NIR spectroscopy combined with 1D-convolutional neural network for breast cancerization analysis and diagnosis.
Near-infrared (NIR) spectroscopy with deep penetration can characterize the composition of biological tissue based on the vibration of the X-H group in a rapid and high-specificity way. Deep learning is proven helpful for rapid and automatic identification of tissue cancerization. In this study, NIR spectroscopic detection equipped with the lab-made NIR probe was performed to in situ explore the change of molecular compositions in breast cancerization, where the diffused NIR spectra were efficiently collected at different locations of cancerous and paracancerous areas. The breast cancerous-paracancerous discriminant model was established based on one-dimensional convolutional neural network (1D-CNN). By optimizing the structure of the neural network, the high classification accuracy (94.67%), recall/sensitivity (95.33%), specificity (94.00%), precision (94.08%) and F1 score (0.9470) were achieved, showing the better discrimination ability and reliability than the K-Nearest Neighbor (KNN, 88.34%, 98.21%, 76.11%, 83.59%, 0.9031) and Fisher Discriminant Analysis (FDA, 90.00%, 96.43%, 81.82%, 87.10%, 0.9153) methods. The experimental results indicate that the application of 1D-CNN can discriminate the cancerous and paracancerous breast tissues, and provide an intelligent method for clinical locating, diagnosis and treatment of breast cancer.


The first conversion of camptothecin to (S)-mappicine by an efficient chemoenzymatic method.
Camptothecin has been converted for the first time to (S)-mappicine via mappicine ketone, which is the sole product of the microwave irradiation of camptothecin. Baker's yeast reduction of mappicine ketone yielded (S)-mappicine in high optical purity.


Clinical utility of ABCB1 genotyping for preventing toxicity in treatment with irinotecan.
Preventing severe irinotecan-induced adverse reactions would allow us to offer better treatment and improve patients' quality of life. Transporters, metabolizing enzymes, and genes involved in the folate pathway have been associated with irinotecan-induced toxicity. We analyzed 12 polymorphisms in UGT1A1, ABCB1, ABCG2, ABCC4, ABCC5, and MTHFR in 158 patients with metastatic colorectal cancer treated with irinotecan and studied the association with grade >2 adverse reactions (CTCAE). Among the most frequent ADRs, the SNPs rs1128503, rs2032582, and rs1045642 in ABCB1 and rs1801133 in MTHFR were associated with hematological toxicity and overall toxicity. The SNP rs11568678 in ABCC4 was also associated with overall toxicity. After correction of P values using a false discovery rate, only ABCB1 variants remained statistically significant. Haplotype analysis in ABCB1 showed an 11.3-fold and 4.6-fold increased risk of hematological toxicity (95% CI, 1.459-88.622) and overall toxicity (95% CI, 2.283-9.386), respectively. Consequently, genotyping of the three SNPs in ABCB1 can predict overall toxicity and hematological toxicity with a diagnostic odds ratio of 4.40 and 9.94, respectively. Genotyping of ABCB1 variants can help to prevent severe adverse reactions to irinotecan-based treatments in colorectal cancer.


Conformational dynamics of loops L11 and L12 of kinesin as revealed by spin-labeling EPR.
The EPR spectra of the spin labels attached to loops L11 and L12 of kinesin were resolved into slow (rotational correlation time, tau=10-45 ns) and fast (tau=2 ns) components. The fraction of the slow component increased considerably when kinesin was complexed with a microtubule (MT). On MT binding and in the presence of nucleotides ADP and AMPPNP, the spin labels on L11, particularly at A252C and L249C, significantly decreased the fraction of the slow component. Moreover, dipolar EPR detected a wide distribution in distance range, 1-2 nm between the two spin labels attached to T242C/A252C or A247C/A252C; this distribution was slightly narrower in the presence of MTs than in their absence. These results suggested that the L11 residues undergo conformational transition on the binding of nucleotides and MT, while these residues remained to fluctuate over a nanometer range.


Copper nanocoils synthesized through solvothermal method.
Recently helical nanostructures such as nanosprings and nanocoils have drawn great interests in nanotechnology, due to their unique morphologies and physical properties, and they may be potential building blocks in sorts of electromechanical, magnetic, photoelectronic and plasmonic devices at micro/nanoscales. In this report, multi-turns copper nanocoils were synthesized through a modified solvothermal method, in which the mixture of water and N-methyl-2-pyrrolidone (NMP) were selected as reaction medium and copolymer poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP/VA 64E) as reductant. In the liquid solution, nanosprings could be formed from relaxed nanocoils and demonstrated high elasticity. These nanocoils and nanosprings are of single crystalline structure, with the characteristics wire diameters ranging from tens to a few hundreds of nanometers and the ring/coil diameters mostly ~10-35 microns. Their growth and deformation mechanisms were then investigated and discussed along with that of previously reported single-turn copper nanorings. This work could be of importance for researchers working on synthesis and applications of novel 1-D helical nanomaterials and their functional devices.


Adjuvant treatment with pegylated interferon α-2a versus low-dose interferon α-2a in patients with high-risk melanoma: a randomized phase III DeCOG trial.
Adjuvant treatment with interferon (IFN)-α-2a improved disease-free survival (DFS) and showed a trend for improving overall survival (OS) in melanoma. This trial was designed to examine whether PEG-IFN is superior to IFN with regard to distant metastasis-free survival (DMFS), DFS and OS. In this multicenter, open-label, prospective randomized phase III trial, patients with resected cutaneous melanoma stage IIA(T3a)-IIIB (AJCC 2002) were randomized to receive PEG-IFN (180 μg subcutaneously 1×/week; 24 months) or IFN α-2a (3MIU subcutaneously 3×/week; 24 months). Randomization was stratified for stage, number of metastatic nodes, age and previous IFN treatment. The primary end point was DMFS; secondary end points were OS, DFS, quality of life (QoL) and tolerability. A total of 909 patients were enrolled (451 PEG-IFN versus 458 IFN). Neither 5-year DMFS [PEG-IFN 61.0% versus IFN 67.3%; hazard ratio (HR) 1.16, P = 0.21] nor 5-year OS (PEG-IFN 73.2% versus IFN 75.2%; HR 1.05, P = 0.70) nor 5-year DFS (PEG-IFN 57.3% versus IFN 60.9%; HR 1.09, P = 0.40) showed significant differences. Subgroup analyses in patients ± ulcerated primaries and of different tumor stages did not find differences in DMFS, OS or DFS between the treatment groups. One hundred and eighteen patients (26.2%) in the PEG-IFN and 61 patients (13.3%) in the IFN population did not receive the full dosage and length of treatment due to adverse events (P < 0.001). Leukopenia and elevation of liver enzymes were more common in the PEG-IFN arm (56% versus 23.5% LCP; 19.1% versus 9.4% AST; 33.0% versus 16.5% ALT). QoL was identical for nearly all domains. PEG-IFN did not improve the outcome over IFN. A higher percentage of patients under PEG-IFN discontinued treatment due to toxicity. NCT00204529.


Teaching students to identify and document social determinants of health.
Social determinants of health (SDH) are responsible for significant health disparities, morbidity and mortality. It is important to acculturate trainees to identify and document SDH. This can elevate their perceptions related to the importance and relevance of SDH. Documentation can encourage trainees to see SDH as factors which medical providers should address. Researchers devised a novel approach to demonstrate the value of SDH to undergraduate medical students. Proprietary diagnostic codes for SDH and procedure codes for action taken to address them, were developed. Students were encouraged to log these into electronic records for clinical encounters. Students' voluntary use of these codes was evaluated. Additionally, students were surveyed on their familiarity with the concept of SDH, their perceptions of the importance of SDH, as well as documenting SDH, twice in the study period, and results were compared. In their second year of use, proprietary codes were compared to newly available SDH related ICD-10 codes. Students utilized proprietary codes more often than SDH related ICD-10 codes. Over 20,000 codes were logged. Comparison of survey items showed modest increases in students' positive perception about the role of SDH in patient health. Students' voluntary logging of SDH codes demonstrates they perceived these factors to be important and relevant to patient encounters. Future analyses will examine students' knowledge, attitudes, beliefs and practice patterns related to SDH.


Endoscopic removal of chondromyxoid fibroma of the ethmoid sinus.
The first case of the endoscopic intranasal excision of chondromyxoid fibroma as an outgrowth of the ethmoid bone is reported. This case appears to represent the second reported type of recurrence of CMF in the head and neck area and the second type of CMF originating in the ethmoid.


DNA triplex with conformationally locked sugar disintegrates to duplex: Insights from molecular simulations.
DNA triplex is a popular, higher-order structural arrangement with several biological importance. In the present article, we examined the impact of replacing regular deoxyribose sugar by conformationally locked sugar on the structure/stability of a DNA triplex. We individually modified single strands of DNA triplex (3'-5' strand/5'-3' strand) and observed the consequences in terms of the overall structural integrity and energetics using all-atom explicit-solvent Gaussian accelerated molecular dynamics simulations at biological salt concentration. As anticipated, the control DNA triplex maintained the structural integrity throughout the simulations. However, it is striking to note that a duplex evolved from both the modified systems (3'-5' modified triplex as well as 5'-3' modified triplex). The resultant duplexes in both cases contain a modified strand and a regular strand, whereas the third strand (regular ssDNA) left the binding site entirely. We observed that the modified ssDNA binds to the regular ssDNA with high affinities in both the hybrid duplexes (∼-64 kcal/mol), significantly higher than the regular ssDNA - regular ssDNA interaction (∼-52 kcal/mol). The remarkable binding of modified ssDNA to regular ssDNA can be utilized to design new antisense oligonucleotides, and the role of such modified oligonucleotides in anticancer therapy is foreseen.


A 28-day oral toxicology study of an aqueous extract of Polypodium leucotomos (Fernblock®).
Fernblock® is a standardized commercial aqueous extraction of the leaves of the tropical fern Polypodium leucotomos promoted as an orally active photoprotective substance. In a previous battery of toxicological tests on Fernblock®, no genotoxicy was observed and no oral toxicity was observed up to 1200 mg/kg bw/day. The current study was conducted in Hsd.Han Wistar rats using doses of 0, 2000, 3500, and 5000 mg/kg bw/day Fernblock® by gavage for 28 consecutive days. No mortality or toxic effects were observed and no target organs were identified. The no observed adverse effect level was determined to be 5000 mg/kg bw/day, the highest dose tested.


