Synthesis, Spectroscopy and Electrochemistry of Fe(II) and Fe(III) Quinonemonooxime Complexes and Their DNA Cleaving Activities.
Iron(II) and iron(III) complexes of 3,5-di-tert-butyl-o-benzoquinonemonooxime were synthesized and characterized by spectroscopic and electrochemical studies. Their ability to cleave DNA has been investigated under aerobic conditions at room temperature and in the presence and absence of H(2) O(2). The plasmid DNA pBR322 was effectively cleaved by these complexes in a concentration dependant manner.


Consequences of Adolescent Ethanol Consumption on Risk Preference and Orbitofrontal Cortex Encoding of Reward.
Critical development of the prefrontal cortex occurs during adolescence, a period of increased independence marked by decision making that often includes engagement in risky behaviors, such as substance use. Consumption of alcohol during adolescence has been associated with increased impulsivity that persists across the lifespan, an effect which may be caused by long-term disruptions in cortical processing of rewards. To determine if alcohol consumption alters cortical encoding of rewards of different sizes and probabilities, we gave rats limited access to alcohol in gelatin during adolescence only. In adulthood, we recorded the electrophysiological activity of individual neurons of the orbitofrontal cortex while rats performed a risk task that varied the level of risk from day-to-day. Rats that had consumed higher levels of alcohol showed increased risk preference in the task compared with control and low alcohol-consuming rats. Patterns of neuronal responses were identified using principal component analysis. Of the multiple patterns observed, only one was modulated by adolescent alcohol consumption and showed strongest modulation after reward receipt. This subpopulation of neurons showed blunted firing rates following rewards in alcohol-consuming rats, suggesting a mechanism through which adolescent alcohol exposure may have lasting effects on reward processing in the context of decision making. The differences in OFC responses between high alcohol consumers and control animals not given access to alcohol support the idea that, regardless of potential variability in innate alcohol preferences, voluntary consumption of alcohol during adolescence biases choice patterns longitudinally through alterations in cortical function.


What is specific to music processing? Insights from congenital amusia.
Musical abilities are generally regarded as an evolutionary by-product of more important functions, such as those involved in language. However, there is increasing evidence that humans are born with musical predispositions that develop spontaneously into sophisticated knowledge bases and procedures that are unique to music. Recent findings also suggest that the brain is equipped with music-specific neural networks and that these can be selectively compromised by a congenital anomaly. This results in a disorder, congenital amusia, that appears to be limited to the processing of music. Recent evidence points to fine-grained perception of pitch as the root of musical handicap. Hence, musical abilities appear to depend crucially on the fine-tuning of pitch, in much the same way that language abilities rely on fine time resolution.


Estimation of glomerular filtration rate from skeletal muscle mass. A new equation independent from age, weight, gender, and ethnicity.
The most used indicator for the renal function is the glomerular filtration rate (GFR). Current used predictive GFR equations were calibrated on patients with chronic kidney disease. Thus, they are not very precise in healthy individuals. The estimation of skeletal muscle mass (SMM) allows the prediction of the daily urinary creatinine excretion (24hUCrE). This study proposes an equation for the estimation of GFR based on SMM (eGFRMuscle) and serum creatinine (SCr). Four hundred sixty-six free-living men underwent a bioelectrical impedance analysis for the evaluation of SMM (kg), a blood withdrawal for the measurement of SCr (mg/dL), and a 24-h urinary collection for the assessment of 24hUCrE (g/24 h). The linear regression analysis between SMM and 24hUCrE and the measurement of SCr allowed developing a predictive equation of eGFRMuscle. The equation predicting eGFRMuscle (ml/min/1.73 m2) was SMM (kg) × 3.06/SCr (mg/dL). eGFRMuscle was statistically different from eGFR predicted by Cockroft-Gault, MDRD Study, and CKD-EPI equations (p = 0.017, p < 0.001, and p < 0.001, respectively). Pairwise comparison of standard error of the area under the ROC curve (AUC) of eGFRMuscle with all the other AUCs of ROC curves highlighted significant differences. The equation presented in this study results in age, weight, gender, and ethnicity independent because it arises directly from SMM estimation. Therefore, the proposed equation could allow evaluating the GFR also in healthy people with low, average, or high weight, and in older people, regardless of GFR and SCr levels.


CircRFX3 contributes to glioma progression through the circRFX3-miR-1179/miR-1229-VASP axis.
Circular RNAs (circRNAs) are implicated in the carcinogenesis of human cancers. However, the functional roles of circRFX3 in glioma are not elucidated. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed for the levels of circRFX3, RFX3, miR-1179, miR-1229 and vasodilator stimulated phosphoprotein (VASP). Actinomycin D assay and RNase R assay were employed to analyze the characteristics of circRFX3. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were conducted for cell proliferation. Transwell assay was used for cell migration and invasion. Flow cytometry analysis was adopted for cell apoptosis. RNA pull-down assay, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to analyze the interaction between miR-1179/miR-1229 and circRFX3 or VASP. Western blot assay was conducted for VASP protein level. Murine xenograft model assay was used to investigate the role of circRFX3 in vivo. CircRFX3 level was increased in glioma tissues and cells. Knockdown of circRFX3 suppressed glioma cell proliferation, migration and invasion and promoted apoptosis in vitro and repressed tumorigenesis of glioma in vivo. MiR-1179 and miR-1229 were identified to be the targets of circRFX3. MiR-1179 or miR-1229 inhibition reversed the impacts of circRFX3 knockdown on glioma cell malignant behaviors. Additionally, VASP was demonstrated to be the target gene of miR-1179 and miR-1229, and VASP overexpression abolished the effect of circRFX3 knockdown on glioma cell progression. CircRFX3 served as a tumor promoter in glioma via modulating miR-1179/miR-1229-VASP axis, which might provide a novel target for glioma therapy.


