Underwater endoscopic mucosal resection for colorectal lesions: a meta-analysis.
Underwater endoscopic mucosal resection (UEMR) of colorectal lesions is emerging as an alternative method to conventional endoscopic mucosal resection (CEMR). This study aimed to evaluate the feasibility and safety of UEMR for colorectal lesions. The PubMed, Embase, Cochrane and Web of Science databases were searched before May 10, 2020. The primary outcomes were en bloc resection rate (feasibility) and adverse event rate (safety). The secondary outcome was recurrence and residual adenoma rate. If there was a comparison between UEMR and CEMR, data about en bloc resection, delayed bleeding, and recurrence and residual adenoma were extracted and compared. The pooling of the effect size was conducted using random-effects models, and the Q-statistic, τ2, and I2 were used to evaluate heterogeneity. Seventeen studies (759 patients, 893 lesions) were included. The pooled estimate for the en bloc resection rate was 59% (95% CI 43-75%) with significant heterogeneity (I2 = 97%). Due to the heterogeneity, it is not suitable to conduct pooled estimates analysis, so the en bloc resection rate was from 10 to 89%. The pooled estimate for delayed bleeding was 2% (95% CI, 1%-3%) and only two cases had perforation. The pooled rate of recurrence and residual adenoma was 5% (95% CI 2%-8%). Compared with CEMR, UEMR could achieve a higher en bloc resection rate (OR 1.61; 95% CI 1.02-2.53; p = 0.04) with a lower rate of recurrence and residual adenoma (OR 0.18; 95% CI 0.07-0.46; p < 0.01). UEMR for colorectal lesions was capable of a high en bloc resection rate, low adverse event rate and low recurrence. UEMR may be considered an effective and safe alternative for treating colorectal lesions.


Interhemispheric compensation: a hypothesis of TMS-induced effects on language-related areas.
Repetitive transcranial magnetic stimulation (rTMS) applied over brain regions responsible for language processing is used to curtail potentially auditory hallucinations in schizophrenia patients and to investigate the functional organisation of language-related areas. Variability of effects is, however, marked across studies and between subjects. Furthermore, the mechanisms of action of rTMS are poorly understood. Here, we reviewed different factors related to the structural and functional organisation of the brain that might influence rTMS-induced effects. Then, by analogy with aphasia studies, and the plastic-adaptive changes in both the left and right hemispheres following aphasia recovery, a hypothesis is proposed about rTMS mechanisms over language-related areas (e.g. Wernicke, Broca). We proposed that the local interference induced by rTMS in language-related areas might be analogous to aphasic stroke and might lead to a functional reorganisation in areas connected to the virtual lesion for language recovery.


Determining the impact of professional body recommendations on the screening of acquired carbapenemase-producing Enterobacterales in England.
Acquired carbapenemase-producing Gram-negative bacteria are an increasing public health concern globally and have been mandatory to report in England since October 2020. However, in light of the COVID-19 (SARS-CoV-2) pandemic, the Royal College of Pathologists (RCPath) released new guidance "for reducing the need for screening of CRE (carbapenem-resistant Enterobacterales) […] in low-risk areas", without defining "low risk". To assess the impact of the RCPath recommendations on screening of carbapenemase-producing Enterobacterales (CPE), an online Select Survey was sent to all NHS acute hospitals in England. The initial survey distribution was between March and April 2021 and the survey was relaunched between November 2021 and March 2022. In total, 54 hospitals completed the survey, representing 39.1% of 138 eligible Trusts. All hospitals had a CPE screening policy in place, and the majority of these reflect UKHSA's Framework of actions to contain CPE. Of the 23 hospitals who reported a reduction in CPE screening, only three (13.0%) indicated that this was due to the RCPath recommendations, with 21 (91.3%) indicating that there had been a natural reduction in the number of patients admitted to the Trust who would have previously been screened due to the COVID-19 pandemic. For most surveyed hospitals, CPE screening was not reduced due to the RCPath recommendations. However, the results highlighted that there is a large amount of individual variation in CPE screening practices and diagnostic testing between hospitals.


Clinical foot measurements as a proxy for plantar pressure testing in people with diabetes.
High plantar pressures are associated with increased foot ulcer risk in people with diabetes. Identification of high plantar pressures in people with diabetes is clinically challenging due to time and cost constraints of plantar pressure testing. Factors affecting foot biomechanics, including reduced joint range of motion and foot deformity, are implicated in the development of high plantar pressures and may provide a method to clinically identify those at risk of pressure related complications. The aim of this study was to investigate the contribution of joint range of motion and foot deformity measures on plantar pressures in a community dwelling group with diabetes. Barefoot (Tekscan HR Mat™) and in-shoe (Novel Pedar-X®) plantar pressure variables, weight bearing ankle dorsiflexion, hallux range of motion, lesser toe deformities and hallux abductus (HAV) scale were assessed in 136 adults with diabetes (52.2% male; mean age 68.4 years). Multivariate multiple linear regression was used to assess the effect of the four biomechanical factors plus neuropathy and body mass index on plantar pressure variables. Non-parametric bootstrapping was employed to determine the difference in plantar pressure variables for participants with two or more foot biomechanical pathologies compared to those with less than two pathologies. Almost one third (32%) of the cohort had two or more foot biomechanical pathologies. Participants with two or more foot biomechanical pathologies displayed significant increases in all barefoot plantar pressure regions (except forefoot), compared to those with less than two pathologies. No significant changes were found for the in-shoe plantar pressure variables. The regression model explains between 9.9% (95%CI: 8.4 to 11.4%) and 29.6% (95% CI: 28.2 to 31%), and between 2.5% (1.0 to 4.0%) and 43.8% (95% CI: 42.5-44.9%), of the variance in the barefoot and in-shoe plantar pressure variables respectively. Participants presenting with two or more factors affecting foot biomechanics displayed higher peak pressures and pressure time integrals in all foot regions compared to those with less than two factors. The tests used in this study could help clinicians detect elevated plantar pressures in people with diabetes and present an opportunity for early preventative interventions.


Soft-tissue osteoma of the hand: case report.
A soft-tissue osteoma is rare. Only 1 previous case involving the hand has been published. We report a 66-year-old man with a soft-tissue osteoma of the palm that was treated by marginal excision.


Hypothermia produced by peripheral and central injections of chlorpromazine in aged rabbits.
Hypothermia produced by IV administration of chlorpromazine (CPZ, 0.5-2.0 mg/kg) in a thermoneutral environment was greater in rabbits 2-4.5 years old than in animals under 24 months of age. One microgram CPZ given intracerebroventricularly (ICV) produced greater hypothermia in the older animals in tests performed in a thermoneutral environment while 0.25 and 0.5 microgram doses did not. The hypothermogenic effect of all three ICV doses of CPZ was enhanced in older rabbits exposed to cold. The brain of the older rabbit appears to be more sensitive to the hypothermogenic effects of CPZ. The findings suggest that this widely used tranquilizer can contribute to accidental hypothermia of the aged.


Natural attenuation of MTBE at two petroleum-hydrocarbon spill sites.
Methyl tert-butyl ether (MTBE) has been used as a gasoline additive to improve the combustion efficiency and to replace lead since 1978. Because it is widely used and it has been disposed inappropriately, MTBE has become a prevalent groundwater contaminant worldwide. In this study, two petroleum-hydrocarbon contaminated sites (Sites A and B) were selected to evaluate the occurrence and effectiveness of natural attenuation of MTBE at these two sites. Field investigation results indicate that the natural attenuation mechanisms of MTBE at both sites were occurring with the first-order attenuation rates of 0.0021 and 0.0048 1day(-1) at Sites A and B, respectively. Results also reveal that the intrinsic biodegradation pattern was the most important mechanism among the natural attenuation processes at both sites. Results from BIOSCREEN simulation suggest that biodegradation was responsible for 78 and 59% of MTBE mass reduction at Sites A and B, respectively. Investigation results show that MTBE plume at Site B could be effectively controlled via natural attenuation processes. However, MTBE plume at Site A has migrated to a farther downgradient area and passed the boundary line of the site. Thus, more active groundwater remedial technologies should be applied at Site A to protect the downgradient environment. Results from this study suggest that natural attenuation might be feasible to be used as a remedial option for the remediation of MTBE-contaminated site on the premise that (1) detailed site characterization has been conducted and (2) the occurrence and effectiveness of natural attenuation processes have been confirmed.


Human organoid models to study SARS-CoV-2 infection.
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the deadliest pandemics in history. SARS-CoV-2 not only infects the respiratory tract, but also causes damage to many organs. Organoids, which can self-renew and recapitulate the various physiology of different organs, serve as powerful platforms to model COVID-19. In this Perspective, we overview the current effort to apply both human pluripotent stem cell-derived organoids and adult organoids to study SARS-CoV-2 tropism, host response and immune cell-mediated host damage, and perform drug discovery and vaccine development. We summarize the technologies used in organoid-based COVID-19 research, discuss the remaining challenges and provide future perspectives in the application of organoid models to study SARS-CoV-2 and future emerging viruses.


Toxoplasma gondii and mast cell interactions in vivo and in vitro: experimental infection approaches in Calomys callosus (Rodentia, Cricetidae).
In the present work, we studied some qualitative and quantitative characteristics of mast cells located in the peritoneal cavity, submandibular and dorsal lymph nodes and ileum of Calomys callosus experimentally infected by Toxoplasma gondii. In uninfected animals, the majority of mast cells had similar ultra-structural characteristics, including several cytoplasmic granules with homogeneous and electron dense contents. However, after 1 h of infection, a significant influx of mast cells into peritoneal cavity was observed. The number of mast cells in this compartment decreased progressively in infected animals, and was significantly lower than the number of mast cells in control animals after 48 h of infection. Mast cells from infected animals or from purified suspensions that were infected in vitro presented significant morphological modifications, suggesting a degranulation process: cytoplasmic granules with electron dense content, fusion of the cytoplasmic granules, intracytoplasmic channels, cytoplasmic granules with flocculent material, plasma membrane rupture and granule contents in the extracellular environment. A remarkable increase in the influx of neutrophils toward the peritoneal cavity of the infected animals was observed after 12 h of infection. Moreover, this event occurred after the mast cell degranulation process took place. The relative increase in the number of mast cells and neutrophils was also followed by an increase in the number of macrophages, but there was a significant decrease in lymphocyte influx. After 48 h of infection, the parasite had spread from the peritoneal cavity to all organs examined. Also, mast cells from these organs showed evident morphological alterations, indicating the presence of the degranulation process. These results suggest that mast cells are deeply involved with the acute phase of the inflammatory response in this experimental model.


