Postmortem tandem mass spectrometry profiling for detection of infection in unexpected infant death.
Numerous hypotheses have been suggested to explain the cause of sudden unexpected infant death, including infection. As part of the autopsy, routine ancillary investigations are performed, including blood/bile tandem mass spectrometry (TMS) primarily for detection of metabolic disease. The aim of this study was to evaluate and assess TMS derived acylcarnitine profiles to determine whether infectious deaths were associated with characteristic profiles. As part of a retrospective study including >2,500 pediatric autopsies at a single specialist centre over a 14 year period, acylcarnitine profiles were reviewed. Using multiple linear regression, standardised residuals were prepared and findings compared between different cause of death groups, including unexplained, focal infection, microbiological infection and accidental injuries. 415 blood samples from SUDI autopsies were identified. Statistically significant differences in TMS profiles were identified between those dying of infection and the unexplained SUDI group, including changes in free carnitine, short chain acylcarnitines and octanoylcarnitine. Cases with microbiological infection diagnosed only from postmortem cultures did not show any significant difference from the unexplained group. Postmortem TMS profiling identifies SUDI deaths which are associated with histological evidence of infection, and an acylcarnitine profile suggesting perturbation of oxidative metabolism. Such findings raise the possibility that more comprehensive TMS profiling may offer additional diagnostic clues beyond screening for metabolic disorders, and may contribute to determination of mode of death.


Systematic Review of Health-Related Quality of Life in Patients with Pulmonary Arterial Hypertension.
The increasing survival of patients with pulmonary arterial hypertension (PAH) has shifted attention towards the disease burden that PAH imposes on patients and healthcare systems. Most studies emphasize epidemiology and medications, while large observational studies reporting on the health-related quality of life (HRQOL) of patients with PAH are lacking. Our objective was to study the HRQOL of patients with PAH and to summarize the factors that influence it. We conducted systematic literature searches in English (PubMed, Web of Knowledge, ScienceDirect and OVID) and Chinese (China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP and SinoMed) databases to identify studies published from 2000 to 2015 assessing the HRQOL of patients with PAH. Search results were independently reviewed and extracted by two reviewers. Of 3392 records identified in the initial search, 20 eligible papers (19 English, 1 Chinese) were finally included. Studies used a range of instruments; the generic 36-item Short Form Survey (SF-36) was the most widely used, and the disease-specific Cambridge Pulmonary Hypertension Outcome Survey (CAMPHOR) was the second mostly widely used. Mean HRQOL scores assessed via the SF-36 (physical component summary [PCS] 25.4-80.1; mental component summary [MCS] 33.2-76.0) and CAMPHOR (symptom scores 3.1-17; total HRQOL 2.8-12.6; activity scores 3.8-18.1) varied across studies, reporting decreased HRQOL in patients. Mental health (depression, anxiety, stress), physical health (exercise capacity, symptoms) and medical therapies were reported to affect HRQOL. We found that PAH places a substantial burden on patients, particularly in terms of HRQOL; however, the paucity of large observational studies in this area requires the attention of researchers, especially in China.


Effects of Remimazolam Anesthesia with Two Induction Doses on Hemodynamics and Recovery Profile in Older Patients: Comparison with Propofol Anesthesia.
Remimazolam has advantages such as hemodynamic stability and rapid onset. We investigated the effects of induction doses on hemodynamics and recovery profiles for remimazolam compared to propofol in older patients. Sixty-nine patients aged >65 years were randomly assigned to either the propofol anesthesia group (P group) or the remimazolam anesthesia group with an induction dose of 6 mg/kg/h (R6 group) or 12 mg/kg/h (R12 group), followed by 1 mg/kg/h. P group was anesthetized with 4 µg/mL of propofol effect-site concentration (Ce) with target-control infusion, followed by 2.5-3 µg/mL of Ce. The primary outcome was the difference between the baseline mean arterial pressure (MAP) and the lowest MAP during anesthesia (ΔMAP). ΔMAP was comparable between the P, R6, and R12 groups (43.8 ± 13.8 mmHg, 39.2 ± 14.3 mmHg, and 39.2 ± 13.5 mmHg, p = 0.443). However, the frequencies of vasoactive drug use were 54.5%, 17.4%, and 30.4% (p = 0.029), and the median doses of ephedrine 3 (0-6) mg, 0 (0-0) mg, and 0 (0-0) mg (p = 0.034), which were significantly different. This study showed remimazolam anesthesia with an induction dose of 6 mg/kg/h, rather than 12 mg/kg/h, could reduce the requirement for vasoactive drugs compared to propofol anesthesia.


A new algorithm for primary hypospadias repair based on tip urethroplasty.
Decision making in hypospadias repair potentially can be simplified by tubularized incised plate (TIP) urethroplasty. The authors report management and outcomes in a consecutive series of primary hypospadias repairs in which the intent was to perform TIP. Records of 106 consecutive boys undergoing hypospadias repair by 1 surgeon were reviewed. Position of the meatus, degree and management of curvature, technical details of the urethroplasty, and postoperative complications were recorded. Curvature was noted in 24 (23%) of patients, but could be corrected with preservation of the urethral plate in all but 3. In another boy, the incised plate was thought "unhealthy" for tubularization. The remaining 102 underwent TIP, of whom, 75 had distal and 27 had proximal hypospadias. Complications, primarily fistulas, occurred in 14 (13%) of these patients. The other 4 boys underwent staged repairs that utilized TIP for the glanular urethra at the second operation. The authors found decision making was no longer determined by meatal location as in the past, but by severity of curvature and appearance of the incised urethral plate. Because severe curvature requiring plate transection or an "unhealthy" incised plate are uncommonly encountered, TIP repair can be performed for most hypospadias operations.


Is Urografin density gradient centrifugation suitable to separate nonculturable cells from Escherichia coli populations?
The ability of Urografin or Percoll density gradient centrifugations to separate nonculturable subpopulations from heterogeneous Escherichia coli populations was analysed. Bacterial counts (total, active and culturable cells) and flow cytometric analyses were carried out in all recovered bands. After Urografin centrifugation, and despite the different origin of E. coli populations, a common pattern was obtained. High-density bands were formed mainly by nonculturable cells. However, the increase in cell density would not be common to all nonculturable cells, since part of this subpopulations banded in low-density zones, mixed with culturable cells. Bands obtained after Percoll centrifugation were heterogeneous and culturable and nonculturable cells were recovered along the gradient. Thus, fractionation in Urografin cannot be only attributed to changes in buoyant densities during the transition from culturable to nonculturable state. Urografin density gradients allow us to obtain enriched fractions in nonculturable subpopulations from a heterogeneous population, but working conditions should be carefully chosen to avoid Urografin toxicity.


Simple and sensitive spectrophotometric method for estimating the nitrogen-fixing capacity of bacterial cultures.
Biological nitrogen fixation (BNF) is a process through which a group of microorganisms called diazotrophs convert unassimilable atmospheric nitrogen into ammonia. In aqueous media, ammonia yields ammonium ions that can be assimilated by microorganisms and plants. To reduce the application of nitrogen fertilizers and their environmental effects, an alternative approach toward sustainable agriculture is the induction of artificial associations between diazotrophs and plants. This has led to increased interest in the search for microorganisms capable of supplying nitrogen to crops. This article presents a simple, economical, and sensitive spectrophotometric method for estimating the BNF capacity of bacteria cultured in a liquid NFb medium, based on the variation of absorbance caused by the change in color of bromothymol blue in the culture medium. The structure and color of this indicator are modified by pH shifts, which depend on the concentration of fixed ammonium ions.•The nitrogen concentration (estimated from the ammonium in the culture medium) showed a positive correlation (R 2 = 0.984) with the absorbance measured at 610 nm. The regression equation obtained through the origin was y = 0.009682140x, where y is the absorbance and x is the nitrogen concentration in the culture medium.•The methods used at present to measure the efficiency of BNF require expensive equipment, which may not be affordable for many laboratories or companies working in this field.•This technique can be used for pure bacterial strains and microbial consortia from soil or commercial products.


Application of a new tactile sensor to thoracoscopic surgery: experimental and clinical study.
We developed a new tactile sensor that could quantify the hardness of objects as changes in the resonance frequency of the sensor (delta f). We have applied it to thoracoscopic operations for the localization of small invisible nodules in the lung. When the sensor probe was moved over the lung surface, a delta f curve was depicted on the computer screen. When the sensor tip reached a point directly above a hard object, a sudden upward jump of the delta f curve was evoked. After experimental studies using pigs, the sensor was applied in 8 patients. More recently we produced a needle sensor to distinguish small nodules from bronchi that may evoke similar upward jumps of the delta f curve. Eight nodules and four bronchi in resected human lungs were probed directly using this sensor. In all of the patients, the hardness of various thoracic structures could be quantified. A total of 10 nodules were found using the sensor and resected thoracoscopically. The needle sensor distinguished nodules from bronchi, as the mean delta f of the bronchial walls (-64 +/- 45.9 Hz) was significantly higher than that of nodules (-526 +/- 168 Hz, p < 0.001). Thoracoscopic detection of small and invisible pulmonary nodules using our new tactile sensor is feasible.


Increasing screening mammography among predominantly Spanish speakers at a federally qualified health center using a brief previsit video.
Assess the impact of a 5min video on screening mammogram referrals and completion. We recruited women ages 40 years or older without a current mammogram at a federally qualified community health center (FQHC). Women were assigned to the intervention or usual care. Immediately prior to their appointments, women in the intervention group viewed a brief video that included a demonstration of how patients may request a mammogram referral. All women completed a pre- and post-visit telephone survey about knowledge of breast cancer screening and patient activation. Mean age was 52 years, 50% had less than a high school education and 75% preferred Spanish. The proportion of mammogram referrals in the intervention group was significantly higher than the control group, 37% vs. 15%, respectively (p<0.01). Similarly, the intervention group had a higher proportion of completed mammograms, 33% vs. 13% (p<0.02). There were no differences in breast cancer knowledge or patient activation between the intervention and control groups. A brief, pre-visit video significantly increased screening mammography referrals and completion in this mostly Spanish-speaking FQHC population. Our intervention demonstrates the effectiveness of a brief-video intervention in a population with low education and low English language proficiency.


