The prognostic value of Kirsten rat sarcoma viral oncogene homolog mutations in resected lung adenocarcinoma differs according to clinical features.
The ninth edition of lung cancer staging system recommends that specific driver mutations should be considered as prognostic factors in survival models. This study comprehensively investigated the prognostic value of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in patients with resected lung adenocarcinomas according to different clinicopathologic and radiologic characteristics. In total, 1464 patients with completely resected primary lung adenocarcinomas were examined for KRAS mutations from November 2008 to March 2015. Age, sex, smoking status, performance status, tumor-node-metastasis stage, radiologic features, and histologic subtypes were collected. Competing risk model was used to estimate the cumulative incidence rate of recurrence. Cox regression multivariable analyses on recurrence-free survival (RFS) and overall survival (OS) were performed. KRAS mutations were more frequent in male subjects (P < .001), current/former smokers (P < .001), invasive mucinous adenocarcinoma (P < .001), and solid tumors (P < .001). In general, KRAS-mutated patients had greater cumulative recurrence rate (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.23-3.08; P < .001) and worse overall survival (OS; HR, 1.88; 95% CI, 1.23-2.87; P < .001) than KRAS wild-type patients. The OS (P < .001) of patients harboring KRAS-G12C/V mutations was shorter than that of other KRAS-mutated patients. Cox multivariable analyses demonstrated that KRAS mutations were independently associated with worse RFS (HR, 5.34; 95% CI, 2.53-11.89; P = .001) and OS (HR, 2.63; 95% CI, 1.03-6.76; P = .044) in part-solid lung adenocarcinomas. For stage I patients, Cox multivariable analyses revealed that KRAS mutation was an independent risk factor for RFS (HR, 2.05; 95% CI, 1.19-3.56; P = .010) and OS (HR, 2.38; 95% CI, 1.29-4.40; P = .005). In this study, we revealed that KRAS mutations was an independent prognostic factor in part-solid tumors and in stage I lung adenocarcinomas. These findings may contribute to the ninth edition of lung cancer staging project.


Time-course of left atrial performance during coronary artery occlusion followed by reperfusion in anesthetized dogs by densitometric analysis of digital atrioventriculographic images.
The left atrial (LA) function during coronary artery occlusion followed by reperfusion using densitometric analysis of digital atrioventriculographic images was evaluated. Eight anesthetized dogs underwent atrioventriculography at baseline, 10 and 60 min after left circumflex coronary artery (LCX) occlusion and 5, 30, 60, and 120 min of reperfusion. Time-density curves were obtained for LA and left ventricle (LV). The ratios of passive atrial video-densitometric change (VC) to total VC (Passive Ratio), and active VC to total VC (Active Ratio) were calculated. Left ventricular ejection fraction (LVEF), peak ejection rate (PER), and peak filling rate (PFR) were derived. Active Ratio, an index of atrial contraction, increased to 144%, and Passive Ratio decreased to 75% of baseline at 60 min of LCX occlusion. Two hours after reperfusion, both Active and Passive Ratios returned to control level. While LVEF reduced to 70%, PER to 67%, LV peak positive dP/dt to 88% of baseline at 60 min after occlusion, and remained depressed at 2 h after reperfusion. However, PFR, LV peak negative dP/dt and LV isovolumic pressure decay rate showed recovery at 2 h after reperfusion. There were significant correlations between PFR and Passive Ratio (r = 0.41), and between Active and Passive Ratios (r = 0.55). Thus, time-course of recovery of LV post-ischemic systolic and diastolic function was different. Return of LA function to control level during 2 h after reperfusion may be depend on recovery of LV diastolic function.


Carcinomatosis is not a contraindication to enteral stenting in selected patients with malignant gastric outlet obstruction.
Endoscopically inserted self-expandable metal stents (SEMSs) are used to palliate malignant gastric outlet obstruction (GOO). Peritoneal disease is considered a relative contraindication to SEMS placement given the risk of multifocal obstruction. To evaluate the success of SEMSs placed in patients with GOO with carcinomatosis. Retrospective review of patients who underwent SEMS placement for malignant GOO. Large, urban cancer center. A total of 215 patients who were scheduled for SEMS placement for GOO. SEMS placement. Technical success, clinical success, early and late SEMS failure, and complications. Technical success was achieved in 192 of 201 patients (95.5%). Of the 9 patients who did not achieve technical success, 6 had carcinomatosis. Among the 116 patients (60%) with carcinomatosis, clinical success was achieved 94 of them (81%). Of these 94 patients, 17 (18%) required reinterventions: 4 for early SEMS failure and 13 for late SEMS failure. Among the 76 patients (40%) without carcinomatosis, clinical success was achieved in 64 of them (84%). Of these 64 patients, 17 (27%) required reinterventions: 4 for early SEMS failure and 13 for late SEMS failure. Complication rates were similar for both groups. This was a retrospective review with experienced clinicians selecting patients whom they thought would benefit from SEMS placement. This is the first study to evaluate the effect of carcinomatosis on the technical and clinical success of SEMSs in the palliation of malignant GOO. We found clinical outcomes comparable to those without peritoneal disease. Carcinomatosis should not be considered a contraindication to SEMS placement in selected patients with malignant GOO.


Permanent His Bundle Pacing: A programming and troubleshooting guide.
Permanent His Bundle Pacing (HBP) has recently gained popularity. However, implanting physicians and those who perform the device checks must invest in additional education in order to accurately program these devices, identify changes in morphology and perform troubleshooting to help achieve the best outcomes for the patients. This paper reviews key aspects of HBP and provides the educational tools for successful HBP follow-up and troubleshooting.


Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA.
We have developed an individualized melanoma vaccine based on transfection of autologous dendritic cells (DCs) with autologous tumor-mRNA. Dendritic cells loaded with complete tumor-mRNA may generate an immune response against a broad repertoire of antigens, including unique patient-specific antigens. The purpose of the present phase I/II trial was to evaluate the feasibility and safety of the vaccine, and the ability of the DCs to elicit T-cell responses in melanoma patients. Further, we compared intradermal (i.d.) and intranodal (i.n.) vaccine administration. Twenty-two patients with advanced malignant melanoma were included, each receiving four weekly vaccines. Monocyte-derived DCs were transfected with tumor-mRNA by electroporation, matured and cryopreserved. We obtained successful vaccine production for all patients elected. No serious adverse effects were observed. A vaccine-specific immune response was demonstrated in 9/19 patients evaluable by T-cell assays (T-cell proliferation/interferon-gamma ELISPOT) and in 8/18 patients evaluable by delayed-type hypersensitivity (DTH) reaction. The response was demonstrated in 7/10 patients vaccinated intradermally and in 3/12 patients vaccinated intranodally. We conclude that immuno-gene-therapy with the described DC-vaccine is feasible and safe, and that the vaccine can elicit in vivo T-cell responses against antigens encoded by the transfected tumor-mRNA. The response rates do not suggest an advantage in applying i.n. vaccination.


[Is it possible to treat obesity in children and adolescents?].
The question of whether or not treatment of obesity in children and adolescents is possible, feasible, or effective cannot be answered at the present time. Obesity is the most common chronic disorder in the industrialized societies. Its impact on individual lives as well as on health economics has to be recognized by physicians and the public alike: obesity at a young age is a major burden for the economy. Huge sums of money are thought to be spent on diet foods, products, and programs to lose weight. Treatments aim to reduce weight and as a consequence cardiovascular risks and other comorbidities. By doing so, economic costs could also substantially be reduced. In addition and most importantly, for the individual the impact of a given treatment on quality of life and social participation might be even more important than the medical benefit as such: especially since children and adolescents very often cannot estimate the medical burden of long-term sequelae of their obesity. Apart from individual therapies, interventions on a population base might be more cost effective and more important. However, the effectiveness of such interventions should also be assessed prospectively and continuously.


Artificial gravity with ergometric exercise can prevent enhancement of popliteal vein compliance due to 4-day head-down bed rest.
Changes of venous compliance may contribute in part to postflight orthostatic intolerance. The purpose of the present study was to determine whether intermittent artificial gravity exposure with ergometric exercise could prevent venous compliance changes in the lower limbs due to simulated weightlessness. Twelve healthy male volunteers were exposed to simulated microgravity for 4 days of head-down bed rest (HDBR). Six subjects were randomly loaded 1.0-2.0 Gz intermittent artificial gravity (at foot level) with 40 W of ergometric workload every day (countermeasure group, CM). The six others served as the control (CON group). Venous compliance was estimated by measuring the corresponding change of cross-sectional area (CSA) of popliteal vein at each minute of various venous occlusion pressure stages. Basal CSA was significantly lower after bed rest in the control group, and preserved in the countermeasure group. The percent increase in the CSA of CON group was significantly greater almost at each minute of various venous cuff pressures after bed rest than before. Compliance of popliteal vein of CON group was significant greater when 40, 60 and 80 mmHg cuff pressure applied after bed rest than before of CON group. In conclusions, a 4-day simulated weightlessness leads to increase of popliteal venous compliance; centrifuge-induced artificial gravity with ergometric exercise can prevent enhancement of popliteal venous compliance due to 4-day head-down tilt bed rest, the effect of the countermeasure on compliance might involve changes in venous filling and changes in venous structure.


Biomimetic conversion of (-)-fusoxypyridone and (-)-oxysporidinone to (-)-sambutoxin: further evidence for the structure of the tricyclic pyridone alkaloid, (-)-fusoxypyridone.
Biomimetic-type reactions of the tricyclic pyridone alkaloid, (-)-fusoxypyridone [(-)-4,6'-anhydrooxysporidinone] (1), recently encountered in an endophytic strain of Fusarium oxysporum, and (-)-oxysporidinone (2) afforded (-)-sambutoxin (3) and an analogue of 1, identified as (-)-1'(6')-dehydro-4,6'-anhydrooxysporidinone (4), thus confirming the structure previously proposed for 1 and suggesting that 1-3 bear the same relative stereochemistry. Oxidation of 4 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) yielded a hitherto unknown sambutoxin analogue, (-)-4,2'-anhydrosambutoxin (5).


The effect of dexamethasone on the functioning of C3 receptor sites on the surfaces of human fibroblasts.
The presence of C3 receptor sites on the cell surfaces of WI-38 fibroblasts was reported in a previous paper. Here the effect of dexamethasone sodium sulfate of C3 receptor site function was studied. The incubation of WI-38 fibroblasts with dexamethasone sodium sulfate produces the biphasic mode of action, i.e., the growth-stimulating phase with low doses (90--230 mug/ml) and the growth-inhibiting phase with high doses (450--900 mug/ml). The function of C3 receptor sites on WI-38 fibroblasts seems to be very stable and cannot be suppressed by the pretreatment of WI-38 fibroblasts with dexamethasone in high concentrations, where the cell growth is inhibited.