Evaluating the benefits of an antihypertensive agent using trials based on event and organ damage: the Systolic Hypertension in the Elderly Long-term Lacidipine (SHELL) trial and the European Lacidipine Study on Atherosclerosis (ELSA).
To assess the benefits of the calcium antagonist lacidipine on the prevention of cardiovascular events and the prevention of organ damage in two long-term clinical trials. SYSTOLIC HYPERTENSION IN THE ELDERLY LONG-TERM LACIDIPINE (SHELL) TRIAL: In the SHELL trial, the efficacy of lacidipine-based treatment is to be compared with that of thiazide-like diuretic (chlorthalidone)-based treatment in elderly patients with isolated systolic hypertension. The incidence of cardiovascular mortality and cardiovascular morbidity over a 5-year period are endpoints. In the ELSA trial, the effects of lacidipine-based treatment and beta-blocker (atenolol)-based treatment on the development and progression of carotid atherosclerosis are to be assessed in hypertensive patients. The primary endpoint of this study is the rate of change in the thickness of the carotid artery wall, measured with B-mode ultrasound.


Lectin-like binding of pertussis toxin to a 165-kilodalton Chinese hamster ovary cell glycoprotein.
Chinese hamster ovary (CHO) cells cluster in the presence of pertussis toxin, a response that is correlated with the ADP-ribosylation of a Mr = 41,000 membrane protein by the toxin. A ricin-resistant line of CHO cells (CHO-15B) which specifically lacks the terminal NeuAc----Gal beta 4GlcNAc oligosaccharide sequence on glycoproteins did not cluster in response to pertussis toxin. These cells do contain the Mr = 41,000 protein substrate for the enzymatic activity of the toxin which suggests that pertussis toxin, like certain plant lectins, does not bind to or is not internalized by the CHO-15B cells. There was no evidence of pertussis toxin binding to gangliosides or neutral glycolipids isolated from CHO cells but the toxin bound to a Mr = 165,000 component in N-octyglucoside extracts of CHO cells that had been separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotted to nitrocellulose. Plant lectins from Ricinus communis and Erythina cristagalli detected a similar size band in CHO cells and also did not react with CHO-15B cells. Unlike pertussis toxin, these plant lectins recognized two other major bands in CHO cell extracts and reacted best after sialidase treatment of nitrocellulose transfers containing CHO cell extracts. Conversely, sialidase treatment abolished binding a pertussis toxin and wheat germ agglutinin, a plant lectin that reacts with multivalent sialic acid residues on glycoproteins, to the Mr = 165,000 band. Purified B oligomer of pertussis toxin also uniquely detected a Mr = 165,000 component in CHO cell extracts while the A subunit of pertussis toxin was unreactive. These results indicate that pertussis toxin binds to a CHO cell glycoprotein with N-linked oligosaccharides and that sialic acid contributes to the complementary receptor site for the toxin. In addition, they suggest that a glycoprotein may serve as a cell surface receptor for pertussis toxin and that this interaction is mediated by a lectin-like binding site located on the B oligomer.


Publisher Correction: Innovative mouse model mimicking human-like features of spinal cord injury: efficacy of Docosahexaenoic acid on acute and chronic phases.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Electrocardiographic prediction of late gadolinium enhancement on cardiac magnetic resonance in Becker muscular dystrophy.
Dystrophin deficiency results in cardiomyopathy and fibrosis with variable onset. Little is known about electrocardiographic abnormalities in Becker muscular dystrophy and their relationship to underlying cardiac pathology. We hypothesized QRS fragmentation is associated with myocardial fibrosis on cardiac magnetic resonance imaging in Becker muscular dystrophy patients. We retrospectively evaluated 44 patients, and extracted data from clinically obtained electrocardiogram and cardiac magnetic resonance. Ventricular function and presence or absence late gadolinium enhancement representing myocardial fibrosis were recorded from imaging. Nearly half (19/42, 45%) of patients interrogated had myocardial fibrosis on cardiac magnetic resonance. Total number of electrocardiogram leads with QRS fragmentation (median 1 vs 4, p < 0.001) and either right or left axis deviation from median was significantly increased (13.6 vs. 44.8°, p < 0.001) in patients with myocardial fibrosis. Decreased leftward voltage in V6 correlated to both increased fibrosis and decreased cardiac function (p < 0.01). The positive likelihood ratio for underlying myocardial fibrosis in patients with two of the three findings on electrocardiogram was 8.47 (p < 0.0001). QRS fragmentation and axis deviation on electrocardiography are strongly predictive of myocardial fibrosis in Becker muscular dystrophy and may inform the use of advanced imaging in evaluation of these patients.


Patho-radiologic correlation of invasive pulmonary aspergillosis in the compromised host.
The autopsy findings and antemortem radiographic abnormalities were correlated in 20 patients with invasive pulmonary aspergillosis to define typical radiographic patterns, their progression and anatomic basis. Sixteen (80%) patients had radiographic abnormalities due to aspergillosis. Fifty-nine percent of the specific radiographic abnormalities seen in these patients were caused by anatomic lesions of asperigillosis and 67% of such anatomic lesions were radiographically definable. The most common initial radiographic pattern was a patchy density (single or multifocal) or a well defined nodule. The densities remained stable in half the patients but progressed, over several weeks to either diffuse consolidation or cavitation in the others. Most anatomic lesions were categorized as either nodular ("target") lesions (1-3 cm in diameter) or hemorrhagic infarctions (5-10 cm in diameter), both due to vascular invasion causing thrombosis and ischemic necrosis. Unlike pulmonary candidiasis, which is usually radiographically undetectable, invasive pulmonary asperigillosis frequently caused radiographically visible lesions.


High symptom burden is associated with impaired quality of life in colorectal cancer patients during chemotherapy:A prospective longitudinal study.
Multiple symptoms can have a negative impact on quality of life (QoL), but there is little information about the impact of multiple symptoms on QoL of patients with colorectal cancer (CRC) during outpatient chemotherapy. Therefore, the purpose was to assess the physical and mental QoL in CRC patients over six months of chemotherapy, to evaluate the association of QoL with the presence of multiple symptoms, and to determine which demographic and clinical characteristics are associated with physical and mental QoL scores. Outpatients with CRC (N = 120) completed the Medical Outcomes Study Short Form (SF-12) and Memorial Symptom Assessment Scale (MSAS) at eight time points during six months of chemotherapy. Linear mixed models for repeated measures were used to analyse QoL over time; and its association with demographic and clinical characteristics; and with the presence of multiple symptoms (e.g., 'numbness/tingling' and 'problems with sexual interest'). The CRC patients had worse physical and mental QoL scores than the general population at all time points. Impaired physical QoL was significantly associated with psychological symptom burden (p < 0.001) and numbness/tingling (p < 0.027). Impaired mental QoL was associated with physical symptom burden (p < 0.001), with being female (p < 0.009), younger age (p < 0.024), and having problems with sexual interest (p < 0.009). Impaired QoL was associated with symptoms in CRC outpatients. This information about the symptoms and characteristics associated with worse QoL during chemotherapy may help clinicians identify and inform at-risk patients.


A text-mining perspective on the requirements for electronically annotated abstracts.
We propose that the combination of human expertise and automatic text-mining systems can be used to create a first generation of electronically annotated information (EAI) that can be added to journal abstracts and that is directly related to the information in the corresponding text. The first experiments have concentrated on the annotation of gene/protein names and those of organisms, as these are the best resolved problems. A second generation of systems could then attempt to address the problems of annotating protein interactions and protein/gene functions, a more difficult task for text-mining systems. EAI will permit easier categorization of this information, it will help in the evaluation of papers for their curation in databases, and it will be invaluable for maintaining the links between the information in databases and the facts described in text. Additionally, it will contribute to the efforts towards completing database information and creating collections of annotated text that can be used to train new generations of text-mining systems. The recent introduction of the first meta-server for the annotation of biological text, with the possibility of collecting annotations from available text-mining systems, adds credibility to the technical feasibility of this proposal.


Cardio-oncology: the Nuclear Option.
Cardio-oncology focuses increased effort to decrease cancer treatment-related cardiotoxicity while continuing to improve outcomes. We sought to synthesize the latest in nuclear cardiology as it pertains to the assessment of left ventricular function in preventative guidelines and comparison to other modalities, novel molecular markers of pre-clinical cardiotoxicity, and its role in cardiac amyloid diagnosis. Planar ERNA (equilibrium radionuclide angiocardiography) provides a reliable and proven means of monitoring and preventing anthracycline cardiotoxicity, and SPECT ERNA using solid-state gamma cameras may provide reproducible assessments of left ventricular function with reduced radiation exposure. While certain chemotherapeutics have vascular side effects, the use of stress perfusion imaging has still not been adequately studied for routine use. Similarly, markers of apoptosis, inflammation, and sympathetic nerve dysfunction are promising, but are still not ready for uniform usage. SPECT tracers can assist in nonbiopsy diagnosis of cardiac amyloid. Nuclear cardiology is a significant contributor to the multimodality approach to cardio-oncology.


Electron paramagnetic resonance studies of the purified cytochrome P-450scc and P-45011beta from bovine adrenocortical mitochondria.
Electron paramagnetic resonance studies have been carried out on two species of cytochrome P-450 (P-450scc and P-45011beta) purified from bovine adrenocortical mitochondria. The g values of the steroid-bound cytochromes in the high spin form were determined at 4.2 degrees K to be 8.07, 3.60 and 1.70 for P-450scc and 8.00, 3.65 and 1.71 for P-45011beta. The E/D values were estimated to be 0.103 for P-450scc and 0.099 for P-45011beta. Either high spin P-450 was converted into the low spin form by the treatment with an NADPH dependent electron donating system and subsequent gel filtration in order to remove the steroid. The g values of the low spin ferric cytochromes were 2.423, 2.247 and 1.914 for P-450scc and 2.430, 2.251 and 1.919 for P-45011beta at 77 degrees K. The values for magnitude of delta/gamma, magnitude of V/gamma and k were 5.69, 5.21 and 1.11 for P-450scc and 5.94, 5.38 and 1.16 for P-45011beta. These studies indicate that there are some differences in the ferric heme environment between P-450scc and P-45011beta.


The occurrence of proteolipid antigens in Schistosoma mansoni.
Adult Schistosoma mansoni were shown to synthesize a peptide containing lipid against which an antiserum could be raised in rabbits. The proteolipid purified by silicic acid chromatography was soluble in chloroform/methanol mixtures, it was very hydrophobic and contained fatty acids in its molecule, as well as other unidentified neutral lipids.