Modulation of oral movements by intranigral 5-hydroxytryptamine receptor agonists in the rat.
Bilateral infusion of 5-hydroxytryptamine (5-HT) agonists into the substantia nigra pars reticulata (SNr) of awake rats was shown to influence oral behavior. The 5-HT1A agonist (R)-8-hydroxy-2-(di-propylamino)- tetralin (8-OH-DPAT) (1.3-13 nmol on each side) produced a dose-dependent depression of vacuous chewing movements (VCMs) that lasted about 20 min. The (R)-8-OH-DPAT-induced depression of VCMs was blocked by the simultaneous intranigral infusion of a specific 5-HT1A antagonist [(-)-(S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin HCl (UH-301)], which had no effect when given alone. Another 5-HT1A agonist [(5-methoxy-N,N-dimethyltryptamine hydrogen oxalate (5-MeO-DMT)] also reduced VCM frequencies. Intranigral infusion of the nonspecific 5-HT-agonists 1-(3-triflouro-methylphenyl) piperazine (TFMPP) and 1(m-chlorophenyl)-piperazine (mCPP) and a 5-HT3 agonist [2-methyl-5-hydroxytryptamine (2-Me-5-HT)] increased VCM after 5- to 10-nmol doses. Another 5-HT3 agonist (1-phenylbiguanide) and a 5-HT2 agonist [1-(4-bromophenyl-2,5-dimethoxy)-2-aminopropane (DOB)] had no significant effect. As most 5-HT receptors in the SNr are of the 5-HT1B subtype, these results suggest that the increased VCM frequency was mediated via nigral 5-HT1B receptors. The importance of 5-HTergic mechanisms in the development of drug-induced dyskinesias is discussed.


Force synergies for multifingered grasping: effect of predictability in object center of mass and handedness.
To grasp with five digits of the hand requires an efficient parceling of contact forces in order to maintain static equilibrium as an object is lifted and held. In a previous study, subjects were asked to reach, grasp and lift a five-digit grip apparatus whose center of mass (CM) location was changed for each block of trials. Despite a modulation of force sharing patterns among the digits as a function of center of mass location, consistent in-phase and out-of-phase relationships between normal forces were found in the frequency domain. In the present study, we have used the same task to assess the effect of (a) predictability of an object's CM location (random vs blocked presentation) and (b) handedness (dominant vs non-dominant hand). Contrary to our original expectations, we found a similar modulation of normal forces to CM location during the hold phase across all conditions. Specifically, the force sharing pattern, i.e., the rank order of force contributed by each digit, emerged very early in the grasp sequence, remaining relatively stable throughout the duration of the lift and hold. Nevertheless, the extent to which force sharing patterns could be discriminated as a function of CM location was lower in the random than in the blocked conditions. Lastly, normal forces exerted by pairs of digits tended to be synchronized, both in-phase (thumb and fingers) and out-of-phase (pairs of digits) across a large proportion of the functional frequency range (up to 10 Hz) in all conditions. The composite of these findings suggests that the central nervous system uses stereotyped control strategies for coordinating multiple grip forces during grasping. Specific aspects of these schemes appear to be affected by predictability of object CM location, but not by hand dominance.


Dynamic susceptibility contrast perfusion imaging in biopsy-proved adult medulloblastoma.
Medulloblastoma (MB) is a high-grade rare brain tumor in adults, with heterogeneous imaging features and variable enhancing patterns. Diffusion and spectroscopy multimodal imaging have already been described in adult MB, yet perfusion has not been explored. This study aimed to evaluate vascularity in adult classic and desmoplastic MB, using perfusion-weighted dynamic susceptibility contrast (DSC) MRI and histopathology. Six histologically proved MB patients were classified as classic (n=3) and desmoplastic (n=3). DSC perfusion MRI was performed in three centers and retrospectively evaluated. Postprocessing included automatic arterial input function, motion and contrast leakage correction. Region of interest (ROI) delineation was performed on three perfusion slices to obtain a total of three cerebral blood volume ratios (rCBV) that were averaged to serve as the main rCBV. Permeability was evaluated on K2 maps. Low rCBVs were observed in all cases (mean rCBV=1.19±0.39). rCBV values were lower than 2 for classic MB and lower than 1 for desmoplastic MB. All cases showed an increase of permeability on K2 maps. Our preliminary results suggest that MB exhibits rCBV values close to 1 and increased permeability on DSC perfusion imaging, especially in desmoplastic cases, which could be explained by fibrous matrix. This type of perfusion pattern contrasts with those given by other enhancing subtentorial tumors such as metastasis, high-grade gliomas or hemangioblastomas.


SCAR/WAVE-mediated processing of engulfed apoptotic corpses is essential for effective macrophage migration in Drosophila.
In vitro studies have shown that SCAR/WAVE activates the Arp2/3 complex to generate actin filaments, which in many cell types are organised into lamellipodia that are thought to have an important role in cell migration. Here we demonstrate that SCAR is utilised by Drosophila macrophages to drive their developmental and inflammatory migrations and that it is regulated via the Hem/Kette/Nap1-containing SCAR/WAVE complex. SCAR is also important in protecting against bacterial pathogens and in wound repair as SCAR mutant embryos succumb more readily to both sterile and infected wounds. However, in addition to driving the formation of lamellipodia in macrophages, SCAR is required cell autonomously for the correct processing of phagocytosed apoptotic corpses by these professional phagocytes. Removal of this phagocytic burden by preventing apoptosis rescues macrophage lamellipodia formation and partially restores motility. Our results show that efficient processing of phagosomes is critical for effective macrophage migration in vivo. These findings have important implications for the resolution of macrophages from chronic wounds and the behaviour of those associated with tumours, because phagocytosis of debris may serve to prolong the presence of these cells at these sites of pathology.


Understanding public perceptions in social media responses to posts about acute severe hepatitis of unknown etiology in Indonesia: a qualitative study.
Acute Severe Hepatitis of Unknown Etiology (ASHUE) emerged as a new global outbreak in Indonesia early May 2022, coinciding with the COVID-19 pandemic. This study aimed to understand public reactions and responses to the emergence of ASHUE Indonesia and to Government-led disease prevention responses. Understanding how the public perceived government-led preventive messaging about the hepatitis outbreak is crucial to controlling viral spread - particularly given the rapid and unforeseen emergence of ASHUE coincided with COVID-19 and public trust in the Indonesian Government to manage health outbreaks was already tenuous. Social media users' responses to information disseminated via Facebook, YouTube, and Twitter were analyzed to understand public perceptions about ASHUE outbreak and their attitudes toward Government-led prevention measures. Data were extracted on a daily basis from 1st May 2022 to 30th May 2022 and analyzed manually. We inductively generated the codes, from which we formed a construct and then grouped to identify themes. A total of 137 response comments collected from 3 social medial platforms were analyzed. Of these, 64 were from Facebook, 57 were from YouTube, and 16 were from Twitter. We identified 5 main themes, including (1) disbelief in the existence of the infection; (2) suspicion about a potential new business after COVID-19; (3) suspicion that COVID-19 vaccine(s) are the cause; (4) religion-related fatalism and (5) trust in government measures. The findings advance knowledge about public perceptions, reactions and attitudes towards the emergence of ASHUE and the efficacy of disease countermeasures. The knowledge from this study will provide an understanding of why disease prevention measures might not be followed. It can be used to develop public awareness programs in Indonesia about both the ASHUE and its possible consequences and the available healthcare support.


Long-term nitrogen addition increases denitrification potential and functional gene abundance and changes denitrifying communities in acidic tea plantation soil.
The response of soil denitrification to nitrogen (N) addition in the acidic and perennial agriculture systems and its underlying mechanisms remain poorly understood. Therefore, a long-term (12 years) field trial was conducted to explore the effects of different N application rates on the soil denitrification potential (DP), functional genes, and denitrifying microbial communities of a tea plantation. The study found that N application to the soil significantly increased the DP and the absolute abundance of denitrifying genes, such as narG, nirK, norB, and nosZ. The diversity of denitrifying communities (genus level) significantly decreased with increasing N rates. Moreover, the denitrifying communities composition significantly differed among the soils with different rates of N fertilization. Further variance partitioning analysis (VPA) revealed that the soil (39.04%) and pruned litter (32.53%) properties largely contributed to the variation in the denitrifying communities. Dissolved organic carbon (DOC) and soil pH, pruned litter's total crude fiber (TCF) content and total polyphenols to total N ratio (TP/TN), and narG and nirK abundance significantly (VIP >1.0) influenced the DP. Finally, partial least squares path modeling (PLS-PM) revealed that N addition indirectly affected the DP by changing specific soil and pruned litter properties and functional gene abundance. Thus, the findings suggest that tea plantation is a major source of N2O emissions that significantly enhance under N application and provide theoretical support for N fertilizer management in an acidic tea plantation system.


Regulatory T cell niche in the bone marrow, a new player in Haematopoietic stem cell transplantation.
Challenges in haematopoietic stem cell transplantation such as low bone marrow (BM) engraftment, graft versus host disease (GvHD) and the need for long-term immunosuppression could be addressed using T regulatory cells (Tregs) resident in the tissue of interest, in this case, BM Tregs. Controlling the adverse immune response in haematopoietic stem cell transplantation (HSCT) and minimising the associated risks such as infection and secondary cancers due to long-term immunosuppression is a crucial aspect of clinical practice in this field. While systemic immunosuppressive therapy could achieve reasonable GvHD control in most patients, related side effects remain the main limiting factor. Developing more targeted immunosuppressive strategies is an unmet clinical need and is the focus of several ongoing research projects. Tregs are a non-redundant sub-population of CD4+ T cells essential for controlling the immune homeostasis. Tregs are known to be reduced in number and function in autoimmune conditions. There is considerable interest in these cells as cell therapy products since they can be expanded in vitro and infused into patients. These trials have found Treg therapy to be safe, well-tolerated, and with some early signs of efficacy. However, Tregs are a heterogeneous subpopulation of T cells, and several novel subpopulations have been identified in recent years beyond the conventional thymic (tTregs) and peripheral (pTregs). There is increasing evidence for the presence of resident and tissue-specific Tregs. Bone marrow (BM) Tregs are one example of tissue-resident Tregs. BM Tregs are enriched within the marrow, serving a dual function of immunosuppression and maintenance of haematopoietic stem cells (HSCs). HSCs maintenance is achieved through direct suppression of HSCs differentiation, maintaining a proliferating pool of HSCs, and promoting the development of functional stromal cells that support HSCs. In this review, we will touch upon the biology of Tregs, focusing on their development and heterogeneity. We will focus on the BM Tregs from their biology to their therapeutic potential, focusing on their use in HSCT.