From Other Journals: A Review of Recent Articles in Pediatric Cardiology.
In this review, we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. Our aim is to provide a summary of the latest articles published recently in other journals in our field. The articles address (1) cardiac resynchronization in children with symptomatic ventricular dysfunction and dyssynchrony which seems to result in higher transplant-free survival, (2) outcomes of aortic leaflet reconstruction including Ozaki procedure to repair aortic valve disease in adolescents, (3) meta-analysis for risk factors of ventricular tachycardia and death after repaired tetralogy of Fallot which reiterates the known risk factors and showed that the severity of pulmonary regurgitation is not in itself associated with outcomes although the ventricular response to regurgitation (dilation and dysfunction) is, (4) preschool promotion of healthy life style did not associate with sustained effect when evaluated later in childhood although repeated intervention seems to have a dose-related effect to promote healthy life style, (5) the lack of beneficial effects of angiotensin-converting enzyme inhibitors in the interstage period, and (6) a new phenomenon of acute heart failure and multisystem inflammatory syndrome in children temporarily related to the COVID-19 pandemic.


Human-, Ovine-, and Bovine-Specific Viral Source Tracking Tools to Discriminate Between the Major Fecal Sources in Agricultural Waters.
This study evaluated the sources of fecal contamination in different river catchments, using a combination of microbial source tracking tools, for human, ruminant, ovine and bovine livestock, in order to define appropriate water management strategies. Every source of waterway pollution was evaluated in river water samples from one urban river catchment and two important farming regions in New Zealand. Fecal pollution was initially measured by testing Escherichia coli and evaluating the presence of human- and ruminant-associated DNA markers of Bacteroidales (BiAdo, BacHum-UCD, BacH, and BacR) and human and ruminant fecal sterols/stanols ratios. Then specific fecal pollution sources were assessed with previously reported quantitative PCR assays targeting human-, bovine-, and ovine-specific viruses: human adenoviruses (HAdV), human JC polyomaviruses, bovine polyomaviruses (BPyV), and ovine polyomaviruses (OPyV). High level of ruminant fecal contamination was detected all over the farming areas, whereas no ruminant sources were identified in the urban river sampling sites. BacR was the most frequently observed ruminant marker and OPyV and BPyV allowed the identification of ovine and bovine fecal sources. The human fecal viral marker (HAdV) was the most frequently observed human marker, highly abundant in the urban sites, and also present in farming areas. This is the first study using simultaneously the ovine and the bovine viral markers to identify and quantify both bovine and ovine fecal pollution.


Acetylation of Tat defines a cyclinT1-independent step in HIV transactivation.
The HIV transcriptional activator Tat is acetylated by p300 at a single lysine residue in the TAR RNA binding domain. We have generated monoclonal and polyclonal antibodies specific for the acetylated form of Tat (AcTat). Microinjection of anti-AcTat antibodies inhibited Tat-mediated transactivation in cells. Similarly, the p300 inhibitor Lys-CoA and siRNA specific for p300 suppressed Tat transcriptional activity. Full-length synthetic AcTat bound to TAR RNA with the same affinity as unacetylated Tat, but formation of a Tat-TAR-CyclinT1 ternary complex was completely inhibited in the presence of AcTat. We propose that Tat acetylation may help in dissociating the Tat cofactor CyclinT1 from TAR RNA and serve to transfer Tat onto the elongating RNA polymerase II.


A revision of Eastern Palaearctic Anthobium Leach, 1819 (Coleoptera: Staphylinidae: Omaliinae: Anthophagini). VI. Fortepunctatum group.
The Fortepunctatum species group is established for two new Anthobium species from China: A. fortepunctatum sp. n. (Gansu, Shaanxi) and A. flavoguttatum sp. n. (Sichuan). The group is defined, briefly discussed, and a key to species is given. Both species are described and illustrated, and their geographical distribution is mapped.


A π-extended tercarbazole-core multi-resonance delayed fluorescence emitter exhibiting efficient narrowband yellow electroluminescence.
Herein, a simple and versatile molecular design for long-wavelength (>550 nm) multi-resonance thermally activated delayed fluoresence emitters is reported. Extending a fully fused polycyclic π-system with an additional para-N-π-N conjugation induces narrowband bright-yellow photoluminescence and electroluminescence emissions at ∼560 nm.


Structure-based screening and design in drug discovery.
Structure-based screening represents an integrated approach for the identification and optimization of hits by the combined use of nuclear magnetic resonance (NMR) spectroscopy, homology modeling and X-ray crystallography. A general feature of the methodology is the introduction of structure-based methods (NMR, modeling and X-ray) early in the drug discovery process to optimize hits in terms of their affinities and specificities. This approach promises to deliver leads with improved physicochemical properties as compared with leads generated from a traditional HTS program. This review presents examples of structure-based screening from published and in-house drug discovery projects.


A Preliminary Discussion on the Safety of Mild Therapeutic Hypothermia in Target Vessels after Endovascular Intervention in Acute Large Vessel Occlusion Cerebral Infarction.
The aim of this study was to discuss the safety of rapid administration of 4°C hypothermic normal saline into the occluded vessels using an intra-arterial catheter to induce mild hypothermia following endovascular thrombectomy in patients with acute large vessel occlusion cerebral infarction. We selected 78 patients with acute large vessel occlusion cerebral infarction who underwent endovascular thrombectomy in the Department of Neurology of our hospital from January 2020 to July 2022 and achieved TICI 2b recanalization. Twenty-five patients were administered 500 mL of 4°C hypothermic normal saline in the occluded vessels at a rate of 25 mL/min to induce mild hypothermia. Twenty pairs of subjects conformed to strict matching and were finally included in the statistical analysis. The two groups of patients differed significantly in white blood cell count and percentage of neutrophils (p < 0.05); however, there were no significant differences in D-dimer, procalcitonin, and BNP levels. The two groups of patients did not differ significantly with respect to the incidence of the following indicators: upper gastrointestinal bleeding; pulmonary infection; venous thrombosis; vasospasms; seizures; and chills (p > 0.05). Mild therapeutic hypothermia in target vessels plus endovascular thrombectomy was shown to be safe in patients with acute large vessel occlusion cerebral infarction.


Clinical Outcome in Patient Undergoing LSCS via ERAS Pathway versus Traditional Pathway: A Prospective Observational Study.
ERAS is an evidence-based management protocol for perioperative care, to accelerate patient recovery. The field of obstetrics has been a late adapter of ERAS pathway for CS, and the literature is limited from Indian population. This prospective non-randomized comparative clinical study was conducted on 190 pregnant patients, out of which 95 were subjected to ERAS protocol (Group 1) and remaining 95 cases were enrolled in existing traditional protocol (Group 2). The primary objective was to compare quality of recovery based on obstetric-specific QoR 11 questionnaire between patients undergoing ERAC and traditional protocol for elective LSCS. Secondary objective was to compare perioperative bleeding, breast feeding initiation and difficulties, first oral intake, ambulation attempts, decatheterization, surgical site infection and length of hospital stay. At 24 h postoperatively, mean QoR score was significantly higher for patients in the ERAC group (85.5 ± 7.46 vs 57.1 ± 11.33, p value < 0.01). In the ERAC group, 50.5% of the mothers started breastfeeding within first hour. The mean duration to start oral intake postoperatively was significantly lower in ERAC group. In the ERAC group, ambulation and decatheterization were attempted within 6 h postoperatively in 86.3%. The mean length of hospital stay was significantly lower for patients in the ERAC group (68.8 ± 1.9 vs 105.4 ± 25.7 h, p value < 0.001). The use of ERAC protocol at cesarean delivery significantly improves quality of recovery and length of hospital stay.


A self-powered photoelectrochemical oxytetracycline aptasensor: An integrated heterojunction photoanode of metal-organic framework derived ZnO nanopolyhedra/graphitic carbon nitride with high carrier density.
The development of effective strategies for the detection of oxytetracycline (OTC) in soil is of great importance for preserving agri-environmental safety and human health. Herein, a novel photoactive material of metal-organic framework (MOF) derived ZnO nanopolyhedra/graphitic carbon nitride (ZnO/g-C3N4) heterojunction was designed by mixing calcination of zeolite imidazole framework-8 (ZIF-8) and melamine. A self-powered photoelectrochemical aptasensor for the sensitive and selective detection of OTC in soil was proposed using ZnO/g-C3N4 as the photoanode. The photoactivity of the MOF derived ZnO nanopolyhedra was regulated effectively by the introduction of g-C3N4, which resulted in a 7-fold increase in the photocurrent of the ZnO nanopolyhedra at a bias potential of 0 V. It was assigned to the higher carrier density of ZnO/g-C3N4. By virtue of the amplified photocurrent of ZnO/g-C3N4, the specificity of the OTC aptamer and the anti-interference ability of the self-powered sensing method, the designed aptasensor demonstrated the advantages of a wide linear range (0.005-200 nM), low limit of detection (1.49 × 10-3 nM), good selectivity and good reproducibility. For real soil sample analysis, satisfactory recoveries were obtained and further verified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).


Bladder cancer in individuals with spinal cord injuries.
Prospective scoping review. To conduct a scoping review of all the literature related to bladder cancer in individuals with spinal cord injuries (SCI). Literature search of the databases Pubmed, CINAHL, ProQuest, PsychINFO and Scopus up to and including August 2012. Articles related to bladder cancer among SCI patients were identified, and data pertaining to epidemiology, risk factors, screening, prevention and management was reviewed and summarized. An association between bladder cancer and SCI was first reported in the 1960s, with some case reports suggesting an alarmingly high rate among SCI patients. More recent epidemiological studies have reported this risk to be substantially lower. However, bladder cancer in SCI patients tends to present at an earlier age and at a more advanced pathological stage than bladder cancer in the general population. Presenting symptoms may be atypical, and early recognition is important to improve prognosis with surgical resection. Several risk factors have been identified, including indwelling catheters, urinary tract infections and bladder calculi. Screening of SCI patients for bladder cancer is routinely recommended in many SCI management guidelines and by expert consensus; however, evidence for screening tools and protocols is lacking. Bladder cancer is a rare, and potentially lethal occurrence in SCI patients. Physicians need to have a high index of suspicion for bladder cancer, particularly among SCI patients managed with long-term indwelling catheters.


Biotechnological implications of filamentation in Saccharomyces cerevisiae.
The genetics governing the morphological switch from round or ovoid cells to filamentous growth in Saccharomyces cerevisiae has received significant interest in relation to sensing and signaling pathways as well as the control of cell processes including budding, elongation and adhesion. Little is known about the environmental signals which trigger these morphological changes from a biotechnological point of view. This review aims to highlight the main causes of filamentous growth in S. cerevisiae in its industrial setting with the purpose of stimulating additional studies within this field.