In vivo effects of fluoride on enamel permeability.
This in vivo study evaluated the effects of topical fluoride application on enamel by repeated scanning electron microscopy analysis of replicas. Baseline fluid droplets were employed as qualitative indication of enamel permeability. CaF(2)-like globules were detected in vivo after fluoride application and were not found after professional brushing, ultrasound action, or chemical extraction. Absence of water permeability of enamel was demonstrated even after removal of CaF(2)-like globules. Droplets reappeared within 1 h in sodium fluoride-treated teeth, but they did not reappear even after 1 week following topical enamel treatment with acidulated phosphate fluoride. Teeth treated with an acidulate fluoride-free solution showed lack of CaF(2)-like globules and no droplets for at least 1 week as detected in acidulate phosphate fluoride-treated teeth. The caries-preventing action of fluoride may be due to its ability to decrease permeability and diffusion pathways. CaF(2)-like globules seem to be indirectly involved in enamel protection over time maintaining an impermeable barrier, and phosphoric acid seemed to play an unexpected fluoride-independent preventive role.


[Functional diagnostic options for advanced and end stage glaucoma].
The visual functional diagnostics for patients with advanced glaucomatous optic neuropathy are subject to challenge. Reduced visual acuity, instable fixation and extensive scotomata frequently lead to incorrect results within the central 30° or 24° field. Static automatic perimetry (SAP) in particular is often hampered by extended examination time and fatigue especially in older patients. Focusing of the examination towards the central 10° field using a dense test grid (2° distance between stimulus locations) allows a more exact assessment of the small remaining central island. Tailoring the examination area towards the central 10° field may be useful even in cases with a mean deviation (MD) of 15 dB. In cases of advanced visual field loss kinetic perimetry is superior to static perimetry for various reasons: sharply demarcated visual field defects can be comparatively easily delineated (edge detection); the results are more reliable because fixation can be easily controlled and fatigue is much less pronounced in this interactive examination procedure. However, manual kinetic visual field testing within the central 5° using the conventional Goldmann perimeter is almost impossible due to technical reasons. Semi-automated kinetic perimetry, presenting moving stimuli along interactively defined vectors is a useful tool under these circumstances. The standardized presentation of kinetic stimuli is also feasible within the pericentral region and has particular advantages also with regard to follow-up examinations. On the other hand, detection and delineation of small visual field remnants are comparatively difficult to handle with this kind of vector-based kinetic perimetry.


Video-based eye tracking performance for computer-assisted diagnostic support of diabetic neuropathy.
Diabetes is currently one of the major public health threats. The essential components for effective treatment of diabetes include early diagnosis and regular monitoring. However, health-care providers are often short of human resources to closely monitor populations at risk. In this work, a video-based eye-tracking method is proposed as a low-cost alternative for detection of diabetic neuropathy. The method is based on the tracking of the eye-trajectories recorded on videos while the subject follows a target on a screen, forcing saccadic movements. Upon extraction of the eye trajectories, representation of the obtained time-series is made with the help of heteroscedastic ARX (H-ARX) models, which capture the dynamics and latency on the subject's response, while features based on the H-ARX model's predictive ability are subsequently used for classification. The methodology is evaluated on a population constituted by 11 control and 20 insulin-treated diabetic individuals suffering from diverse diabetic complications including neuropathy and retinopathy. Results show significant differences on latency and eye movement precision between the populations of control subjects and diabetics, while simultaneously demonstrating that both groups can be classified with an accuracy of 95%. Although this study is limited by the small sample size, the results align with other findings in the literature and encourage further research.


Asymmetry in parkinsonism, spreading pathogens and the nose.
Parkinson's disease, as well as many other parkinsonisms, including most toxic, neurodegenerative and familial types are typically asymmetric. No explanation for this phenomenon exists. A summary of the frequency of asymmetry in a spectrum of parkinsonian disorders is provided. Evidence against asymmetry being the result of normal asymmetries of the substantia nigrais reviewed. Asymmetry either results from a greater susceptibility on one side or a spreading pathology entering or starting on one side of the CNS. With the increasing evidence for spreading pathologies (toxins, viruses, α-synuclein), knowledge of neuroanatomical connections, and literature implicating spreading pathogens from the enteric and olfactory nerves, potential explanations can be theorized and explored, including the possibility of a pathogen preferentially entering or originating in the olfactory bulb on one side, with subsequent involvement of the other side.


Phagocytic function in the isolated perfused rat liver. An experimental model.
An experimental model for measuring the phagocytic function of the isolated perfused rat liver is described. A progressive rise in phagocytosis was observed with increasing liver blood flow. This is due to an increase in total particle uptake by the liver with no alteration in the rate constant for phagocytosis except at the highest flow rate. Phagocytosis is substantially greater in the livers of 100-day-old rats than in 21-day-old rats, but the number of particles ingested per unit weight by the older rats is significantly less. Liver phagocytosis is shown to be both temperature- and oxygen-dependent, but independent of nutritional status and animal gender. This model may be useful for assessing the effects of drugs and toxins on hepatic phagocytosis.


Involvement of glucocorticoid receptor activation on anti-inflammatory effect induced by peroxisome proliferator-activated receptor γ agonist in mice.
Glucocorticoids are effective anti-inflammatory agents widely used for the treatment of acute and chronic inflammatory diseases. Recent in vitro studies have proposed that glucocorticoid receptor (GR) activation is involved in peroxisome proliferator-activated receptor γ (PPARγ) agonist-induced effects. In this study, to examine the involvement of the GR in PPARγ agonist- and retinoid X receptor (RXR) agonist-mediated anti-inflammatory effects in vivo, we tested the anti-inflammatory effects of dexamethasone (a GR agonist) with pioglitazone (a PPARγ agonist) or 6-[N-ethyl-N-(3-isopropoxy-4-isopropylphenyl)-amino] nicotinic acid (NEt-3IP; an RXR agonist) by using an experimental model of carrageenan-induced inflammation. We also evaluated the effects of a GR antagonist on PPARγ agonist- or RXR agonist-induced anti-inflammatory effects. Results showed that the GR antagonist RU486 reduced the anti-inflammatory effects of GR or PPARγ agonists but not those of the RXR agonist. In addition, combinations of GR and PPARγ agonists or GR and RXR agonists had no effect on carrageenan-induced paw edema. Moreover, the PPARγ antagonist GW9662 and RXR antagonist 6-[N-4-(trifluoromethyl)-benzenesulfonyl-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-amino] nicotinic acid (NS-4TF) had no effect on the anti-inflammatory effect of the GR agonist dexamethasone. Therefore, it is suggested that GR activation in vivo does not play a direct role in PPARγ/RXR heterodimer signaling. In contrast, pioglitazone showed a partial anti-inflammatory effect via GR activation. These data provide evidence for the pro-inflammatory activity of pioglitazone.


Two bootstrapping routines for obtaining imprecision estimates for nonparametric parameter distributions in nonlinear mixed effects models.
When parameter estimates are used in predictions or decisions, it is important to consider the magnitude of imprecision associated with the estimation. Such imprecision estimates are, however, presently lacking for nonparametric algorithms intended for nonlinear mixed effects models. The objective of this study was to develop resampling-based methods for estimating imprecision in nonparametric distribution (NPD) estimates obtained in NONMEM. A one-compartment PK model was used to simulate datasets for which the random effect of clearance conformed to a (i) normal (ii) bimodal and (iii) heavy-tailed underlying distributional shapes. Re-estimation was conducted assuming normality under FOCE, and NPDs were estimated sequential to this step. Imprecision in the NPD was then estimated by means of two different resampling procedures. The first (full) method relies on bootstrap sampling from the raw data and a re-estimation of both the preceding parametric (FOCE) and the nonparametric step. The second (simplified) method relies on bootstrap sampling of individual nonparametric probability distributions. Nonparametric 95% confidence intervals (95% CIs) were obtained and mean errors (MEs) of the 95% CI width were computed. Standard errors (SEs) of nonparametric population estimates were obtained using the simplified method and evaluated through 100 stochastic simulations followed by estimations (SSEs). Both methods were successfully implemented to provide imprecision estimates for NPDs. The imprecision estimates adequately reflected the reference imprecision in all distributional cases and regardless of the numbers of individuals in the original data. Relative MEs of the 95% CI width of CL marginal density when original data contained 200 individuals were equal to: (i) -22 and -12%, (ii) -22 and -9%, (iii) -13 and -5% for the full and simplified (n = 100), respectively. SEs derived from the simplified method were consistent with the ones obtained from 100 SSEs. In conclusion, two novel bootstrapping methods intended for nonparametric estimation methods are proposed. In addition of providing information about the precision of nonparametric parameter estimates, they can serve as diagnostic tools for the detection of misspecified parameter distributions.


Alcohol intake in the healthy elderly. Changes with age in a cross-sectional and longitudinal study.
Several cross-sectional studies have shown a decline in alcohol intake with increasing age. Longitudinal studies have failed to confirm this trend, which suggests that cohort effects may account for the reported decline. To address this, both cross-sectional and longitudinal analyses of alcohol use in 270 healthy elderly persons over a seven-year period (1980-1987) were performed. Alcohol consumption was assessed by three-day diet records. One hundred sixty-five subjects (61.1%) remained in the study until 1987; 143 (53%) completed diet records for every year. Longitudinal analysis showed a statistically significant decline in the percent of subjects consuming any alcohol over time (slope = -2% per year; 95% confidence interval -2.8, -1.1%). A cross-sectional analysis of the 1980 data revealed a similar decline in percent drinkers with increasing age (slope = -2.7% per year; 95% confidence interval -4.4, -1.1%). Mean alcohol intake for those who continued to drink did not change over time except among heavy drinkers (consumption of greater than 30 g per day in 1980), who did show a significant decline in mean alcohol intake (P = .02). Thus, in our population the decline in percent of drinkers with age found by a cross-sectional analysis was confirmed in longitudinal analyses, suggesting that this represents a true age-related decline rather than a cohort effect.


