Surgical safety checklists: a review.
Surgical checklists are designed to improve patient outcomes following surgery. While such checklists have been widely implemented worldwide, few studies examine surgical checklists within an Australian context. For this purpose, we have performed a literature review using data from OECD member nations to determine the effectiveness of surgical checklists in improving patient outcomes and factors that contribute to their successful implementation. The databases, Pubmed, Medline, EMBASE, Cochrane and CINAHL were searched using the keywords ('surgical' AND 'checklist') and ( (surgical) AND checklist) AND ( (implementation) OR (utilization) OR (usage) ). Studies were limited to those written in the English language, peer-reviewed, published between January 2000 and December 2012, and including an abstract. Our search yielded 2242 papers, of which 72 papers were identified for their potential relevance and selected for full text review. Of these, nine papers met the inclusion criteria and were reviewed in detail. Evidence that supports the use of surgical checklists in countries with a large number of protocols already in place is limited. Adequate checklist implementation plays a central role in checklist effectiveness, which in turn is dependent on multiple factors. Although evidence from OECD member countries is non-conclusive, it does suggest that surgical checklists, when effectively implemented, have the potential to be effective at reducing complication and mortality rates following surgery. Within an Australian context, more studies are needed to fully establish the potential effectiveness of surgical checklists and to monitor checklist use compliance in order to ensure greater patient safety.


Muscle strength differences in urban and rural populations in Sweden.
The isometric extension and flexion strength of the right knee was investigated in 396 men and 537 women. The probands were randomly selected from the National Population Records, either from the city of Malmö, Sweden, or from a typical agricultural region 60km outside the city. Both the extension and the flexion strength decreased with age in both groups. Between 50 years and 80 years of age the decrease was almost 40%. The urban probands had significantly lower muscle strength in both sexes. The difference was most pronounced for the knee extension strength. Also, the flexion strength was less in the urban population, the difference significant only in octogenarians.


Respiratory monitoring with electrical impedance tomography for lung protective ventilation and alveolar recruitment maneuver in a patient with a single lung transplant and early graft dysfunction.
A case is presented on a patient who underwent left single lung transplantation for emphysema type COPD. There was early graft dysfunction gradeiii during the immediate postoperative period, which required the implantation of an extracorporeal membrane oxygenator (ECMO). Respirator ventilatory parameters were adjusted to avoid lung distension, low tidal volume (Vc) (280ml), high respiratory rates (20rpm), and a positive pressure at end expiration (PEEP) level of 8cmH2O. On monitoring the pulmonary tidal volume distribution by bedside electrical impedance tomography (EIT), it was noted that most of the tidal volume was distributed in the native lung emphysema. An alveolar recruitment manoeuvre was performed, under control of the EIT, that enabled the current volume and distribution and the pressures required to ventilate the transplanted lung to be observed.


Endophthalmitis associated with intravitreal anti-vascular endothelial growth factor therapy injections in an office setting.
To determine the incidence of endophthalmitis following intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents. A retrospective interventional case series. A total of 10,254 intravitreal anti-VEGF injections (406 pegaptanib, 3,501 bevacizumab, and 6,347 ranibizumab) were performed from January 5, 2005 to October 18, 2007. The number of the injections was determined from the injection log books and billing records. The injections were performed as an office based procedure with use of povidone-iodine as a part of preinjection preparation. Preinjection antibiotics, eye drape, or surgical attire were not used. The main outcome measures were the incidence of suspected and proven endophthalmitis. There were three cases of suspected endophthalmitis, one case following bevacizumab injection and two cases following ranibizumab injection. There was no case of culture-proven endophthalmitis. All three patients regained their preinjection visual acuity. The incidence of suspected endophthalmitis was 0.029% (95% confidence interval, 0.006% to 0.085%). There was no difference in the incidence of endophthalmitis between ranibizumab and bevacizumab injections (P = .6). Although there is no consensus regarding the intravitreal injection procedure technique, the incidence of suspected endophthalmitis was very low in a large series of injected patients in a community setting and the incidence compares favorably with that reported in clinical trials where much more extensive preinjection preparation was mandated. We found no difference in the endophthalmitis risk of patients receiving bevacizumab as compared with ranibizumab.


Seroprevalence of schistosomiasis in African patients infected with HIV.
Schistosomiasis is a highly prevalent parasitic infection causing significant morbidity and mortality in sub-Saharan Africa. Infection is asymptomatic for many years. Long-term complications such as portal hypertension and bladder cancer can be prevented by treatment with praziquantel. The aim of this study was to determine the prevalence of schistosomiasis in HIV-infected African patients attending our department. From March 2005, all patients of African origin attending our HIV clinics were tested for schistosomal antibodies using a peroxidase enzyme-linked immunosorbent assay (ELISA). Stool and urine specimens from seropositive patients were examined for ova. All seropositive patients were offered treatment with praziquantel. Of 122 patients tested, 21 (17%) were ELISA positive for schistosomiasis. Ova were found in stools from four patients and on a cervical smear in one patient. There were no significant differences between infected and uninfected patients other than the presence of eosinophilia (48 vs. 6%; P<0.001), and 17 seropositive patients were treated with praziquantel. The seroprevalence of schistosomiasis in HIV-infected patients of African origin in the UK is high. We recommend that screening for schistosomiasis should be offered to these patients and those found to be positive treated with praziquantel.


Assessing Right Ventricular Function in the Perioperative Setting, Part I: Echo-Based Measurements.
This article reviews transesophageal echocardiography-based assessment of perioperative right ventricular function and failure, including catheter-based methods, three-dimensional echocardiography, and their combination to make pressure-volume loops. It outlines right ventricular pathophysiology, multiple assessment methods, and their relationship to analogous transthoracic echocardiogram measurements. technologies used and developed for transthoracic or left ventricular assessment show significant limitations when applied to transesophageal assessment of the right ventricle. The article provides an overview of right ventricular assessment modalities that can be used in transesophageal echocardiography. Ultimately, clinicians must know limitations of measurements, synthesize information, and assess it in the clinical context.


Needle-free jet injection using real-time controlled linear Lorentz-force actuators.
Needle-free drug delivery by jet injection is achieved by ejecting a liquid drug through a narrow orifice at high pressure, thereby creating a fine high-speed fluid jet that can readily penetrate skin and tissue. Until very recently, all jet injectors utilized force- and pressure-generating principles that progress injection in an uncontrolled manner with limited ability to regulate delivery volume and injection depth. In order to address these shortcomings, we have developed a controllable jet injection device, based on a custom high-stroke linear Lorentz-force motor that is feed-back controlled during the time-course of an injection. Using this device, we are able to monitor and modulate continuously the speed of the drug jet, and regulate precisely the volume of drug delivered during the injection process. We demonstrate our ability to control injection depth (up to 16mm) and repeatably and precisely inject volumes of up to 250μL into transparent gels and post-mortem animal tissue.


Cutaneous iontophoretic delivery of CGP69669A, a sialyl Lewis(x) mimetic, in vitro.
The aim was to investigate the feasibility of using iontophoresis for the cutaneous delivery of the E-selectin antagonist CGP69669A, a sialyl Lewis(x) -glycomimetic with potential activity against inflammatory skin diseases. The effects of current density and formulation on iontophoretic transport were evaluated in porcine and human skin in vitro. Cumulative permeation of CGP69669A increased with current density (69.73±9.51, 113.97±26.80 and 160.44±13.79μg/cm(2) at 0.1, 0.3 and 0.5mA/cm(2) , respectively) and drug concentration (37.42±13.13, 78.96±23.13 and 160.44±13.79μg/cm(2) , at 1, 3 and 5mg/ml, respectively). In contrast, passive delivery was negligible. Although permeation from a 2% hydroxyethyl cellulose gel was lower than that from aqueous solution, skin deposition - more relevant for the local treatment of dermatological conditions - was 3-fold higher. The results demonstrated that although CGP69669A cannot be delivered passively into the skin it is an excellent candidate for transdermal iontophoresis, a technique that is ideally suited to the delivery of glycomimetics.


The role of histology in the diagnosis of spondylodiscitis: correlation with clinical and microbiological findings.
The aim of this study was to determine the diagnostic utility of histological analysis in spinal biopsies for spondylodiscitis (SD). Clinical features, radiology, results of microbiology, histology, and laboratory investigations in 50 suspected SD patients were evaluated. In 29 patients, the final (i.e. treatment-based) diagnosis was pyogenic SD; in seven patients, the final diagnosis was mycobacterial SD. In pyogenic SD, the neutrophil polymorph (NP) infiltrate was scored semi-quantitatively by determining the mean number of NPs per (×400) high-power field (HPF). Of the 29 pyogenic SD patients, 17 had positive microbiology and 21 positive histology (i.e. one or more NPs per HPF on average). All non-SD patients showed less than one NP per HPF. The presence of one or more NPs per HPF had a diagnostic sensitivity of 72.4%, specificity 100%, accuracy 100%, positive predictive value (PPV) 81.0%, and negative predictive value (NPV) 61.9%. Sensitivity, specificity, and accuracy were greater using the criterion of positive histology and/or microbiology than positive histology or microbiology alone. Granulomas were identified histologically in seven mycobacterial SD patients, and positive microbiology was detected in four. The diagnosis of pyogenic SD was more often confirmed by positive histology (one or more NPs per HPF on average) than by microbiology, although diagnostic sensitivity was greater when both histology and microbiology were positive. Cite this article: Bone Joint J 2019;101-B:246-252.


Demonstration of anti-idiotypic antibodies directed against IgM rheumatoid factor in the serum of rheumatoid arthritis patients.
We have identified the presence of anti-idiotypic activity against IgMRF in the sera of RA patients. Only patients seropositive for IgMRF had significant levels of anti-idiotypic activity, while seronegative patients and normal volunteers did not. When this anti-idiotypic activity was affinity-purified from a single RA patient, two separate binding activities were identified. IgG antibodies were pepsin-digested to F(ab')2 fragments before affinity-purification to remove the Fc portion capable of binding to IgMRF. Anti-idiotypic F(ab')2 fragments of IgG were eluted from an IgMRF-Sepharose 4B column. These F(ab')2 bound preferentially to IgMRF bearing an idiotype recognized by the anti-idiotypic murine monoclonal 17.109. A second anti-idiotypic F(ab')2 was affinity purified using rabbit anti-human Fc antibody bound to Sepharose 4B. These eluted antibodies behaved as the internal image of IgG, binding five out of seven IgMRF's tested. The binding of both anti-idiotypic F(ab')2 was inhibited with human IgG. The presence of both IgMRF and anti-idiotypic antibodies directed against it in the sera of RA patients suggests that anti-idiotypic antibodies alone are not capable of inhibiting the production of rheumatoid factor.