Extrathoracically adjustable pulmonary artery banding.
A new technique of adjustable pulmonary artery banding is presented. A tourniquet system has been used in eight consecutive infants with complex congenital cardiac anomalies during the past 2 years. They had severe congestive heart failure, and six of them required inotropic support preoperatively. All survived the banding procedure and there were no hospital deaths. Four of the eight infants required additional adjustment of the band to improve hypoxemia or persistent congestive heart failure 3 hours to 4 months postoperatively. Each adjustment was made easily via a small skin incision without thoracotomy. This technique allows fine adjustment by gentle and delicate tightening and loosening of the band during and after operation, so that the technique avoids most mortality and morbidity related to an inappropriate banding and brings satisfactory symptomatic palliation.


Kidney protective effects of baroreflex activation therapy in patients with resistant hypertension.
Baroreflex activation therapy (BAT) is approved for the treatment of resistant hypertension. In addition to blood pressure (BP) reduction, pilot studies suggested several organoprotective effects of BAT. Thirty-two patients with resistant hypertension were prospectively treated with BAT. Besides office BP and 24-hour ambulatory BP (ABP) measurements, detection of a urinary proteome-based classifier (CKD273), which has been shown to predict chronic kidney disease (CKD) progression, was carried out at baseline and after 6 months of BAT. Office BP significantly decreased from 170 ± 25/90 ± 18 to 149 ± 29/82 ± 18 mm Hg. Analysis of CKD273 score and eGFR with CKD-EPI equation at baseline revealed strong correlation (r = 0.568, P < 0.001). After 6 months of BAT, there was no significant change in CKD273 score (-0.061 [95% CI: -0.262 to 0.140], P = 0.601). However, by stratification of the data regarding ABP response, there was a statistically significant (P = 0.0113) reduction in the CKD273 score from a mean of 0.161 [95% CI: -0.093 to 0.414] to -0.346 [95% CI: -0.632 to -0.060] after BAT in patients with systolic ABP decrease of ≥5 mm Hg. These data emphasized potential nephroprotective effects of BAT in patients with sufficient BP response.


Tuberculosis and nontuberculous mycobacterial infections in older adults.
Tuberculosis is one of the world's great public health crises. It is estimated by the World Health Organization that roughly one third of the world's populations, or some 2 billion people, are infected with Mycobacterium tuberculosis, the causative agent. More than 8 million people every year develop active tuberculosis disease, and 2 million die as a result. This article reviews tuberculosis and nontuberculous mycobacterial infections in older adults.


Shallow water meiobenthos of the bermuda platform.
The distribution and abundance of subtidal meiobenthos were studied monthly from June 1967 through May 1968 at five stations on the Bermuda platform: Two in Castle Harbor, two in Baileys Bay, and one in Harrington Sound. Total number of individuals ranged from 12.2-133.3x104/m2 and dry weight biomass from 33-259.3 mg/m2. Free-living nematodes constituted 72.6% of the total numbers and 71.8% of the biomass and were the most abundant organisms at all but one station. Harpacticoid copepods were second in overall abundance and were the most abundant organism at one station. Polychaetes, ostracods, a kinorhynch and a priapulid were also common.Distinct seasonal patterns were observed. Total population values were highest in late spring, lowest in the winter. Nematodes often reached maximum values in the winter and appear to be correlated with minimum temperatures. Copepod abundance was related to reproductive cycles and changing sediment conditions. Copepods were abundant in the medium to coarse-grained sands, nematodes in the finer sediments. Meiofauna was greatly reduced in the lower layers of sediment; this reduction was attributed to decreased interstitial water and oxygen content.Field and laboratory results indicated specific grain size preferences of the Harpacticoida. Epigrowth feeding nematodes were dominant in sandy sediments, deposit feeders in the muds. Epigrowth dominance was probably related to carbon rich aggregated particles coating the sediments.Three distinct harpacticoid "parallel level bottom communities" were defined: (1) the Leptastacus macronyx (T. Scott)- Praeleptomesochra africana (Kunz) community in the submerged "beach sands," (2) the Stenhelia (D.) bermudensis mihi-Typhlamphiascus lamellifer (Sars) -Cletodes dissimilis Willey community in the silty-sands and (3) the Phyllopodopsyllus hermani mihi community in the medium to coarse-grained sands.Diversity analyses of the harpacticoid communities indicated highly evolved, stable assemblages in those areas of low physical stress and less stable, variable assemblages in areas of high physical stress.


Comparison of colour Doppler indices of pelvic arteries in women with bilateral hypogastric artery ligation and controls.
The aim of this study is to compare the blood flows of bilateral uterine, ovarian and arcuate arteries in patients who underwent bilateral hypogastric ligation (BHL), with the controls having similar characteristics. The S/D, the RI and the PI were measured on uterine, arcuate and ovarian arteries in 7 women with BHL and compared with 10 controls. There were not significant differences between the Doppler indices of the two groups. In conclusion, our study suggests that BHL preserves pelvic function and fertility.


Distractions at nurses' stations during intershift report.
Observations of distractions during intershift report at nurses' stations on ten medical-surgical units in an acute-care general hospital are summarized. Almost five times more auditory and visual distractions occurred at nurses' stations at which report took place at an open charting desk than at nurses' stations with a separate reporting area.


The benefits of the explanation of the risks of anesthesia in the day surgery patient.
To ascertain the benefits of the preoperative discussion of the risks of anesthesia with parents of ASA status I or II pediatric day surgery patients. Survey analysis. Pediatric day surgery unit. 54 parents of ASA status I or II pediatric day surgery patients between the ages of 7 months and 16 years. After informed consent for the anesthetic was obtained by a member of the anesthesiology team, the parent(s) were given a questionnaire on their feelings about the explanation of the risks of anesthesia. The questionnaire evaluated how parents felt about their understanding of the risks of anesthesia, the effect of hearing the risks of anesthesia on their anxiety levels, and the benefits of hearing the risks of anesthesia. Over 90% of the parents felt that they understood the risks of anesthesia, that the discussion of the risks would have no effect on their decision to proceed with surgery, and that the explanation of the risks is desirable; 92% considered the explanation desirable either out of a sense of responsibility or because they welcomed better understanding. Our study suggests the benefits of the explanation of the risks of anesthesia appear to be rooted in satisfying parental responsibility and understanding, and not in providing information for decision making or anxiety relief. Anesthesiologists should not feed compelled to always detail all the risks, but should seek to satisfy individual parental needs.


Traumatic optic neuropathy treatment trial (TONTT): open label, phase 3, multicenter, semi-experimental trial.
Intravenously administered erythropoietin (EPO) was firstly commenced (phase 1) in patients with indirect traumatic optic neuropathy (TON) by this group in 2011. It was re-tested by another group (phase 2) in 2014. This multicenter clinical trial was designed to compare its effect with intravenous steroid and observation. Included were TON patients ≥5 years of age and with trauma-treatment interval of ≤3 weeks. Follow-up visits were set at 1, 2, 3, 7, 14, 30, and at least 90 days after treatment. EPO and methylprednisolone were infused intravenously every day for three consecutive days. Primary outcome measure was change in the best corrected visual acuity (BCVA). Secondary outcomes included change in color vision and relative afferent pupillary defect (RAPD), side effects, and factors affecting the final visual improvement. Out of 120 patients, 100 (EPO: 69, steroid: 15, observation: 16) were finally included. All three groups showed a significant improvement of BCVA which was not significantly different between the groups (adjusted for pretreatment BCVA). Color vision was significantly improved in the EPO group. Late treatment (>3 days) (odds ratio = 2.53) and initial BCVA of NLP (odds ratio = 5.74) significantly worsened visual recovery. No side effect was observed in any group. EPO, steroid, and observation showed a significant improvement of BCVA in patients with TON. Initial BCVA of NLP and late treatment (>3 days) were significant risk factors for visual improvement.


Mouse Models of Psoriasis: A Comprehensive Review.
The use of preclinical animal models of psoriasis has significantly increased over the last three decades, with each model having unique strengths and limitations. Some models translate better to human disease, and many have provided unique insight into psoriasis disease pathogenesis. In this comprehensive review, we present a comparative description and discussion of genetic mouse models, xenograft approaches, and elicited methods using cytokine injections into and topical imiquimod onto mice. We provide an inclusive list of genetically modified animals that have had imiquimod applied to or cytokines injected into their skin and describe the outcomes of these manipulations. This review will provide a valuable resource for those interested in working with psoriasis animal models.


Magnetic Particle Imaging tracks the long-term fate of in vivo neural cell implants with high image contrast.
We demonstrate that Magnetic Particle Imaging (MPI) enables monitoring of cellular grafts with high contrast, sensitivity, and quantitativeness. MPI directly detects the intense magnetization of iron-oxide tracers using low-frequency magnetic fields. MPI is safe, noninvasive and offers superb sensitivity, with great promise for clinical translation and quantitative single-cell tracking. Here we report the first MPI cell tracking study, showing 200-cell detection in vitro and in vivo monitoring of human neural graft clearance over 87 days in rat brain.


ApoE gene polymorphisms and metals and their interactions with cognitive function.
To analyze the relationship between plasma metal elements, ApoE gene polymorphisms and the interaction between the two and impaired cognitive function in elderly population. A stratified sample was drawn according to the age of the study population, and 911 subjects were included. Baseline information and health indicators were obtained, and cognitive function status was assessed by health examination, a general questionnaire and Mini-Mental Status Examination. Plasma metal elements were measured, and SNP typing was performed. Binary logistic regression was used to analyze the factors influencing cognitive function status and the association between the SNP genetic pattern of the ApoE gene and cognitive function. The differences in gene frequencies and genotype frequencies of the ApoE rs7412 and rs7259620 genotype frequencies were statistically different between the cognitive impairment group and the control group (P < 0.05). statistically differences were found for the codominant model in rs7412-TT compared with the CC genotype (OR = 3.112 (1.159-8.359), P = 0.024) and rs7259620-AA compared with the GG genotype (OR = 1.588 (1.007-2.504), P = 0.047). Statistically differences were found in the recessive models rs7412-TT compared with (CC + CT) (OR = 2.979 (1.112-7.978), P = 0.030), rs7259620-AA compared with (GG + GA), and rs405509-GG compared with (TT + TG) (OR = 1.548(1.022-2.344), P = 0.039) all of which increased the risk of developing cognitive impairment. The differences in plasma Fe, Cu, and Rb concentrations between the case and control groups were significant (P < 0.05). The regression results showed that the plasma Cd concentrations in the Q1 range was a protective factor for cognitive function compared with Q4 (0.510 (0.291-0.892), P = 0.018). Furthermore, there was a multiplicative interaction between the codominant and recessive models for the Q2 concentrations of Cd and the rs7259620 loci, and the difference was significant, indicating increased risk of developing cognitive impairment (codominant model OR = 3.577 (1.496-8.555), P = 0.004, recessive model OR = 3.505 (1.479-8.307), P = 0.004). There was also a multiplicative interaction between Cd and the recessive model at the rs405509 loci, and the difference was significant, indicating increased risk of developing cognitive impairment (OR = 3.169 (1.400-7.175), P = 0.006). The ApoE rs7412, rs7259620 and rs405509 loci were associated with cognitive impairment in the elderly population, and there was an interaction between plasma metalloid Cd and the rs7259620 and rs405509 loci that increased the risk of cognitive impairment in the elderly population.