Repressive adaptive style and self-reported psychological functioning in adolescent cancer survivors.
Low levels of posttraumatic stress disorder (PTSD), posttraumatic stress symptoms (PTSS), and psychosocial distress have been reported in pediatric cancer survivors. One explanation is the relatively high prevalence of the repressive adaptive style (low distress, high restraint) in this population. We investigated the relationship between this adaptive style and PTSD, PTSS, and psychosocial functioning in 29 adolescent cancer survivors (12 through 18 years). Adolescents categorized as repressors (n = 14) reported moderate/large effect size differences in PTSD, PTSS, and psychosocial distress (lower) as well as QOL (better) compared to non-repressors. Furthermore, repressors reported less PTSD and QOL variability. Thus, the repressive adaptive style, pronounced in this population, may obscure systematic and clinically meaningful adaptive style group differences across psychological measures.


Leptin gene polymorphisms and their phenotypic associations.
In an era of rapidly increasing prevalence of human obesity and associated health problems, leptin gene polymorphisms have drawn much attention in biomedical research. Leptin gene polymorphisms have furthermore drawn much attention from animal scientists for their possible roles in economically important production and reproduction traits. Of the polymorphisms reported for exonic, intronic, and promoter regions of the leptin gene, 16 have been included in association studies in humans, 19 in cattle, and 6 (all exonic or intronic) in pigs. In humans, associations have been found with overweight or (early-onset) obesity, non-insulin-dependent diabetes mellitus, prostate cancer, and non-Hodgkin's lymphoma. In cattle, associations have been found with feed intake, milk yield traits, carcass traits, and reproduction-related traits, and in pigs with feed intake, average daily gain, carcass traits (backfat/leanness), and reproduction performance traits. Many of the polymorphisms were only included in a limited number of association studies, or the phenotypes studied varied largely for a given polymorphism between studies. Therefore, many of the associations found for these polymorphisms need to be confirmed in future studies before firm conclusions can be drawn.


High density polyethylene/graphite nano-composites for total hip joint replacements: processing and in vitro characterization.
The main objective of the present study is to investigate how the thermal, rheological, mechanical and cytotoxicity behavior of High Density Polyethylene (HDPE) can be changed by the addition of graphite nano particles (GNPs) at different contents. The HDPE/GNPs composites were prepared using melt blending in a co-rotating intermeshing twin screw extruder. The in vitro tests results showed that the original material (HDPE) and all HDPE/GNPs composites do not exhibit any cytotoxicity to the WISH cell line. The microscopic examination of the nano-composite tensile-fractured surface found a good distribution of GNPs in the HDPE matrix. The Differential Scanning Calorimetry (DSC) results indicated that the crystallization percentage increased by adding GNPs to HDPE up to 4%. The XRD patterns of the HDPE/GNPs composites showed an increase in peak intensity compared to neat HDPE. This increase echoed the crystallinity results obtained from DSC. The rheological tests showed that the complex viscosity of the HDPE increased as the percentage of GNPs increased due to the restriction of the molecular mobility. The tensile test results showed that with increasing the GNPs content, Young's modulus and the yield strength of the HDPE/GNPs composite increased while the strain at fracture decreased. Finally, the preliminary results of the abrasion test indicated that the abrasion rate decreased by increasing the GNPs ratio up to 4% content. The prepared HDPE/GNPs composites appear to have fairly good comprehensive properties that make them a good candidate as a bearing material for the total joint replacement.


A history of Guy's, King's and St. Thomas' hospitals from 1649 to 2009: 360 years of innovation in science and surgery.
Much has been achieved in the scientific and surgical fields over the last 360 years. Some institutions have contributed disproportionately to these advances. The medical schools and hospitals of Guy's (est. 1721), King's (est. 1840) and St. Thomas' (est. 1173) seem to provide a focus and a catalyst for much innovation and creativity dating back to 1608. This review sets to provide an overview of the major contributors to surgical advances at these institutions over the last 360 years and what factors affected unique to these institutions contributed to the climate of discovery. It is based on a lecture given to the Osler Club of London (est. 1928) at the Royal College of Physicians in London on 4 November 2010. It is the author's premise that the people and the discoveries they made within these institutions within three square miles of London changed the practice and understanding of science and healthcare as we know it today.


Gonadotropin stimulation using P.G. 600® on reproductive success of non-lactating anestrous ewes.
The effect of stimulation with a gonadotropin preparation with combined follicle stimulating and luteininzing hormone like activity on reproductive success in anestrous ewes was evaluated. In Experiment 1, ewes of mixed breeding were treated with CIDR inserts (0.3g progesterone) for 5 days and were assigned randomly to receive either gonadotropin stimulation (3mL i.m. injection of P.G. 600®, 240IU eCG and 120IU hCG) at CIDR removal or no further treatment. Intact raddled rams were joined at insert removal for 30-35 days, and ewes were observed for indications of estrus after 4 days of ram exposure. Pregnancy diagnosis was conducted via transrectal ultrasonography at the time of ram removal and again 20-25 days. The second experiment was similar to Experiment 1, except treated ewes received the gonadotropin 1 day prior to insert removal. In Experiment 1, incidence of estrus was greater for treated ewes (P=0.01), and prolificacy tended to be greater in treated ewes (P=0.06). In Experiment 2, treated ewes had greater conception rates (P=0.01), pregnancy rates to first service (P=0.0007), and tended to have greater overall pregnancy rates than control ewes (P=0.07). A greater percentage of ewes lambed in the gonadotropin treated ewes than in ewes in the control group (P<0.0001), and overall lambing rates in treated ewes were greater than non-treated controls (P<0.0001). In conclusion, gonadotropin treatment 1 day prior to CIDR removal increased reproductive success in progesterone-treated anestrous ewes.


Changes in cognitive functions and quality of life in patients after transcatheter aortic valve implantation.
Transcatheter aortic valve implantation (TAVI) has emerged as a therapeutic option for patients with severe aortic stenosis (AS). However, an association between cognitive functions (CF) and health-related quality of life (HRQoL) in TAVI patients is still unclear. To assess the long-term changes in CF and HRQoL in elderly patients with AS after TAVI. A total of 259 patients who underwent cardiological and psychological TAVI qualification were enrolled and divided into the normal (n = 174) and impaired cognition group (n = 85). CF and HRQoL characteristics assessed at baseline and 13 months were compared between groups. The analysis of multiple linear regression was performed to identify the association between HRQoL and CF and to assess the influence of TAVI on HRQoL. There was no difference in CF between baseline and follow-up. However, an improvement in attention functions and memory skills in the cognitively impaired group was noted at follow-up. In addition, HRQoL scores increased in both groups. An independent predictor associated with HRQoL was global CF (β = -213, p = 0.01), which explained 7% of CF variation. Improvements in all five dimensions of HRQoL, from 4.8% in self-care and up to 33.6% in pain/discomfort, were found. At follow-up, 60% of TAVI patients had improved health, 12% had worse health, 4% showed no change and 24% had a "mixed" change. TAVI is associated with positive changes in the functioning of elderly patients at long-term follow-up.


Purification and properties of tuberculin-active protein from Mycobacterium tuberculosis.
When Mycobacterium tuberculosis was grown on Sauton medium, intracellular tuberculin-active protein was produced. This product was purified by chromatography on DEAE-cellulose and Sephadex G-200 and was obtained in crystalline form. The crystals were plates, somewhat irregular in shape, about 50 mum in length and 25 mum in width. The yield corresponded to a 1.5% over-all recovery of total protein. Ultracentrifugal analysis showed only one major component with a calculated molecular weight of 9700. Sedimentation velocity analysis gave a sedimentation coefficient at 20 degrees (see article) of 1.73 S. The estimated specific activities of tuberculin-active protein were 6.33 times 10-9 tuberculin units per mg of protein-nitrogen for sensitized guinea pigs and 6.33 times 10-11 tuberculin units per mg of protein-nitrogen for humans. This is the most potent tuberculin-active protein that has yet been obtained.


Fractionation and comparison of proteins from bovine uterine fluid and bovine allantoic fluid.
Serum, allantoic fluid and uterine washings obtained from cows at various stages of pregnancy were fractionated by gel filtration and the fractions compared by electrophoretic and immunological methods. Several proteins were detected in uterine washings which were not found in serum. Some of these proteins were sensitive to the experimental conditions used for concentrating the uterine washings, being irreversibly adsorbed onto the glass containers on freeze drying. The number and imtensity of the "uterine-specific" proteins varied with the stage of pregnancy, changes in the electrophoretic patterns being detected just prior to rapid elongation of the embryo and at a stage when luteolysis would have occurred in the unmated cow. Many of the "uterine-specific" proteins were also detected in allantoic fluid.


Utility of magnetic resonance imaging in the evaluation of patients with ST segment elevation on an electrocardiogram.
ST segment elevation is an important electrocardiographic (ECG) change that is typically found in acute myocardial infarction, but may also be seen in a variety of other conditions. MRI plays an important role in the evaluation of these patients. MRI not only establishes the diagnosis, which is essential for appropriate management, but also helps in the assessment of other factors that are important for risk stratification. In this review, we discuss the common and uncommon causes of ST segment elevation and the role of MRI in the evaluation of these disease processes.


GPR37 is processed in the N-terminal ectodomain by ADAM10 and furin.
GPR37 is an orphan G protein-coupled receptor (GPCR) implicated in several neurological diseases and important physiological pathways in the brain. We previously reported that its long N-terminal ectodomain undergoes constitutive metalloprotease-mediated cleavage and shedding, which have been rarely described for class A GPCRs. Here, we demonstrate that the protease that cleaves GPR37 at Glu167↓Gln168 is a disintegrin and metalloprotease 10 (ADAM10). This was achieved by employing selective inhibition, RNAi-mediated downregulation, and genetic depletion of ADAM10 in cultured cells as well as in vitro cleavage of the purified receptor with recombinant ADAM10. In addition, the cleavage was restored in ADAM10 knockout cells by overexpression of the wild type but not the inactive mutant ADAM10. Finally, postnatal conditional depletion of ADAM10 in mouse neuronal cells was found to reduce cleavage of the endogenous receptor in the brain cortex and hippocampus, confirming the physiological relevance of ADAM10 as a GPR37 sheddase. Additionally, we discovered that the receptor is subject to another cleavage step in cultured cells. Using site-directed mutagenesis, the site (Arg54↓Asp55) was localized to a highly conserved region at the distal end of the ectodomain that contains a recognition site for the proprotein convertase furin. The cleavage by furin was confirmed by using furin-deficient human colon carcinoma LoVo cells and proprotein convertase inhibitors. GPR37 is thus the first multispanning membrane protein that has been validated as an ADAM10 substrate and the first GPCR that is processed by both furin and ADAM10. The unconventional N-terminal processing may represent an important regulatory element for GPR37.