Rapid orthogonal screening of forensic drugs using a compact UHPLC-PDA/SQD; a complement to GC-MS.
With the recent development of hand-held and miniature mass spectrometers, low cost and compact mass detectors have become more available and accessible for on-site and routine laboratory use. Here we present a rapid ultra-high performance liquid chromatography-photodiode array/mass spectrometry (UHPLC-PDA/MS) method for the routine screening of a wide variety of illicit drugs using a small and cost effective single quadrupole MS (SQD) with electron spray ionization (ESI). Two libraries for common drugs of forensic interest, a PDA library including retention time (RT) and PDA spectra and a MS library including RT and [M+H]+/[M-H]-, were developed. Using a BEH phenyl column and gradient elution of acetonitrile and 0.1% formic acid, drugs of forensic interest were detected within 8.5min and identified based on their RT/RRT to an internal standard (Codeine-d6), UV spectrum, and/or MS spectrum/(de)protonated molecular mass. The method proved to be efficient, reproducible, and sensitive with a limit of detection (LOD) ≤0.5μg/mL for untargeted screening using PDA and MS in full scan mode and ≤0.1μg/mL for targeted screening by MS in select ion recording (SIR) mode. Improved isomer discrimination was achieved, when a second injection and separation by a charged column (CSH C18) was incorporated into the same acquisition sequence. The method was applied to 20 seized drugs with similar detection limits and identifications by GC-MS. Using an orthogonal separation technique and dual detection systems, the UHPLC-PDA/SQD method serves as an attractive technique for a direct and fast screening of illicit drugs with excellent discrimination power and detection capacity. The developed method can be an alternative screening method to GC-FID and complementary technique to GC-MS for routine forensic drug screening.


Modulation of gallbladder contraction by pirenzepine in humans.
The mechanism(s) by which cholinergic innervation modulates gallbladder contraction are not fully understood. To elucidate the role of muscarinic M1 receptors in the mediation of gallbladder contraction, we investigated gallbladder volume reduction, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) responses in humans during cephalic and intestinal phases of a meal under M1 muscarinic receptor blockade with pirenzepine. In eight healthy subjects, intraduodenal meal- and in seven subjects, sham feeding-induced gallbladder volume reduction was measured by real-time ultrasonography during saline or pirenzepine administration. Plasma CCK and PP were measured by radioimmunoassay. Pirenzepine partially inhibited gallbladder volume reduction in response to an intraduodenal fatty meal. The integrated gallbladder volume reduction over 120 min was 4462 +/- 445%.min compared with 6879 +/- 279%.min in the saline control group (p < 0.01). Integrated plasma CCK and PP responses were unchanged in the presence of pirenzepine. Pirenzepine abolished sham feeding-induced gallbladder contraction and plasma PP response. Sham feeding with either isotonic saline or pirenzepine infusion did not modify fasting plasma CCK levels. M1 muscarinic receptors play an important role in the intestinal and cephalic phases of gallbladder contraction. Plasma CCK response to intraduodenal meal is not influenced by M1 muscarinic receptor blockade with pirenzepine.


Structural studies on bovine heart cytochrome c oxidase.
Among the X-ray structures of bovine heart cytochrome c oxidase (CcO), reported thus far, the highest resolution is 1.8Å. CcO includes 13 different protein subunits, 7 species of phospholipids, 7 species of triglycerides, 4 redox-active metal sites (Cu(A), heme a (Fe(a)), Cu(B), heme a(3) (Fe(a3))) and 3 redox-inactive metal sites (Mg(2+), Zn(2+) and Na(+)). The effects of various O(2) analogs on the X-ray structure suggest that O(2) molecules are transiently trapped at the Cu(B) site before binding to Fe(a3)(2+) to provide O(2)(-). This provides three possible electron transfer pathways from Cu(B), Fe(a3) and Tyr244 via a water molecule. These pathways facilitate non-sequential 3 electron reduction of the bound O(2)(-) to break the OO bond without releasing active oxygen species. Bovine heart CcO has a proton conducting pathway that includes a hydrogen-bond network and a water-channel which, in tandem, connect the positive side phase with the negative side phase. The hydrogen-bond network forms two additional hydrogen-bonds with the formyl and propionate groups of heme a. Thus, upon oxidation of heme a, the positive charge created on Fe(a) is readily delocalized to the heme peripheral groups to drive proton-transport through the hydrogen-bond network. A peptide bond in the hydrogen-bond network and a redox-coupled conformational change in the water channel are expected to effectively block reverse proton transfer through the H-pathway. These functions of the pathway have been confirmed by site-directed mutagenesis of bovine CcO expressed in HeLa cells.


Validation of the Spanish version of the Uterine Fibroid Symptom and Quality of Life (UFS-QoL) questionnaire in women with uterine myomatosis.
To validate the Spanish version of the Uterine Fibroid Symptom and Quality of Life (UFS-QoL) questionnaire in women with uterine myomatosis, in order to assess severity of symptoms, and their impact on health-related quality of life. The participants were recruited in gynaecology clinics. The UFS-QoL questionnaire comprises 37 items, 8 of which assess severity of symptoms, and the remaining 29 assess health-related quality of life in 6 subscales. Internal consistency, concurrent and discriminant validity, test-retest reliability, and the scale's sensitivity to change were evaluated. A total of 619 patients with uterine myomatosis, and 57 women without myomatosis, took part in the study. Cronbach's alpha was 0.97, and the test-retest reliability was 0.90 for the overall scale. The UFS-QoL not only discriminated between patients and healthy controls but also between patients with different degrees of uterine myomatosis. The scale responded to changes after treatment with an effect size of 1.2. The Spanish version of the UFS-QoL questionnaire, used in a sample of the Spanish population, proved a valid and reliable tool to differentiate patients with uterine myomatosis and different grades of symptoms, and to evaluate the impact of the severity of these symptoms on health-related quality of life. In addition, the UFS-QoL proved sensitive to the changes generated by myomatosis treatment.


Randomised controlled trial of efficacy of teaching patients with bipolar disorder to identify early symptoms of relapse and obtain treatment.
To determine the efficacy of teaching patients with bipolar disorder (manic-depressive psychosis) to identify early symptoms of relapse and seek prompt treatment from health services. Single blind randomised controlled trial with matching on four baseline variables using a minimisation algorithm. Mental health services in four NHS trusts (one teaching, three non-teaching). 69 patients with bipolar disorder who had had a relapse in the previous 12 months. Seven to 12 individual treatment sessions from a research psychologist plus routine care or routine care alone. Time to first manic or depressive relapse, number of manic or depressive relapses, and social functioning examined by standardised interviews every six months for 18 months. 25th centile time to first manic relapse in experimental group was 65 weeks compared with 17 weeks in the control group. Event curves of time to first manic relapse significantly differed between experimental and control groups (log rank 7.04, df=1, P=0.008), with significant reductions in the number of manic relapses over 18 months (median difference 30% (95% confidence interval 8% to 52%), P=0.013). The experimental treatment had no effect on time to first relapse or number of relapses with depression, but it significantly improved overall social functioning (mean difference 2.0 (0.7 to 3.2), P=0.003) and employment (mean difference 0.7 (0.1 to 1.3), P=0.030) by 18 months. Teaching patients to recognise early symptoms of manic relapse and seek early treatment is associated with important clinical improvements in time to first manic relapse, social functioning, and employment.


Evaluating screening performances of the Fagerstrom tolerance questionnaire, the Fagerstrom test for nicotine dependence and the heavy smoking index among Taiwanese male smokers.
To compare screening performances of the Fagerstrom Tolerance Questionnaire (FTQ), the Fagerstrom test for nicotine dependence (FTND) and the Heavy Smoking Index (HSI) with a view to determining the optimum cutoff scores using biomarkers as standards. Previous studies proposed inconsistent cutoff scores for the FTQ, the FTND as signalling nicotine dependence and these scores were established by applying diverse standards. Receiver operating characteristic (ROC) analyses were used in pursuit of the study's objectives. Two hundred and forty-five male smokers were recruited in 2005 from among those attending public health stations in southern Taiwan. The three self-report measures of nicotine dependence were compared with the saliva cotinine and expired carbon monoxide (CO). The expired CO level was tested by means of a Micro Smokerlyzer, while salivary cotinine was analysed using an enzyme-linked immunosorbent assay. The areas under the ROC curves for the FTQ, the FTND and the HSI were 0.71, 0.76 and 0.76 for the salivary cotinine and 0.71, 0.79 and 0.80 for the exhaled CO respectively. The sensitivity and specificity of the FTND and the HSI were slightly greater than those for the FTQ. The optimum cutoff scores for the FTQ, the FTND and the HSI as screening tools to establish nicotine dependence would be 5+, 4+ and 3+ respectively. The results indicate that the FTND and the HSI may be more efficacious than the FTQ in assessing nicotine dependence. Further research is needed to confirm these findings, especially among female smokers and for nicotine substitution trials. Relevance to clinical practice. To decrease tobacco-attributable morbidity and mortality, nurses and healthcare professionals need to implement effective smoking cessation interventions. The FTND and the HSI as well as their cutoff scores will be suitably used to assess nicotine dependence in these interventions.


The bioconcentration factor of perfluorooctane sulfonate is significantly larger than that of perfluorooctanoate in wild turtles (Trachemys scripta elegans and Chinemys reevesii): an Ai river ecological study in Japan.
Turtles rank high in the river food chain, and are suitable for predicting the bioconcentrations of chemicals through the food chain. Trachemys scripta elegans (N=46) and Chinemys reevesii (N=51) were captured in a river in Japan, from September to October 2003 and April to June 2004. Surface water samples were collected simultaneously from the same sites at which the turtles were caught. Serum perfluorooctane sulfonate (PFOS) ranged from 2.4 to 486 microg/L, while water PFOS levels ranged from 2.9 to 37 ng/L. The geometric mean (GM) (geometric standard deviation, GSD) of the bioconcentration factor (BCF) of PFOS was 10,964 (2.5). In contrast, the perfluorooctanoate (PFOA) level in water ranged from 16.7-87,100 ng/L, and serum PFOA ranged from <0.2 to 870 microg/L. The GM (GSD) of the BCF of PFOA was 3.2 (7.9). Furthermore, the BCF of PFOA decreased as the PFOA level in the surface water increased. PFOS could be preferentially bioconcentrated in biota, and PFOA, slightly bioconcentrated.


Numerical studies of the lymphatic uptake rate.
Lymphatic uptake is essential for transporting nutrients, wastes, immune cells, and therapeutic proteins. Despite its importance, the literature lacks a quantitative analysis of the factors that affect lymphatic uptake, including interstitial pressure, downstream pressure, and tissue deformation. In this paper, we present a coupled model of a poroelastic tissue with initial lymphatics and quantify the impact of these factors on the rate of lymphatic uptake. Our results indicate that the lymphatic uptake increases with the amplitude of the oscillating downstream pressure when the amplitude exceeds a threshold. Additionally, the cross-sectional area of initial lymphatics increases with the volumetric strain of the tissue, while the interstitial pressure increases when the strain rate becomes negative. Therefore, the lymphatic uptake reaches its maximum when the tissue has positive volumetric strain while being compressed. We have also investigated the effect of intersection angles and positions of two initial lymphatics and concluded that they have minor impacts on lymphatic uptake. However, the lymphatic uptake per unit length of initial lymphatics decreases with their total length. These findings advance our understanding of lymphatic uptake and can guide the development of strategies to accelerate the transport of therapeutics.