Influence of reconsolidation in maintenance of cocaine-associated contextual memories formed during adolescence or adulthood.
Adolescents are at increased risk to develop substance use disorders and suffer from relapse throughout life. Targeted weakening of drug-associated memories has been shown to reduce relapse-like behavior in adult rats, however this process has been understudied in adolescents. We aimed to examine whether adolescent-formed, cocaine-associated memories could be manipulated via reconsolidation mechanisms. To accomplish this objective, we used an abbreviated operant cocaine self-administration paradigm (ABRV Coc-SA). Adult and adolescent rats received jugular catheterization surgery followed by ABRV Coc-SA in a distinct context for 2 h, 2×/day over 5 days. Extinction training (EXT) occurred in a second context for 2 h, 2×/day over 4 days. To retrieve cocaine-context memories, rats were exposed to the cocaine-paired context for 15 min, followed by subcutaneous injection of vehicle or the protein synthesis inhibitor cycloheximide (2.5 mg/kg). Two additional EXT sessions were conducted before a 2 h reinstatement test in the cocaine-paired context to assess cocaine-seeking behavior. We find that both adult and adolescent cocaine-exposed rats show similar levels of cocaine-seeking behavior regardless of post-reactivation treatment. Our results suggest that systemic treatment with the protein synthesis inhibitor cycloheximide does not impair reconsolidation of cocaine-context memories and subsequent relapse during adulthood or adolescence.


Coordinated response of milk bacterial and metabolic profiles to subacute ruminal acidosis in lactating dairy cows.
Bovine milk is an important source of nutrition for human consumption, and its quality is closely associated with the microbiota and metabolites in it. But there is limited knowledge about the milk microbiome and metabolome in cows with subacute ruminal acidosis. Eight ruminally cannulated Holstein cows in mid lactation were selected for a 3-week experiment. The cows were randomly allocated into 2 groups, fed either a conventional diet (CON; 40% concentrate; dry matter basis) or a high-concentrate diet (HC; 60% concentrate; dry matter basis). The results showed that there was a decreased milk fat percentage in the HC group compared to the CON group. The amplicon sequencing results indicated that the alpha diversity indices were not affected by the HC feeding. At the phylum level, the milk bacteria were dominated by Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes both in the CON and HC groups. At the genus level, the HC cows displayed an improved proportion of Labrys (P = 0.015) compared with the CON cows. Results of both the principal components analysis and partial least squares of discriminant analysis of milk metabolome revealed that samples of the CON and HC groups clustered separately. A total of 31 differential metabolites were identified between the two groups. Of these, the levels of 11 metabolites decreased (α-linolenic acid, prostaglandin E2, L-lactic acid, L-malic acid, 3-hydroxysebacic acid, succinyladenosine, guanosine, pyridoxal, L-glutamic acid, hippuric acid, and trigonelline), whereas the levels of the other 20 metabolites increased in the HC group with respect to the CON group (P < 0.05). These results suggested that subacute ruminal acidosis less impacted the diversity and composition of milk microbiota, but altered the milk metabolic profiles, which led to the decline of the milk quality.


The effect of visual deprivation and proprioceptive change on postural sway in healthy adults.
In 39 healthy active people aged 17 to 79 who had not fallen, anteroposterior sway during quiet standing increased slightly with age; there was no increase with age in lateral sway. Sway increased on deprivation of visual information and altered proprioception due to foot pressure sensory change in all age groups, and especially when both forms of sensation were altered concurrently; but the increase of sway on pressure sensory change was no greater in the older than in the younger subjects.


Studying the mechanism and kinetics of fuel desulfurization using CexOy/NiOx piezo-catalysts as a new low-temperature method.
In order to advance desulfurization technology, a new method for excellent oxidative desulfurization of fuel at room temperature will be of paramount importance. As a novel desulfurization method, we developed piezo-catalysts that do not require adding any oxidants and can be performed at room temperature. A microwave method was used to prepare CeO2/Ce2O3/NiOx nanocomposites. Model and real fuel desulfurization rates were examined as a function of synthesis parameters, such as microwave power and time, and operation conditions, such as pH and ultrasonic power. The results showed that CeO2/Ce2O3/NiOx nanocomposites demonstrated outstanding piezo-desulfurization at room temperature for both model and real fuels. Furthermore, CeO2/Ce2O3/NiOx nanocomposites exhibited remarkable reusability, maintaining 79% of their piezo-catalytic activity even after 17 repetitions for desulfurization of real fuel. An investigation of the mechanism of sulfur oxidation revealed that superoxide radicals and holes played a major role. Additionally, the kinetic study revealed that sulfur removal by piezo-catalyst follows a second-order reaction kinetic model.


2-NBDG as a fluorescent indicator for direct glucose uptake measurement.
Evaluation of glucose uptake ability in cells plays a fundamental role in diabetes mellitus research. In this study, we describe a sensitive and non-radioactive assay for direct and rapid measuring glucose uptake in single, living cells. The assay is based on direct incubation of mammalian cells with a fluorescent d-glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG) followed by flow cytometric detection of fluorescence produced by the cells. A series of experiments were conducted to define optimal conditions for this assay. By this technique, it was found that insulin lost its physiological effects on cells in vitro meanwhile some other anti-diabetic drugs facilitated the cell glucose uptake rates with mechanisms which likely to be different from those of insulin or those that were generally accepted of each drug. Our findings show that this technology has potential for applications in both medicine and research.


Evaluation of a parasite lactate dehydrogenase-based colloid gold-immunochromatography assay for diagnosis of Plasmodium falciparum.
To establish a colloid gold-immunochromatography assay (GICA) for detecting Plasmodium falciparum. The monoclonal antibodies (mAbs) against lactate dehydrogenase of P. falciparum (LDHpf) were screened for preparation of GICA strips. With microscopic examination of the blood smears and PCR test as control, GICA was evaluated for its sensitivity, specificity and stability in the diagnosis of malaria in the outpatient clinics in China. Four hybridoma cell lines against LDHpf were prepared. Enzyme-linked immunosorbent assay demonstrated that the 4 mAbs reacted only with P. falciparum, but not with protein of normal human red cell, P. vivax, Toxoplasma gondii, or Schistosoma japonicam. All the 4 mAbs recognized a 33 kD protein designated as LDHpf as shown by Western blot analysis. Compared with the microscopic examination of blood smears and PCR test, GICA had the sensitivities of 88.37% and 86.67% and the specificities of 95.65% and 97.78%, respectively. Concordance between microscopic examination and GICA for P. falciparum infection was 91.55%. GICA established in this study is simple, rapid, sensitive and specific for detecting P. falciparum, and is potentially useful in developing reagent kits for clinical use.


Acidic "peptidophospholipids", a new class of hapten-bearing cell surface modifying reagents.
Covalent coupling of glutamyl-glutamic acid to the amino group of ether-phosphatidylethanolamine (EPE) yields an acidic "peptidophospholipid" (Glu2-EPE) which is water-soluble above pH 7.0 and stable to phospholipase A. The terminal amino group of Glu2-EPE is free for coupling with amino-reactive determinants. We describe the synthesis of various hapten-substituted peptidophospholipids as well as of an intermediate compound, coupled with the heterobifunctional reagent 3-(2'-pyridyl)-dithiopropionic acid N-hydroxysuccinimide ester. The latter derivative allows binding to sulfhydryl-containing molecules, e.g. peptides or proteins. So far, beef and pig insulin as well as trinitrophenyl-substituted ribonuclease A have thus been linked to Glu2-EPE. All derivatives of Glu2-EPE are water-soluble at physiological pH and readily adsorb to cell surfaces from aq. solution. Binding to cells is fast, stable and "non-toxic" over a wide range of concns. The adsorbed determinants are accessible to specific antibodies and facilitate complement-mediated cell lysis. Glu2-EPE thus appears to be a universal carrier molecule for fast, simple and mild modification of cells with foreign determinants, e.g. for Jerne plaque assays.


Mutagenicity of diesel-exhaust particle extract, 1-nitropyrene, and 2,7-dinitrofluorenone in Salmonella typhimurium under various metabolic activation conditions.
The mutagenic activities of 1-nitropyrene (1-NP), 2,7-dinitrofluorenone (2,7-DNF), and a diesel-exhaust extract were compared using the Salmonella typhimurium plate-incorporation assay. Each sample was tested with and without a 9000 X g liver homogenate (S9), both with and without an NADPH-generating system. The samples were also treated with the microsome fraction of S9, cytosol fraction of S9, boiled S9, bovine serum albumin (BSA), and boiled BSA. Salmonella tester strains TA98 and TA98FR1 were used in all treatments; TA98/1,8DNP6 was used to test mutagenic activity without activation. Without the NADPH-generating system, the samples generally had less mutagenic activity than samples treated with the NADPH-generating system. The addition of the NADPH-generating system resulted in marked increases in mutagenic activity of 1-NP in the microsome and S9 treatments, and of all 3 samples in the cytosol fraction treatment. These results indicate that although protein binding reduced the mutagenic activity of diesel-exhaust extract and 1-NP, microsomal activation increased the mutagenic activity of 1-NP. Because 1-NP and 2,7-DNF contributed less than 1.5% of the mutagenic activity of the diesel-exhaust extract, the response to diesel exhaust was not typified by these compounds.


Serious silver sulphadiazine and mafenide acetate dermatitis.
Infrequently reported, serious allergic reactions to topical antimicrobial agents used in the treatment of burn injuries are a potential source of confusion. To avoid misdirected therapy, an understanding of the manifestations of such reactions is important. Two recent cases of serious allergic reactions, one to silver sulphadiazine, one to mafenide acetate, are presented and the literature is reviewed.


The complexity of the overlap method for sequencing biopolymers.
The problem of trying to reconstruct the sequence of a biopolymer by using overlapping fragments obtained from cleaving agents is shown to be computationally intractable. This strongly suggests that any computer program for overlap sequencing, even though it may work well for a limited number of inputs, will not work sufficiently for all inputs. However, if the problem is restricted so that certain crucial fragments are known, called prime strings, a sequence can be found efficiently in all cases. Graph theory techniques for doing so can also be used to count the number of sequences consistent with the fragment data to determine whether a unique sequence has been obtained.