Flow field of a novel implantable valveless counterpulsation heart assist device.
Flow fields are one of the key factors associated with the life threatening formation of thrombi in artificial organs. Therefore, knowledge of flow field is crucial for the design and optimization of a long-term blood pump performance. The blood chamber flow of a novel counterpulsation heart assist device (CPD) has been investigated using laser Doppler velocimetry (LDV), particle image velocimetry (PIV), and near-wall PIV (wall-PIV). The wall-PIV is an in-house developed technique assessing wall shear rates (WSR). These experimental techniques analyzed complex transient three-dimensional (3D) flow fields including major and secondary structures during the whole CPD cycle (ejection, filling, and hold time). PIV measurements in the central plane investigated an evolution (development and destruction) of the blood chamber fully filling vortex as the major CPD flow structure. The wall-PIV measurements identified areas of blood stagnation (vortex center and jet impingements) and quantified WSR at the front housing. Maximal mean WSR of 2,045 ± 605 s(-1) were found at the end of the filling. The LDV, which identified helical flow structure at the outer region of the pump, was used to complete 3D flow analysis and to combine PIV and wall-PIV results. The results suggest good washing behavior of the CPD regarding thrombus formation.


Producing single-stranded DNA probes with the Taq DNA polymerase: a high yield protocol.
We report an efficient procedure to synthesize either single- or double-stranded probes labeled with biotin-11-dUTP, biotin-21-dUTP or digoxigenin-11-dUTP. To produce the single-stranded probe, only a single primer is utilized in a Taq polymerase amplification of 55 cycles. A cytomegalovirus probe is presented. This procedure allows easy production of nonradioactively labeled pure single-stranded probes of any desired length and specificity.


Rapid fingerprinting of extractable and non-extractable polyphenols from tropical fruit peels using direct analysis in real time coupled to orbitrap mass spectrometry.
A simple and rapid direct analysis in real-time coupled to high-resolution mass spectrometry (DART-HRMS) methodology was developed to generate the extractable and non-extractable polyphenols (NEPs) fingerprint for four different passion fruits, G. mangostana, and A. squamosa peels as case-study to investigate the influence of alkaline hydrolysis and enzymatic-assisted extraction (EAE) on the recovery of NEPs. The extraction residue obtained after these treatments was also analyzed by DART-HRMS. Data compiled from DART-HRMS mass spectra were processed with principal component analysis to discriminate among the different treatments. EAE with Depol enzyme enabled to obtain NEPs with the highest signal intensity in DART-HRMS analysis from all peels except for P. edulis and A. squamosa peels. In these two cases, NEPs were better extracted by EAE with Promod enzyme and alkaline hydrolysis. Results showed that the applied treatments were efficient to extract NEPs since their signal intensities in the extraction residues were very low compared with their extracts.


The hidden cost of following currents: Microplastic ingestion in a planktivorous seabird.
Microplastics are increasingly pervasive pollutants, particularly abundant in the neuston where they drift with currents. We assessed dietary microplastic ingestion in the Mediterranean storm petrel (Hydrobates pelagicus melitensis), a small pelagic seabird that forages on plankton and inhabit the Mediterranean sea, one of the most polluted seas worldwide. We collected spontaneous regurgitates from 30 chick-rearing individuals and used GPS tracking data from 7 additional individuals to locate foraging areas. Birds foraged in pelagic areas characterized by water stirring and mixing, and regurgitates from 14 individuals (i.e. 45 %) contained microplastics. Fibers were the dominant shape (56 %), with polyester, polyethylene and nylon being the most frequent polymers. Our findings highlight the potential sensitivity of this species of conservation interest to plastic pollution and suggest that storm petrel regurgitates can be a valuable matrix to investigate microplastic ingestion in planktonic foragers, providing a characterization of spatio-temporal patterns of microplastic exposure in pelagic environments.


Potassium and sodium ions enhance the activity and thermostability of 1,4-α-glucan branching enzyme from Geobacillus thermoglucosidasius in the presence of glycerol.
Metal ions are essential for the performance of metal-dependent proteins and are known to be important for thermophilic proteins containing a large number of charged residues. The performance of thermophilic proteins may be influenced by metal ions through electrostatic interactions between the metal ions and charged residues. In this study, we investigated the effects of metal ions and glycerol on the activity and stability of the thermophilic 1,4-α-glucan branching enzyme (abbreviated GBE; EC 184.108.40.206) from G. thermoglucosidasius STB02. The results indicate that K+ or Na+ enhance the performance of GBE, and that the addition of glycerol further increases the thermostability of GBE. The effects of K+ or Na+ with glycerol on the structure of GBE were further investigated using intrinsic fluorescence spectra and far-UV circular dichroism spectra. The results show that more secondary structural elements are preserved by the addition of K+ or Na+ in the presence of glycerol. The improved maintenance of GBE structural elements after incubation may arise from electrostatic interactions introduced by the added salt, and glycerol provides a hydrophobic environment that strengthens these electrostatic contacts. This provides a useful perspective for understanding the strategy of thermophilic adaptation used by proteins with plenty of charged residues.


Nantenine blocks muscle contraction and Ca2+ transient induced by noradrenaline and K+ in rat vas deferens.
The effect of nantenine, an aporphine alkaloid isolated from Ocotea macrophylla H.B.K., was studied on contractions and Ca(2+) translocation induced by noradrenaline, Ca(2+), or K(+) in the isolated rat vas deferens from reserpinized animals. Concentration-response curves of calcium chloride (CaCl(2)) were performed in the vas deferens, in a Ca(2+)-free nutrient solution, using potassium chloride (KCl, 80 mM) as a depolarizing agent. In these conditions, nantenine (2.35 x 10(-4) and 4.7 x 10(-4) M) significantly reduced the maximum contractions (E(max)) of Ca(2+) (IC(50)=2.6 x 10(-4) M) and noradrenaline (IC(50)=2.9 x 10(-4) M). The contractile responses were totally recovered after the withdrawal of nantenine. In addition, experiments performed to measure simultaneously the contraction and the increase of intracellular Ca(2+) induced by noradrenaline (10(-5) M) or KCl (80 mM) showed that nantenine (2.35 x 10(-4) and 4.7 x 10(-4) M) significantly decreased both effects. The results suggest that a reversible block of Ca(2+) entry could be involved on the non-competitive-like antagonism of nantenine in rat vas deferens.


Overview of systematic reviews of health interventions that aim to prevent and treat overweight and obesity among children.
Childhood overweight and obesity is a global public health issue. Although there is evidence of a reduced prevalence in some countries, there is still much controversy about the efficacy of health interventions that aim to prevent and treat obesity in this specific population. The objective of the present study is to develop an overview of systematic reviews (OSRs) that assesses the effects of school-based, family, and multi-component health interventions for the prevention and treatment of obesity, change in physical activity, dietary, and/or hydration behaviors, and change in metabolic risk factors in school-aged children. This protocol was developed using the methodology proposed by Cochrane. It outlines a comprehensive search in 12 electronic databases to identify systematic reviews of health interventions, including studies that evaluate and how to prevent and/or treat overweight and/or obesity in children aged 6 to 12 years. The risk of bias of the included Systematic Reviews will be assessed with the ROBIS tool. Since the OSRs methodology's purpose is only to harmonize evidence from open access publications, ethical consent is not necessary for the present protocol. In terms of diffusion, a paper will be submitted for publication in a scientific journal to describe the main results obtained through the OSRs. The present overview of the systematic review protocol has been registered in PROSPERO (ID number 218296).


[Obtaining of uterine vacuity in pregnancy loss].
To assess early and late benefits and harms of different management options for first trimester miscarriage and for induction of labor and obtaining of uterine vacuity in case of fetal death beyond of 14weeks of gestation. French and English publications were searched using PubMed and Cochrane Library. Concerning missed miscarriage, expectant management is not recommended (LE1) because it increases the risk of failure, need of unplanned surgical procedure and blood transfusion (LE1). Surgical uterine evacuation remains more effective than medical treatment using misoprostol (LE1), but both techniques involve rare and comparable risks (EL1). When chosen, medical treatment should be a vaginal dose of 800μg of misoprostol, possibly repeated 24 to 48hours later (EL2). Administration of mifepristone prior to misoprostol is not recommended (EL2). In case of incomplete miscarriage, expectant management can be offered because it does not increase the risk of complications, neither haemorrhagic nor infectious (EL1). Medical treatment using misoprostol is not recommended (EL2) because it does not improve the evacuation rate when compared to our first option, and does not reduce the risk of complications (EL2). Surgical uterine evacuation leads to high evacuation rate (97-98%) and low risk of complications, haemorrhagic and infectious (<5%) (EL1). However, this option should not be the only one because of the good efficiency of the expectant management (more than 75% of evacuation) and comparably low risk of complications (EL1). Surgical aspiration should be favoured to curettage because it is quicker, less painful and leads to less bleeding (EL2). After a first trimester miscarriage future fertility is identical with each treatment (EL2). When a trophoblastic retention is suspected, a diagnostic hysteroscopy is recommended (EL2). In case of late intrauterine foetal death beyond 14weeks of gestation and without a past caesarean section, the most efficient protocol seems to be vaginal administration of misoprostol 200 to 400μg every 4 to 6hours (EL2). Twenty-four hours prior to misoprostol the administration of 200mg of mifepristone is recommended (EL3) because it improves the induction-expulsion time and diminishes the quantity of needed misoprostol (and so the complications linked to it) (EL3).


Electrochemical characterization of stimulated norepinephrine overflow in locus coeruleus-hippocampus double brain grafts grown in oculo.
Rat locus coeruleus-hippocampus double in oculo brain grafts were studied with high-speed electrochemical techniques to characterize stimulus-evoked overflow of norepinephrine. Local pressure ejections of KCl into the locus coeruleus (LC) portion of the double graft elicited electrochemical signals in the hippocampal portion that had NE-like reduction/oxidation current ratios. In contrast, electrical stimulation of the LC part of the double graft did not lead to consistently detectable signals in the hippocampal portion of the transplant. These data demonstrate that LC graft neurons are able to release NE in target tissues when stimulated in an appropriate manner, and that the time course and magnitude of the overflow of NE can be detected with sensitive high-speed electrochemical recording techniques.


Redetermination of the crystal structure of di-μ2-hydroxido-bis-[di-tert-butyl-chlorido-tin(IV)] at 100 K.
The structure of the dimeric title compound, [Sn2(C4H9)4Cl2(OH)2], was redetermined at 100 K by use of an area detector to provide new data to improve the structural parameters for detailed analysis. Noteworthy is the folding of the central, non-symmetric, four-membered [SnO]2 ring [dihedral angle about the O⋯O axis = 1.09 (3)°], as well as the elongation of the Sn-Cl bonds [mean value = 2.5096 (4) Å], as a result of inter-molecular O-H⋯Cl hydrogen bonds; the latter lead to a chain-like arrangement of dimeric mol-ecules along [101].