Right temporal-lobe contribution to the retrieval of family relationships in person identification.
We previously reported a patient who exhibited a peculiar form of delusional misidentification. She had a selective deficit in retrieving family relationships between herself and her daughters and husband (i.e., she misidentified her daughters as her sisters and her husband as her father) despite being able to retrieve their names and faces and some person-specific semantic information (e.g., occupation). Based on this finding, the present positron emission tomography study was designed to elucidate the brain mechanisms underlying the retrieval of family relationships in healthy individuals. We found that the right inferior temporal gyrus, in which hypoperfusion was detected in the patient we had reported, was significantly activated during the retrieval of family relationships compared with names and occupations. These findings indicate that the retrieval of the relationships between oneself and one's family members may require a specific cognitive process dissociated from the retrieval of names and other person-specific semantic information.


Time-variant spectral analysis of heart rate variability during parabolic flight with and without LBNP.
Modifications of autonomic activity during parabolic flight were studied by a time-variant model able to estimate low (LF, 0.04-0.14 Hz) and high (HF, 0.14-0.35 Hz) frequency spectral components on a beat-to-beat basis. Ten subjects were studied with and without lower body negative pressure (LBNP). ECG and Gz load were digitized (500 Hz) and RR interval variability series extracted. Beat-to-beat mean RR, variance, LF and HF power were obtained. One-way ANOVA (p<0.01) was used to compare values obtained during starting 1Gz (I), first 1.8Gz (II), 0Gz (III), second 1.8Gz (IV), ending 1Gz (V). Without LBNP, total and LF power increased during 0Gz to 1.69 +/- 1.41 and 2.87 +/- 4.66 respectively (mean +/- SD, normalized by phase I value). With LBNP, their change during 0Gz (1.38 +/- 1.37 and 1.54 +/- l.04 respectively) reached significance only with phase II and phase V. Phase I HF power was higher than in the other phases, both without and with LBNP.


Melting bones: The social construction of postmenopausal osteoporosis in Turkey.
The increased medicalization of different life stages, including menopause, is a subject studied mostly in the Western context. Examining medicalization in the non-Western world advances discussions of body, identity and health. In this paper, I analyze the discourses around postmenopausal osteoporosis in Turkey, focusing on the different constructions of risk in the medical and popular literature. The empirical basis of the paper draws on ethnographic research done in Istanbul, Turkey between June 2006 and March 2007. The research includes participant observation in gynecology clinics, interviews with clinicians and menopausal women and archival research on the representations of menopause in the Turkish media between 1999 and 2006. Referred to as kemik erimesi (melting of the bones) in colloquial Turkish, osteoporosis has been an essential component in the medicalization of menopause in Turkey. I argue that postmenopausal osteoporosis is defined as a combination of embodied risk, which is related to the definition of menopause as a risky period, and lifestyle risk, demonstrated in discussions around "traditional" vs. "modern" clothing and healthcare habits. The Turkish example emphasizes the importance of local conditions in defining medical risk and complicates the embodied vs. lifestyle risk categories.


Integrated proteomics and metabolomics analysis reveals the antifungal mechanism of the C-coordinated O-carboxymethyl chitosan Cu(II) complex.
With wide application in agriculture, copper fungicides have undergone three stages of development: inorganic copper, synthetic organic copper, and natural organic copper. Using chitin/chitosan (CS) as a substrate, the natural organic copper fungicide C-coordinated O-carboxymethyl chitosan Cu(II) complex (O-CSLn-Cu) was developed in the laboratory. Taking Phytophthora capsici Leonian as an example, we explored the antifungal mechanism of O-CSLn-Cu by combining tandem mass tag (TMT)-based proteomics with non-targeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. A total of 1172 differentially expressed proteins were identified by proteomics analysis. According to the metabolomics analysis, 93 differentially metabolites were identified. Acetyl-CoA-related and membrane localized proteins showed significant differences in the proteomics analysis. Most of the differential expressed metabolites were distributed in the cytoplasm, followed by mitochondria. The integrated analysis revealed that O-CSLn-Cu could induce the "Warburg effect", with increased glycolysis in the cytoplasm and decreased metabolism in the mitochondria. Therefore, P. capsici Leonian had to compensate for ATP loss in the TCA cycle by increasing the glycolysis rate. However, this metabolic shift could not prevent the death of P. capsici Leonian. To verify this hypothesis, a series of biological experiments, such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), and enzyme activity measurements were carried out. The results suggest that O-CSLn-Cu causes mitochondrial injury, which consequently leads to excessive ROS levels and insufficient ATP levels, thereby killing P. capsici Leonian.


Solvation of nucleosides in aqueous mixtures of organic solvents: relevance to DNA open basepairs.
Toward the goal of understanding how open basepairs in DNA interact with their heterogeneous environment, we have studied the steady-state intrinsic fluorescence properties of the purine and pyrimidine deoxynucleosides in organic solvents in the presence of small amounts of water. The organic solvents used in the present study were: n-butanol, acetonitrile, methanol, n-propanol, isopropanol, and isobutanol. For n-butanol and acetonitrile, which have a high degree of amphiphilicity and weak hydrogen bonding ability, respectively, the fluorescence spectral properties of the purines are found to depend on the sequence of steps in which the aqueous mixtures were formed. By contrast, no such dependence was observed in the mixtures with any of the other solvents used in the present study. Moreover, no such dependence was observed for the pyrimidines. These findings suggest that the final solvation network around the purines is dependent on the nature of the environment to which they were initially exposed. This would tend to present an impediment to the closing of AT or GC basepairs in DNA that become open as a result of structural fluctuations, DNA bending, or protein-DNA interactions.


Protein phosphatase modulation of the intercellular junctional communication: importance in cardiac myocytes.
The rhythmic contraction of a four-chambered heart is a highly co-ordinated process, requiring the sequential activation of pacemaker cells and the propagation of activity throughout the whole myocardium. Gap-junctional channels, providing enclosed conduits for direct cell-to-cell transfer of ions and small molecules between adjacent cells, allow depolarising currents to flow from excited to non-excited regions of the network and a gradual spreading of the action potential. Gap-junctional channels are dodecamers of transmembrane proteins belonging in chordates to the connexin (Cx) family. In mammalian hearts, cardiomyocytes most prominently express junctional channels built of three Cxs: Cx40, Cx43 and Cx45. As with the great majority of Cx, they are phosphoproteins and exist under different phosphorylated levels. Phosphorylation, a widespread post-translational modification of proteins, is a primary means of mediating signal transduction events that control numerous cellular processes via a highly regulated dynamic interplay of protein kinases (PKs) and protein phosphatases (PPs). These processes appear implicated in the regulation of gap-junctional communication at several stages of the Cx lifecycle, including intracellular Cx trafficking, connexon assembly and disassembly, Cx degradation as well as the gating of gap-junction channels, but the underlying mechanisms remain poorly understood. Although PKs have an established role in this process, less is known about the involvement of PPs. The present review examines the roles played by protein dephosphorylation catalysers in the regulation of the gap-junctional communication in general, with a special focus on the junctional communication between cardiac cells.


Isolation of Kunjin virus from a patient with a naturally acquired infection.
To describe the first isolation of Kunjin virus from a patient with a natural infection. A 48-year-old female egg collector presented with muscle weakness, fatigue and extreme lethargy three weeks after developing rigors, headache, photophobia and nausea. Kunjin virus was isolated from an acute phase serum sample. The patient made a partial recovery after treatment for 10 days with Catovit (Boehringer Ingelheim), one tablet twice a day, and then declined further medical contact. The isolation of Kunjin virus from this patient confirms previous serological observations which suggested that this mosquito-borne virus caused febrile episodes in humans accompanied, on occasion, by polyarthralgia or mild central nervous system signs and symptoms.


Effect of light quality on the C-phycoerythrin production in marine cyanobacteria Pseudanabaena sp. isolated from Gujarat coast, India.
The isolated cyanobacterium containing biopigments like chlorophyll-a, phycoerythrin, phycocyanin, and carotenoid was cultured under different quality of light modes to ascertain biomass and pigment productivity. On the basis of 16S rRNA gene sequence, the isolate was identified as Pseudanabaena sp. Maximum biomass concentration obtained in white-, blue-, and green-light was 0.82, 0.94, and 0.89 g/L, respectively. It was observed that maximum phycoerythrin production was in green light (39.2 mg/L), ensued by blue light (32.2 mg/L), while phycocyanin production was maximum in red light (10.9 mg/L). In yellow light, pigment production as well as the growth rate gradually declined after 12 days. Carotenoid production decreased in blue-, white-, and red-light after 15 days, while in green light it had increased gradually. The present communication suggests that Pseudanabaena sp. can be used for commercial production of phycoerythrin when grown under green light.


Ketanserin attenuates nicotine-induced working memory improvement in rats.
Nicotinic systems have been shown in numerous studies to be important for spatial working memory. Nicotinic systems are certainly not acting alone in the basis of memory function, but act in concert with a variety of other neural systems. Important for these interactions is nicotinic induced release of a variety of neurotransmitters involved in memory function including serotonin (5-HT). We have found that the 5-HT2 receptor antagonist, ketanserin, effectively attenuated nicotine-induced attentional improvement. The current study explored the interaction between nicotinic and serotonergic systems in the performance of a spatial working memory task in the radial-arm maze. Female Sprague-Dawley rats were trained on the win-shift working memory task on the 8-arm radial maze. After 18 sessions of acquisition training the rats were given acute doses of nicotine (0.2 and 0.4 mg/kg), ketanserin (0.5, 1 and 2 mg/kg) or combinations of the two. The vehicle served as the control. As seen in previous studies, nicotine caused a significant improvement in working memory performance as indexed by the number of correct arm entries before the first error (entries to repeat). Ketanserin at the doses tested did not cause a significant effect on choice accuracy, but it did significantly attenuate the improvement caused by the 0.2 mg/kg nicotine dose. The higher 0.4 mg/kg nicotine dose was nearly sufficient to overcome the ketanserin effect. This study shows that, as with attentional function, nicotine-induced working memory improvement is attenuated by the 5-HT2 antagonist ketanserin. Given that many antipsychotic drugs have substantial 5-HT2 antagonist effects, these atypical antipsychotic drugs may reduce the cognitive improvements caused by nicotinic treatments.