The Influence of Access Related Factors on Adherence to Clinical Practice Guidelines for Muscle Invasive Bladder Cancer.
Clinical guidelines for muscle invasive bladder cancer recommend radical cystectomy with pelvic lymph node dissection as the preferred treatment, although adherence to this guideline is variable. We tested whether access related characteristics are associated with guideline adherence for muscle invasive bladder cancer, and whether the association between access related characteristics and guideline adherence varies by geographic region. We analyzed 27,585 patients diagnosed with stage cT2 or cT3/cN0/cM0 urothelial carcinoma between 1998 and 2010 from the National Cancer Database, and examined the relationship between access related variables and treatment with radical cystectomy/pelvic lymph node dissection vs nonradical cystectomy/pelvic lymph node dissection. Multivariate logistic regression models evaluated associations between access related factors and treatment with radical cystectomy/pelvic lymph node dissection at national and geographically stratified levels. A total of 6,386 (23.2%) patients underwent radical cystectomy/pelvic lymph node dissection for muscle invasive bladder cancer. Black patients were less likely to undergo radical cystectomy/pelvic lymph node dissection (OR 0.64) compared to white patients. Uninsured patients (OR 0.62) and those covered by Medicaid (OR 0.81) were less likely to undergo radical cystectomy/pelvic lymph node dissection compared to privately insured patients. Patients living more than 120 miles (OR 2.45) from the treatment hospital were more likely to undergo radical cystectomy/pelvic lymph node dissection than those living in the same zip code. Patients were more likely to undergo radical cystectomy/pelvic lymph node dissection if treated at an academic hospital (OR 2.32) compared to a community hospital, and if treated at a high volume center (OR 1.82) compared to a low volume center. Race, insurance status, income and hospital volume demonstrated significant between-region variation as predictors of treatment with radical cystectomy/pelvic lymph node dissection. Access related factors are associated with disparities in guideline adherence for muscle invasive bladder cancer and the effect of these factors varies by geographic region.


Synthesis, radioiodination and in vivo screening of novel potent iodinated and fluorinated radiotracers as melanoma imaging and therapeutic probes.
In order to develop new iodinated and fluorinated matched-pair radiotracers for Single-Photon Emission Computed Tomography (SPECT)/Positron Emission Tomography (PET) imaging and targeted radionuclide therapy of melanoma, we successfully synthesized and radiolabelled with iodine-125 seven new derivatives, starting from our previously described lead structure 3. The relevance of these radiotracers for gamma scintigraphic imaging of melanoma in rodent was assessed. The tumoural radioactivity uptake was most often high and specific even at early time points (12.1-18.3% ID/g at 3 h p.i. for [(125)I]39-42) and a fast clearance from the non-target organs was observed. Also, calculated effective doses that could be delivered to tumours when using corresponding [(131)I]-labelled analogues were generally higher than 100 cGy/MBq injected (98.9-150.5 cGy/MBq for [(131)I]39-42). These results make compounds 39-42 suitable candidates for (i) PET imaging of melanoma after labelling with fluorine-18 and (ii) targeted radionuclide therapy of disseminated melanoma after labelling with iodine-131.


Experimental evidence for the reorganization of beta-strands within aggregates of the Abeta(16-22) peptide.
Amyloidogenic deposits that accumulate in brain tissue with the progression of Alzheimer's disease contain large amounts of the amyloid beta-peptide. A small fragment of this peptide, comprising residues 16-22 (Abeta(16-22)), forms beta-sheets in isolation, which then aggregate into amyloid fibrils. Here, using isotope edited infrared spectroscopy to probe the secondary structure of the peptide with residue level specificity, we are able to show conclusively that the beta-sheets formed are antiparallel and, following an anneal cycle or prolonged incubation, are in register with the central residue (Phe19) in alignment across all strands. The alignment of strands proceeds via a rapid interchange from one sheet to another. This realignment of the peptide strands into a more favorable registry may have important implications for therapeutics since previous work has shown that well aligned beta-sheets form more stable amyloid fibrils.


Prognosis and treatment pattern of advanced hepatocellular carcinoma after failure of first-line atezolizumab and bevacizumab treatment.
The combination of atezolizumab and bevacizumab (Atezo-Bev) has become the standard first-line therapy for patients with advanced hepatocellular carcinoma (HCC), but the prognosis and treatment pattern after its treatment failure are unclear. We reviewed the medical records of patients who failed first-line Atezo-Bev treatment for advanced HCC from January 2018 to May 2021 in four Taiwan medical centers. Post-first-line survival (PFLS) was defined as the date from the failure of Atezo-Bev treatment to the date of death or last follow-up. A total of 41 patients were included in the study. All patients had Child-Pugh A liver reserve before the initiation of Atezo-Bev treatment, but the liver reserve of 6 (15%) and 7 (17%) patients deteriorated to Child-Pugh B and C, respectively, after treatment failure. The median PFLS was 5.9 months. PFLS significantly differed among patients with various liver reserves after the failure of Atezo-Bev treatment (median 9.6 vs 3.8 vs 1.2 months, for Child-Pugh A, B, and C; p < 0.001). In total, 30 (73%) patients received second-line systemic therapy, and they exhibited significantly longer PFLS (median 8.0 vs 1.8 months, p = 0.033) than patients who did not. Deteriorated liver function and not receiving second-line therapy remained associated with inferior PFLS in multivariate analysis. The most common second-line therapies were sorafenib (n = 19, 63%) and lenvatinib (n = 9, 30%), with no significant differences in efficacies. Receiving second-line therapy and good liver reserve were associated with favorable PFLS after the failure of first-line Atezo-Bev treatment.


Alcohol intoxication and sexual risk intentions: Exploring cultural factors among heavy drinking women.
Sexually Transmitted Infections (STI) rates are the highest of the last 20 years, with people of color and women particularly affected. Ongoing research has identified risk factors (e.g., alcohol intoxication) and protective factors (e.g., risk perception) for sexual risk behaviors, such as inconsistent condom use. Depending on behavioral norms within a group, ethnic identity (EI) - the exploration and sense of belonging to one's ethnicity - may be a risk or protective factor. This study examined the relations between EI, alcohol intoxication, and STI risk perception on sexual risk intentions among women of color (WOC) and white women (WW). Cisgender women (N = 390; 35% WOC; 65% WW) completed measures and were randomly assigned to an alcohol condition (0.10% BrAC vs control). They projected themselves into an eroticized scenario and self-reported two aspects of STI risk perception (personal, partner) and two sexual risk behaviors (condomless sex intentions, condom decision abdication intentions). Path analysis indicated that intoxicated women endorsed higher sexual risk intentions compared to women in the control group. Personal STI risk perception was negatively associated with sexual risk intentions. Indirect effects indicated that race was indirectly associated with both indicators of sexual risk, such that WOC reported higher perceived personal STI risk and subsequently endorsed lower sexual risk intentions compared to WW. Surprisingly, EI was associated with higher perceived partner risk for WW only. Prevention initiatives that address STI risk perception, condom assertion behaviors, and alcohol may be effective for mitigating women's sexual risk behaviors.