Clinical use of the seromuscular jejunal patch for protection of the infected aortic stump.
Pathologic interactions between aortic prostheses and the gastrointestinal tract are very difficult problems in vascular surgery. After excision of the graft and proximal aortic closure, the major unsolved problem has been continued sepsis of the proximal aortic stump with subsequent fatal disruption. To provide healthy tissue for protection of this crucial area, we have devised a method in which a piece of jejunum on its vascular pedicle is opened along its antimesenteric border, the mucosa is removed, and the vascularized muscular wall is anchored to the aortic stump. This seromuscular jejunal patch was used clinically in three patients. Postmortem examinations in two of these patients 4 and 45 days postoperatively revealed no signs of infection, hematoma, or mucocele, and no histologic abnormalities; instead, the examinations did reveal firm tissue adherence between the aortic stumps and the seromuscular patches. The third patient is alive and well 1 year after this procedure. The three patients have demonstrated the feasibility of secure aortic stump protection by placement of well-prepared, vascularized seromuscular jejunal tissue over the potentially infected aortic stump. This technique may prevent postoperative stump dissolution and thus far appears to be a reasonable solution to this usually lethal problem.


Iron oxide/gold core/shell nanomagnetic probes and CdS biolabels for amplified electrochemical immunosensing of Salmonella typhimurium.
There is an imminent need for rapid methods to detect and determine pathogenic bacteria in food products as alternatives to the laborious and time-consuming culture procedures. In this work, an electrochemical immunoassay using iron/gold core/shell nanoparticles (Fe@Au) conjugated with anti-Salmonella antibodies was developed. The chemical synthesis and functionalization of magnetic and gold-coated magnetic nanoparticles is reported. Fe@Au nanoparticles were functionalized with different self-assembled monolayers and characterized using ultraviolet-visible spectrometry, transmission electron microscopy, and voltammetric techniques. The determination of Salmonella typhimurium, on screen-printed carbon electrodes, was performed by square-wave anodic stripping voltammetry through the use of CdS nanocrystals. The calibration curve was established between 1×10(1) and 1×10(6) cells/mL and the limit of detection was 13 cells/mL. The developed method showed that it is possible to determine the bacteria in milk at low concentrations and is suitable for the rapid (less than 1h) and sensitive detection of S. typhimurium in real samples. Therefore, the developed methodology could contribute to the improvement of the quality control of food samples.


Effects of retinoids on the meiosis in the fetal rat ovary in culture.
We investigated the effect of retinoids on the entrance of female germ cells into meiotic prophase and their progression through it, using explants of rat ovaries from 14.5 days post coïtum (dpc) fetuses cultured with or without 10(-6) M retinoic acid (RA) or 10(-9) M retinoic acid receptor alpha (RARalpha) specific agonist. The percentages of oogonia and of oocytes at each meiotic stage in the ovary were evaluated at explantation (D0) and after 3 (D3), 5 (D5) and 9 (D9) days of culture and on equivalent stages in vivo (i. e. 17.5 and 23.5 dpc). The number of germ cells per ovary were counted at D0, D3 and D9. Newly explanted (D0) ovaries contained no germ cell in meiosis. In control medium some germ cells had spontaneously reached the stage leptotene and very few the zygotene on D3. The first pachytene were observed on D5 and the first diplotene on D9. This pattern mimicked that which occurs in vivo although with a slight delay. RA reduced the percentage of oogonia by more than half and increased the percentage of zygotene by more than 22-fold on D3, showing that it accelerated entrance into meiosis. This effect was also observed in response to RARalpha agonist. RA increased the percentage of zygotene and reduced the percentage of pachytene on D9, showing that it can also delay the zygotene/pachytene transition. Lastly, RA reduced the total number of germ cells present on D3 but not on D9. This may be the result of a double effect of RA on the number of germ cells: negative when the cells are in proliferation (D0 to D3) and positive when they entered in meiotic prophase (after D3). Thus, RA is a potential regulator of germ cells meiosis and number in the fetal ovary.


SYNTHESIS AND EVALUATION OF NEW PHTHALAZINE SUBSTITUTED β-LACTAM DERIVATIVES AS CARBONIC ANHYDRASE INHIBITORS.
A new series of phthalazine substituted β-lactam derivatives were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase (hCA I and II) were evaluated. 2H-Indazolo[2,1-b]phthala- zine-trione derivative was prepared with 4-nitrobenzaldehyde, dimedone, and phthalhydrazide in the presence of TFA in DMF, and the nitro group was reduced to 13-(4-aminophenyl)-3,3-dimethyl-3,4-dihydro- 2H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione with SnCl2 · 2H2O. The reduced compound was re- acted with different aromatic aldehydes, and phthalazine substituted imines were synthesized. The imine compounds undergo (2+2) cycloaddition reactions with ketenes to produce 2H-indazolo[2,1-b]phthala-zine-trione substituted β-lactam derivatives. The β-lactam compounds were tested as inhibitors of the CA isoenzyme activity. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. 1-(4-(3,3-dimethyl- 1,6,1 1-trioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2-b]phthalazin-13- yl)phenyl)-2-oxo-4-p-tolylazetidin-3-yl acetate (IC50 = 6.97 µM for hCA I and 8.48 µM for hCA II) had the most inhibitory effect.


Implementation of computer-guided implant planning using digital scanning technology for restorations supported by conical abutments: A dental technique.
Conometric retention has recently been proposed as an alternative to cement- or screw-retention for fixed restorations. Conometric copings can only compensate for slightly nonparallel placement without interfering with retention. This article describes a method of using digital scanning technology to facilitate computer-guided implant planning when an immediate restoration supported by conical abutments is planned with a guided-welded approach. The procedure involves importing the scan data of the conometric coping and of the definitive cast obtained from the surgical template into the implant planning software. This approach increases the accuracy of computer-guided implant planning and reduces the time needed for the surgery.


Heavy metal removal from aqueous solutions using engineered magnetic biochars derived from waste marine macro-algal biomass.
Despite the excellent sorption ability of biochar for heavy metals, it is difficult to separate and reuse after adsorption when applied to wastewater treatment process. To overcome these drawbacks, we developed an engineered magnetic biochar by pyrolyzing waste marine macro-algae as a feedstock, and we doped iron oxide particles (e.g., magnetite, maghemite) to impart magnetism. The physicochemical characteristics and adsorption properties of the biochar were evaluated. When compared to conventional pinewood sawdust biochar, the waste marine algae-based magnetic biochar exhibited a greater potential to remove heavy metals despite having a lower surface area (0.97m2/g for kelp magnetic biochar and 63.33m2/g for hijikia magnetic biochar). Although magnetic biochar could be effectively separated from the solution, however, the magnetization of the biochar partially reduced its heavy metal adsorption efficiency due to the biochar's surface pores becoming plugged with iron oxide particles. Therefore, it is vital to determine the optimum amount of iron doping that maximizes the biochar's separation without sacrificing its heavy metal adsorption efficiency. The optimum concentration of the iron loading solution for the magnetic biochar was determined to be 0.025-0.05mol/L. The magnetic biochar's heavy metal adsorption capability is considerably higher than that of other types of biochar reported previously. Further, it demonstrated a high selectivity for copper, showing two-fold greater removal (69.37mg/g for kelp magnetic biochar and 63.52mg/g for hijikia magnetic biochar) than zinc and cadmium. This high heavy metal removal performance can likely be attributed to the abundant presence of various oxygen-containing functional groups (COOH and OH) on the magnetic biochar, which serve as potential adsorption sites for heavy metals. The unique features of its high heavy metal removal performance and easy separation suggest that the magnetic algae biochar can potentially be applied in diverse areas that require biosorbents for pollutant removal.


Causes of death in the United States, 1999 to 2014.
Statistical methods have been widely used in studies of public health. Although useful in clinical research and public health policy making, these methods could not find correlation among health conditions automatically, or capture the temporal evolution of causes of death correctly. To cope with two challenges above, we implement an unsupervised machine learning model, termed topic models, to investigate the mortality data of the United States. Our model successfully groups morbidities based on their correlation, and reveals the temporal evolution of these groups from 1999 to 2014, which are also validated by existing literature. This work could provide a novel view for clinical practitioners to provide more accurate healthcare service, and for public health policymakers to make better policy.


Correlation between cell morphology and aggrecan gene expression level during differentiation from mesenchymal stem cells to chondrocytes.
A morphological parameter of polygonal index was defined as the ratio of cell adhesion area versus the square of the major cell axis, and cells that had an adhesion area larger than 4000 mum(2) and a polygonal index larger than 0.3 were considered large polygonal cells. Cell morphology tended to change from fibroblast-like to polygonal and the percentage of the large polygonal cells increased almost in proportion to aggrecan mRNA expression level during the differentiation culture of mesenchymal stem cells (MSCs) to chondrocytes. Approximately 80% of the large polygonal cells were negative for MSC marker (CD90, CD166) expression and the aggrecan mRNA expression level of the large polygonal cells was markedly higher than that of cells with other morphologies.


Expression of interleukin-17RC protein in normal human tissues.
Interleukin-17 (IL-17) cytokines and receptors play an important role in many autoimmune and inflammatory diseases. IL-17 receptors IL-17RA and IL-17RC have been found to form a heterodimer for mediating the signals of IL-17A and IL-17F cytokines. While the function and signaling pathway of IL-17RA has been revealed, IL-17RC has not been well characterized. The function and signaling pathway of IL-17RC remain largely unknown. The purpose of the present study was to systematically examine IL-17RC protein expression in 53 human tissues. IL-17RC expression in 51 normal human tissues and two benign tumors (i.e., lymphangioma and parathyroid adenoma) on the tissue microarrays was determined by immunohistochemical staining, using two polyclonal antibodies against IL-17RC. IL-17RC protein was expressed in many cell types including the myocardial cells, vascular and lymphatic endothelial cells, glandular cells (of the adrenal, parathyroid, pituitary, thyroid, pancreas, parotid salivary, and subepidermal glands), epithelial cells (of the esophagus, stomach, intestine, anus, renal tubule, breast, cervix, Fallopian tube, epididymis, seminal vesicle, prostate, gallbladder, bronchus, lung, and skin), oocytes in the ovary, Sertoli cells in the testis, motor neurons in the spinal cord, autonomic ganglia and nerves in the intestine, skeletal muscle cells, adipocytes, articular chondrocytes, and synovial cells. High levels of IL-17RC protein expression were observed in most vascular and lymphatic endothelium and squamous epithelium. The epithelium of the breast, cervix, Fallopian tube, kidney, bladder and bronchus also expressed high levels of IL-17RC, so did the glandular cells in the adrenal cortex, parotid salivary and subepidermal glands. In contrast, IL-17RC protein was not detectable in the smooth muscle cells, fibroblasts, antral mucosa of the stomach, mucosa of the colon, endometrium of the uterus, neurons of the brain, hepatocytes, or lymphocytes. Nevertheless, IL-17RC protein was expressed in the vascular endothelium within the tissues where the IL-17RC-negative cells resided. IL-17RC protein is expressed in most human tissues, the function of which warrants further investigation.