Human umbilical cord mesenchymal stromal cell small extracellular vesicle transfer of microRNA-223-3p to lung epithelial cells attenuates inflammation in acute lung injury in mice.
Acute lung injury (ALI), manifested as strong pulmonary inflammation and alveolar epithelial damage, is a life-threatening disease with high morbidity and mortality. Small extracellular vesicles (sEVs), secreted by multiple types of cells, are critical cellular communication mediators and can inhibit inflammation by transferring bioactive molecules, such as microRNAs (miRNAs). Thus, we hypothesized that sEVs derived from mesenchymal stromal cells (MSC sEVs) could transfer miRNAs to attenuate inflammation of lung epithelial cells during ALI. C57BL/6 male mice were intratracheally administered LPS (10 mg/kg). Six hours later, the mice were randomly administered with MSC sEVs (40 µg per mouse in 150 µl of saline), which were collected by ultracentrifugation. Control group received saline administration. After 48 h, the mice were sacrificed to evaluate pulmonary microvascular permeability and inflammatory responses. In vitro, A549 cells and primary human small airway epithelial cells (SAECs) were stimulated with LPS with or without MSC sEVs treatment. In vitro, MSC sEVs could also inhibit the inflammation induced by LPS in A549 cells and SAECs (reducing TNF-α, IL-1β, IL-6 and MCP-1). Moreover, MSC sEV treatment improved the survival rate, alleviated pulmonary microvascular permeability, and inhibited proinflammatory responses (reducing TNF-α, IL-1β, IL-6 and JE-1) in ALI mice. Notably, miR-223-3p was found to be served as a critical mediator in MSC sEV-induced regulatory effects through inhibition of poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1) in lung epithelial cells. Overall, these findings suggest that MSC sEVs may offer a novel promising strategy for ALI.


Radiation dose reference card for interventional radiology procedures: Experience in a tertiary referral centre.
Fluoroscopy-guided interventions can potentially increase radiation risk to patients, if awareness on angiographic imaging technique and radiation dose is neglected. To develop patient radiation dose reference card from standardized imaging techniques for various radiology interventions performed using flat detector based angiography system. Real-time monitoring of angiographic exposure parameters and radiation dose were performed for 16 types of radiological interventions. Effective dose (ED) was estimated from dose area product (DAP) using PCXMC Monte Carlo simulation software. Radiation risk levels were estimated based on Biological Effects of Ionising radiation (BEIR) report VII predictive models for an Asian population. Pulse rates of 7.5 pps and 0.6 mm Copper filtration during fluoroscopy and 4 frames per second (fps) and 0.1-0.3 mm Cu filtration during image acquisitions were found to reduce radiation dose. Owing to increased number of image acquisitions, DAP was highest during diagnostic spinal angiography 186.7 Gycm2 (44.0-377.5). This resulted in highest ED of 59.4 mSv with moderate risk levels (1 in 1000 to 1 in 500). Most of the radiological interventions had low radiation risk levels (1 in 10,000 to 1 in 1000). The patient radiation dose reference card is valuable to the medical community and can aid in patient counselling on radiation induced risk from radiological interventions.


Effects of β-glucan Rich Barley Flour on Glucose and Lipid Metabolism in the Ileum, Liver, and Adipose Tissues of High-Fat Diet Induced-Obesity Model Male Mice Analyzed by DNA Microarray.
We evaluated whether intake of β-glucan-rich barley flour affects expression levels of genes related to glucose and lipid metabolism in the ileum, liver, and adipose tissues of mice fed a high-fat diet. C57BL/6J male mice were fed a high-fat diet supplemented with high β-glucan barley, for 92 days. We measured the expression levels of genes involved in glucose and lipid metabolism in the ileum, liver, and adipose tissues using DNA microarray and q-PCR. The concentration of short-chain fatty acids (SCFAs) in the cecum was analyzed by GC/MS. The metabolic syndrome indices were improved by barley flour intake. Microarray analysis showed that the expression of genes related to steroid synthesis was consistently decreased in the liver and adipose tissues. The expression of genes involved in glucose metabolism did not change in these organs. In liver, a negative correlation was showed between some SCFAs and the expression levels of mRNA related to lipid synthesis and degradation. Barley flour affects lipid metabolism at the gene expression levels in both liver and adipose tissues. We suggest that SCFAs are associated with changes in the expression levels of genes related to lipid metabolism in the liver and adipose tissues, which affect lipid accumulation.


Methyl beta-carboline-3-carboxylate enhances performance in a multiple-trial learning task in mice.
In contrast to diazepam, a benzodiazepine receptor (BZ-R) ligand, which impairs memory processing, methyl beta-carboline-3-carboxylate (beta-CCM), another BZ-R ligand, administered before a training session, enhances performance in a retention test. This action, however, has only been demonstrated in single trial or single session learning protocols. The present report extends these results to a multiple-trial learning procedure in mice (brightness discrimination in a T-maze with negative reinforcement). The animals were trained for sessions of ten trials per day for six consecutive days. In a first experiment, the sessions during the first three days took place after administration of beta-CCM (0.3 mg/kg), diazepam (2.5 mg/kg) or saline. In a second experiment, especially designed to study the effects of beta-CCM, during the first three days animals received beta-CCM (0.3 mg/kg), Ro 15-1788 (15 mg/kg), beta-CCM + Ro 15-1788, vehicles of these drugs or saline. In the first experiment, performance was improved by beta-CCM and impaired by diazepam in the first three sessions as well as in the final three. In the second experiment, beta-CCM alone, as well as Ro 15-1788 improved performance, and the simultaneous administration of the two drugs suppressed these effects. These results suggest that the performance enhancing effects of beta-CCM observed in single trial learning protocols, during the retention test, can already be observed during drug treatment. They confirm that beta-CCM has an action on acquisition (learning). As the effects of beta-CCM are suppressed by the simultaneous administration of Ro 15-1788, our results could suggest a role for benzodiazepine receptors in learning. This question is discussed.


The Oceanus statue of the Fontana di Trevi (Rome): The analysis of black crust as a tool to investigate the urban air pollution and its impact on the stone degradation.
This paper deals with the analysis of black crust coming from the statue of Oceanus belonging to the Fontana di Trevi (Rome). This monument is undoubtedly one of the main touristic attractions of Rome. During the restoration held between 2014 and 2015, some diagnostic analyses had been carried out. It has been highlighted that the sheltered surfaces suffer the formation of black crust, especially on the marble statues. The possibility to sample those degradation products, together with the unaltered substrate, represented an excellent opportunity to characterize the marble itself, to assess the impact of the urban air pollution on the stone material, and to detect the pollutant on a precise timescale. In fact, it is known that the previous restoration of the fountain had been carried out between 1989 and 1991 then, information about the air pollution over the last 25years can be highlighted, because it has been proved that black crusts act as passive samplers of pollution. In order to fully characterize those samples, several techniques were used, including optical and scanning electron microscopy, X-ray diffraction, laser ablation inductively coupled plasma mass spectrometry, infrared spectroscopy and ion chromatography. Furthermore, a new methodology based on CHN (Carbon, Hydrogen, Nitrogen) analysis has been developed for the quantification of the two main constituents of the carbonaceous fraction present in the black crusts, i.e. OC (organic carbon) and EC (elemental carbon). This integrated approach proposed in the present study allowed us to gain information about the mineralogical phases and the elements within the crusts and at the crust-substrate interface, giving the possibility to identify the pollution sources causing the stone decay within the monument.


Pars Plana Vitrectomy for Vitreomacular Traction Syndrome: Analysing the Preoperative Prognostic Factors.
To identify the prognostic factors affecting the surgical outcomes in patients with vitreomacular traction syndrome undergoing pars plana vitrectomy. This was a retrospective clinical study of 67 eyes of 67 patients with vitreomacular traction syndrome who underwent pars plana vitrectomy. Demographic, clinical, and optical coherence tomography (OCT) characteristics were collected and analyzed. Univariate and multivariate linear regression analysis were used to examine the effect of parameters on change in best-corrected visual acuity (BCVA). At a mean follow-up period of 15.9±12 months (mean±SD), the BCVA improved from 0.7±0.3 LogMAR (mean±SD) to 0.5±0.3. Seven patients developed full-thickness macular hole intraoperatively and tamponade (air, 20% SF6 or 12% C3F8) was used in 41 patients. Retinal breaks were identified intraoperatively in four patients. Regression analysis demonstrated that the preoperative BCVA was the only parameter affecting the postoperative visual outcome. In the present study, the preoperative BCVA plays a predictive role in the surgical outcome of patients with VMT undergoing pars plana vitrectomy. No other preoperative OCT characteristics demonstrated prognostic potential. Further prospective studies are needed in order to examine the role of several factors that could potentially facilitate preoperative patient counselling.


Trypanosoma cruzi: influence of predominant bacteria from indigenous digestive microbiota on experimental infection in mice.
To verify the influence of some predominant components from indigenous microbiota on systemic immunological responses during experimental Chagas disease, germ-free NIH Swiss mice were mono-associated with Escherichia coli, Enterococcus faecalis, Bacteroides vulgatus or Peptostreptococcus sp. and then infected with the Y strain of Trypanosoma cruzi. All the mono-associations predominantly induced a Th1 type of specific immune response to the infection by T. cruzi. A direct correlation was observed between a higher survival rate and increased IFN-gamma and TNF-alpha production (P<0.05) in E. faecalis-, B. vulgatus-, and Peptostreptococcus-associated mice. Moreover, higher levels of anti-T. cruzi IgG1 and anti-T. cruzi IgG2a were also found in mono-associated animals after infection. On the other hand, with the exception of E. faecalis-associated mice, mono-association induced a lower IL-10 production after infection (P<0.05) when compared with germ-free animals. Interestingly, spleen cell cultures from non-infected germ-free and mono-associated mice spontaneously produced higher levels (P<0.05) of IL-10 than cultures from infected mono-associated mice, except again for E. faecalis-associated animals. In conclusion, the presence of the components of the indigenous microbiota skews the immune response towards production of inflammatory cytokines during experimental infection with T. cruzi in gnotobiotic mice. However, the degree of increase in production of cytokines depends on each bacterial component.


Heterogeneity of the immunological deficiency in ataxia-telangiectasia: absence of a clinical-pathological correlation.
We have been impressed by the absence of severe and recurring infections in most of our patients with ataxia-telangiectasia. In this report, our clinical and laboratory data on 25 patients are reviewed. We found a heterogeneity of immunological results and a lack of correlation between these results and clinical well-being.