Modern management of cardiogenic pulmonary edema.
Cardiogenic pulmonary edema (CPE) is a life-threatening condition that is frequently encountered in standard emergency medicine practice. Traditionally, diagnosis was based on physical assessment and chest radiography and treatment focused on the use of morphine sulfate and diuretics. Numerous advances in diagnosis and treatment have been made, however. Serum testing for B-type natriuretic peptide (BNP) has improved the accuracy of diagnoses in these patients. Treatment should focus on fluid redistribution with aggressive preload and afterload reduction rather than simply on diuresis. Some specific medications and noninvasive positive pressure ventilation have been shown to be safe and rapidly effective in improving patients' symptoms and improve outcomes.


Mechanism of Action of Novel Pyrazole Carboxamide Containing a Diarylamine Scaffold against Rhizoctonia solani.
In the last few decades, Rhizoctonia solani causing rice sheath blight has resulted in a lot of economic losses in the world. Therefore, many novel pyrazole carboxamide fungicides have been intensively researched and employed to fight against it. In this regard, in recent years, our group reported a novel pyrazole carboxamide containing a diarylamine scaffold with good antifungal activity against rice sheath blight in the pot test and field trial. Following this project, the antifungal mechanism of action of the pyrazole carboxamide has been elucidated in this work. The antifungal result showed that compound SCU2028, N-[2-[(3-chlorophenyl)amino]-phenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, was equivalent to the commercial fungicide thifluzamide and its EC50 value was 0.022 mg/L against R. solani. Also, the observation results by scanning electron microscopy and transmission electron microscopy showed that it could destroy the fungus' cell walls or membranes and result in the leakage of contents and increase of the number of mitochondria and abnormal morphology. Meanwhile, the result on the mitochondrial membrane potential (MMP) showed that it could decrease R. solani's MMP. Furthermore, the results by label-free quantitative proteomic analysis showed that 1153 proteins were found after R. solani was treated with compound SCU2028, including 212 proteins in the control group and 257 proteins in the treatment group. A total of 142 differential proteins were obtained, of which 92 proteins were upregulated and 50 proteins were downregulated. The differentially expressed proteins affected a series of physiological and biochemical pathways in the mitochondria, endoplasmic reticulum, ribosome, and other related GO and KEGG pathways. In particular, the inhibition of the respiratory chain caused by the TCA cycle and oxidative phosphorylation KEGG pathway indicated that complex II (succinate dehydrogenase) and complex IV (cytochrome oxidase) might be compound SCU2028's main action targets. In addition, multiple experiments of qRT-PCR, enzyme activity detection, and molecular docking confirmed complex II and complex IV as targets. It could be seen that these findings provided a theoretical support for further research and development of the pyrazole carboxamide fungicides.


Body composition and energy expenditure in anorexia nervosa: preliminary data of outpatients with recovering and active disease.
In Anorexia Nervosa (AN) recovery, body mass index (BMI) may not reflect body composition. To investigate recovery, bioelectrical impedance (BIA) parameters and energy expenditure were investigated in patients with active and recovering AN, with emphasis on phase angle (PA), a BIA parameter. BMI, PA, indirect BIA parameters (fat free mass, fat mass, total body water, fat free mass index, fat mass index) and resting metabolic rate (RMR) were obtained. Data from subjects distributed to active AN (ANact, n = 9), recovered AN (ANrec, n = 9) and healthy individuals (HI) (n = 16) were compared employing univariate methods and ordinal logistic regression. In univariate comparison, the BMI would not distinguish recovered individuals; this distinction was observed for the PA (p = < 0,001). PA showed a good capacity to discriminate, between ANrec and HI (AUC = 0.792; CI = 0.564- 1.000; p = 0.017). In 2 models of ordinal logistic regression PA (OR = 0.123; 95% CI 0.030; 0.503 and OR = 0.091; 95% CI 0.016; 0.528) remained as a significant independent variable, indicating that increases in PA are related to higher probabilities of moving from ANact, to ANrec and to HI group. Bivariate regression indicated the presence of a relationship between PA and (R2 = 0.266, p = 0.002). Changes in body composition and energy expenditure were observed in recovered anorexics with normal BMI. PA can play an important role in the assessment of recovering anorexic patients.


Benzanilides with spasmolytic activity: chemistry, pharmacology, and SAR.
The following study describes the synthesis of new benzanilide derivatives and their pharmacological investigation on smooth muscle preparations of guinea pigs. All compounds were synthesized in good yields and showed a spasmolytic activity without significant effect on vascular smooth muscles and heart muscle preparations. Moreover, further pharmacological investigations as well as in silico studies were performed to elucidate the mechanism of action. Compound 3 showed the most potent spasmolytic activity with an IC(50) of 3.25microM.


Prevalence and clinical characteristics of patients with restless legs syndrome with painful symptoms.
The complaint of pain has largely been ignored in the diagnostic criteria for restless legs syndrome (RLS). The purpose of this study was to investigate the prevalence of painful symptoms in RLS, and to compare sleep-related characteristics between the patients who experienced the painful symptoms and those who did not. The patients with RLS were retrospectively screened from July 2011 to December 2013 at a tertiary-care sleep center. For classifying those with pain and those without pain, more than three specialists separately observed the patients' reports and complaints of symptoms, and the final decision was made through consensus. The demographics and clinical characteristics, including sleep, psychiatric-related scales, and polysomnographic data were reviewed for the study. One hundred and sixty patients with RLS were selected, and 23.8% of them reported painful symptoms of RLS. Patients with RLS who experienced painful sensations were found to have lower ferritin levels, more severe RLS symptoms, anxiety and depressive symptoms, and a lower quality of life. The polysomnography data found that patients with RLS who experienced painful sensations had a longer latency to sleep onset and a lower periodic limb movement index (PLMI) (p <0.05). Patients who experienced painful sensations had more severe RLS symptoms and a trend toward lower PLMI during sleep. According to these results, an inference can be made that painful sensations may be one important point in determining the severity of RLS.


