltammetry (SWV) and chronoamperometry. Moreover, the prepared single AuNCs/PtNEs showed the capability for INH sensing with good sensitivity, reproducibility and selectivity, which was demonstrated for INH detection in human urine samples.


Association of the matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of coronavirus disease 2019 (COVID-19); implications of contribution for development of neurological symptoms in the COVID-19 patients.
Seemingly, the Matrix metalloproteinases (MMPs) play a role in the etiopathogenesis of coronavirus disease 2019 (COVID-19). Here in this study, we determined the association of MMP9 rs3918242, MMP3 rs3025058, and MMP2 rs243865 polymorphisms with the risk of COVID-19, especially in those with neurological syndrome (NS). We enrolled 500 patients with COVID-19 and 500 healthy individuals. To genotype the target SNPs, the Real-time allelic discrimination technique was used. To determine serum levels of MMPs, Enzyme-linked immunosorbent assay (ELISA) was exerted. The MMP9 gene rs3918242 and MMP3 gene rs3025058 SNP were significantly associated with increased COVID-19 risk and susceptibility to COVID-19 with NS. The serum level of MMP-9 and MMP-3 was significantly higher in COVID-19 cases compared with the healthy controls. Serum MMP-9 and MMP-3 levels were also higher in COVID-19 subjects with NS in comparison to the healthy controls. The polymorphisms in MMP genes were not associated with serum level of MMPs. MMP9 and MMP3 gene polymorphisms increases the susceptibility to COVID-19 as well as COVID-19 with neurologic syndrome, but they probably have no role in the regulation of serum MMP-9 and MMP-3 levels.


Insulin therapy for reducing cardiovascular risk in patients with type 2 diabetes.
Twenty-four percent of the adult American population have the metabolic syndrome. Although somewhat counterintuitive, carefully regulated treatment with insulin has been shown to reduce insulin resistance and may also retard the development of cardiovascular disease by preventing chronic hyperglycemia, a condition that synergistically contributes to many proatherogenic pathways, including glycoxidation, the polyol pathway, advanced glycation end products, interference with normal metabolic pathways, and stimulation of protein kinase C-beta and proinflammatory pathways. This article describes some of the physiologic changes that occur when hyperglycemia and insulin resistance develop in patients with type 2 diabetes and discusses therapies, including insulin, that normalize glucose and reduce insulin resistance, thereby potentially reducing cardiovascular risk.


Genotyping three SNPs affecting warfarin drug response by isothermal real-time HDA assays.
The response to the anticoagulant drug warfarin is greatly affected by genetic polymorphisms in the VKORC1 and CYP2C9 genes. Genotyping these polymorphisms has been shown to be important in reducing the time of the trial and error process for finding the maintenance dose of warfarin thus reducing the risk of adverse effects of the drug. We developed a real-time isothermal DNA amplification system for genotyping three single nucleotide polymorphisms (SNPs) that influence warfarin response. For each SNP, real-time isothermal Helicase Dependent Amplification (HDA) reactions were performed to amplify a DNA fragment containing the SNP. Amplicons were detected by fluorescently labeled allele specific probes during real-time HDA amplification. Fifty clinical samples were analyzed by the HDA-based method, generating a total of 150 results. Of these, 148 were consistent between the HDA-based assays and a reference method. The two samples with unresolved HDA-based test results were repeated and found to be consistent with the reference method. The HDA-based assays demonstrated a clinically acceptable performance for genotyping the VKORC1 -1639G>A SNP and two SNPs (430C>T and 1075A>C) for the CYP2C9 enzyme (CYP2C9*2 and CYP2C9*3), all of which are relevant in warfarin pharmacogenentics.


The use of strain energy as a convergence criterion in the finite element modelling of bone and the effect of model geometry on stress convergence.
Keyak and Skinner state that the adequacy of a finite element mesh may be verified by confirming that convergence of strain energy has been achieved. The paper concludes by stating that convergence of strain energy does not ensure that a particular mesh is adequate for producing accurate stress/strain results, and that only qualitative results can be achieved from 3D models of bone. This conclusion is challenged and the effect of element size on stress convergence is clarified. The influence of element size on stress convergence in regions of surface irregularity is studied and current methods are discussed that facilitate convergence.


Renal-retinal syndromes: association of retinal anomalies and recessive nephronophthisis in patients with homozygous deletion of the NPH1 locus.
Tapeto-retinal degeneration is frequent in patients with nephronophthisis. Association of the most severe forms of tapeto-retinal dystrophy with NPH identifies a syndrome described first by Senior et al and Loken et al. This syndrome is distinct on molecular grounds from pure renal nephronophthisis (NPH1), which has its gene locus mapped on chromosome 2q13. We describe three families with large homozygous deletion of the NPH1 locus in which mild to moderate ocular lesions due to tapeto-retinal degeneration coexisted and were correlated to renal defects. This new association of NPH1 with retinal dystrophy is characterized by focal lesions of retina and is pauci-symptomatic in clinical presentation. For this reason it may remain unrecognized in most NPH1 patients.


Measurement of intraoperative parathyroid hormone predicts long-term operative success.
A decrease in the intraoperative parathyroid hormone (PTH) level predicts long-term operative success. A case series of consecutive patients undergoing parathyroidectomy with intraoperative PTH measurement. A university hospital. One hundred two patients with sporadic primary hyperparathyroidism underwent parathyroidectomy according to the principles of unilateral exploration with intraoperative PTH measurement. Longitudinal effects on levels of serum calcium and PTH. In 94 of 98 patients who underwent primary exploration because of a solitary adenoma, intraoperative PTH decreased at least 60% 15 minutes after gland excision. The 4 cases in which PTH fell to less than 60% were classified as false negatives. Patients examined for multiglandular disease (n = 4) were correctly predicted not to have an adenoma. Twenty-two patients (22%) were unavailable for 5-year follow-up. These patients were followed up for 2 months to 48 months (median, 24 months), and none developed recurrent primary hyperparathyroidism. Of the remaining 80 patients (78%), all but 1 patient had normal or slightly decreased serum calcium levels (mean +/- SD, 9.24 +/- 0.4 mg/dL [2.31 +/- 0.10 mmol/L]) at 5-year follow-up. One patient with hypercalcemia (10.6 mg/dL [2.65 mmol/L]) was interpreted to have developed renal failure with secondary hyperparathyroidism. Thirty-four patients had elevated serum PTH levels at least once during the postoperative study period, with normal or slightly decreased calcium concentrations. The prediction of late postoperative normocalcemia by means of intraoperative PTH measurement had an overall accuracy of 95%. The measurement of intraoperative PTH during surgery for primary hyperparathyroidism accurately differentiates between single- and multiple-gland disease and ensures good long-term results.


Quercetin 7-rhamnoside reduces porcine epidemic diarrhea virus replication via independent pathway of viral induced reactive oxygen species.
On the base of our previous study we were observed relevant studies on the hypothesis that the antiviral activity of quercetin 7-rhamnoside (Q7R), a flavonoid, won't relate ability of its antioxidant. We were investigated the effects of Q7R on the cytopathic effects (CPE) by CPE reduction assay. Production of DNA fragment and reactive oxygen species (ROS) induced by PEDV infection were studied using DNA fragmentation assay and flow cytometry. In the course of this study it was discovered that Q7R is an extremely potent compound against PEDV. The addition of Q7R to PEDV-infected Vero cells directly reduced the formation of a visible cytopathic effect (CPE). Also, Q7R did not induce DNA fragmentation. Furthermore, ROS increased the infection of PEDV, which was strongly decreased by N-acetyl-L-cysteins (NAC). However, the increased ROS was not decreased by Q7R. Antiviral activity of antioxidants such as NAC, pyrrolidine dithiocarbamate (PDTC), and the vitamin E derivative, trolox, were hardly noticed. We concluded that the inhibition of PEDV production by Q7R is not simply due to a general action as an antioxidants and is highly specific, as several other antioxidants (NAC, PDTC, trolox) are inactive against PEDV infection.


Efficacy of bariatric surgery in improving metabolic outcomes in patients with diabetes. A 24-month follow-up study from a single center in the UAE.
Owing to its impact on weight loss, remission of diabetes mellitus and metabolic syndrome, bariatric surgery has offered hope for grossly obese individuals. In recent years, obesity has increased in the UAE and the use of bariatric surgery has increased in-line with this trend. However, data regarding bariatric surgery outcomes in diabetic Emirati people is scarce. To evaluate the effect of bariatric surgery in patients with diabetes mellitus. This is a retrospective analysis of diabetic patients treated with bariatric surgery with a minimal follow-up of 1 year and extended for some patients (21) to 2 years follow up. A total of 80 patients underwent bariatric surgery. Two surgical procedures were used; laparoscopic sleeve gastrectomy (n=53) or mini-gastric bypass between January 1, 2015, and July 20, 2017. Mean baseline weight was 119.2±31.2 kg, this has significantly dropped to 100.1±23.1, 91.2±22.3, 82.3±17.5, and 81.3±15.3 kg at 3, 6, 12, and 24 months respectively, and this change was statistically significant P<0.001 at each time point. Mean baseline HbA1c was 8.6% ± 2.3% and this dropped significantly to 6.5±1.7, 5.9±1.2, 5.6±0.8, and 5.4±0.7 at 3, 6, 12, and 24 months respectively (P<0.000). In 49 (61.3%) we considered fatty liver based on ultrasound features either with or without elevation in alanine aminotransferase (ALT). We noticed a significant decrease in ALT at 3, 6, and 12 months after surgery. Furthermore, 11 patients (22.4%) showed sonographic features of improvement in fatty liver in addition to normalization of ALT. Bariatric surgery was effective over a follow-up period of 2 years in achieving significant weight loss as well as resulting in improvements in glycemic control, blood pressure, and fatty liver.