Sites of attachment and density assessment in Amblyomma americanum (Acari: Ixodidae) on nursing beef calves.
Primary attachment sites of male, female, and nymphal Amblyomma americanum (L.) on nursing beef calves were the axillary, inguinal and perianal areas of the body. About 50% of all larvae fed on the ears. A density assessment method which uses the number of A. americanum on less than or equal to 5 body areas to predict the total number of ticks (tick burden) on the left side of a calf is presented. Estimates of tick burden for male, female, nymphal and larval A. americanum each require examination of the axillary, inguinal, and perianal body areas. In addition, to estimate larval and male A. americanum, the neck, dewlap and brisket require examination as do the ears for estimates of nymphs and larvae. Mean tick burden in a herd of calves can be estimated by an examination of from 14 to 100% of all calves depending on the level of precision required for the estimate.


Salidroside-regulated lipid metabolism with down-regulation of miR-370 in type 2 diabetic mice.
Salidroside is known for its pharmacological properties and in particular its antioxidation effects. In recent years, it has been recognized that salidroside plays an important role in treating diabetes. Accumulated evidence suggests that microRNAs may be involved in diabetic lipid disorders. We investigated how salidroside regulates lipid metabolism through miR-370 in vivo and in vitro. After 4 weeks of a high-fat diet, and intraperitoneal injection of streptozotocin (100mg/kg), type 2 diabetes was induced in male C56BL/6J mice. After 4 weeks, mice with fasting blood glucose levels above 7.8mmol/l were divided into five groups: those with diabetes mellitus, and those treated with 40mg/kg, 80mg/kg, and 160mg/kg salidroside, and metformin (480mg/kg), for a further 4 weeks. The hypoglycemic effects of salidroside were consistently demonstrated when measuring fasting blood glucose levels, observing insulin-sensitizing effects, and testing oral glucose tolerance. In addition to this, the expressions of miR-370, and related lipid protein expression in primary hepatocytes, were examined in primary type 2 diabetic mice. The present study has shown that the expression levels of miR-370, SREBP-1 and FAS-1 were significantly elevated in the liver of type 2 diabetic mice. In contrast, the elevated expression levels were reversed by salidroside. The addition of salidroside attenuated the effect of miR-370, and reduced the expression of these lipid metabolism proteins in primary hepatocytes. These findings demonstrate that salidroside can directly decrease the expression of miR-370 in type 2 diabetic mice, and particularly in primary hepatocytes, affecting lipid metabolism in the liver.


Phosphorus in rivers--ecology and management.
This paper examines the nature of the risk to riverine ecosystems from artificially enhanced loads of phosphorus, considers the key sources of phosphorus enrichment and ways of controlling them, and provides a framework for developing control strategies. The aquatic plant community is the foundation for a healthy and diverse riverine ecosystem, providing food, shelter and breeding habitats for a wide range of animal species. Phosphorus enrichment in rivers can degrade the plant community by altering the competitive balance between different aquatic plant species, including both higher plants and algae. This has consequences for the whole ecosystem. To promote healthy riverine plant communities and the wide range of animal species dependent on them, phosphorus concentrations need to be reduced to as near to background levels as possible. The risk of adverse effects declines as phosphorus concentrations approach background levels, such that any incremental reduction should be seen as a positive step towards trophic restoration. Pragmatic management targets vary between 0.02 and 0.1 mg(-1) soluble reactive phosphorus, depending on river type, with an interim target of 0.2 mg(-1) for heavily enriched rivers. Continuous point sources of phosphorus, dominated by sewage treatment works, have a highly important influence on levels of bioavailable phosphorus in the water column through the growing season. It is important to tackle point sources comprehensively so that reductions in phosphorus concentrations are maximised during this critical time of year. Diffuse sources of phosphorus, particularly from agriculture, are a major contributor to phosphorus levels in riverine sediments, where it can be utilised by benthic algae and rooted plants. This phosphorus can also be released into the water column by a variety of processes. As point sources are brought under control, the relative contribution from diffuse sources becomes increasingly important. An integrated programme of control, involving proactive action on both point and diffuse sources, will be required in most circumstances to bring phosphorus levels in the water column and sediment down to near background levels.


The new evidence of nucleolar ultrastructural dynamic change: fibrillar centre (FC) fusion in G1 phase and regeneration in S phase.
In higher eukaryotes ribosome production starts at the end of mitosis, increases during G1, is maximal in G2 (Sirri et al., 2000) and stops during prophase (Gébrane-Younès et al., 1997). But the mechanism of the change is still uncovered. Especially in the actively growing mammalian somatic cells usually contain one or several giant fibrillar centres (GFCs) with many tiny fibrillar centre (FCs) (Koberna et al., 2002; Raška et al., 2004; Casafont et al., 2007). The process how the giant fibrillar centre (GFC) and the many tiny fibrillar centres (FCs) were formed is unknown. The present results showed there were processes of FCs fusion in G1 phase and FCs regeneration in S phase respectively in the nucleoli of A 375 cells. A few FCs fused each other in late G1 phase when the process of nucleoli fusion was completed. In S phase, a lot of tiny FCs were regenerated from the periphery of GFC, separated and scattered into nucleolar matrix in late S phase and early G2 phase. The GFC was found to be coexisted with numerous tiny FCs in the nucleolus in G2 phase. The present study provided a new evidence of nucleolar dynamic change during interphase: fibrillar centre (FC) was not to be a stable state subunit of nucleolar compartment but a highly dynamic process that may be the bases of nucleolar morphological architecture organization and its function taking place.


Variation in the volume-outcome relationship after rectal cancer surgery in the United States: Retrospective study with implications for regionalization.
Previous studies have demonstrated improved outcomes for patients with rectal cancer treated at higher-volume hospitals. However, little is known whether heterogeneity in this effect exists. The objective was to test whether the effect of increased annual rectal cancer resection volume on outcomes is consistent across all hospitals treating rectal cancer. Adult stage I to III patients who underwent surgical resection for rectal adenocarcinoma from 2004 to 2016 were identified in the National Cancer Database. We included 120,522 patients treated at 763 hospitals in this retrospective cohort study. Higher volume was linearly and incrementally related to outcomes in unadjusted analyses. In adjusted models, for an average patient at the average hospital, the effect of increasing the annual caseload of rectal cancer resections by 20 resections per year was associated with 8%, (hazard ratio = 0.92, 95% confidence interval = 0.87, 0.97), 18% (odds ratio = 0.82, 95% confidence interval = 0.70, 0.98), and 16% (odds ratio = 0.84, 95% confidence interval = 0.73, 0.95) relative reductions in 5-year overall survival, 30-, and 90-day mortality, respectively, and with a 19% (odds ratio = 1.19, 95% confidence interval = 1.04, 1.36) relative increase in the rate of neoadjuvant chemoradiation. These effects varied by individual hospitals such that 39% of hospitals do not see any benefit in 5-year overall survival associated with higher volumes. Increased volume was associated with lower positive circumferential resection margin rates at 19% of the hospitals. This study confirms that higher-volume hospitals have improved outcomes after rectal cancer surgery. However, there exists significant variation in these effects induced by individual within-hospital effects. Regionalization policies may need to be flexible in identifying the hospitals that would achieve enhanced benefits from treating a larger volume of patients.


Ultrasound simulation training to meet the 2021 Royal College of Radiologists' curriculum for radiology trainees: South East London experience.
To enhance ultrasound teaching delivery to radiology trainees using a simulation course matched to the 2021 Royal College of Radiologists (RCR) curriculum. An ultrasound simulation training course was designed for specialty trainees (ST) 1 in radiology, which was based on the 2021 RCR curriculum and covered the top ultrasound training priorities. The course was piloted initially on two occasions in a 1-day format to the August 2021 and the March 2022 ST1 intake trainees. Based on the feedback, a comprehensive 4-day course was developed and delivered between October and December 2022 for the August 2022 ST1 intake, funded by Health Education England. The outcomes measured were subjective trainee feedback using numerical scores and free text. All King's College Hospital NHS Foundation Trust radiology ST1 trainees from the August 2021 to the August 2022 intake participated in ultrasound simulation training. The training matched the RCR curriculum and increased the trainees' confidence and competency in medical ultrasound. Ultrasound simulation training can be successfully delivered to ST1 trainees to match the 2021 RCR curriculum and enhance training in medical ultrasound for radiologists.


Strong and ubiquitous expression of transgenes targeted into the beta-actin locus by Cre/lox cassette replacement.
Conventional approaches to produce transgenic mice recurrently yield unpredictable patterns and levels of transgene expression, a situation calling for the development of new techniques to overcome these drawbacks in the context of overexpression studies. Here we present an efficient method for rapid and reproducible transgenesis using the recombinase mediated cassette exchange (RMCE) (Bouhassira et al.: Blood 90:3332-3344, 1997) procedure. A lox511-EGFP-TK/neo-loxP cassette was placed under the control of the endogenous mouse beta-actin promoter. Heterozygous mice revealed strong and ubiquitous EGFP expression throughout embryogenesis and adulthood. Reproducibly, the same expression pattern was obtained with RMCE when it was used to replace the EGFP-harboring cassette by ECFP or placental alkaline phosphatase (PLAP) reporter genes (DePrimo et al.: Transgenic Res 5:459-466, 1996). Furthermore, the RMCE procedure proved efficient as well in embryonic stem (ES) cells as directly in zygotes. Our results demonstrate ubiquitous expression of floxed transgenes in the endogenous beta-actin locus and they support the general use of the beta-actin locus for targeted transgenesis.


Caspase-independent death of Leber's hereditary optic neuropathy cybrids is driven by energetic failure and mediated by AIF and Endonuclease G.
Leber's hereditary optic neuropathy (LHON) is associated with mitochondrial DNA point mutations affecting different subunits of complex I. By replacing glucose with galactose in the medium, cybrids harboring each of the three LHON pathogenic mutations (11778/ND4, 3460/ND1, 14484/ND6) suffered a profound ATP depletion over a few hours and underwent apoptotic cell death, which was caspase-independent. Control cybrids were unaffected. In addition to cytochrome c, apoptosis inducing factor (AIF) and endonuclease G (EndoG) were also released from the mitochondria into the cytosol in LHON cybrids, but not in control cells. Exposure of isolated nuclei to cytosolic fractions from LHON cybrids maintained in galactose medium caused nuclear fragmentation, which was strongly reduced by immuno-depletion with anti-AIF and anti-EndoG antibodies. In conclusion, the caspase-independent death of LHON cybrids incubated in galactose medium is triggered by rapid ATP depletion and mediated by AIF and EndoG.