Structural elucidation of the fucose containing polysaccharide of Paenibacillus polymyxa DSM 365.
Paenibacillus polymyxa is an avid producer of exopolysaccharides of industrial interest. However, due to the complexity of the polymer composition, structural elucidation of the polysaccharide remained unfeasible for a long time. By using a CRISPR-Cas9 mediated knock-out strategy, all single glycosyltransferases as well as the Wzy polymerases were individually deleted in the corresponding gene cluster for the first time. Thereby, it was observed that the main polymer fraction was completely suppressed (or deleted) and a pure minor fucose containing polysaccharide could be isolated, which was named paenan II. Applying this combinatorial approach, the monosaccharide composition, sequence and linkage pattern of this novel polymer was determined via HPLC-MS, GC-MS and NMR. Furthermore, we demonstrated that the knock-out of the glycosyltransferases PepQ, PepT, PepU and PepV as well as of the Wzy polymerase PepG led to the absence of paenan II, attributing those enzymes to the assembly of the repeating unit.


Clinical and genetic characterization of severe influenza B-associated diseases during an outbreak in Taiwan.
Mismatches between circulating and vaccine strains of influenza virus had been observed in Taiwan. A comprehensive clinical and genetic analysis of influenza B viruses-associated important diseases was lacking. Clinical and phylogenetic analysis of influenza B viruses during an outbreak in Taiwan. Clinical manifestations of hospitalized, culture-confirmed patients were analyzed from July 2004 to June 2005. Partial genome sequence analysis of hemagglutinin (HA), neuraminidase (NA), and nonstructural (NS) genes were performed in 54 influenza B isolates during the study period, and nine srandomly chosen isolates during 2000 and 2003. Three specific diseases were found in these patients, including 13 of encephalitis/encephalopathy, 28 of influenza-associated myositis (IAM), and one of acute respiratory distress syndrome (ARDS). Three phylogenetic groups were identified, including reassortant strains-group 1 (Victoria lineage of HA, Yamagata lineage of NA, clade A of NS), group 2 (Yamagata lineage of HA, Yamagata lineage of NA, clade A of NS), and group 3 (Yamagata lineage of HA, Yamagata lineage of NA, clade B of NS). Severe influenza B-associated disease in children was not rare and might be fatal. We offered the evidence of co-circulation of the two HA lineages in the same outbreak.


Case report: vertical dengue infection.
To report a case of vertical dengue infection in a newborn from Rio de Janeiro, Brazil, and to review the literature concerning this problem. We report a case of vertical dengue infection. Female neonate, birth weight 3,940 g, term, was admitted to a neonatal intensive care unit on the fifth day of life with fever and erythematous rash. Her mother had had dengue fever 3 days before delivery. Her platelet count was 38,000, dropping to 15,000. She did not have any hemorrhagic episodes, including cerebral hemorrhages. Anti-dengue antibodies (IgM) were positive in the mother and infant. Dengue type 2 was detected in the infant using polymerase chain reaction. This report emphasizes that pediatricians should be aware of the possibility of vertical dengue infection so that early management can be instituted.


Detection of Cryptosporidium and Giardia in molluscan shellfish by multiplexed nested-PCR.
A multiplexed nested-PCR procedure (ABC-PCR) previously developed to detect Cryptosporidium spp. and Giardia duodenalis assemblages A and B in whole human faeces was applied to DNA extracted from filter-feeding molluscs. Species of Cryptosporidium and G. duodenalis were identified by restriction fragment analysis of the PCR products and by DNA sequencing. The extraction and ABC-PCR procedures were shown to be suitable for application to shellfish by amplification of specific target sequences using DNA from Cryptosporidium parvum genotype 2 and G. duodenalis assemblages A and B which were spiked into DNA extracted from mussels. Using 49 molluscan shellfish specimens (18 clam, 22 mussel and 9 oyster samples) from Spain, cryptosporidial oocysts were detected in 56% by immunofluorescence microscopy, and in 44% by ABC-PCR. For detection of Cryptosporidium, there was a significant association, but not total agreement, between the results of microscopy and PCR. G. duodenalis assemblage B was detected from one oyster sample by PCR. Amongst 38 specimens (20 mussel and 18 cockle samples) collected in the UK and tested by the ABC-PCR, G. duodenalis was not detected, and Cryptosporidium was detected in 11% of the samples. Overall, the 26 samples where Cryptosporidium was detected, C. hominis/C. parvum genotype 1 was detected in 1, C. parvum genotype 2 in 22, and the remaining three samples contained either sequences similar to C. parvum genotype 2 or heterogeneous mixtures of Cryptosporidium species. There was no significant association between the level of Escherichia coli detected by conventional microbiological methods and the presence of Cryptosporidium detected by ABC-PCR.


An unusual case of a solitary pulmonary nodule associated with an abscess correctly distinguished by Pet/Ct fusion imaging.
The case of a male patient affected by concomitant solitary pulmonary nodule and chest abscess located on the same side and each close to the other is reported. The importance in differential diagnosis of these two lesions obtained by the 18F-FDG PET/CT fusion imaging examination is discussed.


A systematic review of allostatic load in relation to socioeconomic position: Poor fidelity and major inconsistencies in biomarkers employed.
The association between disease and socioeconomic position (SEP) is well established. Allostatic load (AL), or physiological 'wear and tear', is a concept that aims to elucidate the biological consequences of stress that may underlie these associations. The primary objective of this paper is to review the biomarkers and methods used to operationalise the concept of AL in studies analysing the association between AL and SEP. Four databases (Embase, Global Health, MEDLINE, and PsychINFO) were searched using terms related to AL, biomarkers and SEP. Data extraction focused on the methods used to calculate AL indices. The frequency of pair-wise combinations of biomarkers were used to assess the level of overlap in AL definition between studies. Twenty-six studies analysing the association between AL and SEP were included. There was no consistent method of operationalizing AL across studies. Individual biomarkers and biological systems included in the AL index differed widely across studies, as did the method of calculating the AL index. All studies included at least one cardiovascular- and metabolic-related biomarker in AL indices, while only half of studies included at least one hypothalamic-pituitary-adrenal (HPA) axis biomarker and approximately one third an immune response-related biomarker. All but three studies found evidence of an association between lower SEP and higher AL. Many studies lacked fidelity to the original concept of AL in which stress was considered central. The considerable variation in biomarkers used makes studies in this review difficult to compare. A more critical approach should be taken in the calculation of AL indices in particular to how far it captures the biological effects of psychosocial stress that may underlie socioeconomic differences in health.