Improved diagnostic sensitivity for tuberculous meningitis with Xpert(®) MTB/RIF of centrifuged CSF.
TB meningitis (TBM) diagnosis is difficult and novel diagnostic methods are needed. The World Health Organization recommends Xpert(®) MTB/RIF as the initial TBM diagnostic test based on two studies reporting suboptimal sensitivity (~50-60%). To study the effect of cerebrospinal fluid (CSF) centrifugation on Xpert performance for TBM detection. A total of 107 predominantly human immunodeficiency virus (HIV) infected adults with presumed meningitis were screened prospectively in Kampala, Uganda. CSF was tested using 1) microscopy for acid-fast bacilli; 2) MGIT™ culture; 3) Xpert of 2 ml of unprocessed CSF; and 4) Xpert of centrifuged CSF. Diagnostic performance was measured against an a priori composite reference standard of any positive CSF tuberculosis test. Of 107 participants, 18 (17%) had definite TBM. When CSF was centrifuged, Xpert had better sensitivity (13/18, 72%) than when using 2 ml of unprocessed CSF (5/18, 28%; P = 0.008). The median centrifuged CSF volume was 6 ml (IQR 4-10). Mycobacterial culture yielded 71% (12/17) sensitivity at a median delay of 27 days. Only 39% were positive by both culture and centrifuged Xpert, with additional cases detected by Xpert and culture. CSF centrifugation optimizes the diagnostic performance of Xpert in the detection of TBM. A combination of culture and Xpert detected the largest number of cases.


Transfer of marine mercury to mountain lakes.
Stocking is a worldwide activity on geographical and historical scales. The rate of non-native fish introductions have more than doubled over the last decades yet the effect on natural ecosystems, in the scope of biologically mediated transport and biomagnification of Hg and Hg-isotopes, is unknown. Using geochemistry (THg) and stable isotopes (N, Sr and Hg), we evaluate natal origin and trophic position of brown trout (Salmo trutta fario), as well as mercury biomagnification trends and potential pollution sources to three high-altitude lakes. Farmed trout show Hg-isotope signatures similar to marine biota whereas wild trout shows Hg-isotope signatures typical of fresh water lakes. Stocked trout initially show Hg-isotope signatures similar to marine biota. As the stocked trout age and shifts diet to a higher trophic level, THg concentrations increase and the marine Hg isotope signatures, induced via farm fish feed, shift to locally produced MeHg with lower δ202Hg and higher Δ199Hg. We conclude that stocking acts a humanly induced biovector that transfers marine Hg to freshwater ecosystems, which is seen in the Hg-isotopic signature up to five years after stocking events occurred. This points to the need of further investigations of the role of stocking in MeHg exposure to freshwater ecosystems.


Treatment of perifolliculitis capitis abscedens et suffodiens with the carbon dioxide laser.
We describe the successful use of the carbon dioxide (CO2) laser for localized surgical therapy in a patient with perifolliculitis capitis abscedens et suffodiens that was refractory to conservative treatment.


Author Correction: The future of extreme climate in Iran.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Stability of monoamine metabolites in human cerebrospinal fluid.
Concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in human lumbar cerebrospinal fluid following storage at room temperature and 4 degrees C for intervals up to 72 hours. These monoamine metabolites were quantitated using a high-performance liquid chromatographic-electrochemical detector technique. No significant difference could be detected in any of the three metabolites stored at room temperature for up to 48 hours. Addition of ascorbic acid to CSF had no measurable effect on the levels of HVA and 5-HIAA. Repeated thawing and freezing produced no detectable change in metabolite levels. The results indicate that these monoamine metabolites are stable at room temperature for up to 48 hours after lumbar puncture and that the addition of an antioxidant, such as ascorbic acid, is not necessary. The data also demonstrate that immediate refrigeration or freezing of samples is not required for maintenance of metabolite levels.


Molecularly thin two-dimensional hybrid perovskites with tunable optoelectronic properties due to reversible surface relaxation.
Due to their layered structure, two-dimensional Ruddlesden-Popper perovskites (RPPs), composed of multiple organic/inorganic quantum wells, can in principle be exfoliated down to few and single layers. These molecularly thin layers are expected to present unique properties with respect to the bulk counterpart, due to increased lattice deformations caused by interface strain. Here, we have synthesized centimetre-sized, pure-phase single-crystal RPP perovskites (CH3(CH2)3NH3)2(CH3NH3)n-1PbnI3n+1 (n = 1-4) from which single quantum well layers have been exfoliated. We observed a reversible shift in excitonic energies induced by laser annealing on exfoliated layers encapsulated by hexagonal boron nitride. Moreover, a highly efficient photodetector was fabricated using a molecularly thin n = 4 RPP crystal, showing a photogain of 105 and an internal quantum efficiency of ~34%. Our results suggest that, thanks to their dynamic structure, atomically thin perovskites enable an additional degree of control for the bandgap engineering of these materials.


Religiosity and Patient Activation Among Hospital Survivors of an Acute Coronary Syndrome.
Optimum management after an acute coronary syndrome (ACS) requires considerable patient engagement/activation. Religious practices permeate people's lives and may influence engagement in their healthcare. Little is known about the relationship between religiosity and patient activation. To examine the association between religiosity and patient activation in hospital survivors of an ACS. Secondary analysis using baseline data from Transitions, Risks, and Actions in Coronary Events: Center for Outcomes Research and Education (TRACE-CORE) Study. A total of 2067 patients hospitalized for an ACS at six medical centers in Central Massachusetts and Georgia (2011-2013). Study participants self-reported three items assessing religiosity-strength and comfort from religion, making petition prayers, and awareness of intercessory prayers for health. Patient activation was assessed using the 6-item Patient Activation Measure (PAM-6). Participants were categorized as either having low (levels 1 and 2) or high (levels 3 and 4) activation. The mean age of study participants was 61 years, 33% were women, and 81% were non-Hispanic White. Approximately 85% derived strength and comfort from religion, 61% prayed for their health, and 89% received intercessory prayers for their health. Overall, 58% had low activation. Reports of a great deal (aOR, 2.02; 95% CI, 1.44-2.84), and little/some (aOR, 1.45; 95% CI, 1.07-1.98) strength and comfort from religion were associated with high activation, as were receipt of intercessions (aOR, 1.48; 95% CI, 1.07-2.05). Praying for one's health was associated with low activation (aOR, 0.78; 95% CI, 0.61-0.99). Most ACS survivors acknowledge religious practices toward their recovery. Strength and comfort from religion and intercessory prayers for health were associated with high patient activation. Petition prayers for health were associated with low activation. Healthcare providers should use knowledge about patient's religiosity to enhance patient engagement in their care.


The current role of MRI for guiding active surveillance in prostate cancer.
Active surveillance (AS) is the recommended treatment option for low-risk and favourable intermediate-risk prostate cancer management, preserving oncological and functional outcomes. However, active monitoring using relevant parameters in addition to the usual clinical, biological and pathological considerations is necessary to compensate for initial undergrading of the tumour or to detect early progression without missing the opportunity to provide curative therapy. Indeed, several studies have raised concerns about inadequate biopsy sampling at diagnosis. However, the implementation of baseline MRI and targeted biopsy have led to improved initial stratification of low-risk disease; baseline MRI correlates well with disease characteristics and AS outcomes. The use of follow-up MRI during the surveillance phase also raises the question of the requirement for serial biopsies in the absence of radiological progression and the possibility of using completely MRI-based surveillance, with triggers for biopsies based solely on MRI findings. This concept of a tailored-risk, imaging-based monitoring strategy is aimed at reducing invasive procedures. However, the abandonment of serial biopsies in the absence of MRI progression can probably not yet be recommended in routine practice, as the data from real-life cohorts are heterogeneous and inconclusive. Thus, the evolution towards a routine, fully MRI-guided AS pathway has to be preceded by ensuring quality programme assessment for MRI reading and by demonstrating its safety in prospective trials.