Investigation of SRP9 protein expression in breast cancer.
Signal recognition particle (SRP) promotes co-translational translocation of the proteins through or into the endoplasmic reticulum membrane and it also has elongation arrest function. SRP9 is one of the six protein subunits of SRP and functions in elongation arrest activity by forming a heterodimeric structure with SRP14. It is one of the substrates of ADAR, which has been found to have a role in breast cancer. This study was conducted to investigate the SRP9 protein expression in normal and tumor tissues of patients with breast cancer and determine its prognostic significance. A total of 32 female patients who were diagnosed as having primary breast cancer and underwent surgery were included in the study. Western Blotting was performed to detect SRP9 protein expression levels in normal and tumor tissue samples. Clinical and pathologic characteristics were analyzed to assess the prognostic significance. SRP9 protein expression was statistically higher in the breast cancer tissue samples compared to normal matched tissue, and the mean SRP9 protein expression levels of breast cancer tissue normal tissue samples were 1.019 ± 1.011 and 0.551 ± 0.456, respectively (p = 0.001). SRP9 protein expression levels in tumor tissue of patients with lymph node metastasis, tumor size > 2 cm, estrogen receptor-positive, progesterone receptor-positive, and HER-2 negative were statistically higher than in normal tissue (p < 0.05). It is vital to clarify the roles of molecules such as SRP9 in understanding the pathogenesis of breast cancer. In our study, we showed that SRP9 expression increased in breast cancer and was associated with disease-related parameters.


Virtual reality for COPD rehabilitation: a technological perspective.
Virtual Reality (VR) is a promising technology for implementing personalized, motivating and controlled rehabilitation scenarios. Although its clear potential benefits, VR has been poorly investigated in pulmonary rehabilitation. This review analyses the state of the art, by searching the scientific and grey literature, regarding the use of VR for the rehabilitation of patients with chronic obstructive pulmonary disease, providing a technological perspective. First, the main characteristics of the included systems are presented in terms of visualization devices, way of interaction and type of feedback they provide. Then, results of the selected studies are reported considering feasibility, safety, usability and user experience as outcomes. Finally, the main findings are discussed and future directions for research are outlined.


Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 5-(4-hydroxymethylphenyl)-1-(4-aminosulfonylphenyl)-3-trifluoromethyl-1H-pyrazole and its methanesulfonyl analog: synthesis, biological evaluation and nitric oxide release studies.
A new class of hybrid nitric oxide-releasing anti-inflammatory (AI) ester prodrugs (NONO-coxibs 12a-b) wherein an O(2)-acetoxymethyl 1-(2-carboxypyrrolidin-1-yl)diazen-1-ium-1,2-diolate (11, O(2)-acetoxymethyl PROLI/NO) NO-donor moiety was covalently coupled to the bromomethyl group of 5-(4-bromomethylphenyl)-1-(4-aminosulfonylphenyl)-3-trifluoromethyl-1H-pyrazole (9a), and its methanesulfonyl analog (9b), were synthesized. The diazen-1-ium-1,2-diolate compounds 12a-b released a low amount of NO upon incubation with phosphate buffer (PBS) at pH 7.4 (6.1-8.2% range). In comparison, the percentage NO released was significantly higher (76-77% of the theoretical maximal release of two molecules of NO/molecule of the parent hybrid ester prodrug) when the diazen-1-ium-1,2-diolate ester prodrugs 12a-b were incubated in the presence of rat serum. These incubation studies suggest that both NO and the anti-inflammatory 5-(4-hydroxymethylphenyl)-1-(4-aminosulfonylphenyl)-3-trifluoromethyl-1H-pyrazole (10a), and its methanesulfonyl analog (10b), would be released from the parent NONO-coxib 12a or 12b upon in vivo cleavage by non-specific serum esterases. The hydroxymethyl compounds 10a-b were weak inhibitors of the cyclooxygenase-1 (COX-1) and COX-2 isozymes (IC(50)=3.7-10.5 microM range). However, the hydroxymethyl compounds 10a-b and the parent NONO-coxibs 12a-b exhibited good AI activities (ED(50)=76.7-111.6 micromol/kg po range) that were greater than that exhibited by the reference drugs aspirin (ED(50)=710 micromol/kg po) and ibuprofen (ED(50)=327 micromol/kg po), but less than that of celecoxib (ED(50)=30.9mumol/kg po). These studies indicate hybrid ester AI/NO-donor prodrugs (NONO-coxibs) constitutes a plausible drug design concept targeted toward the development of selective COX-2 inhibitory AI drugs that are devoid of adverse cardiovascular effects.


Purification of antibody reacting with non-enzymatically glucosylated blood group M determinants.
Agglutinins with a specificity for glucose-treated M erythrocytes were found in the serum of a healthy blood donor (Mar). The affinity of these agglutinins to glucose allowed the purification by affinity chromatography on Sephadex G-25. More than 400-fold purification was achieved in a one-step procedure. Protein bound to the column and eluted with glucose solution showed a good recovery of agglutinating activity. The major components of the purified preparation were IgG and IgM.


Treatment-related biomarkers in pulmonary hypertension patients on oral therapies.
Multiple classes of oral therapy are available for the treatment of pulmonary arterial hypertension (PAH), but there is little to guide clinicians in choosing a specific regimen or therapeutic class. We aimed to investigate whether treatment-relevant blood biomarkers can predict therapy response in prevalent PAH patients. This prospective cohort study longitudinally assessed biomarkers along the endothelin-1 (ET-1) and nitric oxide (cGMP, ADMA, SDMA, nitrite, and S-nitrosohemoglobin) pathways along with the cGMP/NT-proBNP ratio over 12 months in patients with WHO Group 1 PAH on oral PAH-specific therapies. The relationship between biomarkers and 6MWD at the same and future visits was examined using mixed linear regression models adjusted for age. As cGMP can be elevated when NT-proBNP is elevated, we also tested the relationship between 6MWD and the cGMP/NT-pro BNP ratio. Patients with PAH with concomitant heart or lung disease or chronic thromboembolic pulmonary hypertension (CTEPH) were included in a sensitivity analysis. The study cohort included 58 patients with PAH treated with either an endothelin receptor antagonist (27.6%), phosphodiesterase-5 inhibitor (25.9%) or a combination of the two (43.1%). Among biomarkers along the current therapeutic pathways, ET-1 and the cGMP/NT-proBNP ratio associated with same visit 6MWD (p = 0.02 and p = 0.03 respectively), and ET-1 predicted future 6MWD (p = 0.02). ET-1 (p = 0.01) and cGMP/NT-proBNP ratio (p = 0.04) also predicted future 6MWD in the larger cohort (n = 108) of PAH patients with concomitant left heart disease (n = 17), lung disease (n = 20), or CTEPH (n = 13). Finally, in the larger cohort, SDMA associated with 6MWD at the same visit (p = 0.01) in all subgroups and ADMA associated with 6MWD in PAH patients with concomitant lung disease (p = 0.03) and PAH patients on ERA therapy (p = 0.01). ET-1, cGMP/NTproBNP ratio, and dimethylarginines ADMA and SDMA are mediators along pathways targeted by oral PAH therapies that associate with or predict 6MWD.


Comparison of dppf-Supported Nickel Precatalysts for the Suzuki-Miyaura Reaction: The Observation and Activity of Nickel(I).
Ni-based precatalysts for the Suzuki-Miyaura reaction have potential chemical and economic advantages compared to commonly used Pd systems. Here, we compare Ni precatalysts for the Suzuki-Miyaura reaction supported by the dppf ligand in 3 oxidation states, 0, I and II. Surprisingly, at 80 °C they give similar catalytic activity, with all systems generating significant amounts of Ni(I) during the reaction. At room temperature a readily accessible bench-stable Ni(II) precatalyst is highly active and can couple synthetically important heterocyclic substrates. Our work conclusively establishes that Ni(I) species are relevant in reactions typically proposed to involve exclusively Ni(0) and Ni(II) complexes.


Effects of exercise interventions on executive function in old adults with mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials.
To assess the effect of exercise interventions on subdomains of executive function (EF) in older adults with mild cognitive impairment (MCI). Nine electronic databases were comprehensively searched from their inception to February 2021. Randomized controlled trials examining the effect of exercise training on EF in MCI were included. Twenty-four eligible articles involving 2278 participants were identified. The results showed that exercise interventions had positive benefits on working memory, switching and inhibition in MCI. Subgroup analysis based on exercise prescriptions revealed that both aerobatic exercise and mind-body exercise had similar positive effect size on working memory. However, only mind-body exercise had significant effect on switching. Exercise training with moderate frequency (3-4 times/week) had larger effect size than low frequency (1-2 times/week) and only moderate frequency had positive benefits on switching. Both short (4-12 weeks), medium (13-24 weeks) and long (more than 24 weeks) exercise duration significantly ameliorate working memory and switching, however with short duration having slight larger effect sizes than medium and long. Exercise significantly improves three subdomains of EF in MCI, especially mind-body exercise. Exercise training sticking to at least 4 weeks with 3-4 times a week tends to have larger effect size.


Improving communication skill training in patient centered medical practice for enhancing rational use of laboratory tests: The core of bioinformation for leveraging stakeholder engagement in regulatory science.
Requests for laboratory tests are among the most relevant additional tools used by physicians as part of patient's health problemsolving. However, the overestimation of complementary investigation may be linked to less reflective medical practice as a consequence of a poor physician-patient communication, and may impair patient-centered care. This scenario is likely to result from reduced consultation time, and a clinical model focused on the disease. We propose a new medical intervention program that specifically targets improving the patient-centered communication of laboratory tests results, the core of bioinformation in health care. Expectations are that medical students training in communication skills significantly improve physicians-patient relationship, reduce inappropriate use of laboratorial tests, and raise stakeholder engagement.


Two new ELISAs using monoclonal H-Y antibody.
Biotin-conjugated monoclonal H-Y antibody was used to detect soluble H-Y antigen, directly, in two novel enzyme-based systems: a sandwich or 'capture' ELISA and an inhibition ELISA. In each case, soluble H-Y was readily detected in samples known to contain the antigen, provided that positive and negative samples were compared on an equivalent protein basis. By adding increasing concentrations of inhibitor (antigen) we define the useful range of the assays to be between 0.6 and 20.0 micrograms of added protein. Both sandwich and inhibition ELISAs gave similar results with antigens tested. The methods can accordingly be applied as direct diagnostics in the study of sex determination and in the assignment of gender.