Failure in the detection of the sentinel lymph node with a combined technique of radioactive tracer and blue dye in a patient with cancer of the vulva and a single positive lymph node.
In early stage vulvar cancer, the sentinel lymph node procedure with a radioactive tracer appears to be a promising new diagnostic tool to predict lymph node status. No detection failures have been published so far in vulvar cancer. We recently experienced failure in the detection of the sentinel lymph node in a patient with a positive lymph node. A 75-year-old patient with a clinical T2N0M0 squamous cell carcinoma replacing the clitoris underwent a sentinel node procedure. A sentinel node was detected only at one groin. An exploration of the other groin showed a positive lymph node totally replaced by tumor. In the case we present, stasis of the lymph flow might be the leading cause of the failure of the sentinel lymph node procedure.


Laboratory degradation studies of four endocrine disruptors in two environmental media.
We investigated the degradation of 17beta-estradiol (E(2)), 17alpha-ethinylestradiol (EE(2)), bisphenol-A (BPA), and 4-n-nonylphenol (4-n-NP) in river water-sediment and groundwater-aquifer material under aerobic and anaerobic conditions. The results showed rapid degradation of all four compounds in both media with >90% of the four compounds degraded within the first 2 to 4 d under both conditions. However, degradation rates were extremely slow for the remaining period. Model derived 50% dissipation time (DT50) values in river water-sediment slurries ranged from 0.24 to 1.5 d (E(2)), 0.29 to 1.1 d (EE(2)), 1.2 to 1.4 d (BPA), and 0.42 d (4-n-NP), while the 90% dissipation time (DT90) values for the four endocrine-disrupting chemicals (EDCs) ranged from 0.9 to 2.8 d under both conditions. A minor difference was observed in DT50 and DT90 values for the four EDCs in groundwater- aquifer material under aerobic conditions as compared with river water-sediment. Under anaerobic conditions, DT90 values ranged from >1,000 d (EE(2)) to >300 d (BPA), in groundwater-aquifer material. Degradation of the four compounds under anaerobic conditions was attributed to the sulfate-, nitrate-, and iron-reducing conditions within the tested media; however, it was postulated that overall degradation of the compounds was also influenced by abiotic factors, accounting for nearly 6 to 40% (river water- sediment) and 0 to 18% (groundwater-aquifer material) under the two conditions tested.


Effects of pH and temperature on benzo[a]pyrene-DNA, -protein, and -lipid adducts in primary rat hepatocytes.
The effects of pH and temperature on benzo[a]pyrene(BaP)-DNA, -protein, and -lipid adducts were compared in rat hepatocytes treated with [3H]-BaP. In primary rat hepatocytes, BaP-DNA, -protein, and -lipid adducts were formed in a concentration-dependent manner (0.31-2.80 mmol BaP), and the formation of BaP-lipid adducts, specifically triglyceride (TG) adducts, correlated well with that of DNA or protein adducts. As incubation time increased (1-24 h), the formation of DNA or protein adducts was also elevated, while BaP-TG adducts decreased after 3 h of reaction. pH had no effect on the formation of [3H]-BaP-DNA, and -protein adducts, and the TG adducts decreased with increasing pH (3.4-11.4). With an increase in incubation temperature (30-45 degrees C), on the other hand, the adduct formation was increased with increasing temperature up to 40 degrees C and then decreased sharply. These results suggest that the physicochemical properties of BaP-DNA, -protein, and -TG adducts might be important to consider when cells or humans who have been exposed to BaP are monitored for biomarkers.


Low level chromium (VI) inhalation effects on alveolar macrophages and immune functions in Wistar rats.
In inhalation chambers, 5-week-old male Wistar rats of the strain TNO-W-74 were continuously exposed to submicron aerosols of sodium dichromate in concentrations from 25 (low level) to 200 micrograms/m3 Cr (high level). Subacute exposure (28 days) to 25 and 50 micrograms/m3 Cr resulted in "activated" alveolar macrophages with stimulated phagocytic activities, and significantly elevated antibody responses to injected SRBC's. After subchronic (90 days) low level exposure there was a more pronounced effect on activation of the alveolar macrophages, with increased phagocytic activities. However, at high Cr (VI) exposure level (200 microgram/m3), inhibited phagocytic function of the alveolar macrophages was seen. In rats which were exposed to this chromium aerosol concentration for 42 days, the lung clearance of inert iron oxide was reduced significantly. The humoral immune system was still stimulated at subchronic low chromium aerosol concentrations of 100 micrograms/m3, but significantly depressed at 200 micrograms/m3 Cr. These results show that respiratory defence and immunologic functions were stimulated or inhibited depending on dose and time of chromium (VI) inhalation.


MRI does not change fetal cardiotocographic parameters.
The aim of this study was to determine whether magnetic resonance imaging (MRI) has any effect on fetal cardiotocographic (CTG) parameters or movement incidence. Sixteen mothers were examined during the last trimester at 28-39 weeks (mean 33 weeks; SD 4) of gestation due to a suspected fetal anomaly found in antenatal ultrasonography (US). MR imaging was performed using Siemens Magnetom Vision 1.5 T equipment with a 25 mT/m peak gradient amplitude. T2-weighted images were produced with HASTE and TRUE-FISP sequences and T1-weighted images with a 2D FLASH sequence. A four-element phase-array coil was used as the receiver. Before and after MRI-examination, a computerized analysis of the fetal heart rate (FHR) was produced. Basal FHR, short-term variation (STV) and fetal movements were calculated. The mean basal FHR was 136 beats/min (SD 11.6) before, and 133 beats/min (SD 8.9) after (P = 0.158). Short-term variation was in the normal range for both CTG-tracings: mean 9.7 ms (SD 2.7) and 8.8 ms (SD 2.8) (P = 0.196). The median for fetal movements before MRI was 48/h, and after MRI 24.5/h (P = 0.98). MRI at high field strength with powerful gradients did not affect fetal heart activity or movement incidence.