Females are more susceptible than male mice to thermal hypernociceptive behavior induced by early-life bisphenol-A exposure: Effectiveness of diphenyl diselenide.
Humans are ubiquitously exposed to bisphenol A (BPA), one of the most used synthetic monomers for manufacturing polycarbonate plastics. BPA exposure leads to abnormal nociceptive perception and neuroinflammation in rodents. This study investigated whether diphenyl diselenide (PhSe)2, a pleiotropic selenium-containing molecule, would be effective against the hypernociceptive behavior induced by the early-life BPA exposure to mice. Three-week-old male and female Swiss mice received intragastrically BPA (5 mg/kg) from 21st to 60th postnatal day. After, the mice received by the intragastric route (PhSe)2 (1 mg/kg) once a day for seven days. After the last day of treatment, the mice performed the hot plate and tail immersion tests. The cerebral cortex samples were used to determine the levels of proteins related to apoptosis and inflammation. The results demonstrated that females were more susceptible than male mice to thermal hypernociception induced by early-life exposure to BPA. (PhSe)2 was effective against the reduction in the latency to paw and tail withdrawal induced by BPA exposure in female mice. Furthermore, (PhSe)2 restored the impairment in the levels of inflammatory proteins (COX-2, IL-1β, and p-JNK/JNK) but not those of apoptosis in the cerebral cortex of female mice exposed to BPA. Collectively, these data showed that females were more susceptible to thermal hypernociceptive behavior induced by early-life exposure to BPA than male mice. The administration of (PhSe)2 reduced thermal hypernociceptive behavior, a sex independent effect, in BPA-exposed mice. (PhSe)2 modulated inflammatory protein levels in the cerebral cortex of female mice exposed to BPA.


6-Meth-oxy-N-methyl-3-nitro-4-nitro-methyl-4H-chromen-2-amine.
In the title compound, C(12)H(13)N(3)O(6), the dihydro-pyran ring adopts a near screw-boat conformation. The dihedral angle between the mean planes of the benzene and dihydro-pyran rings is 6.35 (5)°. An intra-molecular N-H⋯O hydrogen bond generates an S(6) motif, which stabilizes the mol-ecular conformation. In the crystal, weak inter-molecular C-H⋯O, N-H⋯O and C-H⋯π hydrogen bonds contribute to the stabilization of the packing.


Effect of chemical composition on luminescence of thiol-stabilized CdTe nanocrystals.
Judicious selection of the amount of surfactant during synthesis enables a drastic increase in the photoluminescence efficiency of aqueous CdTe nanocrystals (NCs) stabilized by thioglycolic acid (TGA). Elemental determination of the NCs was undertaken to identify the origin of this effect. The molar ratio of (Te + S) to Cd approached unity when the optimum amount of TGA was used during synthesis, whereas the number of S atoms originating from TGA molecules in one NC (2.6 nm of diameter) remained unchanged at 90 ± 3. This indicates that the core lattice composition at the beginning of synthesis, rather than the surface conditions, affects the photoluminescence efficiency of the NCs even after prolonged refluxing.


Renewable and non-renewable energy consumption driven sustainable development in ASEAN countries: do financial development and institutional quality matter?
Energy consumption for sustainable development has become a crucial issue in recent years. The anthropogenic effects of traditional energy sources (non-renewables) underscore the need for renewable energy and efforts to promote its adoption have comprised policy makers' strategies to achieve sustainable development. At the same time, institutional stability is a necessary element needed to meet the goal of sustainable development via improved management of resources and technology diffusion. The literature shows some contradictory findings on this matter and this study aims to clarify. Thus, this research scrutinizes the contribution of renewable and non-renewable energies in sustainable development while also taking into account financial development and institutional quality in ASEAN countries from 1980 to 2018. To assess for co-integration, a pooled mean group (PMG) regression technique is employed and the findings from this technique are verified by using fully modified ordinary least square (FMOLS), dynamic ordinary least square (DOLS), and canonical cointegration regression (CCR) techniques in conjunction with other panel-based econometric procedures to evaluate the robustness of the model. The findings reveal a significantly positive influence for renewable energy and a significantly adverse impact for non-renewable energy with respect to sustainable development in ASEAN countries. In addition, the results indicate that institutional quality and financial development have adverse effects on sustainable development. Therefore, this research recommends sustainable management of non-renewables and greater promotion of renewables by strengthening institutional quality in ASEAN countries.


Fine-needle aspiration of well differentiated small-cell duct carcinoma of the breast.
Historically, fine-needle aspiration of the female breast has been accepted as a useful modality in the diagnosis of ductal as well as other types of breast carcinoma. However, cases of well differentiated small-cell duct carcinoma can be problematic. The differential diagnoses include fibrocystic disease, papillary neoplasia, fibroadenoma, and lobular carcinoma. Retrospectively, 16 cases of well differentiated small-cell duct carcinoma have been identified in the case files of Truman Medical Center/University of Missouri-Kansas City. Patient's ages ranged from 29-81 yr, with the mean being 56.2 yr. The overall cytologic features consisted predominantly of a hypercellular specimen with cohesive and rarely discohesive cells with no demonstrable nuclear atypia. For well differentiated small-cell duct carcinoma, the mean nuclear diameter was greater than that of a red cell (6-8 microns). For the well differentiated small-cell duct carcinoma group, the mean nuclear diameter was 9.86 microns; for fibrocystic disease, 12.86 microns; for papillomas, 8.28 microns; for fibroadenomas, 9.48 microns; and for lobular carcinoma, 11.88 microns. From our data, it appears that specific attention to the clinical presentation, cytologic pattern, and nuclear diameters are useful discriminators for well differentiated small-cell duct carcinoma.


Influence of macrolides, nutritional support and respiratory therapies in diabetes and normal glucose tolerance in cystic fibrosis. A retrospective analysis of a cohort of adult and younger patients.
The development of cystic fibrosis related diabetes is associated with increased morbidity and mortality, worse nutritional status and lung function decline. It is known that patients with cystic fibrosis have a chronic inflammation status and that β pancreatic cells are very sensitive to oxidative stress. So these inflammatory mediators could contribute to the onset of progressive pancreatic fibrosis and, hence, to impair glucose metabolism. So, it could be hypothesized that the treatment with macrolides would protect and preserve β-cell function by decreasing pro-inflammatory cytokines and free oxidative radicals. We retrospectively analyzed a cohort of 64 patients affected of cystic fibrosis, older than 14 years, by using the first pathological 2-h oral glucose tolerance test; peripheral insulin resistance was calculated using the homeostasis model assessment for insulin resistance (HOMA - IR) and pancreatic β-cell function was estimated according to Wareham. The influence of macrolides, microbiological colonization, nutritional support and related clinical parameters were analyzed. Comparing CFRD without FPG and NGT, and after adjustment for microbial colonization, the significance of the use of macrolides was lost (p=0.1), as a risk or protective factor for any of the studied groups. Non-significative associations were found in the use of macrolides, inhaled corticosteroids and nutritional support therapies within the different disorders of carbohydrate metabolism. The anti-inflammatory and immunomodulating effect of macrolides did not seem to affect the β cell function or insulin resistance in patients with cystic fibrosis. The use of inhaled corticosteroids or nutritional supplements have not any influence in the carbohydrate metabolism. Further prospective studies are needed to analyze a potential protective role of macrolides in the development of carbohydrate metabolism alterations in cystic fibrosis.


Vacuum ultraviolet studies on the nature of the radiation inactivation of trypsin.
Trypsin, in powder form and in frozen D(2)O-glucose solutions, at temperatures from 100 degrees to 300 degrees K, was excited with vacuum ultraviolet and near ultraviolet radiation to determine how absorbed photon energy is partitioned into radiative, nonradiative and/or inactivating processes; at 300 degrees K most of the absorbed energy is not reemitted, so that it (0.98-0.99 for excitation at 120 nm and 0.75-0.90 at 280 nm) is potentially available for inactivation. Since the effects of excitation wavelength and temperature on the emission quenching yields are generally different from those on the inactivation yields of dry trypsin, the mere retention of quenched energy by an enzyme does not necessarily lead to its inactivation. Thus, as predicted previously, the radiation inactivation of trypsin must proceed by rather specific mechanisms which undoubtedly depend upon environment-sensitive processes, since the nature of the molecular environment can modify the partitioning of energy so significantly; for example, there are differences in the phosphorescence-to-fluorescence ratio, in the activation energy for quenching, and in the lifetimes and kinetics of the decay of phosphorescence when trypsin in frozen glasses and dry trypsin are excited by various wavelengths of ultraviolet radiation.


A new entry to azomethine ylides from allylic amines and glyoxals: shifting the reliance on amino ester precursors.
The first examples of azomethine ylides derived from allylic amine and glyoxal precursors are reported. The condensation of primary allylic and α-aryl amines with glyoxylates or α-aryl glyoxals affords conjugated azomethine ylides that undergo facile [3 + 2] cycloaddition, providing 5-alkenyl pyrrolidine cycloadducts that cannot be accessed through the classical use of amino esters as ylide precursors.


Climate change and mortality evolution in China.
This paper explores the historical relationship between weather fluctuations and mortality evolution in China. Using panel data on the annual provincial mortality rate and daily weather variables for the 1964-2008 period, we applied a dynamic model structure with sufficient controls to estimate the short-term effects of temperature shocks on China's mortality rate. Our main results show that an additional 1 °C rise in average temperature in a given year increases the annual mortality rate by an average of 3.2%. In addition, days with daily average temperatures exceeding 27 °C (30 °C) are associated with an increase in the annual mortality rate of nearly 0.1% (0.2%) or approximately 9,520 (19,040) additional deaths. In contrast, extremely cold days do not have these effects. By applying a hybrid model structure (the long difference approach) to examine the medium-term effects of temperature changes, we find that there is little evidence of overall adaptation to high temperatures when moving from the short term to the medium term. In addition, by introducing interactions between temperatures and potential modifiers such as access to doctors, hospital beds, air conditioning and refrigerators, we determined that only residential air conditioning played an important role in mitigating the temperature-mortality relationship. However, the penetration of air conditioning in China is still relatively low. These findings indicate that climate change could partially explain the historical phenomenon of China's rising mortality rate during the unprecedented economic boom experienced since the 1980s.