Effects of the COVID-19 pandemic on trauma-related emergency medical service in older people: a retrospective cohort study.
The ever-increasing human life expectancy has currently resulted in a noticeable rise in the world's older population. Addressing the healthcare needs of the older people has become a significant concern for many countries. Moreover, the older people are particularly vulnerable to traumatic events. This study aimed to examine the impact of the COVID-19 pandemic on prehospital care provided by Emergency Medical Services (EMS) for trauma-related cases among the older people in Iran. This retrospective cohort study involved analyzing the medical records of 1,111 older people aged above 60 who experienced traumatic injuries and received pre-hospital emergency services from March 2018 to March 2022. In order to collect the data, the checklist made by the researcher was used and data analysis in SPSS16 was done using the Chi-square test and Fisher's exact test. The age group of 60-74 received the highest number of services both before and after the COVID-19 pandemic. The older men experienced more traumatic events compared to women throughout the study period. The majority of the traumatic events occurred between 8 a.m. and 12 p.m. both before and after the COVID-19 pandemic. The high prevalence rate of geriatric traumas can be primarily attributed to their physical problems and no control over movements caused by old age, as well as unsafe living conditions. To address these issues, it is suggested that facilities be provided to assist with mobility problems. Moreover, constructing suitable pedestrian bridges and regularly checking neighborhoods and surroundings to identify potential risk factors should be prioritized. Once these risk factors are identified, efforts can be made to adjust and eliminate them, thereby minimizing traumatic events and enhancing a safe and friendly environment for the older people.


How Au Outperforms Pt in the Catalytic Reduction of Methane towards Ethane and Molecular Hydrogen.
Within the context of a "hydrogen economy", it is paramount to guarantee a stable supply of molecular hydrogen to devices such as fuel cells. At the same time, catalytic conversion of the environmentally harmful methane into ethane, with a significantly lower Global Warming Potential, turns into a highly desirable challenge. Herein we propose a first-step novel proof-of-concept mechanism to accomplish both tasks simultaneously. For that purpose we provide transition-state barriers and reaction Helmholtz free energies obtained from first-principles Density Functional Theory by taking account vibrations for 2CH4(g) → C2H6(g) + H2(g) to show that molecular hydrogen can be produced by subnanometer Pt38 and Au38 nanoparticles from natural gas. Interestingly, the active sites for the reaction are located on different planes on the two nanoparticles, effectively differentiating the working principle of the two metals. The analysis shows that the complete cycle to reduce CH4 can be performed on Au and Pt with similar efficiencies, but Au requires only half the working temperature of Pt. This substantial decrease of temperature can be traced back to several intermediate steps, but most crucially to the final one where the catalyst must be cleaned from H(⋆) to be able to restart the catalytic cycle. This simple study case provides useful guidelines to capitalize on finite-size effects in small nanoparticles for the design of new and more efficient catalysts. Interestingly, present results obtained for the intermediate steps of the catalytic cycle show an excellent agreement with previous experimental evidence. Finally, we stress the importance of including the final cleaning steps to start a new fresh catalytic cycle.


[Acute cough in infants: impact on families and pharmacists of contraindications of the Agence nationale de sécurité du médicament et des produits de santé (ANSM)].
Although commonplace and usually not serious, acute cough in the context of upper respiratory tract infection is a frequent reason for consultation and generates significant parental anxiety. Parents often request active drug intervention. Following the contraindications in infants of mucolytics, Hélicidine(®), antihistamines, and terpene-based suppositories, issued between 2010 and 2011 by the Agence nationale de sécurité du médicament et des produits de santé (ANSM), we wished to assess whether these contraindications were known by parents and applied in pharmacies. An assessment of compliance with these contraindications was made by a double declarative prospective observational study in Nice, first with 29 pharmacists and pharmacy technicians (4-25 August 2012) and then with 289 parents of infants (December 2011 to April 2012). The rate of noncompliance with contraindications was 23.8 % for parents and 34.5 % of pharmacists and pharmacy technicians. Consumption of cough medicines was inversely correlated to the ability to perform a correct nasal wash (OR=2.3). Only 21 % of parents used nasal wash properly. Full-time work was a risk factor for noncompliance with contraindications (OR=1.91). ANSM contraindications still have a limited impact on pharmacists and families. Therefore, efforts must be pursued to stop delivering cough medicines for infants. The information and educational campaigns should also involve parents and help to improve nasal wash use.


Evaluation of CD98 light chain-LAT1 as a potential marker of cancer stem-like cells in glioblastoma.
Glioma stem cells (GSCs) are a minority population of glioma cells that regarded as the cause of tumor formation and recurrence. Identifying new molecular strategies targeting GSCs must be urgently developed to treat glioblastoma. In this study, one of CD98 light chain-L type amino acid transporter 1 (LAT1) was found as a potential GSC marker. LAT1 served as EAA transporter has been shown to be closely related with tumor invasion, metastasis, angiogenesis, and radiosensitivity. LAT1+ and LAT1- glioma cells were sorted by flow cytometry. Cellular immunofluorescence, sphere-formation arrays, and in vitro limiting dilution experiments were used to identify cell stemness. Differentiated glioma stem cells were cultured, and the expressions of β-tubulinIII, GFAP, and LAT1 were detected by Western blot. Nude mouse models were constructed to observe tumor formation and metastasis in nude mice. LAT1+ glioma cells were testified a small percentage of all cells and selected as the subsequent sorting marker. LAT1+ cells were separated from U87 and U251 cells could express high level of stem cell markers, and possessed GSC properties including self-renewal ability and multi-directional differentiation potential. But LAT1- cells did not have these characteristics. In addition, LAT1+ cells were able to generate tumors in vivo, tumor size of LAT1+ cells formed were much bigger than that of LAT1- cells. Our study, including molecular, cell, vitro and vivo experiments, has shown that LAT1+ cells possess GSC properties, and present for the first time that LAT1 can be used as a new marker for GSCs screening.


Genome-wide identification and expression analysis of the bHLH transcription factor family and its response to abiotic stress in foxtail millet (Setaria italica L.).
Members of the basic helix-loop-helix (bHLH) transcription factor family perform indispensable functions in various biological processes, such as plant growth, seed maturation, and abiotic stress responses. However, the bHLH family in foxtail millet (Setaria italica), an important food and feed crop, has not been thoroughly studied. In this study, 187 bHLH genes of foxtail millet (SibHLHs) were identified and renamed according to the chromosomal distribution of the SibHLH genes. Based on the number of conserved domains and gene structure, the SibHLH genes were divided into 21 subfamilies and two orphan genes via phylogenetic tree analysis. According to the phylogenetic tree, the subfamilies 15 and 18 may have experienced stronger expansion in the process of evolution. Then, the motif compositions, gene structures, chromosomal spread, and gene duplication events were discussed in detail. A total of sixteen tandem repeat events and thirty-eight pairs of segment duplications were identified in bHLH family of foxtail millet. To further investigate the evolutionary relationship in the SibHLH family, we constructed the comparative syntenic maps of foxtail millet associated with representative monocotyledons and dicotyledons species. Finally, the gene expression response characteristics of 15 typical SibHLH genes in different tissues and fruit development stages, and eight different abiotic stresses were analysed. The results showed that there were significant differences in the transcription levels of some SibHLH members in different tissues and fruit development stages, and different abiotic stresses, implying that SibHLH members might have different physiological functions. In this study, we identified 187 SibHLH genes in foxtail millet and further analysed the evolution and expression patterns of the encoded proteins. The findings provide a comprehensive understanding of the bHLH family in foxtail millet, which will inform further studies on the functional characteristics of SibHLH genes.


Minimally invasive procedures for the management of vertebral bone pain due to cancer: The EAPC recommendations.
Image-guided percutaneous ablation methods have proved effective for treatment of benign bone tumors and for palliation of metastases involving the bone. However, the role of these techniques is controversial and has to be better defined in the setting of palliative care. A systematic review of the existing data regarding minimally invasive techniques for the pain management of vertebral bone metastases was performed by experts of the European Palliative Care Research Network. Only five papers were taken into consideration after performing rigorous screening according to inclusion and exclusion criteria (low number of patients, retrospective series, proceedings). According to the present data a recommendation should be made to perform kiphoplasty in patients with vertebral tumors or metastases. However, the strength of this recommendation was based on one randomized controlled study. Several weaknesses and low quality of study design were observed with other techniques. Further randomized controlled trials are required to improve the strength of evidence available to suggest these procedures on large scale. Until then, the balance of evidence favors the use of these procedures in a small select cohort of patients with severe and disabling back pain refractory to medical therapy.


Synthesis and characterization of stevioside having low degree polymerized glucosides using dextransucrase and dextranase.
Transglycosylation is one of enzymatic methods to improve the physical and biochemical properties of various functional compounds. In this study, stevioside glucosides were synthesized using sucrose as a substrate, stevioside (Ste) as an acceptor, and dextransucrase from Leuconostoc mesenteroides B-512 F/KM. The highest Ste conversion yield of 98% was obtained with 50 mg/mL Ste, 800 mM sucrose, and dextransucrase 4 U/mL at 28 °C for 6 h. The concentration of Ste was unchanged while of Ste-G1 was increased from 7.7 mM to 9.1 mM as the Ste acceptor reaction digest was treated with dextranase from Lipomyces starkeyi. Ste-G1 (13-O-β-sophorosyl-19-O-β-isomaltosyl-steviol), Ste-G2 (13-O-(β-(1→6) glucosyl)-β-glucosylsophorosyl-19-O-β-isomaltosyl-steviol), and Ste-G2' (13-O-β-sophorosyl-19-O-β-isomaltotriosyl-steviol) were determined by NMR. These glucosylated Ste showed increased stabilities at pH 2, 60 °C for 48 h as compared to Ste. Ste-G1, Ste-G2, and Ste-G2' inhibited the insoluble glucan synthesis from sucrose by mutansucrase from Streptococcus muntans by the transfer of the glucosyl group of sucrose to Ste-G1, Ste-G2, and Ste-G2'. The relative water solubility of curcumin, pterostilbene or idebenone was increased by Ste or Ste glucosides treatment. Ste and Ste-G1 restored cell viability in RAW264.7 cells at concentrations up to 8 mg/mL and inhibited nitric oxide production in LPS-induced RAW264.7 cells with IC50 of 3.29 and 1.87 mg/mL.


Tension wood fibers are related to gravitropic movement of red mangrove (Rhizophora mangle) seedlings.
Freshly collected viviparous seedlings (propagules) were collected from wild plants of Rhizophora mangle and planted in vertical or horizontal positions. A total of 80 seedlings were examined anatomically at various ages and orientations. After rooting, seedlings reoriented from horizontal to vertical by extreme bending in the hook region of the hypocotyl directly above the basal 1 cm where roots formed. Hypocotyl bending occurred over many months. Trends in position and relative abundance of tension fibers (also called gelatinous fibers) over time were followed. The erection of the seedling was related to increased secondary xylem and the number of tension wood fibers on the upper side of the hook region. However, linear regressions had low coefficient of determination (r(2)) values, presumably related to seedlings with high variability.