Inter- relationships between orthodontics and posture: basic theories.
The first part of the present report deals mainly with the concept of posture - both in static and in dynamic sense - its relationships with equilibrium, weight balance and motion, its phylogenic origin, reasons why any orthodontic professional should be aware of it; moreover, different profile types and their connections with one's own skeletal class are briefly discussed. Two more papers are following on the subject.


Evaluating the Impact of Social and Built Environments on Health-Related Quality of Life among Cancer Survivors.
With almost 17 million U.S. cancer survivors, understanding multilevel factors impacting health-related quality of life (HRQOL) is critical to improving survivorship outcomes. Few studies have evaluated neighborhood impact on HRQOL among cancer survivors. We combined sociodemographic, clinical, and behavioral data from three registry-based studies in California. Using a three-level mixed linear regression model (participants nested within block groups and study/regions), we examined associations of both independent neighborhood attributes and neighborhood archetypes, which capture interactions inherent among neighborhood attributes, with two HRQOL outcomes, physical (PCS) and mental (MCS) composite scores. For the 2,477 survivors, 46% were 70+ years, 52% were non-Hispanic White, and 53% had localized disease. In models minimally adjusted for age, stage, and cancer recurrence, HRQOL was associated with neighborhood socioeconomic status (nSES), racial/ethnic composition, population density, street connectivity, restaurant environment index, traffic density, urbanicity, crowding, rental properties, and non-single family units. In fully adjusted models, higher nSES remained associated with better PCS, and restaurant environment index, specifically more unhealthy restaurants, associated with worse MCS. In multivariable-adjusted models of neighborhood archetype, compared with upper middle-class suburb, Hispanic small town and inner city had lower PCS, and high status had higher MCS. Among survivors, higher nSES was associated with better HRQOL; more unhealthy restaurants were associated with worse HQROL. As some neighborhood archetypes were associated with HRQOL, they provide an approach to capture how neighborhood attributes interact to impact HRQOL. Elucidating the pathways through which neighborhood attributes influence HRQOL is important in improving survivorship outcomes.


Deviation from expected cognitive ability is a core cognitive feature of schizophrenia related to neurophysiologic, clinical and psychosocial functioning.
Cognitive functioning in schizophrenia is characterized by a generalized impairment in current cognitive ability based on traditional population-based norms. However, these norms assume a normal cognitive trajectory and do not directly account for illness-related declines from expected cognitive potential. Indeed, schizophrenia patients exhibit even greater deviation between their observed and expected cognitive functioning based on expanded norms that leverage premorbid variables resistant to illness-related features. The current study further quantified the extent to which illness-related features account for this deviation from expectation and assessed its relationship to neurophysiologic (mismatch negativity, P3a, theta oscillations), clinical, and psychosocial functioning in schizophrenia patients. Expected cognitive ability (PENN-CNB global cognition) in patients (n = 684) was calculated using healthy comparison subject (n = 660) weighted regression based on premorbid variables resistant to illness-related decline (demographics, single-word reading, parental education). The magnitude of any deviation between current (observed) and regression-predicted (expected) cognitive ability was calculated. Results indicated that 24% (n = 164) of the total patient population exhibited significant (≥-1.96 SD) deviation between observed and expected global cognitive ability. Interestingly, 20% of the total patient population (n = 136) had "normal" range cognitive performance when using traditional population-based norms, but also had significant deviation from expected cognitive ability. The magnitude of this deviation was associated with more severe neurophysiologic abnormalities, longer illness duration, higher levels of negative symptoms, and worse psychosocial functioning. Assessment of cognitive deviation is thus a complementary metric for characterizing the severity of illness-related cognitive declines in patients, while also reflecting the expression and severity of key endophenotypes of schizophrenia.


Rapid and Sensitive Differentiating Ischemic and Hemorrhagic Strokes by Dried Blood Spot Based Direct Injection Mass Spectrometry Metabolomics Analysis.
Cerebral infarction (CI) and intracerebral hemorrhage are lethal cerebrovascular diseases, sometimes sharing similar clinical manifestations but with distinct therapeutic strategies. Delayed treatment usually resulted in poor prognosis. A timely diagnosis report is highly warranted especially in emergency. One hundred twenty-nine CI patients, 73 intracerebral hemorrhage (ICH) patients, and 98 controls were enrolled in this study. A direct injection mass spectrometry metabolomics approach was adopted using dried blood spot samples. This targeted metabolomics analysis focused on absolute quantitation of 23 amino acids, 26 carnitine/carnitine esters, and 22 calculated ratios parameters. Compared to the normal control group, CI and ICH showed distinct metabolite changes, respectively. For stroke differentiation, Tyr, C5-OH/C0, Cit, Asn, Pro, Val, Arg/Orn, Leu, and Val/Phe were elevated in the CI group. On the contrary, C5:1, Phe/Tyr, (C0 + C2 + C3 + C16 + C18:1)/Cit, and Met/Leu were of lower levels in the CI group. Using regression model based on some of the above-mentioned parameters, 79.07% of stroke patients from a new set could be definitely confirmed. This study proved the targeted metabolomics analysis was a promising tool for rapid and timely stroke differentiation.


EFFECTS OF GONADOTROPIN-RELEASING HORMONE ANTAGONIST DEGARELIX ON MUSTH AND SERUM TESTOSTERONE CONCENTRATIONS IN ASIAN ELEPHANTS ( ELEPHAS MAXIMUS).
Two male Asian elephants (bulls 1 and 2) in musth were subcutaneously injected with a long-acting gonadotropin-releasing hormone (GnRH) antagonist, degarelix acetate (240 μg/kg; total dose of 960 mg). Musth behavior (MB) and temporal gland secretions (TGS) were monitored and serum testosterone concentrations were determined. In bull 1, MB and TGS ceased on day 1 and reappeared 5.5 mo after the treatment (day 0). During the subsequent musth cycle, MB and TGS ceased on day 1 and did not appear for 4 mo. In bull 2, MB and TGS ceased at day 7 after the treatment. Musth behavior and TGS recurred on Day 11 and continued for 1 wk, then disappeared for 8 mo. Serum testosterone concentrations decreased ( P < 0.05) in all occasions from day 0 (29.8 ± 15.8 ng/ml; mean ± SEM) to day 1 (2.2 ± 1.1 ng/ml), suggesting a sudden drop in circulating testosterone in musth elephants after the GnRH-antagonist treatment.


Epidemiology of paratuberculosis in sheep and goats in southern Spain.
Paratuberculosis is a worldwide, chronic infectious disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) that mainly affects ruminant species. This disease has a significant economic impact on small ruminant production due to the costs of implementing control measures and production losses. A cross-sectional study was carried out to determine the seroprevalence, spatial distribution and risk factors associated with MAP exposure in sheep and goats in Andalusia (southern Spain). Serum samples from 4134 small ruminants (2266 sheep and 1868 goats) in 153 flocks were tested by an in-house ELISA for antibodies against MAP using paratuberculosis protoplasmic antigen 3 (PPA3) as coating antigen. Antibodies against MAP were detected in 8.1% (183/2266; 95% CI: 7.0-9.2%) of sheep and 20.0% (374/1868; 95% CI: 18.2-21.8%) of goats. The true individual seroprevalence was 8.4% (95% CI: 6.9-10.1%) in sheep and 25.2% (95% CI: 22.7-27.8%) in goats. Seropositivity was detected in 66.3% (55/83; 95% CI: 56.1-76.4%) of sheep herds and 90.0% (63/70; 95% CI: 83.0-97.0%) of goat herds. Spatial analysis identified three statistically significant clusters (p < 0.05) associated with areas with higher seroprevalence of MAP. The main risk factors potentially associated with MAP exposure were: species (goat) and absence of perimeter livestock fencing. The results of this study show that MAP is widespread in small ruminant populations in southern Spain and suggest that goats may play a more important role than sheep in the transmission and maintenance of MAP. Because of animal health concerns and the economic consequences of paratuberculosis, appropriate surveillance and control programs are required to reduce the risk of MAP infections in small ruminant flocks in this country.


Measuring Stress-Induced Changes in Defense Phytohormones and Related Compounds.
Measuring quantitative changes in plant hormones and derivatives is crucial to understand how reactive oxygen species trigger signaling cascades to regulate stress responses. In this chapter, we describe the liquid chromatography-mass spectrometry procedure that we use to extract and quantify salicylic acid (SA), jasmonic acid (JA), and related compounds in common extracts of Arabidopsis tissue. The method can provide quantitative data on SA, SA glucosides, and JA, as well as information on oxidized and conjugated forms of these compounds and related derivatives of benzoic acid.


Homozygosity of adenylate kinase allele 3: two cases.
The phenotype AK 3.3 in the isoenzyme system of human adenylate kinase has been found in two members of the Wayampi population of French Guiana.


ChIP-chip: considerations for the design, analysis, and application of genome-wide chromatin immunoprecipitation experiments.
Chromatin immunoprecipitation (ChIP) is a well-established procedure to investigate interactions between proteins and DNA. Coupled with whole-genome DNA microarrays, ChIPS allow one to determine the entire spectrum of in vivo DNA binding sites for any given protein. The design and analysis of ChIP-microarray (also called ChIP-chip) experiments differ significantly from the conventions used for locus ChIP approaches and ChIP-chip experiments, and these differences require new methods of analysis. In this light, we review the design of DNA microarrays, the selection of controls, the level of repetition required, and other critical parameters for success in the design and analysis of ChIP-chip experiments, especially those conducted in the context of mammalian or other relatively large genomes.