Rational design of novel fusion rabies glycoproteins displaying a major antigenic site of foot-and-mouth disease virus for vaccine applications.
Chimeric virus-like particles are self-assembling structures composed of viral proteins that had been modified to incorporate sequences from different organisms, being able to trigger immune responses against the heterologous sequence. However, the identification of suitable sites for that purpose in the carrier protein is not an easy task. In this work, we describe the generation of rabies chimeric VLPs that expose a major antigenic site of foot-and-mouth disease virus (FMDV) by identifying suitable regions in rabies glycoprotein (RVG), as a proof of concept of a novel heterologous display platform for vaccine applications. To identify adequate sites for insertion of heterologous sequences without altering the correct folding of RVG, we identified regions that were evolutionally non-conserved in Lyssavirus glycoproteins and performed a structural analysis of those regions using a 3D model of RVG trimer that we generated. The heterologous sequence was inserted in three different sites within RVG sequence. In every case, it did not affect the correct folding of the protein and was surface exposed, being recognized by anti-FMDV antibodies in expressing cells as well as in the surface of VLPs. This work sets the base for the development of a heterologous antigen display platform based on rabies VLPs. KEY POINTS: • Adequate regions for foreign epitope display in RVG were found. • G-H loop of FMDV was inserted in three regions of RVG. • The foreign epitope was detected by specific antibodies on fusion proteins. • G-H loop was detected on the surface of chimeric VLPs.


Transcriptional regulation of the genes encoding chitin and β-1,3-glucan synthases from Ustilago maydis.
Transcriptional regulation of genes encoding chitin synthases (CHS) and β-1,3-glucan synthase (GLS) from Ustilago maydis was studied. Transcript levels were measured during the growth curve of yeast and mycelial forms, in response to ionic and osmotic stress, and during infection of maize plants. Expression of the single GLS gene was constitutive. In contrast, CHS genes expression showed differences depending on environmental conditions. Transcript levels were slightly higher in the mycelial forms, the highest levels occurring at the log phase. Ionic and osmotic stress induced alterations in the expression of CHS genes, but not following a defined pattern, some genes were induced and others repressed by the tested compounds. Changes in transcripts were more apparent during the pathogenic process. At early infection stages, only CHS6 gene showed significant transcript levels, whereas at the period of tumor formation CHS7 and CHS8 genes were also were induced.


Mohs surgery report: design of an appropriate rhombic flap for a circular defect created by Mohs microscopically controlled surgery.
The rhombic flap is a transposition flap based on exact geometric design. The rhombic transposition principle, however, can be applied to circular as well as to geometric wounds. A method is suggested by which the best rhombic flaps for any specific anatomic site can be generated without conversion of the wound to a rhombic design.


E. coli O104:H4 outbreak and haemolytic-uraemic syndrome.
The first cases of the European epidemic of Shiga toxin-producing Escherichia coli O104:H4 (STEC-O104:H4) infection were reported in Germany in April 2011. To characterize the 2011 STEC-O104:H4 outbreak and its management. A literature review is made to assess the state of the art in STEC-haemolytic-uraemic syndrome (HUS) epidemiology, pathogenesis, management and prognosis, focusing on critically ill adults. References were obtained from the European Center for Disease Control and World Health Organization epidemiological updates, in addition to a PubMed search covering the period from 1980 to August 2011, including all published work on STEC-014:H4 and reviews on HUS management and prognosis. The epidemic originated from a bean and seed sprouts farm in Lower Saxony, and was caused by the O104:H4 strain - a highly antibiotic resistant, hybrid enteroaggregative - Shiga toxin producing E. coli strain (STEC). The infection was characterized by increased HUS (25%) and a higher mortality rate. STEC enteritis and HUS are associated with significant mortality and morbidity, especially amongst patients with severe renal and neurological disorders. Management should center on prompt kidney protection by maintaining adequate renal perfusion, in addition to avoiding diuretics and nephrotoxic agents. The published studies regarding antibiotic treatment lack good quality evidence. However, recent data suggest a potential modulating effect that explains the conflicting data but moreover suggests that azithromycin might be of use. Neutralizing monoclonal antibodies are a promising new therapy for STEC-HUS, with currently ongoing studies. Other treatments have not been shown to be superior to supportive therapy alone.


The crystal structure of TlMgCl3 from 290 K to 725 K.
The title compound, thallium magnesium trichloride, has been identified as a scintillator with both moderate gamma-stopping power and moderate light yield. Knowledge of its crystal structure is needed for further development. This work determines the crystal structure of TlMgCl3 to be hexa-gonal P63/mmc (No. 194) and isostructural with RbMgCl3, contrary to previously reported data. This structure was obtained by single-crystal X-ray diffraction and was further confirmed by neutron diffraction measurements. Extending neutron diffraction measurements to high temperature, the data show that TlMgCl3 maintains this crystal structure from 290 K up through 725 K, approaching the melting point of 770 K. Anisotropic thermal expansion coefficients increase over this temperature range, from 31 to 38 × 10-6 K-1 along the a axis and from 19 to 34 × 10-6 K-1 along the c axis.


Effects of tryptophan supplementation on cashmere fiber characteristics, serum tryptophan, and related hormone concentrations in cashmere goats.
This study was designed to investigate the effects of tryptophan (Trp) supplementation on cashmere fiber characteristics and on serum Trp, melatonin (MEL), prolactin (PRL), insulin-like growth factor 1 (IGF-1), triiodothyronine (T3), and thyroxine (T4) concentrations in cashmere goats during the cashmere fast-growth period. Thirty-six Liaoning cashmere wether goats were stratified on the basis of body weight (28±0.8 kg) and assigned randomly to 1 of the following 4 rumen-protected Trp treatments: 0, 2.0, 4.0, and 6.0 g per goat per day. The experimental period lasted 137 d. Blood samples were collected monthly during the daytime (8:00 AM) and at night (8:00 PM). Tryptophan supplementation improved cashmere growth rates, cashmere weight, and body weight (P=0.001) and increased serum Trp levels, nighttime MEL concentrations, IGF-1, and T3 and T4 concentrations (P<0.05). Across the treatments and sampling months, a highly positive correlation between cashmere growth rate and nighttime serum MEL concentrations was observed (r=0.879, P=0.001). A moderately negative correlation between cashmere growth rates and serum PRL concentrations during the day and at night (rday=-0.645, P=0.007; rnight=-0.583, P=0.018) was observed. A moderately positive correlation between the cashmere growth rate and the daytime serum IGF-1 concentration (r=0.536, P=0.032) was observed, and no correlation was found between the cashmere growth rate and the other serum hormone concentrations. These data indicate that changes in serum concentrations of MEL, IGF-1, and PRL are related to cashmere growth in Liaoning cashmere goats during the cashmere fast-growth period. Under the experimental conditions of the current trial, we suggest that Trp may promote cashmere growth by increasing daytime IGF-1 and nighttime MEL secretion.


Periodontal conditions in a Swedish city population of adolescents: a comparison between smokers and never-smokers.
The aim of this study was to evaluate the influence of smoking on the periodontal conditions of a randomly selected population sample of 19-year-old individuals. A population sample of 272 randomly selected 19-year-old individuals living in Göteborg, Sweden, was clinically examined with regard to oral hygiene, gingivitis, deepened periodontal pockets, probing attachment loss (PAL) and gingival recession. On bitewing radiographs, alveolar bone level and presence of dental calculus were assessed. The subjects were classified as 'never-smokers' or smokers based on information obtained by a questionnaire-based interview. The mean plaque and gingivitis scores were for never-smokers 58% (SE 1.7) and 46% (1.4) respectively, and for smokers 60% (2.2) and 42% (2.1) respectively. Of the never-smokers and smokers respectively, 38% and 35% showed a prevalence of gingivitis of > 50%. The mean number of sites with periodontal pockets > or = 4 mm was 12 (0.9) in never-smokers and 13 (1.4) in smokers. Of both never-smokers and smokers, 75% did not have any site with PAL > or = 2 mm, and only six individuals (3%), all never-smokers, showed more than three sites with a PAL of > or = 2 mm (facial sites). Logistic regression analyses revealed that smoking was a poor discriminator for identification of subjects with periodontal destruction (OR 0.62-1.33). In the present population sample of adolescents, characterised by high prevalence of plaque and gingivitis, smoking habits did not contribute to a higher prevalence or severity of periodontal destruction.


Intronic polymorphism (1541-1542delGT) of the constitutive heat shock protein 70 gene has functional significance and shows evidence of association with lung cancer risk.
Somatic mutations of 11q23.3-linked constitutive heat shock protein 70 gene (HSPA8 alias HSC70) are detected by others in breast carcinomas. To examine whether intragenic, somatic mutations of HSPA8 occur in lung carcinomas, we sequenced its exons 2-8, with adjacent intronic sequences, in a series of DNA samples from non-small-cell lung cancers (NSCLC). Twenty-one polymorphisms were detected, but no somatic mutation. However, we observed an association between the HSC70 1541-1542delGT genotype and the immunohistochemical staining pattern of HSC70 protein. Tumors with weak (+) HSC70 protein staining were more frequent in the carriers of the polymorphic 1541-1542delGT allele than in the homozygotes of the major allele (20% vs. 6%, P=0.05 by Fisher's exact test). This statistically significant association prompted us to test the polymorphism functionally. The method we developed for the functional evaluation of intronic sequence alterations showed that the HSPA8 intron 2 with the deleted GT dinucleotide was associated with noticeable (approximately 20%) and statistically significant (P=0.005) reduction of the reporter gene activity. Our case-control analysis showed that the 1541-1542delGT heterozygous genotype was associated with significantly decreased risk for lung cancer (crude odds ratio (OR)=0.44; 95% confidence interval (CI): 0.23-0.84). To the best of our knowledge, this is the first report on the association between a polymorphism of a gene coding for the chaperone protein and lung cancer risk. Moreover, the simple method reported here, based on the dual-luciferase reporter assay system, can be useful for testing functional significance of polymorphisms located in introns of other genes.