The genes for beta-myosin heavy chain and glycogen phosphorylase are discoordinately regulated during compensatory growth of plantaris muscle in the adult rat.
It has been shown previously that compensatory hypertrophy of the plantaris muscle in adult rats can be induced by surgical removal of the synergistic gastrocnemius muscle. During hypertrophy, muscle transformation also occurs and there is a shift in the fiber type population of the muscle from fast to slow. Towards obtaining a better understanding of the molecular mechanisms controlling this process, we have carried out a kinetic analysis of the change in expression of two muscle-specific genes encoding the slow beta-heavy chain isoform of myosin and the muscle isoform of glycogen phosphorylase. This analysis indicated that significant increases (2-3 fold) in the steady-state levels of slow myosin heavy chain mRNA and protein did not occur until several weeks following ablation of the gatrocnemius muscle. Increases in slow fiber type paralleled the change in beta-myosin heavy chain expression. In contrast, the activity of phosphorylase, as well as the level of its corresponding mRNA, decreased approx. 1.5-2 fold shortly after (2-4 days) ablation of the gastrocnemius and levels remained low for at least several weeks. Significant changes in expression of these genes did not occur in plantaris muscle from sham operated contralateral legs. These studies indicated that changes in the expression of both genes was governed primarily by accumulation of their mRNAs. However, these genes were not coordinately regulated, indicating either that multiple control mechanisms regulate gene expression in this system or that the same controlling factor(s) regulates expression of these genes in temporally different ways.


Incidence of Pyrrolizidine Alkaloids in Herbal Medicines from German Retail Markets: Risk Assessments and Implications to Consumers.
The occurrence of potentially toxic pyrrolizidine alkaloids (PAs) in herbal medicines (HMs) is currently intensely being discussed in Europe. Pyrrolizidine alkaloids, particularly the 1,2-unsaturated PAs, are undesired compounds in HMs due to their potential hepatotoxic and carcinogenic properties. In this study, 98 widely patronized HMs from six popular German retail supermarkets/drugstores, as well as from pharmacies, were analyzed by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry for the presence of PAs. The results showed that about 63% of the HMs were PA positive, whereas the average PA concentration of the samples was 201 μg/kg, the highest concentration of PAs (3270 μg/kg) was attributed to a product that was purchased from the pharmacy and contained Hypericum perforatum L. (St. John's Wort) as an active ingredient. In addition, H. perforatum-containing products were frequently contaminated with PAs from Echium spp., while both Cynara cardunculus L. products and fixed-combination products of Gentiana lutea L., Rumex acetosa L., Verbena officinalis L., Sambucus nigra L., and Primula veris L. products were commonly contaminated with PAs of Senecio spp. The study showed that H. perforatum, C. cardunculus, Urtica dioica L., and fixed-combination products were frequently contaminated with PA levels above the recommended values of both the German and European Medicines Agencies. Copyright © 2017 John Wiley & Sons, Ltd.


Ondansetron and metoclopramide fail to prevent vomiting secondary to ultra-high-dose cisplatin-carboplatin chemotherapy.
To determine the severity of emesis caused by ultra-high-dose cisplatin-carboplatin chemotherapy and to compare the antiemetic efficacy of an ondansetron regimen and a metoclopramide regimen. Forty consecutive patients with stage III or IV epithelial ovarian cancer or advanced or recurrent endometrial cancer were treated with ultra-high-dose cisplatin-carboplatin chemotherapy. No patient had received prior chemotherapy. Chemotherapy consisted of intravenous (IV) cisplatin 70 mg/m2 and IV carboplatin 100 mg/m2 administered on days 1 and 8 every 28 days for five cycles, representing a total monthly organoplatin dose of 207 mg/m2. Patients were randomized to receive metoclopramide, diphenhydramine, prochlorperazine, and lorazepam; or ondansetron, dexamethasone, prochlorperazine, and lorazepam. Patients were blinded and there was no crossover. The metoclopramide dose was 2 mg/kg IV every 2 hours x 3, and the ondansetron dose was 0.15 mg/kg IV every 4 hours x 3. All 40 patients developed vomiting; 21 (52%) developed severe vomiting and seven (17%) required home IV therapy (grade 4). Eight patients (40%) receiving the metoclopramide regimen developed severe vomiting, compared to 13 (65%) in the ondansetron group (P = .50). Two patients (10%) in the metoclopramide group developed grade 4 vomiting, compared to five (25%) in the ondansetron group (P = .45). Except for sedation and amnesia, there were no significant side effects associated with either regimen. Neither regimen was effective in preventing high-dose cisplatin-carboplatin-induced emesis, and the ondansetron regimen did not appear to be superior.


A comparison of methods for measuring event-related potentials.
Visual event-related potentials (ERPs) were recorded from 21 hyperactive children under 2 attention conditions and 4 doses of stimulant drug (methylphenidate). This data base was used to evaluate several methods of EP component measurement. These methods were (1) conventional visual peak and trough selection; (2) automatic feature extraction based on peaks; (3) automatic features extraction based on segments; (4) gross amplitude measures; (5) principal components analysis on normalized data and latency-adjusted data. No one method emerged as the best overall. Rather it is the case that different methods are best suited to different purposes, and criteria for choosing methods are outlined.