Antibacterial and antibiofilm potential of silver nanoparticles against antibiotic-sensitive and multidrug-resistant Pseudomonas aeruginosa strains.
Due to the severity of infections caused by P. aeruginosa and the limitations in treatment, it is necessary to find new therapeutic alternatives. Thus, the use of silver nanoparticles (AgNPs) is a viable alternative because of their potential actions in the combat of microorganisms, showing efficacy against Gram-positive and Gram-negative bacteria, including multidrug-resistant microorganisms (MDR). In this sense, the aim of this work was to conduct a literature review related to the antibacterial and antibiofilm activity of AgNPs against antibiotic-sensitive and multidrug-resistant Pseudomonas aeruginosa strains. The AgNPs are promising for future applications, which may match the clinical need for effective antibiotic therapy. The size of AgNPs is a crucial element to determine the therapeutic activity of nanoparticles, since smaller particles present a larger surface area of contact with the microorganism, affecting their vital functioning. AgNPs adhere to the cytoplasmic membrane and cell wall of microorganisms, causing disruption, penetrating the cell, interacting with cellular structures and biomolecules, and inducing the generation of reactive oxygen species and free radicals. Studies describe the antimicrobial activity of AgNPs at minimum inhibitory concentration (MIC) between 1 and 200 μg/mL against susceptible and MDR P. aeruginosa strains. These studies have also shown antibiofilm activity through disruption of biofilm structure, and oxidative stress, inhibiting biofilm growth at concentrations between 1 and 600 μg/mL of AgNPs. This study evidences the advance of AgNPs as an antibacterial and antibiofilm agent against Pseudomonas aeruginosa strains, demonstrating to be an extremely promising approach to the development of new antimicrobial systems.


Multiple sclerosis at Jordan University Hospital.
A study of multiple sclerosis patients admitted to Jordan University Hospital over a 10-year-period with a comparison with other Western and Middle Eastern series. The case notes of 32 patients with multiple sclerosis were reviewed to determine the age and sex distribution, clinical findings and results of investigations, treatment and outcome. There were 32 patients (24 females, 8 males, 3:1), with mean age at onset of 31.4 years, and range 6-50 years. All patients fulfilled Poser`s criteria for multiple sclerosis. The most common clinical manifestation was myelopathy followed by a polysymptomatic onset. Two-thirds of the patients had a relapsing - remitting course. The yield of cerebrospinal fluid oligoclonal banding was low (20%). The sensitivities of visual evoked potential was 62%, magnetic resonance imaging of brain 100%, magnetic resonance imaging of cervical spine was 70% and of dorsal spine 44%. Intravenous methylprednisolone Igr for 3-5 days was efficient in acute relapses for all patients. Beta-interferon was efficient in 2 out of 7 patients. After a mean follow-up of 5 years, two-thirds of the patients had mild to moderate disability (Extended disability status scale = 2 and 3). The age and sex distribution, clinical and magnetic resonance imaging findings were almost similar to other reports. However the yield of visual evoked potentials was low and that of cerebrospinal fluid oligoclonal banding was very low, the results of treatment with beta-interferon were modest and the outcome at a mean follow-up of 5 years was relatively good.


Electrophysiological effects of lidocaine on isolated guinea pig Purkinje fibers: comparison with its effects on papillary muscle.
1. The effects of lidocaine on action potentials of isolated guinea pig Purkinje fibers were examined and compared with those on the papillary muscle, by use of conventional microelectrode techniques. 2. Lidocaine 2.1 x 10(-4) M significantly depressed the resting membrane potential, amplitude, overshoot, maximum upstroke velocity, and duration of action potential of the Purkinje fibers stimulated at cycle length (CL) 1 sec, while the lower concentration (2.1 x 10(-5) M) produced no significant effect. 3. Various parameters of action potentials from the papillary muscle at CL = 1 sec were also depressed by lidocaine 2.1 x 10(-4) M, but the extent of the depression was less marked than in Purkinje fibers. 4. When the Purkinje fibers were stimulated at various CLs (0.3-10 sec), the shortening of action potential duration induced by lidocaine was more evident at slower stimulus rate.


Invasive dysgerminoma in a girl with 45,X/46,X; mar mosaicism.
We report a 16-year-old girl with features of Turner's syndrome from whom an invasive dysgerminoma was removed. Cytotoxic drugs were given for the next 12 months. Mosaicism of two karyotypes (45,X/46,X; mar) was found in various tissues. The literature is reviewed with special regard to cytogenetic findings and prognosis of malignant growth and differentiation of dysgenetic gonads.


Analyzing protective factors for adolescents' mental health during COVID-19 pandemic in Spain: A longitudinal study.
This study examined the protective role of self-esteem and perceived emotional intelligence on mental health problems in Spanish adolescents during COVID-19 pandemic. Participants (N = 139; Mage = 13.83 years, SD = 0.96; 63.8% female) completed measures before the outbreak of COVID-19 (T1) and during the first wave of the pandemic in Spain (T2). Participants self-reported emotional intelligence, self-esteem, mental health problems and suicidal behavior. Adolescent mental health problems were equally affected by COVID-19 pandemic according to gender, age and lockdown conditions. Adolescents with low levels of emotional intelligence and self-esteem at T1 showed a significant decrease in self-reported anxiety, depression, stress and suicidal behavior at T2. However, adolescents with average or high levels of emotional intelligence and self-esteem at T1 showed no significant changes in mental health problems at T2. Self-esteem at T1 meditated the relationships between emotional intelligence at T1 (clarity and repair) and emotional symptoms at T2 (depression, anxiety and stress). Furthermore, the relationship between self-esteem and anxiety symptoms was moderated by the number of people living together during COVID-19 lockdown. Our findings highlight the protective role of pre-pandemic development of self-esteem and emotional intelligence in mitigating the impact of COVID-19 outbreak on adolescent mental health during the pandemic.


Breaking the COPI monopoly on Golgi recycling.
The unexpected discovery of a transport pathway from the Golgi to the endoplasmic reticulum (ER) independent of COPI coat proteins sheds light on how Golgi resident enzymes and protein toxins gain access to the ER from as far as the trans Golgi network. This new pathway provides an explanation for how membrane is recycled to allow for an apparent concentration of anterograde cargo at distinct stages of the secretory pathway. As signal-mediated COPI-dependent recycling also involves the concentration of resident proteins into retrograde COPI vesicles, the main bulk of lipids must be recycled, possibly through a COPI-independent pathway.


Proteolysis in the maturation of avian retroviruses does not require calcium.
After budding from the plasma membrane, retrovirus particles undergo a process of maturation, which includes changes in morphology caused by several proteolytic cleavages of the precursor of the internal structural proteins, products of the gag gene. Cleavage is mediated by the viral protease, PR. The fact that in most systems cleavage appears to occur only after assembly is complete, suggests that PR may become enzymatically active as a consequence of release of the virion from the cell. Using avian leukosis virus as a model system, we tested the hypothesis that leakage of calcium ions into newly budded virions plays a role in their maturation. We found that in both quail Qt35 cells and monkey COS-1 cells, maturation occurred normally in calcium-free medium and in the presence of EGTA. A calcium ionophore also did not affect maturation. We conclude that calcium influx does not act as a trigger for PR-mediated maturation.


N-H activation of hydrazines by a heterobimetallic Zr-Co complex: promotion of one-electron chemistry at Zr.
A tris(phosphino)amide-ligated Zr-Co heterobimetallic complex has been shown to activate N-H bonds of hydrazine derivatives via a proton-coupled electron transfer process. Such reactivity is highly unusual for an early metal such as Zr, but is promoted by the adjacent redox active Co atom.


Realization of a fractional quantum Hall state with ultracold atoms.
Strongly interacting topological matter1 exhibits fundamentally new phenomena with potential applications in quantum information technology2,3. Emblematic instances are fractional quantum Hall (FQH) states4, in which the interplay of a magnetic field and strong interactions gives rise to fractionally charged quasi-particles, long-ranged entanglement and anyonic exchange statistics. Progress in engineering synthetic magnetic fields5-21 has raised the hope to create these exotic states in controlled quantum systems. However, except for a recent Laughlin state of light22, preparing FQH states in engineered systems remains elusive. Here we realize a FQH state with ultracold atoms in an optical lattice. The state is a lattice version of a bosonic ν = 1/2 Laughlin state4,23 with two particles on 16 sites. This minimal system already captures many hallmark features of Laughlin-type FQH states24-28: we observe a suppression of two-body interactions, we find a distinctive vortex structure in the density correlations and we measure a fractional Hall conductivity of σH/σ0 = 0.6(2) by means of the bulk response to a magnetic perturbation. Furthermore, by tuning the magnetic field, we map out the transition point between the normal and the FQH regime through a spectroscopic investigation of the many-body gap. Our work provides a starting point for exploring highly entangled topological matter with ultracold atoms29-33.


Stat3 inhibits WTX expression through up-regulation of microRNA-370 in Wilms tumor.
Wilms tumor (WT) is a genetically heterogeneous childhood kidney tumor. Several genetic mutations have been identified in WT patients, including inactivation of WTX, somatic stabilizing CTNNB1, and p53 mutations. However, the molecular mechanisms in tumorigenesis remain largely unexplored. Stat3 is a transcription factor that can promote oncogenesis. Stat3 activation is commonly viewed as crucial for multiple tumor proliferation and metastasis. We show that Stat3 is highly activated in Wilms tumor tissues compared to those in adjacent tissues. IL-6 treatment or transfection of a constitutively activated Stat3 in G401 cells promotes cell proliferation. At the molecular level, we further elucidate that Stat3 inhibits WTX expression through up-regulation of microRNA-370. Our results suggest that Stat3/miR-370/WTX regulatory axis might be a critical mechanism in Wilms tumor cells.


Heat-Electricity Coupling Driven Cascade Oxidation Reaction of Redox Couple and Water.
High barriers of water oxidation mediated by redox couple continuously challenge to maximizing efficiency from renewables to hydrogen energy. Here, an electricity-heat complementary strategy was achieved by a heat-electricity-sensitive interconversion of the α-Ni(OH)2/γ-NiOOH redox couple. In our strategy, the thermo-activated effects significantly lower the barrier energies of initial electroxidation of Ni2+/Ni3+ and subsequent chemical water oxidation to the nearly equal value via coupling a low-grade heat field (<100 °C), thereby achieving a consecutive two-step cascade reaction without kinetic delay. As a result, the cascaded water splitting reaction can happen at an extremely low overpotential of 130 mV and affords a low cell voltage of 1.73 V at 100 mA cm-2 at 90 °C in alkaline electrolyte. Our findings open a new avenue to produce hydrogen by complementation and gain effects of different-grade energies.


Measurement of retinal nerve fiber layer thickness, macular thickness, and foveal volume in amblyopic eyes using spectral-domain optical coherence tomography.
Although the changes in the anatomy of the visual cortex and lateral geniculate nucleus as the result of amblyopia have been well documented, retinal involvement is still controversial. Time-domain optical coherence tomography with an axial resolution of 10 μm has been used to evaluate retinal and peripapillary tissues in amblyopic eyes with contradictory results. Spectral domain optical coherence tomography has a greater resolution (5-10 μm) and can determine retinal layers more precisely. Our purpose was assess by means of spectral domain optical coherence tomography whether the retinal nerve fiber layer thickness, macular thickness, and foveal volume of the amblyopic and the fellow eyes differ in patients with unilateral amblyopia. Intereye differences in these parameters were found to be insignificant.