Outlet strut fracture and leaflet escape of Bjork-Shiley convexo-concave valve.
Prosthetic valve fracture is a serious complication and may arise in patient post-valve replacement. We experienced an outlet strut fracture and leaflet escape of a Bjork-Shiley convexo-concave valve. We performed an emergency redo mitral valve replacement and successfully retrieved the fractured strut and escaped leaflet from superficial femoral artery and the abdominal aorta. The patient showed an uneventful postoperative recovery.


Unmanipulated HLA-mismatched/haploidentical peripheral blood stem cell transplantation for high-risk hematologic malignancies.
Haploidentical hematopoietic stem cell transplantation (HSCT) has been increasingly applied in high-risk hematologic patients due to the absence of HLA-matched donors. The aim of this study was to investigate the efficacy and safety of unmanipulated haploidentical allogeneic peripheral blood stem cells transplantation (PBSCT) for hematologic malignancies. Patients who underwent unmanipulated HLA-mismatched/haploidentical PBSCT from July 2007 to March 2010 with high-risk hematologic malignancies were enrolled for retrospective analysis. Twenty-one patients with high-risk hematologic malignancies underwent unmanipulated HLA-mismatched/haploidentical PBSCT with myeloablative conditioning. The numbers of CD34+ cells infused at transplantation were 4.81 (range, 2.61-11.47)×10(6)/kg. Patients achieved myeloid and platelet engraftment at a median of 16.5 and 20 days, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) on Day 100 was 52.7±10.7%, and the 2-year cumulative incidence of chronic GVHD was 39.5±10.6%. The cumulative incidences of cytomegalovirus antigenemia and hemorrhagic cystitis within 100 days after PBSCT were 59.5±16.7 and 34.8±13.3%, respectively. One hundred-day transplantation-related mortality (TRM) rate and the 2-year cumulative TRM rate were 14.3 and 20.5±7.8%, respectively. The 2-year cumulative overall survival was 62.1±11.4% and the probability of disease-free survival at 2 years was 55.6±10.7% with a 16-month median follow-up. Unmanipulated PBSCT is a promising protocol in HLA-mismatched/haploidentical transplant settings.


Understanding the effects of pre-processing on extracted signal features from gait accelerometry signals.
Gait accelerometry is an important approach for gait assessment. Previous contributions have adopted various pre-processing approaches for gait accelerometry signals, but none have thoroughly investigated the effects of such pre-processing operations on the obtained results. Therefore, this paper investigated the influence of pre-processing operations on signal features extracted from gait accelerometry signals. These signals were collected from 35 participants aged over 65years: 14 of them were healthy controls (HC), 10 had Parkinson׳s disease (PD) and 11 had peripheral neuropathy (PN). The participants walked on a treadmill at preferred speed. Signal features in time, frequency and time-frequency domains were computed for both raw and pre-processed signals. The pre-processing stage consisted of applying tilt correction and denoising operations to acquired signals. We first examined the effects of these operations separately, followed by the investigation of their joint effects. Several important observations were made based on the obtained results. First, the denoising operation alone had almost no effects in comparison to the trends observed in the raw data. Second, the tilt correction affected the reported results to a certain degree, which could lead to a better discrimination between groups. Third, the combination of the two pre-processing operations yielded similar trends as the tilt correction alone. These results indicated that while gait accelerometry is a valuable approach for the gait assessment, one has to carefully adopt any pre-processing steps as they alter the observed findings.


Systemic immune-inflammation index could estimate the cross-sectional high activity and the poor outcomes in immunosuppressive drug-naïve patients with antineutrophil cytoplasmic antibody-associated vasculitis.
We investigated whether systemic immune-inflammation index (SII) at diagnosis can estimate the cross-sectional high activity and predict the poor outcomes in immunosuppressive drug-naïve patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). We retrospectively reviewed the medical records of 163 patients with AAV and obtained clinical and laboratory data. We calculated Birmingham vasculitis activity score (BVAS) as well as five-factor score (FFS) (2009) at diagnosis. SII at diagnosis was calculated by the equation of (SII at diagnosis = platelet count × neutrophil count/lymphocyte count at diagnosis). Severe AAV was defined as BVAS at diagnosis ≥16. The odds ratio was assessed using the multivariable logistic regression analysis and cumulative survival rates were compared by the Kaplan-Meier survival analysis. The median age at diagnosis was 58.0 years old and 51 patients were men. The median BVAS was 12.0. Fifty-seven patients had severe AAV. The median SII at diagnosis was 1349.6. In the multivariable analysis, only SII exhibited a significant odds ratio for the cross-sectional severe AAV (P = 0.043). We obtained the cut-off of SII at diagnosis for severe AAV as 1573.56. Patients with SII at diagnosis ≥1573.56 exhibited a significantly high relative risk of the cross-sectional severe AAV compared to those without (relative risk 4.625). Furthermore, patients with SII at diagnosis ≥1573.56 exhibited significantly the lower cumulative relapse free and renal survivals than those without. Systemic immune-inflammation index at diagnosis could estimate the cross-section severe AAV and predict the poor outcomes in AAV patients.


Inactivation of Microcystis aeruginosa by hydrogen-terminated porous Si wafer: Performance and mechanisms.
We proposed a method to inactivate Microcystis aeruginosa by using hydrogen-terminated porous Si (H-PSi) wafer. The influences of oxidation time on the removal of M. aeruginosa were investigated. Samples oxidized by H-PSi wafer were subsequently grown under illuminated culture conditions. The results demonstrated that the optimal oxidation time was about 1h, which could control the growth of M. aeruginosa about 65%, after 3days culture. Simultaneously, extracellular microcystins was decreased from 14.65 to 7.06μgL(-1) and remain relative integrity of M. aeruginosa cells which could avoid secretion of large amounts of organic material. Multiple analysis techniques including fluorescence excitation-emission matrix (EEM) and fluorescence microscope were used to reveal the inhibition mechanisms of M. aeruginosa. Meanwhile, analyses of reactive oxygen level, malondialdehyde content, and superoxide dismutase activity indicated that the damage and inactivate of M. aeruginosa cells are mainly due to accumulation of lipid peroxidation and inhibition of normal physiological metabolism by free radicals produced by H-PSi wafer under visible light irradiation. In conclusion, these results suggest that H-PSi wafer may be useful in controlling growth and survival of M. aeruginosa in many large lakes and reservoirs, thus mitigating many of the economic, esthetic ecological impacts of the invasive alga.


Usefulness of CHROMagar Candida Medium, Biochemical Methods--API ID32C and VITEK 2 Compact and Two MALDI-TOF MS Systems for Candida spp. Identification.
This study was conducted to compare of the yeasts identification results obtained with two new systems using the MALDI-TOF MS technique with the ones obtained using the routine identification methods of Candida spp. in clinical microbiology laboratories. All 124 Candida spp. isolates were recovered from the routine examination of clinical specimens in microbiological laboratories and collected in the Centre of Quality Control in Microbiology in Warsaw (Poland). Our findings confirm the high agreement (98%) of fungal identification using the standard, biochemistry laboratory methods and mass spectrometry technique.


Dermal thickness and echogenicity using DermaScan C high frequency ultrasound: Methodology and reliability testing in people with and without primary lymphoedema.
DermaScan C high frequency ultrasound was investigated for image capture and analysis of dermal measures in people with and without primary lymphoedema. Three repeated images were taken at six sites in people without lymphoedema (NLO). Intra-rater reliability was assessed by taking three sets of measures on images from 10 people and inter-session reliability by capturing three images, lifting the probe from the skin in between. Methods were adjusted, and repeated images from four sites were taken in people with primary lymphoedema (PLO) and reliability re-assessed. Intra-rater reliability in NLO and PLO for echogenicity measures were excellent (NLO ICC(3,1) : .989; PLO .997) across all sites and specific to each site (calf: ICC(3,1) : .989; and foot: ICC(3,1) : .999, respectively). Inter-session reliability was moderate for NLO (ICC(3,1) : .727), improving after method modifications for PLO (ICC(3,1) : .916). When investigated by site, inter-session reliability was good in the foot (ICC(3,1) : .811) and moderate in the calf (ICC(3,1) : .616). Mean thickness analysed by site resulted in good inter-session reliability only in the foot (ICC(3,1) .838). Intra-rater reliability was excellent using the DermaScan C for dermal measures in people with primary lymphoedema. Inter-session reliability required particular attention to method and gain settings.


Super-rational aspiration promotes cooperation in the asymmetric game with peer exit punishment and reward.
Super-rational aspiration induced strategy updating with exit rights has been considered in some previous studies, in which the players adjust strategies in line with their payoffs and aspirations, and they have access to exit the game. However, exit payoffs for exiting players are automatically allocated, which is clearly contrary to reality. In this study, evolutionary cooperation dynamics with super-rational aspiration and asymmetry in the Prisoner's Dilemma game is investigated, where exit payoffs are implemented by local peers. The results show that for different population structures, the asymmetry of the system is always contributive to the participation of the players. Furthermore, we show that under different exit payoffs, super-rationality and asymmetry are conductive to the evolution of cooperation.


Na+, Li+, and Cl- transport by brush border membranes from rabbit jejunum.
Na+, Li+, K+, Rb+, Br-, Cl- and SO4(2-) transport were studied in brush border membrane vesicles isolated from rabbit jejunum. Li+ uptakes were measured by flameless atomic absorption spectroscopy, and all others were measured using isotopic flux and liquid scintillation counting. All uptakes were performed with a rapid filtration procedure. A method is presented for separating various components of ion uptake: 1) passive diffusion, 2) mediated transport and 3) binding. It was concluded that a Na+/H+ exchange mechanism exists in the jejunal brush border. The exchanger was inhibited with 300 microM amiloride or harmaline. The kinetic parameters for sodium transport by this mechanism depend on the pH of the intravesicular solution. The application of a pH gradient (pHin = 5.5, pHout = 7.5) causes an increase in Jmax (50 to 125 pmol/mg protein . sec) with no change in Kt (congruent to 4.5 nM). Competition experiments show that other monovalent cations, e.g. Li+ and NH4+, share the Na+/H+ exchanger. This was confirmed with direct measurements of Li+ uptakes. Saturable uptake mechanisms were also observed for K+, Rb+ and SO4(2-), but not for Br-. The Jmax for K+ and Rb+ are similar to the Jmax for Na+, suggesting that they may share a transporter. The SO4(2-) system appears to be a Na+/SO4(2-) cotransport system. There does not appear to be either a Cl-/OH- transport mechanism of the type observed in ileum or a specific Na+/Cl- symporter.