Evaluation of the Insecticidal Activities of α-Pinene and 3-Carene on Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae).
Pest management in most sub-Saharan subsistence agriculture involves mainly the use of botanicals that are either applied as powders, solvent extracts, ash or essential oils. Two hydrogenated monoterpenes (α-pinene and 3-carene) from Cupressus sempervirens were tested against Sitophilus zeamais in the laboratory to evaluate the contact and fumigation effects on the mortality of adult and immature weevils, progeny production, and grain damage. Contact toxicity of the terpenes was investigated at these concentrations: 0.08, 4, 8 and 12 ppm (terpene/maize), while fumigant action was studied at the following doses: 1, 2, 3, and 4 ppm. The results indicate that insecticidal effects were concentration-dependent since mortality increased with dosage and exposure periods. After a 14-day exposure period at the concentration of 12 ppm of α-pinene and 3-carene/grain, more than 98% mortality of the mature weevils was observed at concentrations of 4.1333 and 1.642 ppm respectively and progeny production was reduced by 98% and 100%, respectively. When α-pinene and 3-carene were applied as fumigants, LC50s (lethal concentrations that generate 50% mortality) of 1.402 and 0.610 ppm were obtained after 24 h of exposure, respectively. At concentrations above 3 ppm, both monoterpenes acted as repellents to weevils and reduced grain damage by 80%. Both monoterpenes inhibited the development of immature stages of the weevil and reduced progeny by up to 94%. These compounds are very promising and effective and could be exploited as novel phytoinsecticides against the maize weevil.


Antiangiogenic and antiapoptotic treatment in advanced melanoma.
Melanoma is οne of the most aggressive forms of skin cancer. Currently available treatments have little overall impact on survival rates of patients with advanced melanoma. Advances in the understanding of the molecular pathways related to tumor growth and metastatic spread have resulted in the development of targeted therapies designed to act on specific genes or molecules of these pathways. Newly introduced agents that target the process of angiogenesis or inhibit antiapoptotic proteins have been investigated in melanoma. Although the use of these agents as monotherapy has yielded disappointing results, their impact on survival when combined with cytotoxic chemotherapy agents is currently under investigation. Larger phase III trials are needed to clarify the optimal clinical benefit that can be expected of this class of agents.


Significance of linkage disequilibrium and epistasis on genetic variances in noninbred and inbred populations.
The influence of linkage disequilibrium (LD), epistasis, and inbreeding on genotypic variance continues to be an important area of investigation in genetics and evolution. Although the current knowledge about biological pathways and gene networks indicates that epistasis is important in determining quantitative traits, the empirical evidence for a range of species and traits is that the genotypic variance is most additive. This has been confirmed by some recent theoretical studies. However, because these investigations assumed linkage equilibrium, considered only additive effects, or used simplified assumptions for two- and higher-order epistatic effects, the objective of this investigation was to provide additional information about the impact of LD and epistasis on genetic variances in noninbred and inbred populations, using a simulated dataset. In general, the most important component of the genotypic variance was additive variance. Because of positive LD values, after 10 generations of random crosses there was generally a decrease in all genetic variances and covariances, especially the nonepistatic variances. Thus, the epistatic variance/genotypic variance ratio is inversely proportional to the LD level. Increasing inbreeding increased the magnitude of the additive, additive x additive, additive x dominance, and dominance x additive variances, and decreased the dominance and dominance x dominance variances. Except for duplicate epistasis with 100% interacting genes, the epistatic variance/genotypic variance ratio was proportional to the inbreeding level. In general, the additive x additive variance was the most important component of the epistatic variance. Concerning the genetic covariances, in general, they showed lower magnitudes relative to the genetic variances and positive and negative signs. The epistatic variance/genotypic variance ratio was maximized under duplicate and dominant epistasis and minimized assuming recessive and complementary epistasis. Increasing the percentage of epistatic genes from 30 to 100% increased the epistatic variance/genotypic variance ratio by a rate of 1.3 to 12.6, especially in inbred populations. The epistatic variance/genotypic variance ratio was maximized in the noninbred and inbred populations with intermediate LD and an average allelic frequency of the dominant genes of 0.3 and in the noninbred and inbred populations with low LD and an average allelic frequency of 0.5. Additive variance is in general the most important component of genotypic variance. LD and inbreeding have a significant effect on the magnitude of the genetic variances and covariances. In general, the additive x additive variance is the most important component of epistatic variance. The maximization of the epistatic variance/genotypic variance ratio depends on the LD level, degree of inbreeding, epistasis type, percentage of interacting genes, and average allelic frequency.


Antenatal diagnosis of epignathus with neonatal survival. A case report.
Antenatal diagnosis was made of bilobed epignathus arising from the fetal palate. The fetus survived. Antenatal recognition of this malformation allows adequate preparation of the neonatal and surgical teams to ensure optimal fetal survival.


Treatment options for patients with coronary artery disease identified as high risk by T-wave alternans testing.
Risk stratification for primary prevention of sudden cardiac death (SCD) remains a major challenge in cardiology. The utility of T-wave alternans (TWA) as a marker of risk of life-threatening ventricular tachycardia and fibrillation is supported by two decades of basic and clinical research. Both frequency- and time-domain methods have been developed, validated, and made available in clinical practice. A principal application of TWA testing has been to improve assessment of patients with depressed left ventricular ejection fraction (EF; </= 40%) who are considered for implantable cardioverter-defibrillator (ICD) implantation for primary prevention of SCD. TWA has been most useful in identifying patients who are unlikely to benefit from ICD therapy. Although patients with low EF should remain an important focus, the absolute number of SCD events is far greater among post-myocardial infarction patients with relatively preserved EF, even though the incidence of SCD in this population is low. Recent studies suggest that TWA testing is predictive in this population as well. Absolute quantification of TWA rather than binary classification into "normal" or "abnormal" appears to be valuable in more finely stratifying the magnitude of arrhythmic risk. Longitudinal testing may be warranted in certain populations, although the optimum interval remains to be determined. Combining TWA with noninvasive markers of autonomic function, such as heart rate turbulence, may further increase predictive accuracy. Future development will likely expand the role of TWA testing with routine exercise and ambulatory electrocardiographic monitoring to screen lower-risk populations and to guide medical and device-based therapy.