Inheritance analysis and family history for microtia: A hospital-based study in China.
Microtia is a congenital anomaly of the outer ear. Although genetic and environmental factors could play a role, no consensus has been established on the pathogenesis and cause of this condition. In this study, we surveyed the frequency and pattern of family history in patients with microtia in a Chinese specialty clinic population. We evaluated data from 672 patients (mean age = 9.2, male-to-female ratio = 2.6:1) with microtia admitted to the Department of Auricular Reconstruction at the Plastic Surgery Hospital of Peking Union Medical College from December 2014 to February 2016. Family history of congenital ear anomalies across three generations was recorded. Pearson chi-square test or Fisher exact test was used to test the associations between the characteristics of microtia and hereditary features. A family history of auricle anomalies was identified in 202 patients (30.1%), of whom, 95 families showed vertical transmission, 14 families skipped a generation, and 120 families showed family aggregations. The incidence of family history varied with grades of microtia (P = 0.001). Patients with preauricular tags or pits (38.3%) had a higher familial incidence of microtia than those with simple microtia (24.1%) (P < 0.001). Patients with a lower grade of microtia demonstrated a higher incidence of family history. Patients with microtia had significantly more relatives with preauricular tags or pits. Microtia and preauricular tags or pits are different manifestations of the same defect, and their significant concurrency among relatives suggests that a considerable proportion of microtia is inherited and could recur with varying degrees of severity in other family members.


Innate sensing of mRNA vaccines.
With the recent success of mRNA vaccines and the approval of several RNA oligonucleotide therapeutics, RNA holds great promise for future drug development. The rise of RNA therapeutics has been enabled by the tremendous progress in our understanding of the sophisticated cellular mechanisms that disarm potentially dangerous exogenous RNA and safeguard RNA homeostasis. Exogenous RNA, such as an mRNA vaccine when injected, faces an intricate system of immune-sensing receptors, restriction factors, and nucleases referred to as nucleic acid immunity. A careful analysis of the functional interaction between the innate response to mRNA, the efficacy to translate the encoded protein antigen, and the quality of the resulting adaptive immunity bears great potential for further improvement of mRNA vaccines and RNA therapeutics for various clinical applications. In this review, we summarize the most recent efforts to advance mRNA vaccines by capitalizing on recent insight in innate RNA sensing.


Lessons Learned From the Implementation of an Integrated Prenatal Opioid Use Disorder Program.
To evaluate key lessons learned from efforts at increasing engagement in integrated prenatal and opioid use disorder services. An interdisciplinary team consisting of a board-certified obstetrician and registered nurse led the implementation of this multipronged approach driven by several plan-do-study-act cycles to develop an integrated prenatal and opioid use disorder program. An urban community health center in Chicago, Illinois, where mental health issues, including substance use, are the leading cause of death for pregnant people. Connections were made with local harm reduction agencies, substance use treatment facilities, and community outreach programs to develop partnerships with organizations providing existing addiction and maternal-child services in the community. Partnership building was achieved through organization needs assessments, dissemination of information about integrated services, and sustained communication. Referral workflow guides and patient education cards were created and distributed to community partners. Incoming referrals were tracked at the clinic site. Use of the referral materials was evaluated via online surveys distributed to community partners. In the 18 weeks of enhanced integration, three patients engaged in services and were initiated on medication for opioid use disorder, two of whom had been referred from agencies targeted in the outreach efforts. Surveys showed that community partners believe the referral guides were easy to use and that the harm reduction information on the patient cards was useful. An urban community health center was equipped to provide comprehensive, integrated services to pregnant people with opioid use disorder, but barriers such as community unawareness and stigma impeded engagement. Sustained collaboration with community partners serving pregnant people with opioid use disorder supports program development and linkage to care. Integrated prenatal and opioid use disorder care is feasible, is destigmatizing in nature, and can lead to improved maternal and fetal outcomes.


Multiple enterovirus genotypes circulating in children hospitalized with acute gastroenteritis in Thailand.
Enterovirus (EV) infection is widespread and can lead to a broad range of clinical symptoms, from mild to severe forms of disease. EVs are not always classified as pathogen and the epidemiological surveillance of EV infection in acute gastroenteritis cases in Thailand remains unexplored. This study aims to investigate the frequency, seasonality and molecular characteristics of EV circulating in children hospitalized with acute gastroenteritis in Chiang Mai, Thailand from 2010 to 2014. A total of 1266 fecal samples were included in this study. RT-PCR amplification of the 5'UTR was used for EV screening and phylogenetic analysis of the VP1 sequence was performed for EV genotyping. EV was detected in 5.8% of infections (73 out of 1266). Based on VP1 sequence analysis, over half (50.8%) of the identified EV cases were caused by species C, and the next two most frequent were species B and A (35.4% and 13.8%, respectively). This study identified 28 different EV genotypes, EV-C96 and coxsackievirus A24 were the most frequent genotype detected (12.3% each). EV was detected throughout the year with an increase of detection rate in December-January and May-June. In conclusion, this study reported the prevalence of EV infection with a wide variety of EV genotypes in children with acute diarrhea.


Chromosomal abnormalities induced by iodine-125 in mouse germ cells.
Swiss albino male mice were injected intraperitoneally with 0, 185, 370 or 555 kBq (0, 5, 10 or 15 microCi) of iodine-125 (125I). All the animals were killed on the sixtieth day and chromosomal aberrations were screened in spermatocytes at meiotic metaphase I. A significant increase in the percentage of chromosomal aberrations including translocations (0, 1.2, 1.8 and 2.3 per cent translocations in controls, 185, 370 and 555 kBq groups respectively) was recorded at all dose levels indicating the clastogenic effects of 125I in mouse spermatocytes.


Experimental model of cisplatin ototoxicity in chinchillas.
Cisplatin is an important antineoplastic agent. Its ototoxicity has been well defined, both in human and animal studies. However, animal models of systemic cisplatin administration have been complicated by multiple toxic effects. We studied cisplatin ototoxicity in an animal model involving topical application of cisplatin to the round-window membrane. Adult chinchillas were anesthetized with ketamine and pentobarbital, and auditory function was tested with the use of auditory brain-stem responses to various stimuli (clicks and 8-and 16-kHz tone bursts). Each animal was used as its own control. The middle-ear cavity was exposed through the bulla. In the experimental ear, a 25-microl solution of 0.25 mg cisplatin/1.0 ml normal saline solution was applied to the round-window membrane. In the control ear, 25 microl normal saline solution was applied to the round-window membrane. Follow-up auditory brain-stem response testing was conducted 7 days after treatment. A significant increase in threshold in the experimental ears was seen on comparison with the control ears. This finding suggests that application of cisplatin to the round-window membrane is a useful animal model in which to study cisplatin ototoxicity.


A signal detection approach to the combined effects of work stressors on alcohol consumption.
To test the relationship between work stress and alcohol consumption and the efficacy of signal detection analysis in a work stress-alcohol consumption study. The study was part of a Work Site Health Project, which included a stress reduction program, at a manufacturing company in Osaka, Japan. The study design was a cross-sectional survey. The participants were Japanese male whitecollar workers (N = 457; 30 to 50 years old) in the head administrative office of a large manufacturing company. Measurements consisted of demographic variables of the workers (age, marital status, manner of living and Type A personality), work stress measures, working hours and alcohol consumption. Of eight independent variables, six significant predictors of heavy alcohol consumption were identified in the first signal detection analysis. Of these six variables, job demand and skill discretion were work-stress-related measures. In the second multiple regression analysis, skill discretion and job demand were significant predictors of alcohol consumption among the workers in two of the seven subgroups categorized by the first signal detection analysis. It was revealed that work stress did relate to alcohol consumption. However, the effect of the work stress upon alcohol consumption was limited to specific types of workers with multiple specific attributes. It was also inferred that the signal detection approach is an effective approach to the work stress alcohol consumption relationship.


An institution's initial experience with port-access minimally invasive cardiac surgery.
To assess the learning curve associated with Port-Access minimally invasive cardiac surgery. Retrospective. Single university hospital. Initial 10 patients undergoing Port-Access minimally Invasive cardiac surgery. Minimally invasive cardiac surgery. All 10 patients experienced an uneventful intraoperative and immediate postoperative course. Only one patient experienced postoperative cardiovascular morbidity, which was an episode of new-onset atrial fibrillation after mitral valve surgery that was successfully treated with pharmacologic therapy. Extubation times and postoperative discharge times were less than historic controls receiving the same anesthetic technique at the same institution. This institution's initial experience with 10 patients undergoing Port-Access minimally invasive cardiac surgery suggests an acceptable learning curve and decreased extubation and postoperative discharge times, which should translate into reduced health care costs.


Lifting Triplet Energy and Bipolar Characteristics by Limiting the Rotation of the Peripheral Groups in Host Materials to Achieve High-Efficiency Blue OLED.
Bipolar host materials with high triplet energy are of great significance for highly efficient blue organic light-emitting diodes (OLEDs). In this work, three donor-acceptor-donor (D-A-D) type host materials with identical non-rigid diphenylsulfone center but differing in rotation degree of peripheral amino substituted derivatives from rotating freely diphenylamine (SODP) to rotating partially iminodibenzyl (SOId) and rotating restricted carbazole (SOCz) were designed and synthesized. It was demonstrated that the triplet energy (ET ) level of the materials promoted by limiting the rotation degree of the peripheral groups, which was 2.72 eV for SODP, 2.73 eV for SOId and 2.78 eV for SOCz, respectively. Besides, the results of the single-carrier devices indicate SOCz possess better bipolar characteristic. Using FIrpic as guest emitter, the blue OLED with SOCz as host material exhibited superior device performance with a low turn-on voltage of 3.3 V, a maximum current efficiency (CE) of 30.1 cd A-1 , a maximum power efficiency (PE) of 32.2 lm W-1 , and a maximum external quantum efficiency (EQE) of 14.0%. This work provides a beneficial guideline for realizing promising host materials in efficient blue OLEDs.