Efficacy and safety of traditional Chinese medicine treatment for idiopathic pulmonary fibrosis: An exploratory, randomized, double-blinded and placebo controlled trial.
Background and objective: Idiopathic pulmonary fibrosis (IPF) is a critical disease, with limited treatments available. Clinical practices show that traditional Chinese medicine (TCM) has certain efficacy. This study was preliminarily to evaluate the efficacy and safety of TCM treatment based on syndrome differentiation in IPF. Methods: A study design of exploratory, multi-centers, randomized, double-blinded, placebo controlled trial has been adopted. A total of 80 IPF patients from four sub-centers were enrolled. All the patients were randomly assigned into TCM group (TCMG) or control group (CG) in 1:1. Patients in TCMG were given CM granules, as patients in CG given with the placebo of CM granule. All the patients received a 26-week treatment. The efficacy was assessed by acute exacerbations (AEs) of IPF, pulmonary function, clinical symptoms, dyspnea scores (mMRC), health-related quality of life (HRQoL), 6-min walk test (6MWT) and all-cause mortality. Safety has also been assessed. Results: A total of 67 patients completed the trial with 35 in TCM group and 32 in control group. Meaningful differences have been observed in mean changes in AEs (-1.56 times; 95% CI, -2.69 to -0.43, p = 0.01), DLco% (5.29; 95% CI, 0.76 to 9.81, p = 0.02), cough scores (-0.38 points; 95% CI, -0.73 to -0.04, p = 0.03), and 6MWT (30.43 m; 95% CI, 2.85 to 58.00, p = 0.03), with no statistical differences in FEV1, FVC, expectoration, chest tightness, Shortness of breath, Fatigue, Cyanosis, mMRC, CAT, SF-36, and SGRQ total scores in 26 weeks after treatment than before treatment. At of the end of follow-up, a total of 10 patients died, including three and seven in the TCM and control group respectively. And the HR (Hazard ratio) for CM granules in all-cause mortality was 0.39 (95% CI, 0.10-1.52). The drug-related adverse events were not observed. Conclusion: CM granules, as compared with placebo, could reduce frequencies of AEs, improve pulmonary function, HRQoL, exercise capacity and symptoms and signs for IPF to some extent with acceptable side-effect.


Paroxetine.
Paroxetine is a widely used antidepressant that has received attention regarding suicide risk in younger patients. The purpose of this paper is to review the pharmacology, efficacy and safety of paroxetine in the affective disorders. The authors performed a PubMed search for all literature in English crossing the words 'paroxetine' and 'Paxil' against the words 'serotonin transporter,' 'clinical trials,' 'depression' and 'SSRI'. A search for paroxetine-related information at the FDA website and under the clinical trial register of the GSK website were also performed. Paroxetine is a serotonin re-uptake inhibitor with good selectivity and no significant active metabolites. Paroxetine is approved (ages >or= 18 years) for the treatment of major depressive disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder (social phobia), post-traumatic stress disorder, and generalized anxiety disorders. Drug - drug interactions involving the CYP enzyme system have been documented, as well as concern for increased suicidality risk in younger adults and recent FDA alerts regarding teratogenicity, serotonin syndrome and persistent pulmonary hypertension.


Reproducibility studies for anti-DNA antibody detection in systemic lupus erythematosus and related diseases. FIAX fluorometric immunoassay and Farr radioimmunoassay.
We compared the FIAX fluorometric immunoassay for antiDNA antibodies with a Farr radio-immunoassay. Neither was precise; coefficients of variation usually exceeded 10%. The 2 assays correlated well (r = 0.87). Both were almost completely specific for numbers of sera with elevated antiDNA preferable to the Farr assay and probably to all other antiDNA assays currently used in clinical situations, although its reproducibility needs improvement.


Increased yield of biotransformation of exemestane with β-cyclodextrin complexation technique.
In this study, 6-methylenandrosta-4-ene-3,17-dione and Hydroxypropyl-β-cyclodextrin (HP-β-CD) were used to form a complex, which could be then biotransformed by Arthrobacter simplex ATCC6946 to obtain the antitumor drug exemestane. The complex was analyzed by UV, DSC and TG techniques, while the products were analyzed by HPLC, NMR and MS. These results confirmed that the β-cyclodextrin not only improved the water-solubility of 6-methylenandrosta-4-ene-3,17-dione, but also greatly enhanced the biocompatibility during the biotransformation process. This result may be applied to other precursors which have poor aqueous solubility in the biotransformation processes.


A new Haemocystidium (Apicomplexa: Plasmodiidae) species of the dhub lizard, Uromastyx aegyptia microlepis , in Abu Dhabi, distinguished by the absence of pigment.
The spiny-tailed lizard, Uromastyx aegyptia microlepis , in Abu Dhabi is parasitized by Haemocystidium apigmentada n. sp., and 2 species of Hepatozoon . The elongate gametocytes of H. apigmentada are 13-19 × 6-9 µm, with length × width (LW) 90-133 µm(2), and L/W ratio 1.56-3.17. Gametocyte dimensions do not differ by sex. Gametocytes are unpigmented. Hepatozoon species 1 has gamonts with a consistently terminal nucleus, with dimensions of 13-16 × 4.5-7 µm, LW of 58-104 µm(2), and L/W ratio of 2.00-3.22. Hepatozoon species 2 gamonts have a broad nucleus at the midbody, and dimensions of 13-15.5 × 5-7 µm, LW of 71-109 µm(2), and L/W ratio of 1.93-3.00.


Improving Postoperative Acute Kidney Injury Rates Following Primary Total Joint Arthroplasty.
Perioperative hip and knee arthroplasty complications remain a significant clinical and financial burden. Our institution has shifted to developing protocols to decrease these perioperative complications. This study focuses on acute kidney injury (AKI) rate status post primary total joint arthroplasty (TJA). Current literature demonstrates a 2%-15% incidence of AKI following TJA. However, there is a paucity of published literature on protocols that have effectively reduced AKI rates following TJA. The purpose of this study is to evaluate the effect that our institutionally developed perioperative renal protocol had on the postoperative AKI rates. A retrospective cohort study was performed. Patient demographics, baseline creatinine, and postoperative creatinine values during the patient's hospitalization were collected and analyzed. The preintervention cohort data contained all patients at our institution who underwent a primary TJA from November 1, 2016 to January 1, 2018. The postintervention cohort included all primary TJA patients from July 1, 2018 to February 2, 2020. AKI was defined using the AKI Network classification system comparing baseline and postoperative creatinine values. A multivariate analysis was performed to determine the statistical significance of our results. Before intervention 1013 patients underwent a primary TJA with 68 patients developing an AKI postoperatively. After intervention 2169 patients underwent primary TJA with 90 patients developing an AKI (6.71% vs 4.15%; P = .0015, odds ratio = 0.59, 95% confidence interval = 0.42-0.82). This study demonstrated that implementation of a perioperative renal protocol can significantly reduce AKI rates. A reduction in AKI rates following TJA will result in improved outcomes and secondarily decrease the financial impact of postoperative complications seen following TJA.


Use of a recommended evaluation scheme in the assessment of a new digoxin radioimmunoassay kit.
A new digoxin radioimmunoassay kit with a magnetizable solid-phase antibody was assessed using a recommended evaluation scheme. The kit was found to have acceptable performance characteristics, and the results are presented in the format recommended in the evaluation scheme to maximize comparability with data from other such studies. While the evaluation protocol was found to be generally workable and valid, modifications are suggested to enhance its applicability to an immunoassay system.


The effect of air pollution and emotional and behavioral problems on preschoolers' overweight and obesity.
Childhood overweight and obesity (OWO) has risen dramatically in both developed and developing countries over the past few decades, creating a huge burden of disease. Ambient air pollution and emotional and behavioral problems are important influencing factors of OWO in preschoolers, but few studies have evaluated the impact of air pollution and emotional and behavioral problems on OWO of preschoolers in rural areas and their potential interactions. This study selected 3802 preschool children from 26 kindergartens in 4 rural areas of Anhui Province for a cross-sectional study. A total of 3636 individuals were included in the final analysis. In this study, outdoor air pollutants (PM2.5 and O3) were derived from the China Air Pollution Tracking (TAP) data set, matching preschoolers' external air pollution exposure according to their kindergarten address codes to neighborhoods or administrative villages. OWO were assessed based on WHO Child Growth and Development Standards. Generalized linear model (GLM) and interplot model were used to evaluate the separate effects and potential interactions of air pollutants and emotional and behavioral problems on preschoolers' OWO. In the separate analysis, we found a significant positive association between air pollution and emotional and behavioral problems and OWO among preschoolers. In the interaction analysis, air pollution could enhance the positive effect of emotional and behavioral problems on OWO in preschoolers. In addition, the effect of air pollution and emotional and behavioral problems on overweight and obesity was stronger in preschoolers aged 5 to 6 years. Finally, we also found a stronger positive association between emotional and behavioral problems among girls, macrosomia, non-left-behind children, and preschoolers without eating problems. This study provided a scientific basis for the control of air pollution and overweight and obesity among preschool children in Anhui Province.


Neonatal intestinal obstruction from omphalomesenteric duct remnants.
Three cases of omphalomesenteric band obstruction in early infancy with various radiographic presentations, including intermittent obstruction in one, are reported. Small-bowel volvulus was found in all three patients at surgery. One case progressed to bowel necrosis with portal venous gas. A survey of the mode of presentation, surgical findings, and pathology of 135 published cases of intestinal obstruction in children demonstrates that a closed loop, with or without volvulus, is the most common complication of remnant bands.


Sensitivity to activated protein C in patients with deep vein thrombosis during early puerperium period.
In this study, we used an endogenous thrombin potential (ETP)-based assay to examine the response to activated protein C (APC) during early puerperium of 6 Japanese patients of deep vein thrombosis (DVT) and pulmonary embolism (PE) without a history of familial thrombophilia or antiphospholipid syndrome. The patient group comprised 6 Japanese women diagnosed for DVT or PE at Hamamatsu University School of Medicine, between July 1997 and April 2000. The control group comprised 30 healthy Japanese women in early puerperium. APC-sensitivity ratio (APC-sr), complete blood count (CBC), and other coagulant variables (thrombin-antithrombin-complex (TAT) and fibrin/fibrinogen-degration product (FDP)-D-dimer levels) were determined. Mean APC-sr was 2.0 +/- 0.3 in the control group and significantly higher (3.3 +/- 1.0) in the patient group (P < 0.05). The FDP-D-dimer level was significantly higher in the patient group than in the control group, but there was no significant difference in the TAT complex level. We conclude that sensitivity to APC is reduced in patients with DVT or PE during early puerperium. Although further clinical studies are needed to confirm, it appears that sensitivity to APC detected by ETP-based assay could become a useful marker to estimate the occurrence of DVT or PE.