Anemia after gastrectomy in long-term survivors of gastric cancer: A retrospective cohort study.
The prevalence of gastric cancer in Korea is increasing, and anemia is one of the most common complications of a gastrectomy. The purpose of this study was to estimate the incidence of anemia and assess its associated factors in long-term gastric cancer survivors. This study was a retrospective cohort study of gastric cancer patients who visited a single medical center from January 2009 to December 2014 in Korea. We included 385 patients who survived for at least five years after gastrectomy with no recurrence or metastasis. Anemia was defined by World Health Organization criteria (Hb < 12 g/dL in women and <13 g/dL in men). Hemoglobin levels decreased from 14.24 ± 1.23 mg/dL before surgery to 13.60 ± 1.57 mg/dL one year after surgery (P < 0.001). The cumulative incidence rate of anemia after surgery increased linearly from 18.7% in the first year to 39.5% in the fifth year. The risk of anemia was higher in females (RR, 2.00; 95% CI, 1.26-3.18), patients that received total gastrectomy (RR, 3.00; 95% CI, 2.09-4.30) and patient with diabetes (RR, 1.87; 95% CI, 1.05-3.22). A higher postoperative BMI decreased the risk of anemia (RR, 0.38; 95% CI, 0.22-0.67). During five years of follow-up after gastrectomy, the incidence of anemia steadily increased, and the risk of anemia was higher in females, total gastrectomy patients, patients with diabetes, low BMI patients.


[Assessment of the effectiveness of analgesics in the pain laboratory].
In 1987 the Fifth World Congress on Pain was held in Hamburg with about 2,500 participants, for the first time in Germany after the previous congresses in Florence, Montreal, Edinburgh and Seattle. --In the following lines, Professor Bromm, one of the organisers of the congress, gives a brief insight into modern methods to measure the efficacy of analgesics.


Chronic vulvar fissure: approach with cross-linked hyaluronic acid.
This report aims to prospectively describe the effectiveness and safety of injected cross-linked hyaluronic acid (HA) for the treatment of chronic vulvar fissures. A descriptive prospective case series design including 15 patients affected by chronic vulvar fissures who were treated with cross-linked HA filler between December 2020 and July 2021. The validated 21-item Vulvovaginal Symptoms Questionnaire (VSQ) was used to evaluate the results from baseline up to 9 months after the HA infiltration. A total of 15 patients suffering from chronic vulvar fissures were treated with an injection of 19 mg/mL HA filler. We found a significant improvement in VSQ scores at the end of the treatment compared to baseline. Patients reported excellent tolerance of the procedure, and no complications were recorded. Cross-linked HA infiltration of the vulvar vestibule and posterior vaginal wall appeared to be a promising approach for chronic vulvar fissures.


Financial impact of radiological reports on medical-legal evaluation of compensation for meniscal lesions.
To evaluate any discrepancy between radiological reports for clinical purposes and for medicolegal purposes and to quantify its economic impact on repayments made by private insurance companies for meniscal injuries of the knee. The medical records obtained pertaining to 108 knee injury patients (mean age 43.3 years) assessed over a period of 12 months were analysed. Clinical medical reports, aimed at assessing the lesion, and medicolegal reports, drawn up with a view to quantifying compensation, were compared. Unlike reports for clinical purposes in reports for medicolegal purposes, in the evaluation of meniscal lesions, in addition to morphological features of lesions, chronological, topographical, severity and exclusion criteria were applied. To estimate the economic impact resulting from the biological damage, we consulted an actuarial table based on the 9-point minor incapacity classification system. Meniscal lesions not compatible with a traumatic event and therefore not eligible for an insurance payout were found in 56 patients. Of these, 37 failed exclusion criteria, while 19 failed to meet chronological criteria. This difference resulted in a reduction in compensation made by private insurance companies with savings estimated with a saving between euro 203,715.41 and euro 622,315.39. The use of a clinical report for medicolegal purposes can be a source of valuation error, as chronological and/or dynamic information regarding the trauma mechanism may be lacking. Therefore, the use of a full radiological appraisal allows a better damage's assessment and an adequate compensation for injuries.


The effect of diet on plasma carnitine, triglyceride, cholesterol and arterial carnitine levels in cynomolgus monkeys.
Plasma carnitine, cholesterol, and triglycerides were measured over a 13-week period in male cynomolgus monkeys (M. fascicularis) that were fed a control diet (Purina Monkey Chow, n = 5) and a semisynthetic hypercholesterolemic diet (n = 15). Plasma cholesterol levels rose from 100 +/- 5 to 743 +/- 50 mg/dl in the cholesterol-fed group during the 13-week period but remained below 133 +/- 13 mg/dl in the control group. Plasma triglyceride levels tended to be lower in the cholesterol-fed group, particularly at 4 week (28 +/- 3 vs 42 +/- 7 mg/dl, P less than 0.05). Plasma carnitine levels rose from 43 +/- 4 to 53 +/- 5 nmol/ml within two weeks in the cholesterol-fed group and remained above control values for the duration of the study. Carnitine levels were significantly higher in the carotid arteries of cholesterol-fed animals relative to control (224 +/- 25 vs 109 +/- 15 pmol/mm in situ length, P less than 0.01). Higher mean values of carnitine were also found in iliac, subclavian, and coronary arteries of cholesterol-fed animals but not in femoral arteries.


[Hypoglycemia with loss of consciousness during insulin therapy as an initial symptom of Addison's disease. Report of 2 cases].
Within a six-month period, two type-I diabetics were admitted because of labile metabolic state with recurrent severe hypoglycaemia and unconsciousness. In both patients electrolytes were normal on admission. There were at first only few pointers to Addison's disease. But in both primary adrenocortical insufficiency was demonstrated to be the cause of the symptoms. Serological tests suggested an autoimmune genesis. Recurrent severe hypoglycaemia and unconsciousness in insulin-treated diabetics indicates that adrenocortical insufficiency should be excluded.


Immunostimulatory properties and antiviral activity of modified HBV-specific siRNAs.
Sequence-specific gene silencing by small interfering RNA (siRNA) is an intense area of focus in the development of novel therapeutic agents. Currently, there are two major hurdles to achieving clinically effective siRNA-based therapeutics: establishment of an efficient delivery system that transfers the siRNA to the correct tissue(s); and the reduction of unintended immunotoxicity associated with unmodified siRNA. We have developed a novel liver-specific delivery system of apolipoprotein A-I-decorated cationic lipids (DTC-Apo). Here, we show that intravenous injection of an unmodified hepatitis B virus (HBV)-specific siRNA encapsulated in DTC-Apo activates the innate immune response in mice. However, 2'-O-methyl (2'-OMe) modification of siRNA sense-strand uridine or uridine/adenosine residues efficiently abrogated the immunostimulatory properties of the siRNA and also silenced viral replication. In contrast, pyrimidine modification by 2'-OMe or 2'-fluoro (2'-F) substitution failed to circumvent liposome-induced immune recognition. Our findings provide useful information for the design of chemically-modified siRNAs for in vivo applications.


Coping of siblings of children with developmental disabilities in the Bedouin community.
This is the first study that examines the coping of siblings of children with developmental disabilities in comparison with siblings of children without disabilities in the Bedouin community in Israel. For this purpose, the study examines the components of self-esteem, stress, and growth. Data were collected from 200 adolescents. The findings of this study show that siblings to children with developmental disabilities have a similar degree of self-esteem to those siblings to children without disabilities, whereas siblings to children with developmental disabilities have higher levels of stress perception and growth compared to siblings f children without developmental disabilities. In addition, a negative correlation was found between perception of stress and growth and a positive correlation between self-esteem and growth.


Studies on solvent precipitation of levan synthesized using Bacillus subtilis MTCC 441.
Levan is a water soluble biopolymer widely used in food, pharma, personal care and aquaculture industries. In this work, levan was synthesized by Bacillus subtilis MTCC 441 using sucrose as a sole carbon source. Effects of pH, sucrose concentration, nitrogen source, nitrogen concentration, inoculum size and agitation speed on levan production were studied. Yeast extract (YE) was found to be the best nitrogen source. Sucrose concentration - 100 g/L, pH - 7, YE concentration - 2 g/L, inoculum size 10% (v/v) and RPM - 150 were found to be optimal values for levan production. Effects of precipitation pH (3-12), choice of solvent (ethanol, isopropanol, acetone, and methanol) and supernatant to solvent ratio (1:1 to 1:6) on levan yield were also studied. Isopropanol resulted in maximum levan recovery among the four solvents considered. Optimal pH and supernatant to solvent ratio for levan precipitation were found to be 11 and 1:5, respectively. Corresponding levan yield was 0.395 g/g of sucrose supplied. The product obtained was characterized using FTIR, 1H-NMR, 13C-NMR, and GPC. The cytotoxicity of the precipitated levan was studied on EA.hy926 cell line using MTT assay and the compound was proven to be non-toxic to the cells.


Engineered silica nanocarriers as a high-payload delivery vehicle for antioxidant enzymes.
Antioxidant enzymes for the treatment of oxidative stress-related diseases remain a highly promising therapeutic approach. As poor localization and stability have been the greatest challenges to their clinical translation, a variety of nanocarrier systems have been developed to directly address these limitations. In most cases, there has been a trade-off between the delivered mass of enzyme loaded and the carrier's ability to protect the enzyme from proteolytic degradation. One potential method of overcoming this limitation is the use of ordered mesoporous silica materials as potential antioxidant enzyme nanocarriers. The present study compared the loading, activity and retention activity of an anti-oxidant enzyme, catalase, on four engineered mesoporous silica types: non-porous silica particles, spherical silica particles with radially oriented pores and hollow spherical silica particles with pores oriented either parallel to the hollow core or expanded, interconnected bimodal pores. All these silica types, except non-porous silica, displayed potential for effective catalase loading and protection against the proteolytic enzyme, pronase. Hollow particles with interconnected pores exhibit protein loading of up to 50 wt.% carrier mass, while still maintaining significant protection against proteolysis.