Venous thrombosis epidemiology, pathophysiology, and anticoagulant therapies and trials in severe acute respiratory syndrome coronavirus 2 infection.
Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus confers a risk of significant coagulopathy, with the resulting development of venous thromboembolism (VTE), potentially contributing to the morbidity and mortality. The purpose of the present review was to evaluate the potential mechanisms that contribute to this increased risk of coagulopathy and the role of anticoagulants in treatment. A literature review of coronavirus disease 2019 (COVID-19) and/or SARS-CoV-2 and cell-mediated inflammation, clinical coagulation abnormalities, hypercoagulability, pulmonary intravascular coagulopathy, and anticoagulation was performed. The National Clinical Trials database was queried for ongoing studies of anticoagulation and/or antithrombotic treatment or the incidence or prevalence of thrombotic events in patients with SARS-CoV-2 infection. The reported rate of VTE among critically ill patients infected with SARS-CoV-2 has been 21% to 69%. The phenomenon of breakthrough VTE, or the acute development of VTE despite adequate chemoprophylaxis or treatment dose anticoagulation, has been shown to occur with severe infection. The pathophysiology of overt hypercoagulability and the development of VTE is likely multifactorial, with evidence supporting the role of significant cell-mediated responses, including neutrophils and monocytes/macrophages, endothelialitis, cytokine release syndrome, and dysregulation of fibrinolysis. Collectively, this inflammatory process contributes to the severe pulmonary pathology experienced by patients with COVID-19. As the infection worsens, extreme D-dimer elevations, significant thrombocytopenia, decreasing fibrinogen, and prolongation of prothrombin time and partial thromboplastin time occur, often associated with deep vein thrombosis, in situ pulmonary thrombi, and/or pulmonary embolism. A new phenomenon, termed pulmonary intravascular coagulopathy, has been associated with morbidity in patients with severe infection. Heparin, both unfractionated heparin and low-molecular-weight heparin, have emerged as agents that can address the viral infection, inflammation, and thrombosis in this syndrome. The overwhelming inflammatory response in patients with SARS-CoV-2 infection can lead to a hypercoagulable state, microthrombosis, large vessel thrombosis, and, ultimately, death. Early VTE prophylaxis should be provided to all admitted patients. Therapeutic anticoagulation therapy might be beneficial for critically ill patients and is the focus of 39 ongoing trials. Close monitoring for thrombotic complications is imperative, and, if confirmed, early transition from prophylactic to therapeutic anticoagulation should be instituted. The interplay between inflammation and thrombosis has been shown to be a hallmark of the SARS-CoV-2 viral infection.


Energy Level, Crystal Morphology and Fluorescence Emission Tuning in Cocrystals via Molecular-Level Engineering.
Organic donor-acceptor complexes as new organic semiconductor class have attracted wide attention, due to their potential applications in functional optoelectronics. Herein, we present two new charge transfer cocrystals of di-cyanodiazafluorene -perylene (DCPE) and di-cyanodiazaflfluorene-pyrene (DCPY) through a rational cocrystal-engineering strategy. Although they are both 1 : 1 mixed stacking cocrystals with similar chemical structures, the DCPE cocrystal possesses a non-centrosymmetric space group and narrower band gap compared to DCPY cocrystal, because of the non-covalent bonding variation. The electrostatic potential accumulated in the lateral facets leads to highly twisted DCPE nanobelts, and the small band gap causes near infrared fluorescence. Meanwhile, the DCPY crystals with centrosymmetric space groups and weaker intermolecular interactions exhibited an untwisted morphology and red emission. This study will be helpful for the design and understanding of functional cocrystal materials that can be used in flexible micro/nano-mechanics, mechanical energy, and optical devices.


Taxonomy of phototrophic green and purple bacteria: a review.
The presently existing classification for the green and purple bacteria comprises physiological-ecological assemblages of phototrophic bacteria with anoxygenic photosynthesis. The taxonomic units of the different levels were based entirely on common phenotypic traits, including morphological, cytological, physiological and biochemical characteristics. Since degrees of resemblance form the basis of the grouping, this classification cannot reflect the genetic or evolutionary relatedness of these bacteria, neither among themselves nor with other bacteria. The advantage of the artificial system, however, is the use of features which can be established in most laboratories and which allow the comparison and identification of newly isolated strains with those already studied and described. The four existing families correspond to the four major recognized, ecophysiological groups, the Chlorobiaceae and Chloroflexaceae among the green bacteria, and the Chromatiaceae and Rhodospirillaceae among the purple bacteria. Our knowledge of all these groups is incomplete; this is reflected by the fact that seven new species have been described during the past three years (6th Newsletter on phot. bacteria, Trüper and Hansen, 1982). The description of the new genus and species Erythrobacter longus (Shiba and Simidu, 1982) is also interesting, as it comprises aerobic chemoorganotrophic marine bacteria which form bacteriochlorophyll a and carotenoids; however, no strains were able to grow phototrophilcally. Significant success is currently being obtained in the different approaches toward elucidating the genetic relationships within and outside of the purple and green bacteria. Detailed studies of the lipopolysaccharides of several species and genera of the Rhodospirillaceae (Weckesser et al., 1979, and more recent paper) have proven to be very useful for the recognition of relationships or dissimilarities between the species of a genus or between different genera. Amino acid sequence studies of cytochromes c from Rhodospirillaceae, other bacteria and eukaryotic organisms (Dickerson, 1980) have led to the recognition of four different groups of cytochrome c molecules (long, medium and two groups of short protein chains). The subdivision of the Rhodospirillaceae into three species groups, each possessing one of the three types of cytochrome c, proved to be in total agreement with the results of oligonucleotide cataloging of the 16 S ribosomal RNA of these bacteria (Gibson et al., 1979). The latter method also revealed that several chemotropic bacteria, including the nitrifying bacteria, are more closely related to certain purple bacteria than different species of the purple bacteria among themselves (Seewaldt et al., 1982).(ABSTRACT TRUNCATED AT 400 WORDS)


Association between left atrial myopathy and sarcomere mutation in patients with hypertrophic cardiomyopathy: insights into left atrial strain by MRI feature tracking.
Left atrial (LA) myopathy, characterized by LA enlargement and mechanical dysfunction, is associated with worse prognosis in hypertrophic cardiomyopathy (HCM) while the impact of sarcomere mutation on LA myopathy remains unclear. We aimed to assess the association between LA myopathy and sarcomere mutation and to explore the incremental utility of LA strain in mutation prediction. A total of 105 consecutive HCM patients (mean age 47.8 ± 11.9 years, 71% male) who underwent HCM-related gene screening and cardiac MRI were retrospectively enrolled. LA volume, ejection fraction and strain indices in reservoir, conduit, and booster-pump phases were investigated respectively. Fifty mutation-positive patients showed higher LA maximal volume index (59.4 ± 28.2 vs 43.8 ± 18.1 mL/m2, p = 0.001), lower reservoir (21.3 ± 7.9 vs 26.2 ± 6.6%, p < 0.001), and booster-pump strain (12.1 ± 5.4 vs 17.1 ± 5.0%, p < 0.001) but similar conduit strain (9.2 ± 4.5 vs 9.1 ± 4.5%, p = 0.909) compared with mutation-negative patients. In multivariate logistic regression, LA booster-pump strain was associated with sarcomere mutation (odds ratio = 0.86, 95% confidence interval: 0.77-0.96, p = 0.010) independent of maximal wall thickness, late gadolinium enhancement, and LA volume. Furthermore, LA booster-pump strain showed incremental value for mutation prediction added to Mayo II score (AUC 0.798 vs 0.709, p = 0.024). In HCM, mutation-positive patients suffered worse LA enlargement and worse reservoir and booster-pump functions. LA booster-pump strain was a strong factor for sarcomere mutation prediction added to Mayo II score. The independent association between sarcomere mutation and left atrial mechanical dysfunction provide new insights into the pathogenesis of atrial myopathy and is helpful to understand the adverse prognosis regarding atrial fibrillation and stroke in mutation-positive patients. • In patients with hypertrophic cardiomyopathy, left atrial (LA) reservoir and booster-pump function, but not conduit function, were significantly impaired in mutation-positive patients compared with mutation-negative patients. • LA booster-pump strain measured by MRI-derived feature tracking is feasible to predict sarcomere mutation with high incremental value added to Mayo II score.


Randomized, sham-controlled trial of acupuncture for post-cataract surgery dry eye disease.
To determine the efficacy of acupuncture in patients with post-cataract surgery dry eye disease (DED). Ninety participants with post-cataract surgery DED were randomly assigned (1:1) to receive true acupuncture (n = 44) or non-penetrating sham acupuncture (n = 46) twice weekly for 8 weeks. The primary outcome was the change from baseline to week 8 in the noninvasive tear film break-up time (TFBUT). Participants were followed until week 12. Secondary outcomes included Ocular Surface Disease Index (OSDI) score, tear meniscus height (TMH), corneal fluorescein staining (CFS) score, meiboscore and corrected distance visual acuity (CDVA). The estimated mean change from baseline in the noninvasive TFBUT was 1.52 for true acupuncture versus 0.77 for sham acupuncture (adjusted difference -0.75 [95% CI -1.39 to -0.12]; P = 0.02) at week 8 and 1.49 for true acupuncture versus 0.81 for sham acupuncture (adjusted difference -0.68 [95% CI, -1.29 to -0.07]; P = 0.029) at week 12. The mean change in the OSDI score was -20.13 for true acupuncture versus -13.44 for sham acupuncture (adjusted difference 6.69 [95% CI, 0.64 to 12.74]; P = 0.031) at week 8, but revealed no statistically between-group differences at week 12. Mean changes in TMH, CFS score, meiboscore and CDVA did not differ significantly between the two groups. Among patients with post-cataract surgery DED, acupuncture compared with sham acupuncture resulted in statistically significant benefit on tear film stability. Chinese Clinical Trial Registry (ChiCTR1800020132).