Restraint use in the acute-care hospital setting: A cross-sectional multi-centre study.
Restraints are likely to negatively affect patients' health and therefore a reduction in their usage is recommended for all health-care settings. To date, research on restrictive practices has concentrated on mental health and long-term care settings. In the acute-care hospital setting few studies have been published and these studies mainly focus on physical/mechanical restraints in specific subpopulations and/or on intensive care units. However, to ensure restraints are used as little as possible in the acute-care hospital setting, it seems important to investigate more comprehensively the use of restraints, to include all types of restraints irrespective of ward type or subpopulations and to identify factors associated with restraint use. The aim of this study was to investigate restraint use regardless of ward type in the acute-care hospital setting, including restraint type, reasons for restraint use, process indicators when using restraints and restraint use-associated patient characteristics. Using a cross-sectional multi-centre design, data were collected by means of an annual international prevalence measurement in acute-care hospitals in Switzerland and Austria. All hospitalised patients aged 18+ who gave informed consent were included. Data were collected at three measurement points between 2016 and 2018. Descriptive and multivariate logistic regression analyses were performed. A total of 29,477 patients hospitalised in 140 hospitals were included in this study. The prevalence rate for the use of at least one restraint over a 30-day period was 8.7% (n = 2577), with mechanical restraints representing the highest proportion of restraint type used (55.0%, n = 1417). The main reason for restraint use was fall prevention (43.8%, n = 1129), followed by confusion or delirious behaviour (20.4%, n = 525). In 64.3% of the cases (n = 1657), restraint use was documented in the patient file. Regular evaluation occurred in 42.9% of the cases (n = 1105). Care dependency had the strongest association with restraint use (odds ratio [OR] 25.00, 95% confidence interval [CI] 21.01-29.78 for completely dependant patients in comparison to completely independent patients), followed by mental and behavioural disorders (OR 2.36, 95% CI 2.15-2.59). Restraints are often utilised in hospitals in complex care situations such as with patients at risk of falling or with delirium. When using restraints the consideration of processes like documentation and evaluation shows great potential for improvement. Standardisation of these processes and education of the interprofessional team could be beneficial for raising awareness and for the sustainable reduction of restraint use. Tweetable abstract: In hospitals restraints are often used in complex care situations. However, their use seems to be insufficiently documented and evaluated.


Cardiovascular and renal effects of alpha-trinositol in ischemic heart failure rats.
Previous studies have demonstrated that alpha-trinositol (D-myo-inositol-1.2.6-trisphosphate; PP56) may act as a functional neuropeptide Y (NPY) inhibitor. Because NPY is known to be a potent vasoconstrictor, the effects of alpha-trinositol on renal function, vascular responses and the potentiating effects of NPY were investigated in rats with congestive heart failure (CHF) induced by ligation of the left coronary artery. Incremental doses of alpha-trinositol were given to conscious rats (bolus 2, 4 or 10 mg/kg i.v. followed by a 15-minute infusion 20, 40 and 100 mg/kg/h, respectively). Urinary volume, sodium and potassium excretions were significantly increased in both CHF and sham-operated control animals after alpha-trinositol administration compared with saline. Diuresis and natriuresis were observed also during co-administration of alpha-trinositol with NPY but not with norepinephrine (NE). In the pithed CHF rats, threshold doses of NPY potentiated the pressor effects of endothelin-1 (ET-1) and angiotensin II (AII), but not preganglionic nerve stimulation or phenylephrine administration. Alpha-trinositol antagonized both the pressor response to NPY and the potentiation by NPY of pressor responses to effects of ET-1 and AII. Our data show that alpha-trinositol exhibis diuretic and natriuretic effects as well as vascular antagonistic effects on NPY in normal and CHF rats. These effects of alpha-trinositol may be due to an interaction with NPY mediated antidiuresis and antinatriuresis.


Prevalence of suicidal behavior in adolescents in India: A systematic review and meta-analysis.
Suicidal behaviour (SB) in adolescents is an emerging public health issue globally. The present study was undertaken to estimate the overall prevalence of SB among the adolescents (10-19 years of age) in India. In this systematic review and meta-analysis (SRMA), an extensive literature search in PubMed, Scopus, EBSCO, Web of Science, ProQuest, Embase, Cochrane, and preprint servers (medRxiv, arXiv, bioRxiv, BioRN, ChiRxiv, ChiRN, and SSRN) and assessment of all published articles until 28th February 2023 as per the PROSPERO registration protocol (CRD42023385550), was undertaken. Studies from India which reported the prevalence of suicidal ideation, suicide attempt, and suicidal plan were included. The quality of the included studies was assessed by risk of bias assessment tool. R version 4.2 was used to conduct all the relevant analyses. Heterogeneity was assessed, and a random effects model for estimating the pooled prevalence of the outcomes was applied. Subgroup analyses were planned based on region, locality (urban/rural) and the study settings (educational institutions/community-based). A meta-regression to analyze the effects of potential moderators on outcomes was done. Sensitivity analyses were planned based on the removal of outliers and poor-quality studies. Publication bias was tested by Doi plot and LFK index. Pooled prevalence of suicide attempts, suicide ideations and suicide plans RESULTS: A total of 20 studies were identified as eligible for the systematic review, and 19 studies were identified as eligible for the meta-analysis. The pooled prevalence of suicidal ideation was estimated to be 11% (95 % CI 7-15); heterogeneity between the studies was high (I2 98 %, p < 0.01). The pooled prevalence of suicidal attempts and suicidal plan was estimated to be 3 % each (95 % CI 2-5); with heterogeneity being high (I2 96 %, p < 0.01). Subgroup analysis revealed a significant variation in suicidal ideation and attempts between different regions of India (South > East > North), and higher prevalence among the educational-institute-based settings and urban areas. Overall, the prevalence of suicidal behavior among the adolescents in India is high, and they experience all types of suicidal behavior (ideations, plans and attempts).


Acute restraint stress activates functional NK1 receptor in the colon of female rats: involvement of steroids.
Psychological factors have been implicated in the aetiology of irritable bowel syndrome characterised by intestinal altered motility and visceral hypersensitivity. Similar disorders have been found in rats under stressful conditions. The role of tachykinins in bowel dysfunctions caused by stress is not fully documented. Therefore, we investigated the influence of stress on NK1 receptor activation at the colonic level in female rats. The stress procedure used consisted of two hours of partial restraint. Histamine release was measured from colonic samples of control and stressed animals and the effect of SR140333, a NK1 receptor antagonist, on substance P induced histamine release was determined. Involvement of steroids has been evaluated in this response. NK1 receptor antagonist was found to inhibit substance P induced histamine release in samples from stressed female rats but not in samples from control animals. Previous treatment of female rats with RU 486 abolished this effect observed in stressed animals. Similarly, in samples from stressed female rats previously ovariectomised, SR140333 failed to inhibit substance P induced histamine release but previous treatment with both progesterone and oestrogen restored its effect. Stress induces NK1 receptor activation in the colon, and ovarian steroids are involved in this response.


Key role of hydrazine to the interaction between oxaloacetic against phosphoenolpyruvic carboxykinase (PEPCK): ONIOM calculations.
The interactions between oxaloacetic (OAA) and phosphoenolpyruvic carboxykinase (PEPCK) binding pocket in the presence and absence of hydrazine were carried out using quantum chemical calculations, based on the two-layered ONIOM (ONIOM2) approach. The complexes were partially optimized by ONIOM2 (B3LYP/6-31G(d):PM6) method while the interaction energies between OAA and individual residues surrounding the pocket were performed at the MP2/6-31G(d,p) level of theory. The calculated interaction energies (INT) indicated that Arg87, Gly237, Ser286, and Arg405 are key residues for binding to OAA with the INT values of -1.93, -2.06, -2.47, and -3.16 kcal mol(-1), respectively. The interactions are mainly due to the formation of hydrogen bonding interactions with OAA. Moreover, using ONIOM2 (B3LYP/6-31G(d):PM6) applied on the PEPCKHS complex, two proton transfers were observed; first, the proton was transferred from the carboxylic group of OAA to hydrazine while the second one was from Asp311 to Lys244. Such reactions cause the generation of binding strength of OAA to the pocket via electrostatic interaction. The orientations of Lys243, Lys244, His264, Asp311, Phe333, and Arg405 were greatly deviated after hydrazine incorporation. These indicate that hydrazine plays an important role in terms of not only changing the conformation of the binding pocket, but is also tightly bound to OAA resulting in its conformation change in the pocket. The understanding of such interaction can be useful for the design of hydrazine-based inhibitor for antichachexia agents.


HIV Drug Resistance among Patients Failing Therapy at a Tertiary Center in Oman: A Case Record Review.
We sought to estimate the prevalence of HIV drug resistance and describe the common HIV genetic mutations in patients failing antiretroviral therapy (ART). We also investigated the impact of HIV resistance tests results on patients' management. We conducted a retrospective record review for all HIV genotypic resistance tests requested at the HIV clinic of a tertiary HIV center in Muscat, Oman, from April 2011 to May 2017. A total of 98 genotypic resistance tests for 84 patients failing ART were analyzed; 82 tests for 69 patients (83.7%, 95% confidence interval: 76.4-91.0) showed resistance to at least one ART drug. M184V/I, K103N/S, and G190A/S/E were the most common mutations detected. Among the tests with a resistant virus, 78.0% were followed by switching ART based on the resistance test profile resulting in virus load suppression after six months in 60.9% of the cases. HIV drug resistance is very common among HIV patients failing ART in Oman, and should be considered in those patients. Switching ART treatment based on the resistance test result leads to a good virological response in adherent patients.


Salicylanilides as inhibitors of the protein tyrosine kinase epidermal growth factor receptor.
A pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGFR protein tyrosine kinase and a putative binding mode of 4-anilinoquinazoline suggest that a salicylic acid function could serve as the pharmacophore replacement of a pyrimidine ring. Superpositions by CAMM of salicylanilides with the potent EGFR tyrosine kinase inhibitor 4-[(3'-chlorophenyl)amino]-6,7-dimethoxyquinazoline showed that salicylanilides should act as tyrosine kinase inhibitors. A series of salicylanilides was synthesized and their inhibitory activity against tyrosine kinases determined. Some of them indeed proved to be potent and selective EGFR tyrosine kinase inhibitors. The most potent ones being 28, 16, 20, 6, and 15, with IC(50) in the 23-71 nM range.