Melatonin rescued methotrexate-induced spatial deficit and hyperhomocysteinemia and increased asymmetric dimethylarginine in plasma and dorsal hippocampus in developing rats.
With the improvement of the survival rates in children acute lymphoblastic leukemia (ALL), some children ALL survivors show impaired cognitive function. Methotrexate (MTX), an essential component in ALL treatment, has been reported to be related to neurologic sequelae and to increased oxidative stress through its interactions with enzymes in the folate pathway. Asymmetric dimethylarginine (ADMA) is the main endogenous inhibitor of nitric oxide synthase, and increased ADMA may result from increased oxidants. Melatonin is an antioxidant; however, its role in MTX neuropathy is not well studied. We developed a rat model mimicking child ALL treatment to explore peripheral and central homocysteine and ADMA regulation after MTX and found potential treatment choice. Preweaning male Sprague-Dawley rats were used in this study. Experiment 1 evaluated spatial performance in rats with intrathecal (IT) MTX, intraperitoneal (IP) MTX, or combined IT and IP MTX, protocols mimicking ALL treatment in children. Experiment 2 focused on rats with combined IT and IP MTX, evaluating spatial performance and plasma and dorsal hippocampal homocysteine and ADMA levels, their regulation, and the protective effect of melatonin. Combined IT and IP MTX treatment caused in spatial deficits in developing rats, and melatonin restored the spatial performance. Alterations in peripheral and central homocysteine and ADMA concentrations and their regulation were found and could be alleviated by melatonin treatment. Combined IP and IT MTX treatment caused spatial deficits in developing rats. Melatonin could restore spatial performance through alleviating the effects on the imbalance of oxidative stress.


Succinate recovers mitochondrial oxygen consumption in septic rat skeletal muscle.
Mitochondrial dysfunction, particularly affecting complex I of the respiratory chain, could play a fundamental role in the development of multiple organ failure during sepsis. Increasing electron flow through complex II by addition of succinate may improve mitochondrial oxygen utilization and thus adenosine triphosphate production. Ex vivo animal study. University research laboratory. Male adult Wistar rats. Fecal peritonitis was induced in conscious, fluid-resuscitated, hemodynamically-monitored rats. Sham-operation and naïve animals acted as controls. At 48 hrs, clinical severity was graded. Soleus muscle was taken for measurement of mitochondrial complex activities and oxygen consumption. The effect of glutamate plus malate (complex I substrates) and succinate (complex II substrate) on mitochondrial respiration was assessed. In the presence of glutamate plus malate, mitochondrial oxygen consumption was abnormally low in skeletal muscle tissue from moderately-to-severely septic animals as compared with naïve and sham-operation controls (both p < .01). On addition of succinate, mitochondrial respiration was augmented in all groups, particularly in moderately-to-severely septic animals (39% +/- 6% increase) as compared with naïve (11% +/- 5%; p < .01) and sham-operation controls (10% +/- 5%; p < .01). In the presence of succinate, mitochondrial oxygen consumption was similar between the groups. Succinate increases mitochondrial oxygen consumption in ex vivo skeletal muscle taken from septic animals, bypassing the predominant inhibition occurring at complex I. This warrants further exploration in vivo as a putative therapeutic modality.


Twisted cystic artery disclosed by 3-dimensional computed tomography angiography for torsion of the gallbladder.
Torsion of the gallbladder is a rare condition that most commonly affects elderly women. The symptoms of torsion mimic acute cholecystitis, but several clinical features and imaging findings can be useful for distinguishing it from typical acute cholecystitis. However, preoperative identification remains difficult. Three-dimensional angiography reconstructed by preoperative multidetector row computed tomography is useful for definitive diagnosis of torsion of the gallbladder. Demonstration of a twisted cystic artery by 3-dimensional computed tomography angiography represents specific and direct evidence of this condition, which allows immediate diagnosis and treatment.


Seven Common Allergen Groups Causing Eyelid Dermatitis: Education and Avoidance Strategies.
Eyelid dermatitis is most commonly attributed to allergic response. This retrospective clinical study identifies common allergens with eyelid involvement and addresses a literary gap by providing a clear approach for effective management of periorbital allergic contact dermatitis (ACD) recurrence. Charts of 215 patients diagnosed with periorbital dermatitis who were patch tested with Mayo Clinic Standard Series, Extended Standard Series, and personal products from 2013 to 2017 were examined. Positive reaction rates for patients with eyelid involvement were compared to those without. Findings were also compared to North American Contact Dermatitis Group (NACDG) 2013-2014 and Mayo Clinic Contact Dermatitis Group (MCCDG) 2011-2015 general patch test populations. The 215 patients showed more common allergy to shellac, benzalkonium chloride, acrylates, and surfactants than the NACDG and MCCDG study populations. Periorbital ACD allergen groups eliciting the highest positive reaction rates were, in descending order: metals, shellac, preservatives, topical antibiotics, fragrances, acrylates, and surfactants. Of the corticosteroids, only tixocortol pivalate (the screening agent for prednisolone and fluorometholone) and budesonide elicited positive reactions. The top seven eyelid ACD allergen groups were identified. Avoidance of these allergens can be straightforward, with initial empiric counseling and free, online allergen avoidance programs. Patients who are unresponsive to avoidance should undergo patch testing.


Bioluminometric assay of ATP in mouse brain: Determinant factors for enhanced test sensitivity.
Firefly luciferase bioluminescence (FLB) is a highly sensitive and specific method for the analysis of adenosine-5-triphosphate (ATP) in biological samples. Earlier attempts to modify the FLB test for enhanced sensitivity have been typically based on in vitro cell systems. This study reports an optimized FLB procedure for the analysis of ATP in small tissue samples. The results showed that the sensitivity of the FLB test can be enhanced several fold by using ultraturax homogenizer, perchloric acid extraction, neutralization of acid extract and its optimal dilution, before performing the assay reaction.


Spastic quadriplegia in Western Australia. II: Pedigrees and family patterns of birthweight and gestational age.
Pedigrees were obtained for all 74 index children and for three controls for each case. Recurrence of similar spastic quadriplegic phenotypes occurred in two families. A karyotype of 46,XY,dup(13)(q14q34), resulting in a partial trisomy 13, was found in another case. Rates of miscarriages and stillbirths plus neonatal deaths were higher among siblings of index cases than in siblings of birth-year controls, but were similar to siblings of birthweight controls. Average birthweights and gestational ages were lower in index cases than in birth-year controls. Children with spastic quadriplegia had significantly lower birthweights and gestational ages than their siblings. However, they also tended to come from families with a pattern of low birthweight and preterm delivery. The differences between families remained after controlling for factors affecting birthweight.


Development of an Effective Sonotrode Based Extraction Technique for the Recovery of Phenolic Compounds with Antioxidant Activities in Cherimoya Leaves.
The leaves of Annona cherimola Mill (cherimoya) are a potential source of phenolic compounds that have been shown to have beneficial properties. Therefore, this study focuses on establishing an ultrasonic-assisted extraction of phenolic compounds in cherimoya leaves using a sonotrode. For that purpose, a Box-Behnken design based on a response surface methodology (RSM) was used to optimize factors, such as amplitude, extraction time and solvent composition to obtain the maximum content of phenolic compounds by HPLC-MS and the maximum in-vitro antioxidant activity by DPPH, ABTS and FRAP assays in 'Fino de Jete' cherimoya leaves. The optimal conditions were 70% amplitude, 10 min and 40:60 ethanol/water (EtOH/H2O) (v/v). The results obtained under these optimum conditions by using a sonotrode were compared with those from an ultrasonic bath; briefly, recovery of phenolic compounds by sonotrode was 2.3 times higher than a bath. Therefore, these optimal conditions were applied to different varieties 'Campas', 'Fino de Jete' and 'Negrito Joven' harvested in the Tropical Coast of Granada (Spain). A total of 39 phenolic compounds were determined in these cherimoya leaf extracts, 24 phenolic compounds by HPLC-MS and 15 proanthocianidins by HPLC-FLD. 5-p-coumaroylquinic acid, lathyroside-7-O-α-l-rhamnopyranoside and quercetin hexose acetate were first identified in cherimoya leaves. The most concentrated phenolic compounds were the flavonoids, such as rutin and quercetin hexoside and proanthocyanidins including monomers. Almost no significant differences in the phenolic content in these cultivars were found (11-13 mg/g d.w. for phenolic compounds and 11-20 mg/g d.w. for proanthocyanidins). In addition, sonotrode ultrasonic-assisted extraction has been shown to be an efficient extraction technique in the phenolic recovery from cherimoya leaves that could be implemented on an industrial scale.


Global coverage of interventions to prevent and manage drug-related harms among people who inject drugs: a systematic review.
Harm reduction and treatment programmes are essential for reducing harms for people who inject drugs (PWID). We aimed to update estimates from a 2017 review of global coverage of needle and syringe exchange programmes (NSPs), opioid agonist treatment (OAT), and other harm reduction services that target PWID (eg, take-home naloxone [THN] programmes, supervised consumption facilities, and drug checking services). We did a systematic review of available evidence from peer-reviewed and grey literature databases for studies published between Jan 1, 2017, and May 31, 2022. Programmatic data were collected on the availability of services, the number of sites, people accessing services, and equipment distributed in countries where there is evidence of injecting drug use. National estimates of coverage of OAT (ie, number of people accessing OAT per 100 PWID) and NSPs (ie, number of needles and syringes distributed per PWID per year) were generated where available using the most recent data. Regional and global estimates were derived and compared with WHO indicators. The study was registered with PROSPERO (CRD42020173974). We included 195 studies and found there were 90 countries implementing OAT (75% of the PWID population) and 94 countries implementing NSPs (88% of the global PWID population). Only five countries (2% of the global PWID population) are providing high coverage of both services. Far fewer countries were implementing THN programmes (n=43), supervised consumption facilities (n=17), and drug checking services (n=26), with nine countries implementing all five services. Globally, we estimated there were 18 (95% uncertainty interval [UI] 12-27) people accessing OAT per 100 PWID, and 35 (95% UI 24-52) needles and syringes being distributed per person who injects drugs per year. More countries reported high (OAT 24; NSPs 10), moderate (OAT 8; NSPs 15), and low (OAT 38; NSPs 47) coverage of services compared with the previous review. Global coverage of OAT and NSPs has increased modestly in the past 5 years but remains low for most countries. Programmatic data on other key harm reduction interventions are scarce. Australian National Health and Medical Research Council.