Chemopreventive effects of Ginkgo biloba extract in estrogen-negative human breast cancer cells.
Excessive level of estrogen is considered as a main cause of breast cancer, therefore, many studies have focused on estrogen receptor (ER)-positive breast cancer, even though ER-negative cancer has a poor prognosis than ER-positive breast cancer. We evaluated the anti-cancer effects of Ginkgo biloba extract (GBE) in estrogen-independent breast cancer. GBE has been traditionally used as a platelet activating factor, a circulatory stimulant, a tonic, and anti-asthmatic drug, and anti-cancer agent. However, anti-cancer effects of GBE on ER-negative breast cancer have not been proved yet. In this study, we tested chemotherapeutic potential of GBE in the MDA-MB-231 (ER-negative) human breast cancer cell line. Our results showed that cytotoxicity effects of GBE in MDA-MB-231 lead to DNA fragmentation at high concentrations (500 and 1,000 μg/ml). Caspase-3 was significantly activated and mRNA levels of apoptosis-related genes (Bcl-2 and Bax) were altered. These results indicate that GBE induces apoptosis in MDA-MB-231 cells. It is presumed that GBE has chemopreventive effects in ER-independent breast cancer through anti-proliferation and apoptosis-inducing activities.


Anti-inflammatory/anti-fibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against Schistosoma mansoni-induced liver fibrosis.
Praziquantel (PZQ) is an isoquinoline derivative (2-cyclohexylcarbonyl-1, 2, 3, 6, 7, 11b-hexahydro-4H-pyrazino{2,1-a}-isoquinoline-4-one), and is currently the drug of choice for all forms of schistosomiasis. Silymarin, a standardized milk thistle extract, of which silibinin is the main component, is known for its hepatoprotective, anti-inflammatory, antioxidant activities, and hepatocyte regeneration. This study investigates the anti-inflammatory/anti-fibrotic effects of silymarin and/or PZQ on schistosomal hepatic fibrosis. Schistosoma mansoni-infected mice were divided into two large groups (I & II), each with four subgroups and were run in parallel. (i) Infected untreated; (ii) treated with silymarin, starting from the 4th (3 weeks before PZQ therapy) or 12th (5 weeks after PZQ therapy) weeks post infection (PI); (iii) treated with PZQ in the 7th week PI; and (iv) treated with silymarin, as group (ii) plus PZQ as group (iii). Comparable groups of uninfected mice run in parallel with the infected groups. Mice of groups I and II were killed 10 and 18 weeks PI, respectively. Hepatic content of hydroxyproline (HYP), serum levels and tissue expression of matrix metalloproteinase-2 (MMP-2), transforming growth factor-β1 (TGF-β1) and number of mast cells were determined. In addition, parasitological, biochemical and histological parameters that reflect disease severity and morbidity were examined. Silymarin caused a partial decrease in worm burden; hepatic tissue egg load, with an increase in percentage of dead eggs; modulation of granuloma size, with significant reduction of hepatic HYP content; tissue expression of MMP-2, TGF-β1; number of mast cells, with conservation of hepatic reduced glutathione (GSH). PZQ produced complete eradication of worms, eggs and alleviated liver inflammation and fibrosis. The best results were obtained, in most parameters studied, in groups of mice treated with silymarin in addition to PZQ. Our results point to silymarin as a promising anti-inflammatory and anti-fibrotic agent; it could be introduced as a therapeutic tool with PZQ in the treatment of schistosomal liver fibrosis, but further studies on mechanisms of silymarin and PZQ in chronic liver diseases may shed light on developing therapeutic methods in clinical practice.


Specificity and idiotype analysis of a monoclonal anti-DNA antibody.
The binding properties and idiotypes of a monoclonal anti-DNA antibody were studied to investigate the control of specificity in this autoimmune response. This antibody, A9, was derived from the fusion of spleen cells of an MRL-lpr/lpr mouse and the cell line X63-Ag8.653. In inhibition binding studies, A9 showed preference for single-stranded DNA and bound both ribo- and deoxyribohomopolymers. An antiserum prepared in a rabbit against A9 showed anti-idiotypic specificity after absorption with BALB/c immunoglobulins and the BALB/c myeloma MOPC 195. At least two distinct idiotypic specificities could be demonstrated by this serum, one apparently exclusive to A9 and one commonly expressed in sera of MRL-lpr/lpr mice. Serum levels of the commonly expressed A9 idiotype were also elevated in sera of C3H mice expressing the lpr gene suggesting association with B-cell activation induced by this genetic mechanism. The demonstration of a commonly expressed A9 idiotype indicates that some autoantibody variable region determinants may be genetically controlled.


Methodological issues in social support and social network research.
With the plethora of articles describing a relationship between social support and/or social network and health status, it was considered useful to take stock of the current status of research in this area, focusing on two critical methodological issues: clarity of definition, and validity and reliability of the measurement instruments. Of the 33 instruments reviewed only modest agreement was found in conceptual definition, and frequently the concepts were not defined or ill-defined. Of particular concern is the definitional confusion between social support and social network. Variables used to operationalize these concepts confirm this lack of specificity and ambiguity in definition. As for validity and reliability, many of the investigators reported no data on these issues; others provided information that only modestly supported the validity or reliability of their instrument. The conclusion of this assessment suggests the need to clarify the essential elements of social support and social networks in order to better distinguish between the behavioral (support) and structural (network) variables that may be affecting health status. A question is also raised as to the likelihood of a single questionnaire being designed that would accurately measure the perceptions of support or supportive behaviors in the variety of supportive research that will continue to be studied. Finally, more rigorous standards need to be used by investigators in establishing the validity and reliability of the instruments in order to improve their predictive utility.


Clinical Characteristics, Complications, and Treatment Practices in Patients With RHD: 6-Year Results From HP-RHD Registry.
Despite the high prevalence of rheumatic heart disease (RHD) in developing countries such as India, data on characteristics, complications, and treatment practices are lacking. The HP-RHD (Himachal Pradesh Rheumatic Heart Disease) registry aimed at reporting these parameters in patients with RHD from a northern state of India. A total of 2,005 consecutive patients of RHD were enrolled over a period of 6 years (2011 to 2016) in the present study. The clinical characteristics, complications, and treatment practices were systematically recorded. The mean age for patients with RHD was 40.3 ± 14.3 (range 5 to 83 years). RHD predominantly affected females (72.3%) and population from rural background (92%). Multivalvular involvement was frequent (43.2%), mitral valve was the commonest affected valve (83.3%). The majority of the patients had moderate-to-severe valvular dysfunction (69.3%). Mitral and tricuspid valve involvement was more frequent in female subjects compared with more frequent aortic valve involvement in male subjects (p < 0.001). The major adverse cardiovascular events were recorded in 23.4% patients at the time of registry and comprised mainly advanced heart failure (15.6%), peripheral embolism (4.1%), and stroke (3.9%). The independent risk determinants of major adverse cardiovascular events (were advanced age (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 1.00-1.02), severe mitral stenosis (OR: 1.73; 95% CI: 1.34-2.20), severe tricuspid regurgitation (OR: 2.11; 95% CI: 1.48-3.02), presence of pulmonary artery hypertension (OR: 1.33; 95% CI: 1.04-1.69), and atrial fibrillation (OR: 1.64; 95% CI: 1.28-2.11). Evidence-based use of oral anticoagulant therapy was documented in 77.7% of high-risk patients. Only 28.5% of study population was receiving secondary prophylaxis. Complications in patients with RHD increase with age and worsening valvular dysfunction. Programs focused on early detection and evidence-based management will assist in improving outcomes.


How providing a low-cost water filter pitcher led Latino parents to reduce sugar-sweetened beverages and increase their water intake: explanatory qualitative results from the Water Up!@Home intervention trial.
This study sought to explain results of the Water Up!@Home randomised controlled trial where low-income parents were randomised to receive an educational intervention +a low-cost water filter pitcher or only the filter. Parents in both groups had reported statistically significant reductions in sugar-sweetened beverages (SSB) and increases in water intake post-intervention. Qualitative explanatory in-depth interviews analysed thematically and deductively. Washington, DC metropolitan area, USA. Low-income Latino parents of infants/toddlers who had participated in the Water Up! @Home randomised controlled trial. The filter-stimulated water consumption in both groups by (1) increasing parents' perception of water safety; (2) acting as a cue to action to drink water; (3) improving the flavour of water (which was linked to perceptions of safety) and (4) increasing the perception that this option was more economical than purchasing bottled water. Safe and palatable drinking water was more accessible and freely available in their homes; participants felt they did not need to ration their water consumption as before. Only intervention participants were able to describe a reduction in SSB intake and described strategies, skills and knowledge gained to reduce SSB intake. Among the comparison group, there was no thematic consensus about changes in SSB or any strategies or skills to reduce SSB intake. A low-cost water filter facilitated water consumption, which actively (or passively for comparison group) displaced SSB consumption. The findings have implications for understanding and addressing the role of water security on SSB consumption.