Plantar pressure distribution during standing in women with end-stage hip osteoarthritis.
Patients with hip osteoarthritis (OA) experience abnormal movement patterns and reduced loading of the affected leg. The plantar contacts the ground and receives force from the ground. Plantar pressure distribution may differ in patients with hip OA compared to healthy adults and may influence physical functioning in these patients. We investigated whether plantar pressure distribution during standing differed between patients with hip OA and healthy adults. We also analyzed the relationship between plantar pressure distribution and walking ability and the factors affecting plantar pressure distribution. Maximum plantar pressure distribution during standing for 20 seconds was investigated in patients with hip OA (n = 62; OA group) and in healthy adults (n = 53; Control group). Statistical comparisons between these groups were made using Fisher's exact test and residual analysis. In the OA group, leg length discrepancy, range of hip extension, leg loading, knee extensor strength, and 10 m walking time were assessed; multiple linear regression and logistic regression analyses were used to examine the relationships between these factors and maximum plantar pressure distribution. Maximum plantar pressure distribution was different between the OA and control groups. In the OA group, maximum plantar pressure distribution was one of the significant predictors of 10 m walking time. Additionally, leg length discrepancy was a significant predictor of maximum plantar pressure distribution in this group. During standing, the proportion of patients for whom the maximum plantar pressure region was the heel tended to be lower in the group with hip OA compared to the healthy adults. Plantar pressure distribution may have an importance for evaluating walking ability in patients with hip OA. Correcting leg length discrepancy and loading under the heel could adjust plantar pressure distribution in patients with hip OA.


The effect of maltose on dextran yield and molecular weight distribution.
Dextran synthesis has been studied since the Second World War, when it was used as blood plasma expander. This polysaccharide composed of glucose units is linked by an alpha-1,6-glucosidic bond. Dextransucrase is a bacterial extra cellular enzyme, which promotes the dextran synthesis from sucrose. When, besides sucrose, another substrate (acceptor) is also present in the reactor, oligosaccharides are produced and part of the glucosyl moieties from glucose is consumed to form these acceptor products, decreasing the dextran yield. Although dextran enzymatic synthesis has been extensively studied, there are few published studies regarding its molecular weight distribution. In this work, the effect of maltose on yield and dextran molecular weight synthesized using dextransucrase from Leuconostoc mesenteroides B512F, was investigated. According to the obtained results, maltose is not able to control and reduce dextran molecular weight distribution and synthesis carried out with or without maltose presented the same molecular weight distribution profile.


Waist circumference percentiles for 7- to 15-year-old Australian children.
The purpose of this study was to develop age- and sex-specific reference values for waist circumference using data obtained from Australian children and adolescents. Subjects were 8439 7-to-15 y olds (4277 males and 4162 females) who participated in the 1985 Australian Health and Fitness Survey. Waist circumference (WC) was measured in the standing position at the level of the umbilicus to the nearest 0.1 cm using a constant tension tape. Descriptive statistics for each whole-year age group (e.g., 10.0-10.99 y, etc.) within sex were calculated. Construction of the smoothed centile curves was performed using the LMS method. Mean WC increases in both males and females, with the values being similar between males and females prior to age 11 y, after which values are slightly higher in males. The range of values varied by age and sex groups but approximated 30-60 cm. Smoothed percentile curves and percentile values for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles are presented for boys and girls. WC increases with age in boys and girls, and boys have higher values than girls at nearly every age-specific percentile. These data can be added to the existing international reference values for WC of children and adolescents which should be used to create international cut-off points similar to those for the body mass index (BMI). Future studies should consider the immediate and long-term consequences of an elevated WC in children and also examine the interaction of BMI and WC on chronic disease risk factors.


Nucleotide sequence for the hemD gene of Escherichia coli encoding uroporphyrinogen III synthase and initial evidence for a hem operon.
1. The hemD gene, encoding uroporphyrinogen III synthase, has been located adjacent to the hemC gene at 85 min on the Escherichia coli chromosome. 2. The entire nucleotide sequence (741 base pairs) of the hemD gene is reported. 3. E. coli strains harbouring plasmics containing the hemD gene produce greatly elevated levels of uroporphyrinogen III synthase. 4. Purified uroporphyrinogen III synthase, isolated from the hemD-containing strain ST1046, has an Mr of 29,000, in close agreement with that predicted from the nucleotide sequence. 5. The existence of a hem operon is suggested.


Local destabilisation of a DNA double helix by a T--T wobble pair.
Nuclear magnetic resonance is a technique which permits direct observation of the Waton--Click hydrogen-bonded ring imino protons (guanine N1H and thymine N3H). As the formation and disruption of hydrogen bonds of double-helical RNA and DNA structures are key events during various biological processes, NMR thus provides a useful tool for studying the fluctuational mobility of the individual base pairs. Indeed, several NMR studies of oligo- and polynucleotides have been carried out to probe the structure and dynamics of nucleic acids in solution (for a review see ref. 1). The present study constitutes the first part of our attempt to assess the influence of non-complementary base pairs on the stability of nucleic acid double helices. We report the spectral assignment and temperature-dependent NMR profiles of the hydrogen-bonded imino protons of the two DNA fragments shown in Fig. 1. The assignment is based solely on experimental grounds using the principle of chemical modification. It will be demonstrated that the introduction of a non-complementary (wobble) base pair in a DNA duplex introduces an extra melting site in addition to the sequential melting which starts with the terminal base pairs in the double helix structure.


FluMag-SELEX as an advantageous method for DNA aptamer selection.
Aptamers are ssDNA or RNA oligonucleotides with very high affinity for their target. They bind to the target with high selectivity and specificity because of their specific three-dimensional shape. They are developed by the so-called Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process. We have modified this method in two steps-use of fluorescent labels for DNA quantification and use of magnetic beads for target immobilization. Thus, radioactive labelling is avoided. Immobilization on magnetic beads enables easy handling, use of very small amounts of target for the aptamer selection, rapid and efficient separation of bound and unbound molecules, and stringent washing steps. We have called this modified SELEX technology FluMag-SELEX. With FluMag-SELEX we have provided a methodological background for our objective of being able to select DNA aptamers for targets with very different properties and size. These aptamers will be applied as new biosensor receptors. In this work selection of streptavidin-specific aptamers by FluMag-SELEX is described. The streptavidin-specific aptamers will be used to check the surface occupancy of streptavidin-coated magnetic beads with biotinylated molecules after immobilization procedures.


[Pathway of a patient within a healthcare unit].
Care in prison must be based as much as possible on the model used for the general population. The system of psychiatric care in prisons comprises three levels of provision. The presentation of the pathway of a young patient with severe mental disorders shows the possibilities and the difficulties involved in caring within a healthcare unit.


Fatalities related to medical restraint devices-asphyxia is a common finding.
A total of seven detailed death investigations is reported where death occurred while being restrained by a belt or a protective cover. The casualties were elderly persons who mostly showed considerable pre-existing diseases, especially dementia and coronary atherosclerosis. Concerning the cause of death, three groups were differentiated: (I) mechanical asphyxia from strangulation. (II) Mechanical asphyxia from thoracic/abdominal compression. (III) Compression of thorax/abdomen without clear signs of asphyxia. Subgroups II and III each involved one case of rib fractures without preceding resuscitation. In subgroup III, the presence of considerable compression of the trunk and the absence of a natural cause of death strongly indicate a causal connection between compression and death, e.g. from a shortened course of fatal asphyxia, endocrine stress reactions or a head-down-position: cardiac arrest in a helpless situation. The method of restraint was inadequate in most cases in that only one device was used which did not restrict the capability to move sufficiently. A good clinical documentation including medical indication, duration and method of restraint and a description/photograph of the original on-site appearance is essential but was not present in most cases. Therefore, prophylaxis is based on a clear medical indication, the proper use of restraint devices, detailed instructions of the nursing personnel and close monitoring. The forensic investigation should aim at a complete reconstruction based on autopsy, histology, toxicology and inspection of the scene and the medical records.


Face recognition and aging: effects of target age and memory load.
In the present study, we investigated age-related decline in face recognition memory and whether this decline is moderated by the age of the target faces and by the number of faces that the participant must learn (memory load). Thirty-two participants in each of three age groups (18-39 years, 60-75 years, and 76-96 years) completed a face recognition task. Signal detection analyses confirmed that face recognition accuracy declined with age. However, this finding was qualified by an interaction between participant age and target age, which revealed that the age-related decline in face recognition accuracy occurred only for young target faces. Increased memory load was associated with comparable performance decrements across all age groups. However, memory load appears not to be the cause of these decrements. Instead, they appear to be a product of recognition load (the number of stimuli presented in the recognition phase).


Spatial-Temporal EEG Fusion Based on Neural Network for Major Depressive Disorder Detection.
In view of the major depressive disorder characteristics such as high mortality as well as high recurrence, it is important to explore an objective and effective detection method for major depressive disorder. Considering the advantages complementary of different machine learning algorithms in information mining process, as well as the fusion complementary of different information, in this study, the spatial-temporal electroencephalography fusion framework using neural network is proposed for major depressive disorder detection. Since electroencephalography is a typical time series signal, we introduce recurrent neural network embedded in long short-term memory unit for extract temporal domain features to solve the problem of long-distance information dependence. To reduce the volume conductor effect, the temporal electroencephalography data are mapping into a spatial brain functional network using phase lag index, then the spatial domain features were extracted from brain functional network using 2D convolutional neural networks. Considering the complementarity between different types of features, the spatial-temporal electroencephalography features are fused to achieve data diversity. The experimental results show that spatial-temporal features fusion can improve the detection accuracy of major depressive disorder with a highest of 96.33%. In addition, our research also found that theta, alpha, and full frequency band in brain regions of left frontal, left central, right temporal are closely related to MDD detection, especially theta frequency band in left frontal region. Only using single-dimension EEG data as decision basis, it is difficult to fully explore the valuable information hidden in the data, which affects the overall detection performance of MDD. Meanwhile, different algorithms have their own advantages for different application scenarios. Ideally, different algorithms should use their respective advantages to jointly address complex problems in engineering fields. To this end, we propose a computer-aided MDD detection framework based on spatial-temporal EEG fusion using neural network, as shown in Fig. 1. The simplified process is as follows: (1) Raw EEG data acquisition and preprocessing. (2) The time series EEG data of each channel are input as recurrent neural network (RNN), and RNN is used to process and extract temporal domain (TD) features. (3) The BFN among different EEG channels is constructed, and CNN is used to process and extract the spatial domain (SD) features of the BFN. (4) Based on the theory of information complementarity, the spatial-temporal information is fused to realize efficient MDD detection. Fig. 1 MDD detection framework based on spatial-temporal EEG fusion.