Chlorination of secondary treated wastewater with sodium hypochlorite (NaOCl): An effective single alternate to other disinfectants.
The present study provides details about the usefulness of chlorination in the recovery effluents of sewage, and to make it useable for irrigation purposes. Chlorination is one of the effective simplified, and cost-effective traditional methods for disinfection. The study was done for the period of March, 2019 to February, 2020. The disinfection process was optimized by adding sodium hypochlorite to the secondary treated effluents with the help of jar apparatus at a mixing speed of 100 rpm. To optimize the various process variables such as dose, and contact time, several concentrations of NaOCl (0.5, 1, 1.5, 2, 2.5, 3.0) ppm were carefully chosen at different time intervals of 15, 30, and 60 min respectively, which were centered on the foregoing studies. The factors like seasonal variation on MPN index of total coliforms (TCs), CR ∗ T concept, and effect of pH on log elimination of TCs, outcome of pH with rate constant (k), and results of pH against dilution coefficient (n) was also studied. The Chick-Watson, Rennecker-Marinas, Collin-Selleck, and modified Selleck models have shown good reliability to the experimental data of chlorine disinfection to be fit into these kinetic models for the treatment of sewage wastewater. The upgraded CR ∗ T values were attained by using disinfection models. Among these four models, the kinetic modeling by Collin-Selleck, and Selleck-White was investigated as the best modeling to be fitted more finely to the chlorination experimental data to count for the effectiveness of NaOCl. The selected indicator organism in the optimization process of chlorine was Total coliforms (TCs). The residual chlorine and most probable number per log unit (Log) for TCs were measured before the start and after the termination of the disinfection process. The World Health Organization (WHO) standard for pathogenic removal from wastewater, and to irrigate the crops is 3- to 4-log and the chlorine residual under 1 mg/l limit was accomplished.


Associations of Military Service History and Health Outcomes in the First Five Years After Traumatic Brain Injury.
For many years, experts have recognized the importance of studying traumatic brain injury (TBI) among active-duty service members and veterans. A majority of this research has been conducted in Veterans Administration (VA) or Department of Defense settings. However, far less is known about military personnel who seek their medical care outside these settings. Studies that have been conducted in civilian settings have either not enrolled active duty or veteran participants, or failed to measure military history, precluding study of TBI outcomes by military history. The purpose of the present study was to determine associations between military history and medical (prevalence of 25 comorbid health conditions), cognition (Brief Test of Adult Cognition by Telephone), and psychological health (Patient Health Questionnaire-9 [PHQ-9], Generalized Anxiety Disorder-7, suicidality [9th item from PHQ-9]) in the first 5 years after TBI. In this prospective study, we analyzed data from the TBI Model Systems National Database. Participants were 7797 individuals with TBI admitted to one of 21 civilian inpatient rehabilitation facilities from April 1, 2010, to November 19, 2020, and followed up to 5 years. We assessed the relationship between military history (any versus none, combat exposure, service era, and service duration) and TBI outcomes. We found specific medical conditions were significantly more prevalent 1 year post-TBI among individuals who had a history of combat deployment (lung disorders, post-traumatic stress disorder [PTSD], and sleep disorder), served in post-draft era (chronic pain, liver disease, arthritis), and served >4 years (high cholesterol, PTSD, sleep disorder). Individuals with military history without combat deployment had modestly more favorable cognition and psychological health in the first 5 years post-injury relative to those without military history. Our data suggest that individuals with TBI with military history are heterogeneous, with some favorable and other deleterious health outcomes, relative to their non-military counterparts, which may be driven by characteristics of service, including combat exposure and era of service.


A register-based observational cohort study on persistent frequent users of emergency services in a Finnish emergency clinic.
The focus of emergency room (ER) treatment is on acute medical crises, but frequent users of ER services often present with various needs. The objectives of this study were to obtain information on persistent frequent ER service users and to determine reasons for their ER service use. We also sought to determine whether psychiatric diagnoses or ongoing use of psychiatric or substance use disorder treatment services were associated with persistent frequent ER visits. A cohort (n = 138) of persistent frequent ER service users with a total of 2585 ER visits during a two-year-period was identified. A content analysis was performed for 10% of these visits. Register data including International Classification of Primary Care 2 (ICPC-2) -codes and diagnoses were analyzed and multivariable models were created in order to determine whether psychiatric diagnoses and psychosocial reasons for ER service use were associated with the number of ER visits after adjusting for covariates. Patients who were younger, had a psychiatric diagnosis and engaged in ongoing psychiatric and other health services, had more ER visits than those who were not. Having a psychiatric diagnosis was associated with the frequency of ER visits in the multivariable models after adjusting for age, gender and ongoing use of psychiatric or substance use disorder treatment services. Reasons for ER-service use according to ICPC-2 -codes were inadequately documented. Patients with psychiatric diagnoses are overrepresented in this cohort of persistent frequent ER service users. More efficient treatments paths are needed for patients to have their medical needs met through regular appointments.


Leukotrienes are active in the rosette inhibition assay mimicking the action of 'early pregnancy factor'.
Lipoxygenase metabolites have been found to be active in the rosette inhibition assay by inducing increased rosette inhibition titres. Leukotrienes B4, C4, D4 and E4 were identified as possessing this activity. The cycloxygenase products, prostaglandins E2, D2 and F2 alpha had no such activity; however, prostaglandin E2 and to a lesser degree prostaglandin D2 could counteract the activity of the leukotrienes in this assay. The identified leukotrienes are the first characterised molecules known to display activity in the assay. In this respect they mimic the action of early pregnancy serum, an action ascribed to a so called 'early pregnancy factor'.


Escherichia coli Shiga toxin 1 and TNF-alpha induce cytokine release by human cerebral microvascular endothelial cells.
Infection with Shiga toxin (Stx)-producing Escherichia coli can lead to development of hemolytic uremic syndrome (HUS). Patients with severe HUS often exhibit central nervous system (CNS) pathology, which is thought to involve damage to brain endothelium, a component of the blood-brain barrier. We hypothesized that this neuropathology occurs when cerebral endothelial cells of the blood-brain barrier, sensitized by exogenous TNF-alpha and stimulated by Stx1, produce and release proinflammatory cytokines. This was tested by measuring changes in cytokine mRNA and protein expression in human brain endothelial cells (hBEC) in vitro when challenged by TNF-alpha and/or Stx. High doses of Stx1 alone were somewhat cytotoxic to hBEC; Stx1-treated cells produced increased amounts of IL-6 mRNA and secreted this cytokine. IL-1beta and TNF-alpha mRNA, but not protein, were increased, and IL-8 secretion increased without an observed increase in mRNA. Cells pretreated with TNF-alpha were more sensitive to Stx1, displaying greater Stx1-induction of mRNA for TNF-alpha, IL-1beta, and IL-6, and secretion of IL-6 and IL-8. These observations suggest that in the pathogenesis of HUS, Stx can induce cytokine release from hBEC, which may contribute toward the characteristic CNS neuropathology.


Targeting EZH2 regulates the biological characteristics of glioma stem cells via the Notch1 pathway.
Glioma is the most common malignant brain tumor, and its behavior is closely related to the presence of glioma stem cells (GSCs). We found that the enhancer of zeste homolog 2 (EZH2) is highly expressed in glioma and that its expression is correlated with the prognosis of glioblastoma multiforme (GBM) in two databases: The Cancer Genome Atlas and the Chinese Glioma Genome Atlas. Additionally, EZH2 is known to regulate the stemness-associated gene expression, proliferation, and invasion ability of GSCs, which may be achieved through the activation of the STAT3 and Notch1 pathways. Furthermore, we demonstrated the effect of the EZH2-specific inhibitor GSK126 on GSCs; these results not only corroborate our hypothesis, but also provide a potential novel treatment approach for glioma.


Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.
Restitution through intracardiac pacing has been used to assess arrhythmia vulnerability. We examined whether analyses of sequential beat-to-beat QT and TQ interval measures can be used to quantify ECG restitution changes under normal sinus rhythm. The QT, R-R and TQ intervals were examined 22.5 hour Holter monitoring before and after oral sotalol in normal male and female volunteers. Additionally, comparisons were made to those observed in the time-matched dataset prior to torsades de pointes in a heart diseased patient that received a single dose of sotalol. Sotalol increased QT, R-R and TQ intervals 71, 101, and 125 ms after 160 mg (n = 38) and 194, 235, and 135 ms after 320 mg (n = 19) during maximum plasma concentrations, respectively. The percentage of beats with a QT/TQ ratio >1 was reduced 25% over the entire 22.5 hours after sotalol and the lower TQ interval boundary (5th quantile) was increased 22-30%. In contrast, 99% of the beats prior to torsades de pointes had a QT/TQ ratio > 1 and the median TQ interval was below the lower 98% confidence bounds of normals before and after sotalol. ECG restitution changes are quantifiable under varying states (nocturnally, beta-adrenergic blockade, QT prolongation) in healthy subjects.


Iron coordination in liquid FeAl2O4.
The structure of aerodynamically levitated liquid [Formula: see text] was measured by neutron diffraction with isotope substitution (NDIS). Classical and ab initio molecular dynamics simulations were performed and their results were found to be in close agreement with each other and the NDIS data. The results reveal that molten [Formula: see text] may be considered as an ionic liquid without any preference for particular short-range structural motifs. This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 1)'.


Gastric submucosal abscess caused by Edwardsiella tarda infection: a case report.
Edwardsiella tarda is a motile, facultatively anaerobic gram-negative bacillus that is isolated from a wide spectrum of animals in aquatic environments but rarely causes infection in humans. Here, we describe the case of a gastric submucosal abscess caused by E. tarda infection. The patient was a 74-year-old man with a history of hypertension and chronic alcohol consumption who was admitted to our hospital for abdominal pain, appetite loss and vomiting. Contrast-enhanced computed tomography (CT) revealed choledocholithiasis in the common bile duct, a gastric wall abscess and an intra-abdominal abscess. Endoscopic ultrasound (EUS)-guided drainage with antibiotics successfully cured the patient. The combination of CT, endoscopy and EUS-guided drainage with antibiotic therapy might be effective for diagnosis and treatment of a gastric submucosal abscess caused by E. tarda infection.