Educational paper : retinal haemorrhages in abusive head trauma in children.
Retinal haemorrhages are an important component of the clinical effects of non-accidental head injuries which have significant visual morbidity. Their importance extends into the legal investigations of carers of children with subdural haemorrhages and encephalopathy who are suspected of having been non-accidentally injured. The vital precision in diagnosis relies not just on the presence of retinal haemorrhages but on the severity, extent, bilaterality and their location in the retina. Inadequate documentation of ophthalmological clinical findings and too short a follow-up to allow proper assessment of severity each give rise to difficulties for both expert witnesses and the courts.


Hydrogels for Gasotransmitter Delivery: Nitric Oxide, Carbon Monoxide, and Hydrogen Sulfide.
Gasotransmitters, gaseous signaling molecules including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2 S), maintain myriad physiological processes. Low levels of gasotransmitters are often associated with specific problems or diseases, so NO, CO, and H2 S hold potential in treating bacterial infections, chronic wounds, myocardial infarction, ischemia, and various other diseases. However, their clinical applications as therapeutic agents are limited due to their gaseous nature, short half-life, and broad physiological roles. One route toward the greater application of gasotransmitters in medicine is through localized delivery. Hydrogels are attractive biomedical materials for the controlled release of embedded therapeutics as they are typically biocompatible, possess high water content, have tunable mechanical properties, and are injectable in certain cases. Hydrogel-based gasotransmitter delivery systems began with NO, and hydrogels for CO and H2 S have appeared more recently. In this review, the biological importance of gasotransmitters is highlighted, and the fabrication of hydrogel materials is discussed, distinguishing between methods used to physically encapsulate small molecule gasotransmitter donor compounds or chemically tether them to a hydrogel scaffold. The release behavior and potential therapeutic applications of gasotransmitter-releasing hydrogels are also detailed. Finally, the authors envision the future of this field and describe challenges moving forward.


Remediation of hexavalent chromium in contaminated soil by Fe(II)-Al layered double hydroxide.
In this study, high-efficiency and low-cost Fe(II) and Al(III) layered double hydroxide (Fe-Al-LDH) was synthesized and used for the remediation of Cr(VI) contaminated soil. The Fe-Al-LDH characteristics were analyzed with different techniques. The results of X-ray diffraction (XRD) and transmission electron microscopy (TEM) analyses revealed its highly crystalline structure with sheet morphology, and a Brunauer-Emmett-Teller (BET) surface area of 46.85 m2/g. In addition, the remediation tests indicated that adding 1 g/L of Fe-Al-LDH to a solution of Cr(VI)-contaminated soil, at a soil to solution ratio of 1 g: 5 mL, completely immobilized the pre-adsorbed Cr(VI) in the soil (2079.84 mg/kg). Additionally, the Fe-Al-LDH could be used in a wide range of pH conditions and no Cr(VI) was detected in the leaching solution. Based on the characterization of X-Ray Diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS), and X-ray photoelectron spectroscopy (XPS) analysis, it is proposed that adsorption and reduction may be involved in the mechanism of Cr(VI) immobilization by Fe-Al-LDH. At the beginning of the reaction, Cr(VI) entered the layer structure of the LDH or was adsorbed on the surface of the LDH. Then, Fe(II) was involved in reducing the Cr(VI) to Cr(III) and was oxidized to Fe(III). Part of the Cr(VI) and Cr(III) were co-precipitated with Fe(III) and Al (III) during the formation of iron oxide or hydroxide.


Persistent Müllerian duct syndrome associated with genetic defects in the regulatory subunit of myosin phosphatase.
Can mutations of genes other than AMH or AMHR2, namely PPP1R12A coding myosin phosphatase, lead to persistent Müllerian duct syndrome (PMDS)? The detection of PPP1R12A truncation mutations in five cases of PMDS suggests that myosin phosphatase is involved in Müllerian regression, independently of the anti-Müllerian hormone (AMH) signaling cascade. Mutations of AMH and AMHR2 are detectable in an overwhelming majority of PMDS patients but in 10% of cases, both genes are apparently normal, suggesting that other genes may be involved. DNA samples from 39 PMDS patients collected from 1990 to present, in which Sanger sequencing had failed to detect biallelic AMH or AMHR2 mutations, were screened by massive parallel sequencing. To rule out the possibility that AMH or AMHR2 mutations could have been missed, all DNA samples of good quality were analyzed by targeted next-generation sequencing. Twenty-four samples in which the absence of AMH or AMHR2 biallelic mutations was confirmed were subjected to whole-exome sequencing with the aim of detecting variants of other genes potentially involved in PMDS. Five patients out of 24 (21%) harbored deleterious truncation mutations of PP1R12A, the gene coding for the regulatory subunit of myosin phosphatase, were detected. In addition to PMDS, three of these patients presented with ileal and one with esophageal atresia. The congenital abnormalities associated with PMDS in our patients are consistent with those described in the literature for PPP1R12A variants and have never been described in cases of AMH or AMHR2 mutations. The role of chance is therefore extremely unlikely. The main limitation of the study is the lack of experimental validation of the role of PPP1R12A in Müllerian regression. Only circumstantial evidence is available, myosin phosphatase is required for cell mobility, which plays a major role in Müllerian regression. Alternatively, PPP1R12A mutations could affect the AMH transduction pathway. The study supports the conclusion that failure of Müllerian regression in males is not necessarily associated with a defect in AMH signaling. Extending the scope of molecular analysis should shed light upon the mechanism of the initial steps of male sex differentiation. The study was funded by la Fondation Maladies Rares, GenOmics 2021_0404 and la Fondation pour la Recherche Médicale, grant EQU201903007868. The authors report no conflict of interest. N/A.


Salvageable waste associated with intravitreal injections: A local medical waste management approach.
Healthcare waste management is a globally challenging issue with an increased prevalence of disposable, single-use materials in developed countries and a rapidly ageing population continuing to drive an increase in the use of medical resources. One manifestation of this within ophthalmology is the increasing number of intravitreal injections given for conditions such as age-related macular degeneration and diabetic macular oedema. A prospective controlled cohort study was performed over 5 weeks in 2021 during which two sites were selected to compare different approaches to sorting the waste generated by intravitreal injections. At Site A all waste associated with these injections was placed in standard hospital waste bins. Site B was the intervention arm where a real-time sorting of waste occurred. The number of injections given and waste amounts were recorded. 116 and 286 injections were given at Sites A and B, respectively over the study period. Site A generated an average of 470.7 g of waste per injection compared with 175.1 g at our intervention site. This represents a 62.8% reduction (p < 0.001). At Site B, where waste was sorted, a total of 50.1 kg of medical waste was generated from these injections during the study period of which 33.8 kg (67.5%) was salvageable. This is the first quantification of the medical waste associated with intravitreal injections, a burgeoning treatment for macular degeneration and diabetic retinopathy among other conditions. This study demonstrates a significant reduction in the amount of medical waste produced using an easily implementable real-world methodology.


Predicted versus expressed adipokinetic hormones, and other small peptides from the corpus cardiacum-corpus allatum: a case study with beetles and moths.
This mass spectrometric study confines itself to peptide masses in the range of 500-1500Da. Adipokinetic hormones (AKHs) that are predicted from the genome of the red flour beetle, Tribolium castaneum, and the silk moth, Bombyx mori, are shown to exist as expressed peptides in the corpora cardiaca (CC) of the respective species as evidenced by various mass spectrometric methods. Additionally, some related species were included in this study, such as the tenebrionid beetles Tribolium brevicornis and Tenebrio molitor, as well as the moths Spodoptera frugiperda, Spodoptera littoralis, Mamestra brassicae and Lacanobia oleracea, to investigate whether AKH peptides are structurally conserved in the same genus or family. Interestingly, the AKH peptide of T. brevicornis is identical to that of T. molitor but not to the ones of its close relative T. castaneum. Moreover, other peptides in T. brevicornis, such as various FXPRL amides (=pyrokinins), also match the complement in T. molitor but differ from those in T. castaneum. All the CC of beetles lacked the signal for the mass of the peptide corazonin. All moths have the nonapeptide Manse-AKH expressed in their CC. In addition, whereas the silk moth has the decapeptide Bommo-AKH as a second peptide, all other moths (all noctuids) express the decapeptide Helze-HrTH. In M. brassicae and L. oleracea a novel amidated Gly-extended Manse-AKH is found as a possible third AKH. The noctuid moth species also all express the same FLRF amide-I, corazonin, and a group-specific isoform of a gamma-PGN-(=gamma-SGNP) peptide. In L. oleracea, however, the latter peptide has a novel sequence which is reported for the first time, and the peptide is code-named Lacol-PK.