Death and transfiguration among bacteria.
When bacteria are placed in sub-optimal environments, they can respond by increasing the frequency of mutants created by base substitution, frame-shift and transposition mutations. Also, during periods of restrictive growth, 'dead' bacterial cells may transfer genetic material to neighboring colony-forming cells. This can be beneficial, resulting in a heterogeneous population that may exhibit differentiation and even produce killer cells. These discoveries reveal several conundrums about the control of an organism over mutations and the supposed randomness of genetic variation.


Associations between seasonal ambient air pollution and adverse perinatal outcomes: a retrospective cohort study in Wenzhou, China.
Prenatal exposure to ambient air pollution has been associated with adverse perinatal outcomes in previous studies. However, few studies have examined the interaction between air pollution and the season of conception on term low birth weight (TLBW) or macrosomia. Birth registry data of singleton live births in Wenzhou, China, between January 2015 and December 2016 were accessed from the Wenzhou Maternal and Child Health Information Management platform, and data on the ambient air pollutants in Wenzhou were obtained from the Chinese Air Quality Online Monitoring and Analysis Platform. Single-/two-pollutant binary logistic regression models were used to assess the associations between ambient air pollutants (PM2.5, PM10, NO2, SO2, and O3) and TLBW/macrosomia, further exploring whether the season of conception interacts with air pollution to impact birth weight. Finally, 213,959 term newborns were selected, including 2452 (1.1%) infants with TLBW and 13,173 (6.1%) infants with macrosomia. In the single-/two-pollutant models, we observed an increased risk of TLBW associated with maternal exposure to PM2.5, PM10, SO2, and NO2 during the entire pregnancy, especially in the 2nd trimester. Maternal exposure to O3 during the 1st trimester was associated with increased macrosomia risk, and O3 exposure during the 3rd trimester was associated with increased TLBW risk. Pregnant women who conceive in the warm season may experience a more adverse ambient air environment that is related to the risks of TLBW. These findings add to the evidence suggesting that air pollution and the season of conception may have synergistic effects on adverse perinatal outcomes, especially TLBW. Further prospective cohort studies are needed to validate our results.


The phospholipid-deficient pho1 mutant of Arabidopsis thaliana is affected in the organization, but not in the light acclimation, of the thylakoid membrane.
The pho1 mutant of Arabidopsis has been shown to respond to the phosphate deficiency in the leaves by decreasing the amount of phosphatidylglycerol (PG). PG is thought to be of crucial importance for the organization and function of the thylakoid membrane. This prompted us to ask what the consequences of the PG deficiency may be in the pho1 mutant when grown under low or high light. While in the wild-type, the lipid pattern was almost insensitive to changes in the growth light, PG was reduced to 45% under low light in the mutant, and it decreased further to 35% under high light. Concomitantly, sulfoquinovosyl diacylglycerol (SQDG) and to a lesser extent digalactosyl diacylglycerol (DGDG) increased. The SQDG increase correlated with increased amounts of the SQD1 protein, an indicator for an actively mediated process. Despite of alterations in the ultrastructure, mutant thylakoids showed virtually no effects on photosynthetic electron transfer, O2 evolution and excitation energy allocation to the reaction centers. Our results support the idea that PG deficiency can at least partially be compensated for by the anionic lipid SQDG and the not charged lipid DGDG. This seems to be an important strategy to maintain an optimal thylakoid lipid milieu for vital processes, such as photosynthesis, under a restricted phosphate availability.


Conjunctival thickness as a predictive imaging biomarker for the glaucoma filtration surgery outcome: An optical coherence tomography study.
To analyse the preoperative conjunctival thickness in glaucomatous patients undergoing filtration surgery (FS), using optical coherence tomography (OCT). The conjunctival status represents one of the most critical determinants of the FS outcome. Retrospective study. Sixty-seven patients candidate to FS for uncontrolled glaucoma were enrolled. OCT was performed at the superior bulbar conjunctiva before FS, and at bleb site at the last follow-up (LF-up) after surgery. Preoperative full, epithelial, and stromal conjunctival thickness (FCT, CET, CST) and reflectivity (CR), and LF-up bleb-wall thickness (BT), reflectivity (BR) and intraocular pressure (IOP), were the major outcomes. The relations between preoperative parameters and LF-up-IOP, BT and BR were calculated. FS was completely successful in 23 patients (group 1), successful with medications in 22 (group 2), and failed in 22 (group 3). FCT, CET and CST were lower, whereas CR higher, in group 3 compared to groups 1 and 2 (P < .05); BT was lower (P < .001), whereas BR higher (P < .05) in group 3 compared to group 1. FCT and CST were predictors of FS outcome with lower thickness associated with increased odds of failure (odds ratio 0.922, P = .08; 0.941, P = .025). LF-up-IOP inversely correlated with FCT and CST (r = -0.447, P = .003; r = -0.408, P = .007), whereas positively correlated with CR (r = 0.789, P < .001). Preoperative conjunctival thickness and reflectivity show significant correlations with the FS outcome, both in terms of IOP and bleb-wall features. Therefore, they may be proposed as predictive imaging biomarkers to estimate the risk of filtration failure.


Reduced joint assessment vs comprehensive assessment for ultrasound detection of synovitis in juvenile idiopathic arthritis.
To propose a reduced joint power Doppler US (PDUS) assessment and provide preliminary evidence of its validity, feasibility, reliability and sensitivity to change compared with a comprehensive (i.e. 44 joints) PDUS assessment in evaluating synovitis in JIA. This multicentre study included 42 children with active JIA with ≥4 clinically involved joints requiring modified therapy. At each visit, clinical and PDUS assessments were performed blinded. Each joint was scored for greyscale (GS) synovitis and power Doppler signal according to a 4-point semiquantitative scale with calculation of US composite indices and US composite joint counts. A process of data reduction based on the frequency of US joint involvement was performed to obtain a reduced PDUS assessment. The relationship between the comprehensive and the reduced PDUS assessments was investigated by Spearman's coefficient at all visits, as well as the relationship between changes in the two PDUS assessments during follow-up. In addition, the metric properties of the comprehensive and the reduced PDUS assessments were tested. The 10-joint PDUS assessment, including bilateral knee, ankle, wrist, elbow and the second MCP joints, detected 100% of children with GS synovitis and power Doppler signal. The two PDUS assessments were highly correlated at all visits. The reduced model had a higher responsiveness than the comprehensive model. Intraobserver and interobserver agreement was good for both US findings. The 10-joint PDUS assessment is valid and feasible for assessment of synovitis in JIA in clinical practice.


Switching nanoprecipitates to resist hydrogen embrittlement in high-strength aluminum alloys.
Hydrogen drastically embrittles high-strength aluminum alloys, which impedes efforts to develop ultrastrong components in the aerospace and transportation industries. Understanding and utilizing the interaction of hydrogen with core strengthening elements in aluminum alloys, particularly nanoprecipitates, are critical to break this bottleneck. Herein, we show that hydrogen embrittlement of aluminum alloys can be largely suppressed by switching nanoprecipitates from the η phase to the T phase without changing the overall chemical composition. The T phase strongly traps hydrogen and resists hydrogen-assisted crack growth, with a more than 60% reduction in the areal fractions of cracks. The T phase-induced reduction in the concentration of hydrogen at defects and interfaces, which facilitates crack growth, primarily contributes to the suppressed hydrogen embrittlement. Transforming precipitates into strong hydrogen traps is proven to be a potential mitigation strategy for hydrogen embrittlement in aluminum alloys.


Using quantitative CT perfusion for evaluation of delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage.
DCI is a serious complication following aneurysmal SAH leading to permanent neurologic deficits, infarction, and death. Our aim was to prospectively evaluate the diagnostic accuracy of CTP and to determine a quantitative threshold for DCI in aneurysmal SAH. Patients with SAH were prospectively enrolled in a protocol approved by the institutional review board. CTP was performed during the typical time period for DCI, between days 6 and 8 following SAH. Quantitative CBF, CBV, and MTT values were obtained by using standard region-of-interest placement sampling of gray matter. The reference standard for DCI is controversial and consisted of clinical and imaging criteria in this study. In a subanalysis of vasospasm, DSA was used as the reference standard. ROC curves determined the diagnostic accuracy by using AUC. Optimal threshold values were calculated by using the patient population utility method. Ninety-seven patients were included; 41% (40/97) had DCI. Overall diagnostic accuracy was 93% for CBF, 88% for MTT, and 72% for CBV. Optimal threshold values were 35 mL/100 g/min (90% sensitivity, 68% specificity) for CBF and 5.5 seconds (73% sensitivity, 79% specificity) for MTT. In the subanalysis (n = 57), 63% (36/57) had vasospasm. Overall diagnostic accuracy was 94% for CBF, 85% for MTT, and 72% for CBV. Optimal threshold values were 36.5 mL/100 g/min (95% sensitivity, 70% specificity) for CBF and 5.4 seconds (78% sensitivity, 70% specificity) for MTT. CBF and MTT have the highest overall diagnostic accuracy. Threshold values of 35 mL/100 g/min for CBF and 5.5-second MTT are suggested for DCI on the basis of the patient population utility method. Absolute threshold values may not be generalizable due to differences in scanner equipment and postprocessing methods.


Bacterial contamination of the anterior chamber during phacoemulsification cataract surgery.
To determine the incidence of bacterial contamination of the anterior chamber after phacoemulsification cataract surgery with intraocular lens (IOL) implantation. Department of Ophthalmology, Royal Prince Alfred Hospital, Sydney, Australia. Ninety-eight consecutive eyes of 96 patients having phacoemulsification cataract surgery with IOL implantation were included in this prospective study. Two intraoperative anterior chamber aspirates were obtained from each patient, 1 taken at the start and the other at the conclusion of surgery. In addition, preoperative and postoperative conjunctival swabs were acquired. The 4 specimens were cultured using direct culturing techniques under aerobic and anaerobic conditions for 14 days. No preoperative antibiotics were used. The incidence of intraoperative anterior chamber contamination was 0% (95% confidence interval, 0%-3.7%) as all intraoperative anterior chamber samples proved culture negative. Sixty-five percent of the preoperative conjunctival swabs were positive for growth, with corynebacteria, coagulase-negative staphylococci, and Propionibacterium acnes being the most frequently cultured organisms. Sixteen percent of the postoperative conjunctival swabs were positive for growth, with corynebacteria and coagulase-negative staphylococci being the most common bacteria. One patient developed culture-positive postoperative endophthalmitis; using pulsed-field gel electrophoresis for further typing, the implicated Staphylococcus epidermidis was indistinguishable from that isolated from the patient's preoperative conjunctival swab. The bacterial contamination rate of the anterior chamber after phacoemulsification and IOL implantation was extremely low. Additional findings support the conjunctiva as being a primary source of bacteria causing postoperative endophthalmitis as well as the ability of povidone-iodine to reduce the conjunctival bacterial load.