Genetic algorithm as a variable selection procedure for the simulation of 13C nuclear magnetic resonance spectra of flavonoid derivatives using multiple linear regression.
In order to accurately simulate (13)C NMR spectra of hydroxy, polyhydroxy and methoxy substituted flavonoid a quantitative structure-property relationship (QSPR) model, relating atom-based calculated descriptors to (13)C NMR chemical shifts (ppm, TMS=0), is developed. A dataset consisting of 50 flavonoid derivatives was employed for the present analysis. A set of 417 topological, geometrical, and electronic descriptors representing various structural characteristics was calculated and separate multilinear QSPR models were developed between each carbon atom of flavonoid and the calculated descriptors. Genetic algorithm (GA) and multiple linear regression analysis (MLRA) were used to select the descriptors and to generate the correlation models. Analysis of the results revealed a correlation coefficient and root mean square error (RMSE) of 0.994 and 2.53ppm, respectively, for the prediction set.


Three-Dimensional Printed Model Fabrication and Effectiveness Evaluation in Fetuses With Congenital Heart Disease or With a Normal Heart.
The purpose of this study was to investigate the technical feasibility and accuracy of applying 3-dimensional (3D) printing of normal and abnormal fetal hearts based on spatiotemporal image correlation (STIC) volume-rendered data. Spatiotemporal image correlation volume images of 15 healthy fetuses and 15 fetuses with cardiac abnormalities were collected, and Mimics software (Materialise NV, Leuven, Belgium) was used to postprocess the volume data to obtain a 3D digital model of fetal heart and large blood vessel morphologic characteristics and to output the file to a 3D printer for printing the 3D model of the fetal heart and large blood vessels. The effect accuracy of the 3D printed model was qualitatively evaluated by showing the 3D anatomic structure of the model combined with echocardiographic or autopsy results, and the dimensional accuracy of the 3D printed model was quantitatively evaluated by comparing the measured data of the model and echocardiography. In all 30 fetuses, STIC volume data of the fetal heart were successfully reprocessed and printed out, which could visually display the morphologic characteristics of the fetal heart chamber and passage of the great vessels under normal and abnormal pathologic conditions. No significant differences in all of the heart size parameters were found between the 3D digital model, 3D printed model, and routine echocardiographic images (all P > .05). Moreover, the size parameters were concordant well between the methods, and all of the data points fell within the limits of agreement. It is feasible to 3D print the fetal heart using STIC volumetric images as the data source, and the 3D printed model can fully and accurately display abnormal anatomic structures of the heart.


Optimization of Light-Inducible Gal4/UAS Gene Expression System in Mammalian Cells.
Light-inducible gene expression systems represent powerful methods for studying the functional roles of dynamic gene expression. Here, we developed an optimized light-inducible Gal4/UAS gene expression system for mammalian cells. We designed photoactivatable (PA)-Gal4 transcriptional activators based on the concept of split transcription factors, in which light-dependent interactions between Cry2-CIB1 PA-protein interaction modules can reconstitute a split Gal4 DNA-binding domain and p65 transcription activation domain. We developed a set of PA-Gal4 transcriptional activators (PA-Gal4cc), which differ in terms of induced gene expression levels following pulsed or prolonged light exposure, and which have different activation/deactivation kinetics. These systems offer optogenetic tools for the precise manipulation of gene expression at fine spatiotemporal resolution in mammalian cells.


Tolerance to habitat fragmentation influences the colonization of new habitat by forest birds.
We examined the relationship between the ability of bird species to persist in fragmented forests and their ability to colonize new forest habitat. Using a long-term data set on the colonization of a forest plantation, we tested the hypothesis that bird species tolerant to habitat fragmentation would detect and colonize the new habitat faster than intolerant species. The forest plantation under study is situated on an area of land reclaimed from the sea (a polder) in the central part of The Netherlands. We constructed an index of tolerance to habitat fragmentation and included it as a predictor variable in a set of three logistic regression models that compared the probability of colonization over four consecutive time periods. After controlling statistically for the effects of regional incidence, preferred habitat and life-history characteristics, there was a significant effect of tolerance to fragmentation on the ability of species to colonize the plantation, and a marginal effect on the timing of colonization. We then examined the effect of the same index of tolerance to fragmentation on colonization patterns over a larger spatial scale. Multivariate regression models showed that the proportion of three polders of different ages occupied by forest bird species was dependent upon the regional incidence of a species, its preferred habitat and its tolerance to fragmentation. The results support the hypothesis that species tolerant to habitat fragmentation detect and colonize new habitat faster than those intolerant to habitat fragmentation.


Relationship between resilience and death anxiety of the older adults during the coronavirus disease 2019 (COVID-19) pandemic.
The outbreak of coronavirus disease 2019 (COVID-19) caused an increase in the incidence of physical and psychological problems, particularly in the older adult. Considering the special physical and mental health conditions of the older adult, they were more exposed to psychological problems associated with the pandemic, such as death anxiety. Therefore, assessing the psychological status of this group is necessary in order to implement appropriate interventions. The present study aimed to investigate the relationship between resilience and death anxiety in the older adult during the COVID-19 pandemic. This descriptive-analytical study was conducted on 283 older adult people over the age of 60 years. The older adult population was selected from 11 municipal districts of Shiraz, Iran, using the cluster sampling method. The resilience and death anxiety scales were used for data collection. Data analysis was performed in SPSS version 22, using Chi-square test, t-test, and Pearson's correlation coefficient test. A P-value less than 0.05 was considered statistically significant. The mean and standard deviation of the older adult's resilience and death anxiety scores were 64.16 ± 9.59 and 6.3 ± 2.95, respectively. There was a significant correlation between resilience and death anxiety scores (P < 0.01, r=-0.290). Also, sex (P = 0.00) and employment status (P = 0.00) were significantly associated with the older adult's resilience. Besides, sex (P = 0.010) and employment status (P = 0.004) were significantly related to death anxiety. Our findings showcase levels of resilience and death anxiety in older adults during the covid-19 pandemic and suggest that resilience and death anxiety are inversely linked. This has implications on policy planning for future major health events.


Seed set in Phormium: interactive effects of pollinator behaviour, pollen carryover and pollen source.
Fruit and seed set was studied in New Zealand flax (Phormium tenax Phormiaceae) a large monocot that preferentially sets outcrossed seeds. Fruit set was low and in particular situations could result from insufficient pollinator visitation. Observations of pollinator (Meliphagidae) movements showed that birds preferentially visited male phase flowers and predominantly moved pollen within inflorescences of the same plant. More dominant 'resident' birds moved more between plants that subordinate 'non-resident' birds. Combination of results of fluorescent dye carryover with known bird movements allowed predictions of fruit set and seed size that closely approximated observed levels. Resident birds account for almost half the observed foraging bouts but are predicted to be responsible for the vast majority of the viable seeds.


Multicolor flow cytometry in clinical samples for platelet signaling assessment.
Availability of multichannel cytometers and specific commercial antibodies makes flow cytometry a new option to simultaneously assess multiple intracellular platelet signaling pathways for clinical purposes, in small volume of blood or low platelet count. To describe a multicolor flow cytometry with fluorescent barcoding technique for screening signaling pathways downstream membrane receptors of major platelet agonists (adenosine diphosphate, thrombin, thromboxane, and collagen). By comparison with immunoblotting, we first selected the target phosphoproteins, AKT, P38MAPK, LIMK, and SPL76; the times of stimulation; and phosphoflow barcoding conditions. We then performed a clinical study on whole blood of patients without evidence of blood platelet disorder on standard biological screening, consulting for trivial or occasionally provoked bleeds without familial antecedent (bleeding of unknown origin, n = 23) or type-1 von Willebrand disease (n = 9). In addition, we included a small group of patients with definite platelet disorders (Glanzmann thrombasthenia, δ-storage pool deficiency, and immune glycoprotein VI-related disease with granule secretion defect). The range, kinetics, and distribution of fluorescence intensity were established for each agonist-target protein combination. Principal component analysis indicates a correlation in response to a target phosphoprotein (AKT and P38MAPK) to different agonists but no correlation in the response of different target phosphoproteins to the same agonist. The heterogeneity of individual responses in the whole population displayed was analyzed using clustering algorithm. Patients with platelet storage pool deficiency were positioned as lowest responders on the heatmap. In complement of functional tests, this study introduces a new approach for rapid platelet signaling profiling in clinical practice.


Quantitative structure-activity relationship studies of threo-methylphenidate analogs.
Complementary two-dimensional (2D) and three-dimensional (3D) Quantitative Structure-Activity Relationship (QSAR) techniques were used to derive a preliminary model for the dopamine transporter (DAT) binding affinity of 80 racemic threo-methylphenidate (MP) analogs. A novel approach based on using the atom-level E-state indices of the 14 common scaffold atoms in a sphere exclusion protocol was used to identify a test set for 2D- and 3D-QSAR model validation. Comparative Molecular Field Analysis (CoMFA) contour maps based on the structure-activity data of the training set indicate that the 2' position of the phenyl ring cannot tolerate much steric bulk and that addition of electron-withdrawing groups to the 3' or 4' positions of the phenyl ring leads to improved DAT binding affinity. In particular, the optimal substituents were found to be those whose bulk is mainly in the plane of the phenyl ring. Substituents with significant bulk above or below the plane of the ring led to decreased binding affinity. Suggested alterations to be explored in the design of new compounds are the placement at the 3' and 4' position of the phenyl ring of electron-withdrawing groups that lie chiefly in the plane of the ring, for example, halogen substituents on the 3',4'-benzo analog, 79. A complementary 2D-QSAR approach-partial least squares analysis using a reduced set of Molconn-Z descriptors-supports the CoMFA structure-activity interpretation that phenyl ring substitution is a major determinant of DAT binding affinity. The potential usefulness of the CoMFA models was demonstrated by the prediction of the binding affinity of methyl 2-(naphthalen-1-yl)-2-(piperidin-2-yl)acetate, an analog not in the original data set, to be in good agreement with the experimental value.


Antioxidant activity and contents of leaf extracts obtained from Dendropanax morbifera LEV are dependent on the collecting season and extraction conditions.
This study compared the antioxidant activity of extracts from Dendropanax morbifera (D. morbifera) Levillis leaves. The concentrations of flavonoids and polyphenols were measured in extracts of D. morbifera leaves. The antioxidant activities were examined by ABTS and DPPH radical scavenging activity and ferric reducing antioxidant power (FRAP). Total flavonoid and polyphenol contents, and FRAP were highest in the 30% ethanol extract collected in May. The ABTS and DPPH radical scavenging activities were the highest in the 60% ethanol extract harvested in May. For investigating the relationship between antioxidant activity and specific polyphenols, rutin and chlorogenic acid of the polyphenol component were quantified by LC-MS/MS analysis. The concentrations of them were highest in the 60% ethanol extract collected in May, and showed positive correlations with antioxidant activities. The optimal extraction conditions to yield the most effective antioxidant activity were obtained using a 60% ethanol extraction solvent with samples collected in May.