Ferrocenyl Schiff base as novel antioxidant to protect DNA against the oxidation damage.
The antioxidant capacities of ferrocenyl Schiff bases including o-(1-ferrocenylethylideneamino)phenol (OFP), m-(1-ferrocenylethylideneamino)phenol (MFP), and p-(1-ferrocenylethylideneamino)phenol (PFP) were evaluated in 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), Cu(2+)/glutathione (GSH), and hydroxyl radical (()OH)-induced oxidation of DNA, and in trapping 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+(.)), respectively. OFP, MFP and PFP possessed similar activities to trap DPPH and ABTS+(.). All the ferrocenyl Schiff bases employed herein behaved as prooxidants in Cu(2+)/GSH- and (.)OH-induced oxidation of DNA except that OFP exhibited weak antioxidant activity in ()OH-induced oxidation of DNA. PFP, OFP and MFP can terminate about 15.2, 11.3, and 9.4 radical-chain-propagations in AAPH-induced oxidation of DNA. Especially, the introduction of ferrocenyl group to Schiff base increased the antioxidant effectiveness more remarkably than benzene-related Schiff bases.


Zoonotic diseases: sharing insights from interdisciplinary research.
Researchers and others involved with the Zoonoses and Emerging Livestock Systems (ZELS) initiative gathered in Tanzania earlier this year to discuss progress with projects being carried out as part of the five- year programme. Mary Ryan and Sarah Cleaveland report.


Ischemic Stroke in Non-Gender-Related CHA2DS2-VA Score 0~1 Is Associated With H2FPEF Score Among the Patients With Atrial Fibrillation.
Ischemic strokes (ISs) can appear even in non-gender-related CHA2DS2-VA scores 0~1 patients with atrial fibrillation (AF). We explored the determinants associated with IS development among the patients with non-gender-related CHA2DS2-VA score 0~1 AF. In this single-center retrospective registry data for AF catheter ablation (AFCA), we included 1,353 patients with AF (24.7% female, median age 56 years, and paroxysmal AF 72.6%) who had non-gender-related CHA2DS2-VA score 0~1, normal left ventricular (LV) systolic function, and available H2FPEF score. Among those patients, 113 experienced IS despite a non-gender-related CHA2DS2-VA score of 0~1. All included patients underwent AFCA, and we evaluated the associated factors with IS in non-gender-related CHA2DS2-VA score 0~1 AF. Patients with ISs in this study had a lower estimated glomerular filtration rate (eGFR) (p < 0.001) and LV ejection fraction (LVEF; p = 0.017), larger LA diameter (p < 0.001), reduced LA appendage peak velocity (p < 0.001), and a higher baseline H2FPEF score (p = 0.018) relative to those without ISs. Age [odds ratio (OR) 1.11 (1.07-1.17), p < 0.001, Model 1] and H2FPEF score as continuous [OR 1.31 (1.03-1.67), p = 0.028, Model 2] variable were independently associated with ISs by multivariate analysis. Moreover, the eGFR was independently associated with IS at low CHA2DS2-VA scores in both Models 1 and 2. AF recurrence was significantly higher in patients with IS (log-rank p < 0.001) but not in those with high H2FPEF scores (log-rank p = 0.079), respectively. Among the patients with normal LVEF and non-gender-related CHA2DS2-VA score 0~1 AF, the high H2FPEF score, and increasing age were independently associated with IS development (ClinicalTrials.gov Identifier: NCT02138695).


Monocyte chemoattractant protein-1 expression in intimal hyperplasia of vein grafts in a rat model.
Most cardiovascular surgeons prefer artery grafts to vein grafts. Monocyte chemoattractant protein-1 (MCP-1) is the most potent chemoattractant factor for monocytes/macrophages (Mo/Mphi). We conducted experiments based on our hypothesis that intimal hyperplasia (IH) is more severe in vein grafts than in situ artery grafts, due to differences in Mo/Mphi infiltration, and that the expression of MCP-1 is different in vein grafts compared with in situ artery grafts. Lewis rats were subjected to either epigastric vein to common femoral artery interposition grafts (VG: n = 34) or common femoral artery reanastomoses (FA: n = 34). IH was defined as the intimal area/total area (intimal ratio, Ri). Immunohistochemistry was also performed, using a monoclonal antibody (ED-1), specific for rat Mo/Mphi. MCP-1 mRNA expression was examined by a reverse transcription-polymerase chain reaction, and compared with S-26 mRNA expression. After 2 weeks, the Ri of the VGs became significantly larger than the Ri of the FA anastomoses (P < 0.01). ED-1+ cell numbers were significantly elevated in the VG compared with the FA anastomoses, after 1 day, 2 weeks (P < 0.05), and 4 weeks (P < 0.01). MCP-1 mRNA expression was significantly increased in the VGs by 1 day (P < 0.05). These results show that there could be a direct correlation between the significant increases in MCP-1 mRNA expression, Mo/Mphi infiltration, and the development of IH in vein grafts, not seen in FA anastomoses.


Association between a Multidisciplinary Team Approach and Clinical Outcomes in Patients Undergoing Extracorporeal Cardiopulmonary Resuscitation in the Emergency Department.
Despite recent improvements in advanced life support, the overall survival rate after cardiac arrest remains low. We aimed to examine the association of a multidisciplinary team approach with clinical outcomes in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) in the emergency department (ED). This retrospective, single-center, observational study included 125 patients who underwent ECPR in the ED between May 2004-December 2018. In January 2014, our institution implemented a multidisciplinary extracorporeal membrane oxygenation (ECMO) team. Eligible patients were classified into pre-ECMO-team (n=65) and post-ECMO-team (n=60) groups. The primary outcome was in-hospital mortality. In-hospital mortality (72.3% vs. 58.3%, p=0.102) and poor neurological outcomes (78.5% vs. 68.3%, p=0.283) did not differ significantly between the pre- and post-ECMO-team groups. However, among the 60 patients who experienced in-hospital cardiac arrest, in-hospital mortality (75.8% vs. 40.7%, p=0.006) and poor neurological outcomes (78.8% vs. 48.1%, p=0.015) significantly decreased after the multidisciplinary team formation. Multivariable logistic regression analysis showed that the multidisciplinary team approach (adjusted odds ratio, 0.20; 95% confidence interval, 0.07-0.61; p=0.005) was an independent prognostic factor for in-hospital mortality in in-hospital cardiac arrest patients. A multidisciplinary team approach was associated with improved clinical outcomes in in-hospital cardiac arrest patients undergoing ECPR in the ED. These findings may help in improving the selection criteria for ECPR in the ED. Further studies to overcome the study limitations may help improving the outcomes of out-of-hospital cardiac arrest patients.


Multi-omics Analyses Provide Insight into the Biosynthesis Pathways of Fucoxanthin in Isochrysis galbana.
Isochrysis galbana is considered an ideal bait for functional foods and nutraceuticals of humans because of its high fucoxanthin (Fx) content. However, multi-omics analysis of the regulatory networks for Fx biosynthesis in I. galbana has not been reported. In this study, we report a high-quality genome assembly of I. galbana LG007, which has a genome size of 92.73 Mb, with a contig N50 of 6.99 Mb and 14,900 protein-coding genes. Phylogenetic analysis confirmed the monophyly of Haptophyta, with I. galbana sister to Emiliania huxleyi and Chrysochromulina tobinii. Evolutionary analysis revealed an estimated divergence time between I. galbana and E. huxleyi of ∼ 133 million years ago. Gene family analysis indicated that lipid metabolism-related genes exhibited significant expansion, including IgPLMT, IgOAR1, and IgDEGS1. Metabolome analysis showed that the content of carotenoids in I. galbana cultured under green light for 7 days was higher than that under white light, and β-carotene was the main carotenoid, accounting for 79.09% of the total carotenoids. Comprehensive multi-omics analysis revealed that the content of β-carotene, antheraxanthin, zeaxanthin, and Fx was increased by green light induction, which was significantly correlated with the expression of IgMYB98, IgZDS, IgPDS, IgLHCX2, IgZEP, IgLCYb, and IgNSY. These findings contribute to the understanding of Fx biosynthesis and its regulation, providing a valuable reference for food and pharmaceutical applications.


The vacuous chewing movement (VCM) model of tardive dyskinesia revisited: is there a relationship to dopamine D(2) receptor occupancy?
Tardive dyskinesia (TD) is a late side effect of long-term antipsychotic use in humans, and the vacuous chewing movement (VCM) model has been used routinely to study this movement disorder in rats. Recent receptor occupancy studies in humans and rats have found that antipsychotics given in doses which lead to moderate levels of D(2) receptor blockade can achieve optimal clinical response while minimizing the emergence of acute motor side effects. This suggests that clinicians may have been using inappropriately high doses of antipsychotics. A review of the existing VCM literature indicates that most animal studies have similarly employed antipsychotic doses that are high, i.e. doses that lead to near complete D(2) receptor saturation. To verify whether the incidence or severity of VCMs would decrease with lower antipsychotic doses, we conducted initial experiments with different doses of haloperidol (HAL) given either as repeated daily injections or as depot injections over the course of several weeks. Our results demonstrate that (1) the incidence of VCMs is significantly related to HAL dose, and (2) significant levels of VCMs only emerge when haloperidol is continually present. These findings are consistent with the possibility that total D(2) occupancy, as well as 'transience' of receptor occupation, may be important in the development of late-onset antipsychotic-induced dyskinetic syndromes.


Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle.
Dynamic interaction between lipid droplets (LDs) and mitochondria controls the mobilization of long-chain fatty acids (LCFAs) from LDs for mitochondrial β-oxidation in skeletal muscle in response to energy stress. However, little is known about the composition and regulation of the tethering complex mediating LD-mitochondrion interaction. Here, we identify Rab8a as a mitochondrial receptor for LDs forming the tethering complex with the LD-associated PLIN5 in skeletal muscle. In rat L6 skeletal muscle cells, the energy sensor AMPK increases the GTP-bound active Rab8a that promotes LD-mitochondrion interaction through binding to PLIN5 upon starvation. The assembly of the Rab8a-PLIN5 tethering complex also recruits the adipose triglyceride lipase (ATGL), which couples LCFA mobilization from LDs with its transfer into mitochondria for β-oxidation. Rab8a deficiency impairs fatty acid utilization and decreases endurance during exercise in a mouse model. These findings may help to elucidate the regulatory mechanisms underlying the beneficial effects of exercise on lipid homeostasis control.