[Phenolic derivatives in intermediate medications in endodontics. 1. A review of the literature].
The authors review the literature on phenolic derivatives, a widely used compound antiseptic for intermediate endodontic medication. There is interest in these substances owing to the frequency of their clinical application in order to maintain the antiseptic conditions obtained during the course of the chemico-mechanical preparation of the radicular canal.


The stability of carboplatin in ambulatory continuous infusion regimes.
Several anti-cancer agents are administered by continuous infusion in an attempt to improve the therapeutic index obtained with solid tumours. In Exeter this approach, combined with the use of ambulatory infusion pumps, forms the basis of a home oncology programme in which a complete course of medication in pre-filled syringes is supplied on an out-patient basis. It is essential to ensure that the drug remains stable during storage prior to use and also during infusion where the temperature of the drug solution in a holster-worn ambulatory pump can reach 37 degrees C. In this study the stability of a carboplatin infusion (20 mg in 2 ml) in pre-filled syringes under storage and in-use conditions was determined using a stability-indicating HPLC assay. There was no loss of carboplatin from pre-filled syringes stored at 4 degrees C for 5 days. At 37 degrees C, the loss of carboplatin was 3.1% over 24 h.


Wheelchair-mounted accelerometers for measurement of physical activity.
To evaluate the validity of a wheelchair frame-mounted accelerometer for the assessment of physical activity of wheelchair users. Twelve collegiate wheelchair basketball players participated in this study. The study was conducted in a modern indoor gymnasium at a university in the USA. A randomized, crossover experimental design was used to investigate accelerometer output, participant heart rate, and distance travelled. Participants performed two trials of wheeling at a combination of two different effort levels (light and moderate: Prescribed using perceived exertion) and two different modes (continuous and stop-go). Accelerometer vector magnitude activity counts (VM), heart rate (HR), and distance travelled were significantly different between light and moderate effort (p < 0.01). The continuous and stop-go wheeling modes were not significantly different (p = 0.37) for VM, but were significantly different (p < 0.01) for both HR and distance. Between-trial reliability of all data collapsed for the effort and mode combinations were: VM: r = 0.85; HR: r = 0.86; and distance: r = 0.96. A wheelchair frame-mounted accelerometer differentiated between perceptually-prescribed low and moderate effort levels and may prove to be a valid instrument in the detection of a wheelchair users' physical activity. [Box: see text].


Successful surgical treatment for a thrombus straddling a patent foramen ovale: a case report.
Paradoxical embolism (PDE) occurs after embolic material passes from the venous to the arterial circulation through a right-to-left shunt, which is frequently a patent foramen ovale (PFO). We describe the case of a patient with deep venous thrombosis and an intracardiac thrombus straddling a PFO and who was successfully treated with an emergency surgery.


Multi-omic Analysis of the Interaction between Clostridioides difficile Infection and Pediatric Inflammatory Bowel Disease.
Children with inflammatory bowel diseases (IBD) are particularly vulnerable to infection with Clostridioides difficile (CDI). IBD and IBD + CDI have overlapping symptoms but respond to distinctive treatments, highlighting the need for diagnostic biomarkers. Here, we studied pediatric patients with IBD and IBD + CDI, comparing longitudinal data on the gut microbiome, metabolome, and other measures. The microbiome is dysbiotic and heterogeneous in both disease states, but the metabolome reveals disease-specific patterns. The IBD group shows increased concentrations of markers of inflammation and tissue damage compared with healthy controls, and metabolic changes associate with susceptibility to CDI. In IBD + CDI, we detect both metabolites associated with inflammation/tissue damage and fermentation products produced by C. difficile. The most discriminating metabolite found is isocaproyltaurine, a covalent conjugate of a distinctive C. difficile fermentation product (isocaproate) and an amino acid associated with tissue damage (taurine), which may be useful as a joint marker of the two disease processes.


Comparison between transcutaneous PO2 and pulse oximetry for monitoring O2-treatment in newborns.
213 paired tcpO2/paO2-data and 186 paired tcSO2/SaO2-data measured in 25 newborns (10 term, 15 prematures) were compared. The correlation coefficient for tcpO2/paO2 was 0.796, for tcSO2/SaO2 0.944. Sensitivity for discriminating between normo- and hypoxemia (paO2 less than 50 torr) was 82% for the tcpO2- and 88% for the tcSO2-method. Positive predictive values for discriminating between normo- and hypoxemia were 88% for both methods. Sensitivity for discrimination between normo- and hyperoxemia (paO2 greater than 100 torr) was 85% for the tcpO2- and 100% for the tcSO2-method. Positive predictive values for the discrimination between normo- and hyperoxemia were 58% and 25% for tcpO2- and tcSO2 respectively. Pulse oximetry proved to be less cumbersome than the tcpO2-method. However, as tcpO2, it could not be used in some very immature newborns and in those with circulatory instability. In conclusion, these preliminary results show a similar discrimination between normoxemia and hypo-hyperoxemia for both methods. A better sensitivity of pulse oximetry for hyperoxemia is counteracted by a lesser positive predictive value.


Translation control of UCP2 synthesis by the upstream open reading frame.
Uncoupling protein 2 (UCP2) belongs to a family of transporters of the mitochondrial inner membrane. In vivo low expression of UCP2 contrasts with a high UCP2 mRNA level, and induction of UCP2 expression occurs without change in mRNA level, demonstrating a translational control. The UCP2 mRNA is characterized by a long 5' untranslated region (5'UTR), in which an upstream open reading frame (uORF) codes for a 36-amino-acid sequence. The 5'UTR and uORF have an inhibitory role in the translation of UCP2. The present study demonstrates that the 3' region of the uORF is a major determinant for this inhibitory role. In this 3' region, a single-base substitution that kept the codon sense unchanged significantly modified UCP2 translation, whereas some important amino acid changes had no effect. We discuss our results within the framework of the existing models explaining initiation of translation downstream of a uORF.


Comparative Evaluation of Safety and Efficacy of Glimepiride and Sitagliptin in Combination with Metformin in Patients with Type 2 Diabetes Mellitus: Indian Multicentric Randomized Trial - START Study.
Modern sulfonylureas like glimepiride offer effective glycemic control with extrapancreatic benefits and good tolerability. The objective of the present study was to evaluate and compare safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus (T2DM). In this open-label, randomized, comparative, multicenter study, a total of 305 T2DM patients who were either drug naïve or uncontrolled on metformin were randomized to glimepiride 1 or 2 mg/sustained-release metformin 1000 mg once daily (glimepiride group, n = 202) or sitagliptin 50 mg/metformin 500 mg twice daily (sitagliptin group, n = 103) for 12 weeks. Primary endpoint was change in glycosylated hemoglobin (HbA1c). Secondary endpoints were change in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), body mass index (BMI) and to assess overall safety profile. At 12 weeks, there was a statistically significant difference in the mean HbA1c reduction in glimepiride group (0.42%) as compared to sitagliptin group (0.30%) (P = 0.001). Mean reduction in FPG and PPG was also statistically significant in the glimepiride group as compared to the sitagliptin group (P = 0.008). There was no significant difference in terms of change in BMI (0.07 ± 0.39 kg/m2 vs. 0.08 ± 0.31 kg/m2) in glimepiride and sitagliptin groups, respectively, (P = 0.644) between both the groups. The incidences of hypoglycemic events were also comparable among both the groups. In T2DM patients, glimepiride/metformin combination exhibited significant reduction in glycemic parameters as compared to sitagliptin/metformin combination. Moreover, there was no significant difference between both the groups in terms of change in BMI and incidence of hypoglycemia.


Role of Gut Microbiome in COVID-19: An Insight Into Pathogenesis and Therapeutic Potential.
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an unprecedented global crisis. Although primarily a respiratory illness, dysregulated immune responses may lead to multi-organ dysfunction. Prior data showed that the resident microbial communities of gastrointestinal and respiratory tracts act as modulators of local and systemic inflammatory activity (the gut-lung axis). Evolving evidence now signals an alteration in the gut microbiome, brought upon either by cytokines from the infected respiratory tract or from direct infection of the gut, or both. Dysbiosis leads to a "leaky gut". The intestinal permeability then allows access to bacterial products and toxins into the circulatory system and further exacerbates the systemic inflammatory response. In this review, we discuss the available data related to the role of the gut microbiome in the development and progression of COVID-19. We provide mechanistic insights into early data with a focus on immunological crosstalk and the microbiome's potential as a biomarker and therapeutic target.


Structural and functional studies of the 252 kDa nucleoporin ELYS reveal distinct roles for its three tethered domains.
In metazoa, the nuclear envelope (NE), together with the embedded nuclear pore complexes (NPCs), breaks down and reassembles during cell division. It is suggested that ELYS, a nucleoporin, binds to chromatin in an initial step of postmitotic NPC assembly and subsequently recruits the essential Y-subcomplex, the major scaffolding unit of the NPC. Here, we show that ELYS contains three domains: an N-terminal β-propeller domain, a central α-helical domain, and a C-terminal disordered region. While the disordered region is responsible for the interactions with chromatin, the two preceding domains synergistically mediate tethering to the NPC. We present the crystal structure of the seven-bladed β-propeller domain at 1.9 Å resolution. Analysis of the β-propeller surface reveals the regions that are required for NPC anchorage. We discuss the possible roles of ELYS in the context of the NPC scaffold architecture.


Sex- and Brain Region-specific Changes in Gene Expression in Male and Female Rats as Consequences of Methamphetamine Self-administration and Abstinence.
Sex differences in METH use exist among human METH users and in animal models of METH addiction. Herein, we tried to identify potential differences in gene expression between female and male rats after Methamphetamine self-administration (METH SA). Rats were trained to self-administer METH using two 3-hours daily sessions for 20 days. Cue-induced drug seeking was measured on withdrawal days 3 (WD3) and 30 (WD30). Rats were euthanized twenty-four hours after WD30. Prefrontal cortex (PFC) and hippocampus (HIP) were dissected to measure mRNA expression. Both female and male rats increased their METH intake and showed increased METH seeking during withdrawal. Female had higher basal level expression of hypocretin receptor 1 (Hcrtr1) and prodynorphin (Pdyn) mRNAs in the PFC and HIP. Basal corticotropin releasing hormone receptor 1 (Crhr1), Crh receptor 2 (Crhr2), hypocretin receptor 2 (Hcrtr2) and opioid receptor kappa 1 (Oprk1) mRNA levels were higher in the PFC of females. Male rats had higher basal levels of Crh and Crhr1 in HIP. METH SA was associated with increased Crh and Crhr1 in the HIP of both sexes and Crhr2 only in female HIP. Importantly, increased Crh and Crhr1 mRNA levels correlated positively with incubation of METH craving in both sexes, supporting their potential involvement, in part, in the regulation of this behavioral phenomenon. When taken together, our results identified sexual dimorphic baseline differences in rats. We also detected dimorphic responses in animals that had self-administered METH. These observations highlight the importance of understanding the molecular neurobiology of sex differences when therapeutic interventions are planned against METH addiction.