Effects of different oxygen conditions on pollutants removal and the abundances of tetracycline resistance genes in activated sludge systems.
The individual and combined effects of tetracycline (TC) and divalent copper (Cu2+) on the performance of activated sludge systems and the abundances of tetracycline resistance genes (TRGs) in activated sludge, under both aerobic and anaerobic conditions, were studied. Activated sludge systems received TC (0.2 mg L-1) and Cu2+ (5 mg L-1) separately or jointly under either aerobic or anaerobic conditions. The addition of TC did not affect the performance of activated sludge systems and the addition of Cu2+ and mixed TC/Cu2+ inhibited biological phosphorus removal. The TC removal efficiencies in systems under aerobic and anaerobic conditions were 98.4%-99.7% and 96.8%-99.9%, respectively, and Cu2+ promoted TC removal in activated sludge systems. The TC degradation product was 4-epitetracycline (ETC) in activated sludge systems under both aerobic and anaerobic conditions. The total relative abundances of TRGs (tetA, tetC, tetE, tetM, tetO, tetW, tetX and tetB(P)) in activated sludge showed opposite development trends under the two oxygen conditions and aerobic condition was beneficial to the attenuation of high-risk TRGs. The results of this study might improve evaluation of the combined effects of antibiotics and heavy metals on wastewater biological treatment systems.


Integrating Ecosystem Services Into Water Resource Management: An Indicator-Based Approach.
Natural ecosystems are fundamental to local water cycles and the water ecosystem services that humans enjoy, such as water provision, outdoor recreation, and flood protection. However, integrating ecosystem services into water resources management requires that they be acknowledged, quantified, and communicated to decision-makers. We present an indicator framework that incorporates the supply of, and demand for, water ecosystem services. This provides an initial diagnostic for water resource managers and a mechanism for evaluating tradeoffs through future scenarios. Building on a risk assessment framework, we present a three-tiered indicator for measuring where demand exceeds the supply of services, addressing the scope (spatial extent), frequency, and amplitude for which objectives (service delivery) are not met. The Ecosystem Service Indicator is measured on a 0-100 scale, which encompasses none to total service delivery. We demonstrate the framework and its applicability to a variety of services and data sources (e.g., monitoring stations, statistical yearbooks, modeled datasets) from case studies in China and Southeast Asia. We evaluate the sensitivity of the indicator scores to varying levels data and three methods of calculation using a simulated test dataset. Our indicator framework is conceptually simple, robust, and flexible enough to offer a starting point for decision-makers and to accommodate the evolution and expansion of tools, models and data sources used to measure and evaluate the value of water ecosystem services.


Colorectal cancer among Asians and Pacific Islanders in the U.S.: survival disadvantage for the foreign-born.
Asian Americans and Pacific Islanders (AAPI) have better colorectal cancer survival than other racial populations. However, immigrants face challenges that may place them at higher risk for late diagnosis and death. To compare survival between the foreign- and U.S.-born, we identified 17,302 AAPI colorectal cancer patients between 1973 and 1998 from the Surveillance, Epidemiology, and End-Results (SEER) Program. Patients were categorized as foreign-born or U.S.-born using multiple imputation methods. Foreign birth was associated with higher risk for death from any cause (hazard ratio [HR] 1.29; 95% CI 1.23-1.36) and with modestly higher risk after adjustment for selected demographic characteristics (HR 1.13; 95% CI 1.05-1.21) and registry site (HR 1.05; 95% CI 0.98-1.14). Although foreign-born AAPI were more likely to present later, additional adjustment for cancer stage reduced but did not eliminate their higher risk of death (HR 1.09; 95% CI 1.01-1.18) Compared to the U.S.-born, foreign-born AAPI have poorer survival following colorectal cancer diagnosis. Future investigation of the care processes after diagnosis may be important in understanding these differences.


The association between season, day length, and temperature on clinical outcomes after cryopreserved embryo transfer.
To investigate whether there is an association between season, temperature, and day length at oocyte retrieval and/or embryo transfer (ET) and clinical outcomes in frozen ET cycles. Retrospective cohort study. Large academically affiliated research hospital. A total of 3,004 frozen ET cycles from 1,937 different women with oocyte retrieval and transfer between 2012 and 2017. None. Implantation, clinical pregnancy, spontaneous abortion, and live birth. Frozen ETs with oocyte retrieval dates in summer had 45% greater odds of clinical pregnancy (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.15-1.82) and 42% greater odds of live birth (OR, 1.42; 95% CI, 1.13-1.79) compared with those with oocyte retrieval dates in winter. A 41% greater odds of clinical pregnancy (OR, 1.41; 95% CI, 1.16-1.71) and 34% greater odds of live birth (OR, 1.34; 95% CI, 1.10-1.62) were observed among transfers with an average temperature at oocyte retrieval in the highest tertile (17.2-33.3 °C) compared with those in the lowest tertile (-17.2-6.7 °C). There were no consistent associations between clinical outcomes and day length at oocyte retrieval or between season, day length, or temperature at transfer of thawed embryos. Warmer temperatures at oocyte retrieval are associated with higher odds of clinical pregnancy and live birth among frozen ET cycles. The consistent associations seen with oocyte retrieval dates and the lack of associations observed with ET dates suggest that any seasonality effects on in vitro fertilization success are related to ovarian function and not uterine receptivity.


Enhancement of fibrinolysis by bispecific monoclonal antibodies reactive to fibrin and plasminogen activators.
Murine hybrid hybridomas secreting bispecific monoclonal antibodies (bs mAbs) were constructed by fusing hybridomas secreting an anti-tissue plasminogen activator (tPA) or anti-urokinase (UK) mAb with hybridomas secreting a mAb which binds to human fibrin but not to fibrinogen. The bs mAbs reactive to both fibrin and PA (tPA or UK) were purified by affinity chromatography employing the respective antigen-coupled columns and characterized by fibrin-binding, amidolytic and fibrinolytic assays. Immunochemical conjugation of PAs and the bs mAbs did not impair the catalytic activity of PAs at all and made it possible to concentrate PAs on fibrin clot. Pretreatment of fibrin with the bs mAbs enhanced the fibrin-binding of PAs and the subsequent fibrinolysis.


Capillary electrophoresis methods for the analysis of antimalarials. Part II. Achiral separative methods.
An exhaustive review of applications of achiral capillary electrophoresis methods to the analysis of antimalarials is presented. It covers quality control of formulations, analysis in biological fluids and food, determination of physico-chemical properties (pKa, partition coefficient and interaction studies). Miscellaneous applications are also considered.


Acute coronary syndrome in an anomalous mid-LAD right coronary artery: Don't forget to look twice before turning left.
A 68-year-old female with past medical history of hypertension, hyperlipidemia, multiple sclerosis, diverticulitis, and tobacco use presented with 1 day of atypical chest pain after a recent diverticulitis flare. Initial workup was notable for a normal electrocardiogram but elevated high sensitivity troponin T (616 ng/L). Due to persistent symptoms, the patient was given antiplatelet therapy and taken urgently to the catheterization lab where she was found to have complete occlusion of an anomalous right coronary artery branching off the mid-left anterior descending artery. Angioplasty was performed with a drug-eluting stent and her symptoms resolved. The patient recovered well and was discharged on appropriate medical therapy. This case demonstrates a case of acute coronary syndrome in an extremely rare coronary congenital abnormality. Further research is needed on when to be suspicious for coronary anomalies on patients presenting with myocardial infarction.


Genetic control of the immune response to myoglobin. XVI. Control of antibodies with preselected specificities following immunization with free synthetic peptides representing the antigenic sites or surface non-immunogenic locations in the protein.
Previous studies in this laboratory have resulted in the determination of the antigenic structure of myoglobin. The present work was carried out to investigate the genetic control of the murine antibody response to myoglobin following immunization with free (i.e., not coupled to a carrier) synthetic antigenic sites or other peptides corresponding to surface regions of myoglobin that are not immunogenic when the native molecule is the immunizing antigen. Synthetic peptides corresponding to antigenic site 1 (peptide 15-22), site 2 (peptide 56-62), site 3 (peptide 94-100), site 4 (peptide 113-120), site 5 (peptide 145-151) and two surface regions, peptide 1-6 and peptide 121-127, were injected in complete Freund's adjuvant in different strains of mice. Serum antibodies specific for myoglobin were subsequently obtained and were measured by means of a radioimmune plate binding assay in which Mb was used as the solid phase antigen. It was found that the genetic control of the antibody response to myoglobin following immunization with the free synthetic peptides was different from the genetic control obtained following immunization with native myoglobin. The significance of this finding is discussed.


Pharmacological targeting of allergen-specific T lymphocytes.
Allergic disorders are the result of a complex pathophysiology, involving major cellular lineages and a multitude of humoral factors of the innate and adaptive immune system, and have the tendency to involve multiple organs. Consequently, even standard pharmacological treatment of allergies is rarely specific but usually targets more than one pathway/cellular system at a time. Accordingly, many of the classic anti-allergic drugs have a critical impact also on T helper cells, which are pivotal not only during the sensitization but also the maintenance phase of allergic diseases. Recent years have seen a dramatic increase of novel drugs with the potency to interfere, more or less specifically, with T lymphocyte function, which might, possibly together with classic anti-allergic drugs, help harnessing one of the central cellular players in allergic responses. A major theme in the years to come will be a thoughtful combination of previously established with recently developed treatment modalities.


Stressful life events severity in patients with first and recurrent depressive episodes.
Stressful life events are associated with depression and their role in first onset and recurrences is a promising but controversial perspective of research. The objective is to analyze the role of number of previous episodes and life events exposure in a large sample of primary care depressive patients taking into account life events severity. 10,257 patients with DSM-IV criteria for a current single or recurrent major depressive episode were recruited by 2,056 general practitioners in a cross-sectional epidemiological study. Patients answered the Montgomery-Asberg Depression Rating Scale, the Patient Health Questionnaire and the Social Readjustment Rating Scale (SRRS). Stressful life events were categorized into three levels of severity (severe, moderate and mild). All relevant confounding variables were analyzed: age, gender, depression severity, somatic symptoms severity and length of episode. We found a significant positive correlation with number of episodes and depression severity. There was no significant correlation of SRRS scores with age, gender and length of episode. ANOVA exploring life events severity with regard to number of episodes showed statistically differences in SRRS total score, moderate life events and mild life events (F = 15.14, p < 0.001) but not for severe life events. Prevention and treatment strategies for recurrent depression need to manage life stressful events during mild and long-term periods and not just in the initial recurrences of the disease.