Synergistic effects of sequential infection with highly pathogenic porcine reproductive and respiratory syndrome virus and porcine circovirus type 2.
Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of porcine reproductive and respiratory syndrome (PRRS) and porcine circovirus type 2 (PCV2) is associated with postweaning multisystemic wasting syndrome (PMWS) in pigs. Coinfection with highly pathogenic PRRSV (HP-PRRSV) and PCV2 in the field has recently become extensive in some Asian countries. A synergistic pathogenicity between PRRSV and PCV2 infections has previously been reported. However, the consequences of the sequential infection of pigs with these two viruses are unknown. Thirty 35-day-old piglets were randomly divided into six groups (n = 5 each): HP-PRRSV/PCV2 (group 1, inoculated with HP-PRRSV, then inoculated with PCV2 one week later), PCV2/HP-PRRSV (group 2, inoculated with PCV2, then inoculated with HP-PRRSV one week later), HP-PRRSV+PCV2 (group 3, inoculated with HP-PRRSV and PCV2 concurrently), HP-PRRSV (group 4, inoculated with HP-PRRSV), PCV2 (group 5, inoculated with PCV2), and the control (group 6, uninfected). This experiment lasted 28 days. Clinical symptoms and rectal temperatures were recorded each day after inoculation, body weight was recorded weekly, and serum samples were obtained for viral nucleic acid quantification and antibody titration. Variations in CD3+, CD4+ CD8-, CD3+, CD4-, and CD8+ cells, natural killer (NK) cells, and mononuclear cells were determined by flow cytometry. The serum concentrations of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), and macrophage granulocyte-colony stimulating factor (GM-CSF) were determined. Pathological changes in different tissues from the experimentally infected pigs were recorded. The piglets in group 1 had the highest viral loads, the lowest antibody titers, the most-severe clinical signs, and the highest mortality (3/5, 60%; the mortality in the other groups was 0%), and interstitial pneumonia was more severe in this group compare to the other HP-PRRSV infected groups. The serum levels of IFN-γ, TNF-α, IL-10, and GM-CSF varied (increased or decreased) most widely in group 1, as did each immunocyte subgroup. HP-PRRSV infection followed by PCV2 infection enhanced the replication of both viruses in the experimental piglets and led to more-severe clinical signs and lesions, indicating greater synergistic effects during the sequential infection of piglets with HP-PRRSV and then PCV2.


Posterior lateral hypothalamic axon terminals are in contact with trigeminal premotor neurons in the parvicellular reticular formation of the rat medulla oblongata.
This study was performed to understand the anatomical substrates of hypothalamic modulation of jaw movements. After cholera toxin B subunit (CTb) injection into the parvicellular reticular formation (RFp) of the rat medulla oblongata, where many trigeminal premotor neurons have been known to exist, numerous CTb-labeled neurons were found in the posterior lateral hypothalamus (PLH) bilaterally with a clear-cut ipsilateral dominance. After ipsilateral injections of biotinylated dextran amine (BDA) into the PLH and CTb into the motor trigeminal nucleus (Vm), the prominent distribution of BDA-labeled axon terminals around CTb-labeled neurons was found in the RFp region just ventral to the nucleus of the solitary tract and medial to the spinal trigeminal nucleus ipsilateral to the injection sites. Within the neuropil of the RFp, BDA-labeled axon terminals made an asymmetrical synaptic contact predominantly with dendrites and additionally with somata of the RFp neurons, some of which were labeled with CTb. It was further revealed that these BDA-labeled axon terminals were immunoreactive for vesicular glutamate transporter 2. The present data suggest that the PLH plays an important role in the control of jaw movements by exerting its glutamatergic excitatory action upon RFp neurons presynaptic to trigeminal motoneurons.


Advances in 3D printing of food and nutritional products.
The main advantage of both 3D printing (3DP) and 3D food printing (3DFP) over other technologies is the enormous capacity of both techniques for customization. Its use makes it possible to obtain products without planning and implementing a complex and costly manufacturing process. This makes 3DFP a technology of choice for the preparation of food products that meet specific needs, such as controlled nutritional or rheological properties. However, further technological developments are still needed before 3DFP can be considered fully useful for innovative and demanding applications. If both preparation and post-processing of materials based on 3D printing are optimized, aiming to reduce production time and/or complication for non-expert users, this would open a whole new range of possibilities. It is in this sense that the development of advanced 3DFP systems becomes a must. This chapter reviews current advances in extrusion-based 3D food printing systems, with in situ gelation and mixing as key aspects to better exploit the potential of 3DFP. On one hand, 3DFP systems based on in situ gelation (G3DFP) provide greater control over the final properties of the printed products, as the selection of adequate printing parameters gives the possibility of influencing the gelation process. On the other hand, mixing is indispensable for true 3DFP automation, so that the formulations do not have to be prepared by the user. Different innovative 3DFP systems based on gelling and/or mixing are presented in this chapter. Finally, the status and future of extrusion-based 3DFP, and its application in the production of customized foods for specific needs, are also overviewed.


Denoising diffusion probabilistic models for 3D medical image generation.
Recent advances in computer vision have shown promising results in image generation. Diffusion probabilistic models have generated realistic images from textual input, as demonstrated by DALL-E 2, Imagen, and Stable Diffusion. However, their use in medicine, where imaging data typically comprises three-dimensional volumes, has not been systematically evaluated. Synthetic images may play a crucial role in privacy-preserving artificial intelligence and can also be used to augment small datasets. We show that diffusion probabilistic models can synthesize high-quality medical data for magnetic resonance imaging (MRI) and computed tomography (CT). For quantitative evaluation, two radiologists rated the quality of the synthesized images regarding "realistic image appearance", "anatomical correctness", and "consistency between slices". Furthermore, we demonstrate that synthetic images can be used in self-supervised pre-training and improve the performance of breast segmentation models when data is scarce (Dice scores, 0.91 [without synthetic data], 0.95 [with synthetic data]).


Thermodynamics of the isothermal interaction of beta-lactoglobulin with guanidinium chloride and urea.
A thermodynamic study of the isothermal interaction of beta-lactoglobulin with guanidinium chloride and urea has been performed. Enthalpies of interaction of the two denaturants have been obtained by calorimetric measurements, and the free energy of interaction calculated from previously determined preferential binding of denaturants. In separate dilatometric experiments the volume changes accompanying the interaction of guanidinium chloride with beta-lactoglobulin have also been determined.


Capillary electrochromatographic separation of enantiomers on chemically bonded type of cellulose derivative chiral stationary phases with a positively charged spacer.
Positively charged chiral stationary phases (CSPs) were prepared for capillary electrochromatography (CEC) separation of enantiomers by chemically immobilizing cellulose derivatives onto diethylenetriaminopropylated silica (DEAPS) with tolylene-2,4-diisocyanate (TDI) as a spacer reagent. Anodic electroosmotic mobility was observed in both nonaqueous and aqueous mobile phases due to the positively charged amines on the surface of the prepared CSPs. For comparison, the traditionally used 3-aminopropyl silica (APS) was also adopted as the base material instead of DEAPS to prepare CSP. It was observed that the EOF on the DEAPS-based CSP was 18%-60% higher than that on the APS-based CSP under nonaqueous mobile phase conditions. Separation of enantiomers in CEC was performed on the positively charged CSPs with the nonaqueous mobile phases of pure ethanol or mixture of hexane-alcohol and the aqueous phases of acetonitrile-water or 95% ethanol. Fast separation of enantiomers was achieved on the newly prepared CSPs.


S-adenosyl-L-methionine facilitates recovery from deficits in delayed response and hand movement tasks following brain lesions in monkeys.
Effects of S-adenosyl-L-methionine (SAMe) on deficits in a trained delayed response task or trained hand movement tasks after lesions in bilateral dorsolateral prefrontal cortices or the hand-arm area of the unilateral motor cortex in monkeys were studied. Lesions disturbed the delayed response task or hand movement tasks moderately or severely for 1 week to several months depending on the extent of the lesion and nature of the task. Although treatment with small doses of SAMe (10 mg/kg/day, i.m.) had no effect on these disturbances, treatment with moderate doses of SAMe (20 or 30 mg/kg/day, i.m.) reduced impairments and promoted recovery from both disturbances. Pretreatment with SAMe (30 mg/kg/day, i.m.) facilitated recovery from delayed response task deficits due to administration of reserpine (0.3 mg/kg, i.m.) in monkey with bilateral prefrontal cortical lesions, but not in intact monkey. The data suggest that SAMe improves recovery from behavioral disturbances due to brain damage, and this is partly due to increased monoamine turnover rate.