Concealed antidromic re-entrance during rapid atrial pacing in the Wolff-Parkinson-White syndrome.
In a patient with Wolff-Parkinson-White syndrome, rapid atrial pacing up to rates of 140/min resulted in A-H prolongation; increases in rate up to 200/min, however, failed to lengthen A-H further. The delta-H interval increased as rate rose to 120/min, but remained stable thereafter. These and other findings suggest retrograde activation of the His bundle via the accessory pathway at rates greater than 140/min. Such a phenomenon: 1) prevents initiation of PSVT with atrial pacing; 2) prevents one from determining the anterograde block rate of the AV node; 3) represents concealed antidromic re-entrance, which may theoretically lead to antidromic re-entrant PSVT.


Post-migration geographical mobility, mental health and health service utilisation among Somali refugees in the UK: a qualitative study.
Migration is known to be associated with poor health outcomes for certain marginalised and socially disadvantaged populations. This paper reviews a number of reasons why residential mobility in the 'host' country may be associated with poor mental health for refugee populations and reports on a qualitative study of Somalis living in London, UK, and their beliefs about the relationship between residential mobility, poor health and health service use. Two discussion groups were undertaken with 13 Somali professionals and four groups with 21 lay Somalis in East and South London, UK. Lay Somalis did not wish to move accommodation but felt they were forced to move. Some Somali professionals believed that the nomadic history of Somalis made them more likely to elect to move in order to escape problems of living, but this was not supported by the lay group. Frequent geographical movements were seen as stressful and undesirable, disrupted family life and child development and were detrimental to well being. Residential mobility was also perceived to interfere with health care receipt and therefore should be more comprehensively assessed in larger quantitative studies.


(-)Epigallocatechin-gallate (EGCG) prevents mitochondrial damage in isoproterenol-induced cardiac toxicity in albino Wistar rats: a transmission electron microscopic and in vitro study.
Altered mitochondrial function and free radical-mediated tissue damage have been suggested as important pathological events in isoproterenol (ISO)-induced cardiotoxicity. This study was undertaken to know the preventive effect of (-)epigallocatechin-gallate (EGCG) on mitochondrial damage in ISO-induced cardiotoxicity in male Wistar rats. Rats were pretreated with EGCG (30 mg/kg) orally using an intragastric tube daily for a period of 21 days. After that, ISO (100mg/kg) was subcutaneously injected to rats at intervals of 24h for 2 days. ISO-induced rats showed significant increase in mitochondrial lipid peroxidation products (thiobarbituric acid reactive substances and lipid hydroperoxides) and significant decrease in mitochondrial antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and reduced glutathione). Also, significantly decreased activities of tricarboxylic acid cycle enzymes such as isocitrate, succinate, malate and alpha-ketoglutarate dehydrogenases and respiratory chain marker enzymes such as NADH-dehydrogenase and cytochrome-c-oxidase were observed in mitochondrial heart of myocardial infarcted rats. Prior treatment with EGCG (30mg/kg body weight) significantly prevented these alterations and restored normal mitochondrial function. Transmission electron microscopic findings also correlated with these biochemical parameters. In vitro studies on the effect of EGCG on scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS(+)), superoxide anion (O(-)), and hydroxyl (OH) radicals also confirmed the free radical scavenging and antioxidant activity of EGCG. Thus, the observed effects are due to the free radical scavenging and antioxidant potential of EGCG. Thus, this study confirmed the preventive effect of EGCG on isoproterenol-induced mitochondrial damage in experimentally induced myocardial infarction in Wistar rats.


[Polymorphisms associated with dental caries in pediatric populations: a systematic review].
Single nucleotide polymorphisms (SNPs) have been reported to play an important role in the etiology of dental caries. The aim of this research was, through a systematic review, to identify SNPs recently associated with dental caries in pediatric populations. We included studies performed in humans up to 18 years of age that evaluated the relationship between SNPs and dental caries from 2017 to 2022. Articles that covered other study variables were excluded. PubMed, ScienceDirect and Web of Science were used to search for information and the included articles were evaluated with one of the Joanna Briggs Institute's tools. Twenty-five articles were selected, 60% of which were given high methodological quality. A total of 10,743 research subjects, ranging in age from 20 months to 17 years, participated in the study. The SNPs considered risk factors were identified in the genes miRNA202, VDR, AMELX, TUFT1, KLK4, MBL2, ENAM, DEFB1, HLA-DRB1, TAS1R1, DSPP, RUNX2 and MMP13; those considered protective factors were identified in the genes MMP20, AMBN, MMP9, TIMP2, TNF-α, VDR, IL1B, ENAM and HLA-DRB1. This systematic review presents the genetic polymorphisms that are associated with the etiology of caries in children and adolescents, some of which act as risk factors and others as protective factors against the disease.


Triple quantum filtered spectroscopy of homonuclear three spin-1/2 systems employing isotropic mixing.
We report the design and performance evaluation of novel pulse sequences for triple quantum filtered spectroscopy in homonuclear three spin-1/2 systems, employing isotropic mixing (IM) to excite triple quantum coherence (TQC). Our approach involves the generation of combination single quantum coherences (cSQC) from antisymmetric longitudinal or transverse magnetization components employing isotropic mixing (IM). cSQC's are then converted to TQC by a selective 180° pulse on one of the spins. As IM ideally causes magnetization to evolve under the influence of the spin coupling Hamiltonian alone, TQC is generated at a faster rate compared to sequences involving free precession. This is expected to be significant when the spins have large relaxation rates. Our approach is demonstrated experimentally by TQC filtered 1D spectroscopy on a (1)H AX2 system (propargyl bromide in the presence of a paramagnetic additive), as well as a (31)P linear AMX system (ATP in agar gel). The performance of the IM-based sequences for TQC excitation are compared against the standard three pulse sequence (Ernst et al., 1987) and an AX2 spin pattern recognition sequence (Levitt and Ernst, 1983). The latter reaches the unitary bound on TQC preparation efficiency starting from thermal equilibrium in AX2 systems, not considering relaxation. It is shown that in systems where spins relax rapidly, the new IM-based sequences indeed perform significantly better than the above two known TQC excitation sequences, the sensitivity enhancement being especially pronounced in the case of the proton system investigated. An overview of the differences in relaxation behavior is presented for the different approaches. Applications are envisaged to Overhauser DNP experiments and to in vivo NMR.


Long microvenous allografts in rabbit femoral arteries and veins.
In this study the patency of long microvenous allografts in rabbits with and without immunosuppressive drug therapy was investigated. Eighty-two microvenous autografts (controls) and allografts were transplanted into rabbit femoral vessels. Veno-venous autograft controls were 100% patent at 3 weeks. Rejection of non-immunosuppressed veno-venous allografts consistently produced occlusion between 15-20 days. Thrombus filled the lumen, and a leucocyte invasion destroyed the graft wall. In contrast vein allografts into arteries were 100% patent at 3 weeks; this was reduced to 50% at 4 weeks. Low (5 mg/kg/day) and high (20 mg/kg/day) doses of hydrocortisone over 21 days improved the 3 week patency in veno-venous allografts to 28.5% and 57.0% respectively. Cyclosporin A (15 mg/kg/day) over 8 or 22 days significantly increased the patency rate of veno-venous allografts to 100%. Only cyclosporin A treated rabbits maintained allografts of normal vein morphology to 3 weeks.


STIM1 is a core trigger of airway smooth muscle remodeling and hyperresponsiveness in asthma.
Airway remodeling and airway hyperresponsiveness are central drivers of asthma severity. Airway remodeling is a structural change involving the dedifferentiation of airway smooth muscle (ASM) cells from a quiescent to a proliferative and secretory phenotype. Here, we show up-regulation of the endoplasmic reticulum Ca2+ sensor stromal-interacting molecule 1 (STIM1) in ASM of asthmatic mice. STIM1 is required for metabolic and transcriptional reprogramming that supports airway remodeling, including ASM proliferation, migration, secretion of cytokines and extracellular matrix, enhanced mitochondrial mass, and increased oxidative phosphorylation and glycolytic flux. Mechanistically, STIM1-mediated Ca2+ influx is critical for the activation of nuclear factor of activated T cells 4 and subsequent interleukin-6 secretion and transcription of pro-remodeling transcription factors, growth factors, surface receptors, and asthma-associated proteins. STIM1 drives airway hyperresponsiveness in asthmatic mice through enhanced frequency and amplitude of ASM cytosolic Ca2+ oscillations. Our data advocates for ASM STIM1 as a target for asthma therapy.


New high-yield synthesis of 18F-labelled 2-deoxy-2-fluoro-D-glucose.
A new high-yield synthesis for the production of 18F-2-FDG has been developed by reacting 18F-labelled acetyl hypofluorite, prepared by in situ reaction of 18F-molecular fluorine with sodium acetate in glacial acetic acid, and tri-acetyl-D-glucal at room temperature. Molecular fluorine labelled with 18F was produced by a 20Ne(d, alpha) 18F reaction. 1,3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-D-glucopyranose is extracted with methylene chloride, evaporated to dryness and hydrolyzed, yielding 98% radiochemically pure 18F-2-FDG. Overall radiochemical yield is about 24 +/- 3%. The specific activity of the final product at the end of synthesis is about 25.38 GBq/mmol (685 mCi/mmol). The synthesis time is approximately 60 min. The synthesis proves that small medical cyclotrons are able to produce 18F-molecular fluorine at the levels needed for the synthesis of 18F-2-FDG used in functional imaging with positron emission tomography.


Glutamatergic postsynaptic block by Pamphobeteus spider venoms in crayfish.
The effects of toxins from venom glands of two south american spiders (Pamphobeteus platyomma and P. soracabae) on glutamatergic excitatory synaptic transmission were studied in the neuromuscular junction of the opener muscle of crayfish. The toxins selectively and reversibly blocked both excitatory postsynaptic currents and potentials in a dose-dependent manner. They also reversibly abolished glutamate-induced postsynaptic membrane depolarization. They had no effect on resting postsynaptic membrane conductance nor on postsynaptic voltage-gated currents. The synaptic facilitation and the frequency of miniature postsynaptic potentials were unaffected by the toxins, indicating that presynaptic events were not modified. Picrotoxin, a selective antagonist of the gamma-aminobutyric acid (GABA)A receptor, did not modify toxin effects. We conclude that both toxins specifically block the postsynaptic glutamate receptor-channel complex.