Expression of intercellular adhesion molecule-1 on the surface of peripheral blood and decidual lymphocytes of women with pregnancy-induced hypertension.
If overexpression of intercellular adhesion molecule-1 (CD54) on lymphocytes exists it could have important implications for the pathophysiology of pregnancy-induced hypertension (PIH). CD54 "in vitro" expression (described as (%) of CD54+cells and CD54 mean fluorescence intensity, MFI) on the peripheral blood and decidual lymphocytes of pregnant with pre-eclampsia (PE) (n=16), transient hypertension (TH) (n=12), and controls (n=9). The percent (%) of CD54+peripheral blood lymphocytes, CD54 MFI on them and CD54 MFI on decidual lymphocytes were increased especially in PE. During PE the (%) of CD54 decidual lymphocytes correlated negatively with platelet count. In TH the positive correlation between the blood pressure and the (%) of CD54 peripheral blood lymphocytes as well as CD54 MFI on decidual lymphocytes were found. (1) PIH, especially PE, is accompanied by overexpression of intercellular adhesion molecule-1 (ICAM-1) on peripheral blood and decidual lymphocytes studied "in vitro", (2) Some of the parameters studied seem to correlate with clinical markers of PIH intensity but this fact needs further investigations using larger subject groups.


[Detection of ECG alterations typical for myocardial ischemia : New methods 2021].
The electrocardiogram (ECG) represents an essential diagnostic tool in cardiology and beyond. Classical ECG devices enable the registration of up to 12 leads, whereas modern ECG systems enable additional leads even with a reduced number of electrodes. Additionally, "smart" devices even enable patients to record an ECG at home. Evaluation of a potential additional benefit of using various modern ECG systems for the detection of ECG alterations typical for myocardial ischemia. Presentation of various signs of ischemia in the ECG according to the latest guidelines. Demonstration of modern ECG systems and their potential advantage in the detection of signs of ischemia in the ECG based on current study results. Modern ECG systems with vector-based electrocardiography can facilitate and optimize the detection of ischemic ECG alterations. Smart nonvector-based devices for patients are primarily useful for detection of arrhythmias and do not replace the 12-lead ECG for detection of ischemia, even though they can be useful for documentation of temporary ECG alterations also within the ST-segment. The ECG systems based on vector electrocardiography can improve the detection of ECG alterations typical for ischemia compared to the conventional 12-lead ECG.


SARS-CoV-2 surveillance in medical and industrial wastewater-a global perspective: a narrative review.
The novel coronavirus SARS-CoV-2 has spread at an unprecedented rate since late 2019, leading to the global COVID-19 pandemic. During the pandemic, being able to detect SARS-CoV-2 in human populations with high coverage quickly is a huge challenge. As SARS-CoV-2 is excreted in human excreta and thus exposed to the aqueous environment through sewers, the goal is to develop an ideal, non-invasive, cost-effective epidemiological method for detecting SARS-CoV-2. Wastewater surveillance has gained widespread interest and is increasingly being investigated as an effective early warning tool for monitoring the spread and evolution of the virus. This review emphasizes important findings on SARS-CoV-2 wastewater-based epidemiology (WBE) in different continents and techniques used to detect SARS-CoV-2 in wastewater during the period 2020-2022. The results show that WBE is a valuable population-level method for monitoring SARS-CoV-2 and is a valuable early warning alert. It can assist policymakers in formulating relevant policies to avoid the negative impacts of early or delayed action. Such strategy can also help avoid unnecessary wastage of medical resources, rationalize vaccine distribution, assist early detection, and contain large-scale outbreaks.


EVALUATION OF THE EFFECTIVENESS OF THE GASTRODUODENITIS PREVENTION PROGRAM IN PATIENTS OF RETIREMENT AGE WITH ESSENTIAL ARTERIAL HYPERTENSION WHO TOOK PART IN THE PROGRAM ,AFFORDABLE MEDICINES- UNDER THE IBCR.
The aim: To assess the e!ectiveness of the gastroduodenitis prevention program we have developed in patients of retirement age with essential arterial hypertension who participate in the «A!ordable Medicines» program. Materials and methods: A combined (retrospective and prospective) study was conducted, in which 150 patients took part. The main group consisted of 100 patients of retirement age with essential arterial hypertension and gastroduodenitis, which arose against the background of treatment of essential arterial hypertension. The control group consisted of 50 patients of retirement age with essential arterial hypertension without gastroduodenitis. For this category of the population developed a program for the prevention of gastroduodenitis. To assess the e!ectiveness of this prevention program, an «incremental cost-benefit ratio» (#C$R) is used. Results: An assessment of the e!ectiveness of the gastroduodenitis prevention program we developed in patients of retirement age with essential arterial hypertension who participate in the «A!ordable Medicines» program. Conclusions: Identified categories of patients for whom the developed prevention program is effective.


PIKA provides an adjuvant effect to induce strong mucosal and systemic humoral immunity against SARS-CoV.
Severe Acute Respiratory Syndrome (SARS) is a deadly infectious disease caused by SARS Coronavirus (SARS-CoV). Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvants, especially with more efficient and economical needle-free vaccination are always needed more urgently in a pandemic. The development of a safe and effective mucosal adjuvant and vaccine for prevention of emergent infectious diseases such as SARS will be an important advancement. PIKA, a stabilized derivative of Poly (I:C), was previously reported to be safe and potent as adjuvant in mouse models. In the present study, we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly (I:C) derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus. Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites, co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity. When intranasal immunization was used, PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response. Overall, PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.


Prior Spontaneous or Induced Abortion Is a Risk Factor for Cervical Dysfunction in Pregnant Women: a Systematic Review and Meta-analysis.
A history of abortion is associated with cervical dysfunction during pregnancy, but there remains uncertainty about whether risk can be stratified by the abortion type, the abortion procedure, or number of previous abortions. The objective of this study was to verify the relationship between cervical dysfunction measures in pregnancies with and without a history of termination. Embase and Medline databases were searched from 01 January 1960 to 01 March 2022 resulting in a full-text review of 28 studies. The Newcastle-Ottawa Scale (NOS) was used to assess the quality and risk of bias for non-randomized studies. The meta-analysis consisted of 6 studies that met all inclusion and exclusion criteria and included a combined total of 2,513,044 pregnancies. Cervical dysfunction was defined as either cervical insufficiency/incompetence in 4 of the studies and as short cervix in the others. Results from a random-effects model using reported adjusted odds ratios (aOR) estimated an increase in the odds of 2.71 (95% CI 1.76, 4.16) for cervical dysfunction in the current pregnancy related to a history of induced or spontaneous abortion. Subgroup analyses with only induced abortions (surgical/medical) estimated an aOR of 2.54 (95% CI 1.41, 4.57), while studies limited to surgical abortions had an aOR of 4.08 (95% CI 2.84, 5.86). The risk of cervical dysfunction in the current pregnancy was also found to be dependent on the number of previous abortions. In this meta-analysis, a prior history of abortion, and specifically induced abortions, was associated with cervical dysfunction. The protocol was registered in PROSPERO (CRD42020209723).


High irisin and low BDNF levels in aqueous humor of high myopia.
The pathogenesis of myopia remains unclear. Both genetic and environmental factors play a role in the disease progression. Reasons including reduced physical activity (PA) and low-grade intraocular inflammation may be involved in the development of myopia. To analyze the levels of irisin, brain-derived neurotrophic factor (BDNF) and other intraocular cytokines in aqueous humor of high myopia patients, and to evaluate the roles of PA and inflammation in developing myopia. We collected aqueous humor samples from patients with axial length (AL) over 26 mm (n = 35) or shorter than 25 mm (n = 38) during cataract extraction surgery. Samples were assayed using the enzyme-linked immunosorbent assay (ELISA) kit for irisin and a multiplex immunoassay kit for BDNF, interleukin (IL)-6, IL-8 and IL-10, and tumor necrosis factor alpha (TNF-α). Irisin levels in the aqueous samples of the highly myopic eyes were significantly higher than in the control group (p = 0.027). The BDNF levels of the highly myopic group were significantly lower than in the control group (p = 0.043). Median level of leukemia inhibitory factor (LIF) for highly myopic group (2.035 pg/mL) was statistically significantly higher than in the control group (0.750 pg/mL) (U = 210.5, Z = -4.495, p < 0.001). Interleukin 1 receptor antagonist (IL-1ra) level in the aqueous samples of the highly myopic group was significantly lower than in the shorter AL group (p = 0.049). Interleukin 6, IL-8 and IL-10 levels were not significantly different between the 2 groups (p = 0.501, p = 0.059 and p = 0.192, respectively). Tumor necrosis factor α levels could only be detected in 30 samples and median levels in the 2 groups were not statistically significantly different (U = 99, Z = -0.482, p = 0.650). No correlation was found between IL-6, IL-8, IL-10 and TNF-α, and the AL (p > 0.05). Irisin was positively correlated with AL (p = 0.028, r = 0.287). The BDNF was negatively correlated with AL (p = 0.040, r = -0.246). Interleukin 1ra was negatively correlated with AL (p = 0.038, r = -0.276). There was also a correlation between LIF and AL (p < 0.001, r = 0.486). Higher irisin level in high myopia group opens a new direction to discover the relationship between PA and myopia. The decreased BDNF in high myopia group probably demonstrates the connection between myopia and neurodegenerative disease.


Reduced concentration of serum growth hormone (GH)-binding protein in children with chronic renal failure: correlation with GH insensitivity. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.
Growth retardation in children with chronic renal failure (CRF) despite normal or elevated GH levels indicates a peripheral insensitivity to the action of GH. One possible molecular mechanism is a reduced density of GH receptors in GH target organs. In humans, the circulating high affinity GH binding protein (GHBP) is thought to reflect GH receptor expression, because it is derived from the extra-cellular domain of the GH receptor by proteolytic cleavage. We, therefore, analyzed serum GHBP levels by ligand-mediated immunofunctional assay in 126 children with CRF compared to reference values obtained by analysis of 773 healthy children. In 77% of CRF patients, serum GHBP concentrations were below the mean for age- and gender-matched controls. The decrease in serum GHBP levels was related to the degree of renal dysfunction. In advanced CRF (glomerular filtration rate, < 35 mL/min.1.73 m2), mean age- and gender-adjusted GHBP levels were -1.40 +/- 0.18 SD score; 36% of patients had GHBP levels below the normal range (< -2 SD score). Children with end-stage renal disease (n = 26) had the lowest GHBP levels (-2.25 +/- 0.22 SD score). Multiple linear regression analysis revealed that body mass index, rather than glomerular filtration rate, is the prevailing determinant of serum GHBP levels in CRF. GHBP levels correlated with both the spontaneous growth rate ( r = 0.44; P < 0.0001) and the growth response to GH therapy (r = 0.48; P < 0.005), indicating decreased sensitivity to both endogenous and exogenous GH. Subcutaneous GH therapy did not consistently affect serum GHBP levels after 3 months of treatment. It is suggested that low GHBP levels in children with CRF represent a quantitative tissue GH receptor deficiency as one of the molecular mechanisms of GH insensitivity.