Splicing of the late mRNAs of polyoma virus does not occur in the cytoplasm of the infected cell.
The three mRNAs that encode the capsid proteins of polyoma virus are produced by the excision of different sequences from continuous transcripts of the L strand of viral DNA. All three of the mRNAs have long half lives, and the larger species are not converted to the smaller ones to any measurable extent within the cytoplasm. Therefore the cytoplasmic proportions of late polyoma mRNAs are predetermined by splicing that is confined to the nucleus of the infected cell and which is complete by the time that mRNA is transported to the cytoplasm.


[The attitude of the mentally ill patient to hospitalization and to treatment and recovery procedures of the rehabilitation department].
The attitude of the patient to hospitalization and therapeutic procedures employed in the rehabilitation department has been investigated in a series of 87 mental patients. The orientation of the patient with regard to participation in the therapeutic process has been found to correlate with the patient's mental activity and emotional-volitional potential as well as with his empathic properties and attitude to hospitalization. The patient's attitude toward hospitalization was related to the structure of his attitudes toward specific types of rehabilitation procedures. Two general therapeutic orientations of mental patients characterized by their attitude toward admission to a rehabilitation department as toward "institutionalization" or "rehabilitation" have been determined.


Two masquerade presentations of retinoblastoma.
Masquerade syndromes are disorders occurring with intraocular inflammation misdiagnosed as uveitis. The underlying causes may be benign or malignant conditions, and one of the most important diagnoses to take into consideration in children is retinoblastoma. We present two cases with uncertain early misdiagnosis whose definite diagnosis eventually was retinoblastoma.


Comparative serum and urine analyses by dual-detector anion-exchange chromatography.
A high-pressure anion-exchange chromatographic system has been modified to provide measurement of large numbers of molecular constituents in serum and for direct comparison to similar measurement in urine. Operating parameters have been adopted which greatly extend the range of elution for strongly retained anionic constituents and limit resolution of early-eluting basic and neutral compounds which were of less interest in this study. Dual monitoring by UV absorption and fluorescence produced by cerate oxidation provides both sensitive and wide-ranging detection capability. Comparative serum and urine chromatograms for a clinically normal subject, a subject after ingesting the drug 4-hydroxyacetanilide, and an infant suffering from extreme acidosis, illustrate the potential usefulness of this analysis in studying the origin, transport, in vivo reactions, and disposition of metabolites.


The [lactate]/[pyruvate] ratio and alcohol metabolism: experiments with naloxone in fasting normal male volunteers.
Naloxone administration to fasting normal male volunteers reverses the acute ethanol-induced increase in the blood [lactate]/[pyruvate] ratio, but fails to lower blood-ethanol concentration. The results are discussed in relation to factors affecting ethanol elimination and the mechanism of antagonism of acute alcohol intoxication by naloxone.


Free energy simulations and MM-PBSA analyses on the affinity and specificity of steroid binding to antiestradiol antibody.
Antiestradiol antibody 57-2 binds 17beta-estradiol (E2) with moderately high affinity (K(a) = 5 x 10(8) M(-1)). The structurally related natural estrogens estrone and estriol as well synthetic 17-deoxy-estradiol and 17alpha-estradiol are bound to the antibody with 3.7-4.9 kcal mol(-1) lower binding free energies than E2. Free energy perturbation (FEP) simulations and the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method were applied to investigate the factors responsible for the relatively low cross-reactivity of the antibody with these four steroids, differing from E2 by the substituents of the steroid D-ring. In addition, computational alanine scanning of the binding site residues was carried out with the MM-PBSA method. Both the FEP and MM-PBSA methods reproduced the experimental relative affinities of the five steroids in good agreement with experiment. On the basis of FEP simulations, the number of hydrogen bonds formed between the antibody and steroids, which varied from 0 to 3 in the steroids studied, determined directly the magnitude of the steroid-antibody interaction free energies. One hydrogen bond was calculated to contribute about 3 kcal mol(-1) to the interaction energy. Because the relative binding free energies of estrone (two antibody-steroid hydrogen bonds), estriol (three hydrogen bonds), 17-deoxy-estradiol (no hydrogen bonds), and 17alpha-estradiol (two hydrogen bonds) are close to each other and clearly lower than that of E2 (three hydrogen bonds), the water-steroid interactions lost upon binding to the antibody make an important contribution to the binding free energies. The MM-PBSA calculations showed that the binding of steroids to the antiestradiol antibody is driven by van der Waals interactions, whereas specificity is solely due to electrostatic interactions. In addition, binding of steroids to the antiestradiol antibody 57-2 was compared to the binding to the antiprogesterone antibody DB3 and antitestosterone antibody 3-C4F5, studied earlier with the MM-PBSA method.


Simplifying the surgical approach to glanular and coronal hypospadias: longitudinal urethral incision and glanuloplasty.
Meatal advancement with glanuloplasty incorporated (MAGPI) is an appropriate approach for most glanular and coronal hypospadias. The very low incidence of complications with this technique (i.e., fistulas, meatal regression and stenosis) makes MAGPI very competitive if compared with other approaches proposed for similar anatomical defects. In certain cases, however, the MAGPI approach has led to an unsatisfactory neo meatus; instead of a natural slit-like appearance, the meatus can look too rounded and puckered. The last 84 patients referred to our unit with indications suitable for MAGPI (mean age 39 months) were operated on using a novel approach: the glanuloplasty was associated with a simple deep urethral plate incision, extending along the urethral channel, and left unsutured. At minimum follow up of 12 months two meatal regressions to mid glans were recorded. No meatal stenosis was seen in this series. This approach allowed us to achieve a conical glans with a natural looking meatus, avoiding urethral sutures.


Case of Paracoccus yeei infection documented in a transplanted heart.
After a successful cardiac transplantation, routine endomyocardial biopsies showed severe infiltrates comparable with myocarditis. Polymerase chain reaction analysis of native myocardial samples revealed infection with Paracoccus yeei, and the clinical condition of the patient deteriorated. After administration of ciprofloxacin, his clinical condition improved, and further biopsies showed no infiltrates in the cardiac specimens. To our knowledge this is the first documented case of P. yeei infection in a heart transplant patient.


Interception and attenuation of atmospheric pollution in a lowland ash forested site, Old Pond Close, Northamptonshire, UK.
A study of interception of chemicals at an ash plantation forest in southern-central England shows the modification of acidic pollution as it passes from precipitation, through the vegetation cover and the soil to generate surface runoff. Precipitation is highly acidic (pH 3.7-4.8, alkalinity -16 to -200 microEq/l) and it is enriched in the strong acid anions associated with acidification (sulfate and nitrate) as well as ammonium and the trace elements aluminium and zinc. The concentration of both sea-salt and pollutant components varies considerably over time and this is linked to washout from the atmosphere during precipitation events as marked by an inverse relationship between concentration and volume of catch. The catchment is also supplied by sea-salt and pollutant additions as dry deposition: gaseous inputs of SO(x) may also increase sulfate deposition. Through the vegetation, much of the acidity is neutralised and, particularly during the growth period, calcium, magnesium and potassium is cycled, while sodium and nitrate are partially removed. Within the catchment, weathering ensures that further base cation production occurs leading to enhanced neutralisation of acidity and the generation of positive alkalinities. As a result, surface runoff becomes buffered with alkalinity approximately 490 microEq/l and pH approximately 7.9. Thus, although the acidification input from the atmosphere is high, this does not translate to acidic runoff due to within-canopy and within-soil processes.


Analyzing the biological traits of snakes in Avicenna's Canon of medicine and making a comparison with contemporary serpentology.
Snakes are a group of reptiles in the order of squamata that have been the subject of scientific research for years. This study aimed to determine the biological characteristics of snakes that were mentioned in Avicenna's Canon of Medicine to compare with modern serpentology. Data were obtained from the Canon of Medicine using keywords concerning snakes and also appropriate literature in PubMed, Scopus, Web of Science, Scientific Information Database (SID), and IranDoc. Our results revealed that Avicenna divided snakes into three classes including highly, moderately, and slightly venomous snakes that are comparable to modern serpontology. Moreover, Avicenna clarified physiological factors such as age, gender, size, psychological state, hunger state, physical features, the type of living climate, habitat, and the time of snakebite. Considering the snake features presented in the Canon of Medicine, even though is not feasible to make a full comparison between Avicenna's snake knowledge and modern serpentology but some characteristics can be still applicable. Conclusively, the present study suggested that the criteria used for the identification and classification of snakes have changed from the medieval ages to the nowadays.