Novel 5-(1-aryl-1H-pyrazol-3-yl)-1H-tetrazoles as glycogen phosphorylase inhibitors: An in vivo antihyperglycemic activity study.
In this study, we report the ring transformation of 3-arylsydnone into 1-aryl-1H-pyrazole-3-carbonitriles via [3 + 2] cycloaddition with acrylonitrile. 1-Aryl-1H-pyrazole-3-carbonitrile underwent [2 + 3] cycloaddition with sodium azide to afford 5-(1-aryl-1H-pyrazol-3-yl)-1H-tetrazoles which were further subjected to N-alkylation with aryl/heteroaryl alkyl halides to afford 1,5- and 2,5-disubstituted tetrazoles. Furthermore, the title compounds were screened for in vivo antihyperglycemic activity using albino Wistar rats of either sex. Compounds 4a, 6b, 7a, 7b, 8b, and 9b showed maximum fall in the blood glucose levels in streptozotocin-induced diabetic rats after 5-7 days of administration. In support of antidiabetic activity, we also performed the experimental in vivo studies, namely, effect of compounds on enzymes (serum glutamic oxaloacetic transaminase, serum glutamic-pyruvic transaminase, creatinine, urea, and total protein), antihyperlipidemic, and histopathology. Moreover, the molecular docking study has been performed for potent molecules among the series with glycogen phosphorylase as target enzyme, and this study corroborated the experimental in vivo results.


An automated device for immunocytochemistry.
A microprocessor controlled device for automation of immunoenzyme histological and cytological staining procedures is described. As the sequence of processing is controlled by a computer program, the apparatus is flexible and the possibility of technical errors is reduced.


Ultratrace analysis of per- and polyfluoroalkyl substances in drinking water using ice concentration linked with extractive stirrer and high performance liquid chromatography - tandem mass spectrometry.
Detection of drinking water contaminants is vital to the protection of human health. One group of contaminants that have recently generated serious concerns over health risks are per- and polyfluoroalkyl substances (PFAS). These compounds are very bio-persistent, leading to their detection in all types of water sources, including drinking water. While analysis of drinking water for PFAS is important, it is currently arduous to detect ultratrace levels of these contaminants. Specifically, current ultratrace PFAS analysis methods are difficult, costly, require large sample volumes, and consume relatively large volumes of organic solvent. In the present work, an analytical method using Ice Concentration Linked with Extractive Stirrer (ICECLES) and high performance liquid chromatography-tandem quadrupole mass spectrometry (HPLC-MS/MS), was developed and validated to provide simple and ultratrace analysis of drinking water for 14 PFAS. The method featured a relatively low sample volume requirement (10 mL), automated extraction, minimal matrix effects, and minimal organic solvent use (i.e., the method requires only 50 µL of methanol per sample). The method produced a wide linear range of 0.5 to 500 ng/L, ultratrace limits of detection (0.05 to 0.3 ng/L), and good accuracy and precision (i.e., 87 to 108% accuracy and ≤19% relative standard deviation as a measure of precision). This method was tested on drinking water samples from across the United States and detected at least one PFAS compound in 52 of the 53 drinking water samples tested. Perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), and perfluoroheptanoic acid (PFHpA) were detected in 89, 96, and 77% of the samples tested with maximum concentrations of 268 ng/L for PFHxA, 213 ng/L for PFOA, and 75.7 ng/L for PFHpA. Additionally, perfluorononanoic acid, perfluorodecanoic acid, and perfluoroheptanoic acid were each detected in at least one drinking water sample at concentrations > 20 ng/L. The availability of the method presented here allows ultratrace detection of PFAS while circumventing many of the disadvantages of current methods.


The measurement of postoperative pain: a comparison of intensity scales in younger and older surgical patients.
The psychometric properties of pain intensity scales for the assessment of postoperative pain across the adult lifespan have not been reported. The objective of this study was to compare the feasibility and validity of the Numeric Rating Scale (NRS), Verbal Descriptor Scale (VDS), and Visual Analog Scale (horizontal (VAS-H) and vertical (VAS-V) line orientation) for the assessment of pain intensity in younger and older surgical patients. At 24h following surgery, 504 patients, who were receiving i.v. morphine via patient-controlled analgesia, completed the pain intensity measures and the McGill Pain Questionnaire (MPQ) in a randomized order. They were asked which scale was easiest to complete, the most accurate measure, and which they would most prefer to complete in the future, as an index of face validity. The amount of opioid self-administered was recorded. Age differences in postoperative pain intensity were not found. However, elderly patients obtained lower MPQ scores and self-administered less morphine than younger people. Psychometric analyses suggested that the NRS was the preferred pain intensity scale. It had low error rates, and higher face, convergent, divergent and criterion validity than the other scales. Most importantly, its properties were not age-related. The VDS also had a favourable profile with low error rates and good face, convergent and criterion validity. Finally, difficulties with VAS use among the elderly were identified, including high rates of unscorable data and low face validity. Its use with elderly postoperative patients should be discouraged.


Identification of novel cAMP responsive element modulator (CREM) isoforms expressed by osteoblasts.
CREM, the cyclic adenosine monophosphate (cAMP) responsive element modulator, belongs to a multigene family of cAMP-responsive transcription factors. CREM encodes a variety of different isoforms by utilizing four promoters and a complex pattern of alternative messenger ribonucleic acid (mRNA) splicing. We showed previously that parathyroid hormone induces the CREM P2 promoter products known as ICER (inducible cAMP early repressor) in osteoblasts. Herein we report that osteoblasts also express at least 15 CREM transcripts initiated from the P1 promoter, including 7 novel transcripts that result from alternative splicing. It is of interest that we found that CREM-X contains both exon theta1, previously identified only in P3 promoter products, and a new exon termed L, which is located upstream of exon theta1.


Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer.
The recent whole-genome scan for breast cancer has revealed the FGFR2 (fibroblast growth factor receptor 2) gene as a locus associated with a small, but highly significant, increase in the risk of developing breast cancer. Using fine-scale genetic mapping of the region, it has been possible to narrow the causative locus to a haplotype of eight strongly linked single nucleotide polymorphisms (SNPs) spanning a region of 7.5 kilobases (kb) in the second intron of the FGFR2 gene. Here we describe a functional analysis to define the causative SNP, and we propose a model for a disease mechanism. Using gene expression microarray data, we observed a trend of increased FGFR2 expression in the rare homozygotes. This trend was confirmed using real-time (RT) PCR, with the difference between the rare and the common homozygotes yielding a Wilcox p-value of 0.028. To elucidate which SNPs might be responsible for this difference, we examined protein-DNA interactions for the eight most strongly disease-associated SNPs in different breast cell lines. We identify two cis-regulatory SNPs that alter binding affinity for transcription factors Oct-1/Runx2 and C/EBPbeta, and we demonstrate that both sites are occupied in vivo. In transient transfection experiments, the two SNPs can synergize giving rise to increased FGFR2 expression. We propose a model in which the Oct-1/Runx2 and C/EBPbeta binding sites in the disease-associated allele are able to lead to an increase in FGFR2 gene expression, thereby increasing the propensity for tumour formation.


Wnt-induced secreted proteins-1 play an important role in paraquat-induced pulmonary fibrosis.
The objective of this article is to observe the expression of Wnt-induced secreted proteins-1 (WISP1) in paraquat (PQ)-induced pulmonary fibrosis (PF) to explore the role of WISP1. Healthy individuals were included in the control group. Patients who had acute lung injury or PF were included in the PF group. Venous blood samples were collected from the patients on days 1 and 3 following PQ poisoning to detect the expression levels of the WISP1 gene and protein concentration. Any changes in the patients' blood gas analysis index were reviewed. In addition, chest computed tomography (CT) and x-ray images were observed to evaluate the relationship between WISP1 expression and disease severity. The expression of the WISP1 gene and the serum WISP1 protein concentration were higher in patients with PQ poisoning combined with PF than in patients without PF (P < 0.01). Serum PQ concentration was positively correlated with WISP1 gene expression (r = 0.621, P < 0.01), and serum WISP1 protein concentration (r = 0.596, P < 0.01) was considered a risk factor [odds ratio (OR) = 4.356, P < 0.05] for PQ-induced PF. Concurrently, the results of the adjusted and non-adjusted OR value for WISP1 gene expression and WISP1 protein concentration on day 1 was, respectively, as follows: OR = 12.797, 95% confidence interval (CI) (2.478-66.076), P = 0.002, OR' = 11.353, P = 0.005; and OR = 1.545, 95% CI (1.197-1.995), P = 0.001, OR' = 1.487, P = 0.003. The CT scan of a 20-year-old male with PQ-induced PF (20 ml) was observed, and it showed a typical hyaline-like lesion in the lungs on day 22 after poisoning; on day 33 after poisoning, the lungs showed localised consolidation combined with air bronchography. The expression of WISP1 was higher in the patients with PQ-induced PF compared with the patients without PF. Accordingly, WISP1 plays an important role in PQ-induced PF.


All-cause mortality in insulin-treated diabetic patients: a 20-year follow-up.
To establish all-cause mortality rates, and risk factors for mortality in insulin-treated diabetic individuals living in Canterbury, New Zealand. Insulin-treated diabetic subjects (n=995) on the Canterbury Diabetes Registry were followed up over 20-year and vital status determined. Death rates were standardised and hazard regression was used to model the effects of demographic covariates on relative survival time. Six subjects had emigrated, the remaining 989 diabetic subjects contributed a total of 13705.53 person-years of follow-up, a mean of 13.7 years per subject. During follow-up 525 deaths occurred in subjects' aged 17.3-96.7, (261 females, 264 males). All-cause mortality rates in diabetic subjects exceeded those in the general population at all ages. SMRs were slightly higher for females than males in almost all age-at-onset groups, being 2.48 (95% CI: 2.18-2.78) for females and 2.17 (95% CI: 1.91-2.43) for males overall, but reaching a peak in the <30 age at onset group for both females and males being 4.25 (3.07-5.44) and 3.26 (2.49-4.03), respectively. Mortality rates for diabetic individuals remain high, resulting in shortened life spans relative to the general population. This study provides a baseline for further studies of mortality and changes in mortality within New Zealand.