Autonomic heart rate control at rest and during unloading of the right ventricle in repaired tetralogy of Fallot in adolescents.
Arrhythmias in patients with repaired tetralogy of Fallot (ToF) might be due in part to altered autonomic heart rate control caused by altered right ventricle hemodynamics. This study investigated autonomic heart rate control in adolescents with ToF at rest and during unloading of the right ventricle. A total of 17 patients with ToF and 56 healthy controls aged 12 to 18 years underwent orthostatic stress with lower body negative pressure of -20 mm Hg. Heart rate, blood pressure, and stroke volume were recorded noninvasively. Indices of heart rate variability were computed in time and frequency domains. All patients with ToF also underwent cardiac magnetic resonance imaging, demonstrating pulmonary regurgitation and right ventricular dilation. At rest, heart rate variability indices of vagal heart rate control were nonsignificantly lower in the patients with ToF compared with controls. During lower body negative pressure, heart rate increased more in controls than patients with ToF (p <or=0.001). Further, most heart rate variability indices decreased in controls, but increased in patients with ToF (p <or=0.01 or p <or=0.001 for all variables), suggesting vagal activation in the patients with ToF. In conclusion, adolescents after ToF repair have fairly normal heart rate control at rest despite altered right ventricular hemodynamics. During unloading of the right ventricle, however, vagal heart rate control increases in the patients with ToF and decreases in the controls.


Role of conserved arginine in the heme distal site of HutZ from Vibrio cholerae in the heme degradation reaction.
HutZ from Vibrio cholerae is a dimeric enzyme that catalyzes degradation of heme. The highly conserved Arg92 residue in the HutZ family is proposed to interact with an iron-bound water molecule in the distal heme pocket. To clarify the specific role of Arg92 in the heme degradation reaction, the residue was substituted with alanine, leucine, histidine or lysine to modulate electrostatic interactions with iron-bound ligand. All four Arg92 mutants reacted with hydrogen peroxide to form verdoheme, a prominent intermediate in the heme degradation process. However, when ascorbic acid was used as an electron source, iron was not released even at pH 6.0 despite a decrease in the Soret band, indicating that non-enzymatic heme degradation occurred. Comparison of the rates of heme reduction, ligand binding and verdoheme formation suggested that proton transfer to the reduced oxyferrous heme, a potential rate-limiting step of heme degradation in HutZ, is hampered by mutation. In our previous study, we found that the increase in the distance between heme and Trp109 from 16 to 18 Å upon lowering the pH from 8.0 to 6.0 leads to activation of ascorbic acid-assisted heme degradation by HutZ. The distance in Arg92 mutants was >19 Å at pH 6.0, suggesting that subunit-subunit interactions at this pH are not suitable for heme degradation, similar to Asp132 and His63 mutants. These results suggest that interactions of Arg92 with heme-bound ligand induce alterations in the distance between subunits, which plays a key role in controlling the heme degradation activity of HutZ.


Growth of Listeria monocytogenes and Yersinia enterocolitica on cooked modified-atmosphere-packaged poultry in the presence and absence of a naturally occurring microbiota.
Cooked poultry cuts were inoculated with five-strain composite mixtures of either Listeria monocytogenes or Yersinia enterocolitica (1,000 CFU/150-g piece), packaged in 44:56 CO2-N2, and stored at 3.5, 6.5, or 10 degrees C for up to 5 weeks. Both L. monocytogenes and Y. enterocolitica grew under all test conditions. The presence of a naturally occurring microbiota did not influence the growth of either pathogen. Addition of lactate with the shelf life extender ALTA 2341 lengthened the lag phases of L. monocytogenes and Y. enterocolitica but did not prevent their growth.


N-Rich hetero-porous defective carbon induced by trace B-doping enables efficient oxygen reduction.
A facile boron doping strategy to improve the nitrogen retention in carbon-based catalysts is developed toward efficient oxygen reduction reaction via offsetting the electron migration. By considering the hetero-porous structure at the same time, this B, N co-doped catalyst outperforms commercial Pt/C in terms of both activity and stability.


Reassessing the availability of crop residue as a bioenergy resource in India: A field-survey based study.
Second-generation bioenergy, a carbon neutral or negative renewable resource, is crucial to achieving India's net-zero emission targets. Crop residues are being targeted as a bioenergy resource as they are otherwise burned on-field, leading to significant pollutant emissions. But estimating their bioenergy potential is problematic because of broad assumptions about their surplus fractions. Here, we use comprehensive surveys and multivariate regression models to estimate the bioenergy potential of surplus crop residues in India. These are with high sub-national and crop disaggregation that can facilitate the development of efficient supply chain mechanisms for its widespread usage. The estimated potential for 2019 of 1313 PJ can increase the present bioenergy installed capacity by 82% but is likely insufficient alone to meet India's bioenergy targets. The shortage of crop residue for bioenergy, combined with the sustainability concerns raised by previous studies, imply a need to reassess the strategy for the use of this resource.


Irreversible binding of [3H](-)N-chloroethylnorapomorphine to mammalian brain tissue.
A proposed dopamine (DA) receptor labeling agent, [3H](-)N-chloroethylnorapomorphine (3H-NCA) underwent relatively little chemical change at 25 degrees C and pH 6.4 up to an hour of incubation. At low (nM) concentrations it bound rapidly and avidly to a membrane preparation of calf caudate nucleus, but the binding did not saturate over two hours of incubation or at ligand concentrations between 0.2 nM and 10 microM. While similarly bound [3H]-(-)apomorphine was rapidly displaced by DA and other agents that interact with DA receptors, 3H-NCA could not be displaced by unlabeled DA, apomorphine and (+)butaclamol, nor by denaturation of the tissue with trichloracetic acid (TCA). There was no evidence of selectivity of binding of 3H-NCA in regions of rat brain, and binding occurred even to TCA-denatured caudate tissue. Catechol-aporphines prevented binding of 3H-NCA to calf caudate membranes by up to 30%, but this effect was not stereoselective and was lost at concentrations of 3H-NCA above 100 nM. In contrast, DA and ADTN as well as neuroleptics and adrenergic agonists had no such effect. The results suggest that while 3H-NCA may bind irreversibly, and possibly covalently, it does not have high selectivity for labeling dopamine D-3 or D-2 receptor sites, but may be partially selective for an aporphine binding site.


Presynaptic NR2A-Containing NMDARs Are Required for LTD between the Amygdala and the Perirhinal Cortex: A Potential Mechanism for the Emotional Modulation of Memory?
Visual recognition memory relies on long-term depression-like mechanisms within the perirhinal cortex and the activation of the lateral amygdala can enhance visual recognition memory. How the lateral amygdala regulates recognition memory is not known, but synaptic plasticity at amygdala-perirhinal synapses may provide a mechanism for the emotional enhancement of recognition memory. In this study, we investigate the mechanisms of long-term depression (LTD) at the amygdala-perirhinal synapse in male Lister Hooded rats. We demonstrate that LTD at this input relies on NR2A-containing NMDARs, located presynaptically. Therefore, the underlying mechanisms of LTD, at the amygdala-perirhinal input, which may regulate the emotional context for recognition memory, are different to previously described postsynaptic NR2B-NMDAR mechanisms of intraperirhinal LTD that subserve recognition memory.


MENX.
Multiple endocrine neoplasias (MEN) are a group of hereditary disorders characterized by tumors arising in more than one neuroendocrine tissue. There are two major forms which can occur in humans, MEN type 1 (MEN1) and MEN type 2 (MEN2). These syndromes are transmitted as autosomal dominant traits with high penetrance and have a different tumor spectrum. MEN1 and MEN2 are caused by germline mutations in the MEN1 and RET genes, respectively. Recently, a variant of the MEN syndromes was discovered in a rat colony and was named MENX since affected animals develop tumors with a spectrum that shares features with both MEN1 and MEN2 human syndromes. Extensive genetic studies identified a germline mutation in the Cdkn1b gene, encoding the p27 cell cycle inhibitor, as the causative mutation for MENX. Capitalizing on these findings, heterozygous germline mutations in the human homologue, CDKN1B, were searched for and identified in patients with multiple endocrine tumors. As a consequence of this discovery, a novel human MEN syndrome, named MEN4, was recognized which is caused by mutations in p27. Altogether these studies identified Cdkn1b/CDKN1B as a novel tumor susceptibility gene for multiple endocrine tumors in both rats and humans. Here I review the phenotypic features and the genetics of the MENX rat syndrome. I briefly address the main functions of p27 and how they are affected by the MENX-associated mutation. Finally, I present examples of how this animal model might be exploited as a translational platform for preclinical studies of pituitary adenomas.


An ELISA capture assay for the E7 transforming proteins of HPV16 and HPV18.
ELISA capture assays were established for the E7 transforming proteins of HPV16 and HPV18, based on a range of previously characterised polyclonal and monoclonal antibodies. No cross-reactivity was observed in the ELISAs between HPV18 E7 and HPV16 E7. Immunoreactive E7 protein (iE7) was measured in a series of HPV-transformed cell lines, and ranged from 0.6 to 17.7 ng iE7/mg cell protein. iE7 was labile at 22 degrees C (t1/2 = 37 min) but relatively more stable at 4 degrees C (t1/2 = 210 min). HPV16 E7 protein at concentrations from 0.10 to 0.69 ng iE7/mg cell protein was detected in 5 of 13 smears from women with abnormal cervical cytology. Assay of E7 protein may play a role in the detection of HPV-induced cervical lesions with malignant potential.