Differential expression of chemokine receptors on peripheral blood B cells from patients with rheumatoid arthritis and systemic lupus erythematosus.
Chemokines and their receptors are essential in the recruitment and positioning of lymphocytes. To address the question of B cell migration into the inflamed synovial tissue of patients with rheumatoid arthritis (RA), peripheral blood naive B cells, memory B cells and plasma cells were analyzed for cell surface expression of the chemokine receptors CXCR3, CXCR4, CXCR5, CCR5, CCR6, CCR7 and CCR9. For comparison, B cells in the peripheral blood of patients with the autoimmune disease systemic lupus erythematosus (SLE) or with the degenerative disease osteoarthritis (OA) were analyzed. Expression levels of chemokine receptors were measured by flow cytometry and were compared between the different patient groups and healthy individuals. The analysis of chemokine receptor expression showed that the majority of peripheral blood B cells is positive for CXCR3, CXCR4, CXCR5, CCR6 and CCR7. Whereas a small fraction of B cells were positive for CCR5, practically no expression of CCR9 was found. In comparison with healthy individuals, in patients with RA a significant fraction of B cells showed a decreased expression of CXCR5 and CCR6 and increased levels of CXCR3. The downregulation of CXCR5 correlated with an upregulation of CXCR3. In patients with SLE, significant changes in CXCR5 expression were seen. The functionality of the chemokine receptors CXCR3 and CXCR4 was demonstrated by transmigration assays with the chemokines CXCL10 and CXCL12, respectively. Our results suggest that chronic inflammation leads to modulation of chemokine receptor expression on peripheral blood B cells. However, differences between patients with RA and patients with SLE point toward a disease-specific regulation of receptor expression. These differences may influence the migrational behavior of B cells.


Enhanced carbonic anhydrase expression with calcification and fibrosis in bronchial cartilage during COPD.
Pulmonary cartilage plays a crucial structural role determining the physiologic airway compressibility and distensibility, necessary for proper mechanical function. This functionality deteriorates with aging due to increased stiffness of both airway muscle and cartilage, as well as, decreased renewal capacity. Altered airway remodeling has been suggested as a pathogenic driver of chronic obstructive pulmonary disease (COPD) through mechanisms still incompletely understood. Using paraffin-embedded lung tissue sections from archived autopsy material from COPD with non-COPD age matched controls a histopathologic analysis focused on inflammation, fibrosis and calcification was performed with special stains (Masson's trichrome and Von Kossa) and immunohistochemistry for carbonic anhydrase IV (CA IV) and Ki-67. COPD lung tissues showed increased peribronchial inflammation compared to the non-COPD. Coarse amphophilic crystalline deposits in bronchial cartilage were more frequently observed in COPD sections, which were compatible with early dystrophic calcification of the extracellular matrix and chondrocytes. Moreover, Von Kossa staining revealed a significant calcium deposition in the cartilages from COPD in comparison to the controls. Interestingly, Ki-67 immunostains demonstrated a higher overall proliferative rate, including epithelial cells, in COPD. Furthermore, Masson's trichrome staining revealed relatively increased peribronchial collagen deposition associated with a fibrotic stromal response, which may be secondary to the inflammatory milieu in COPD. To further characterize the tissue microenvironment associated with dystrophic calcification, immunohistochemistry for CA IV was used, revealing significantly increased expression in chondrocytes and peribronchial tissue in COPD. Our findings demonstrate that dystrophic calcification of the extracellular matrix and chondrocytes can be linked to CA IV expression in COPD and suggest that pH changes in pulmonary tissue associated with inflammation and calcification may play an active role in COPD.


Inhibition of bacterial adhesion by epigallocatechin gallate attached polymeric membranes.
Microbial adhesion and formation of biofilms cause a serious problem in several areas including but not limited to food spoilage, industrial corrosion and nosocomial infections. These microbial biofilms pose a serious threat to human health since microbial communities in the biofilm matrix are protected with exopolymeric substances and difficult to eradicate with antibiotics. Hence, the prevention of microbial adhesion followed by biofilm formation is one of the promising strategies to prevent these consequences. The attachment of antimicrobial agents, coatings of nanomaterials and synthesis of hybrid materials are widely used approach to develop surfaces having potential to hinder bacterial adhesion and biofilm formation. In this study, epigallocatechin gallate (EGCG) is attached on p(HEMA-co-GMA) membranes to prevent the bacterial colonization. The attachment of EGCG to membranes was proved by Fourier-transform infrared spectroscopy (FT-IR). The synthesized membrane showed porous structure (SEM), and desirable swelling degree, which are ideal when it comes to the application in biotechnology and biomedicine. Furthermore, EGCG attached membrane showed significant potential to prevent the microbial colonization on the surface. The obtained results suggest that EGCG attached polymer could be used as an alternative approach to prevent the microbial colonization on the biomedical surfaces, food processing equipment as well as development of microbial resistant food packaging systems.


Comment on "a peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys".
A study reporting that a peptidomimetic adipotide reduces weight loss in obese monkeys by inducing apoptosis of blood vessels surrounding white adipose tissue may instead reflect a direct effect of adipotide on food consumption.


Activity Pacing Self-Management in Chronic Fatigue Syndrome: A Randomized Controlled Trial.
To evaluate the effectiveness of an activity pacing self-management (APSM) intervention in improving performance of daily life activities in women with chronic fatigue syndrome (CFS). A total of 33 women with CFS (age 41.1±11.2 yr) were randomly allocated to APSM (experimental group; n=16) or relaxation (control group; n=17). Main outcome measures included the Canadian Occupational Performance Measure (COPM; primary) and Checklist Individual Strength (CIS). COPM scores changed significantly over time in both groups (p=.03). The change in Satisfaction scores showed a significant difference in favor only of APSM (effect size=0.74 [0.11, 1.4]). CIS scores decreased significantly in the experimental group only (p<.01). APSM was found to be feasible and effective in optimizing participation in desired daily life activities in women with CFS. Replication in a larger sample with long-term follow-up is required.


Sugar-conjugated dendritic mesoporous silica nanoparticles as pH-responsive nanocarriers for tumor targeting and controlled release of deferasirox.
In this work, a new pH-responsive nanocarrier based on mesoporous silica nanoparticle which was functionalized by polyamidoamine dendrimer with sugar conjugation was designed for targetable and controllable delivery of deferasirox to cancer cells. To obtain the optimum conditions for the preparation of drug-loaded nanocarrier, the response surface method was employed. The effect of drug/silica ratio, temperature, and operation time on loading efficiency of deferasirox was evaluated, and high loading content achieved under optimized condition. The in vitro drug release studies at different pHs proved the pH-sensitivity of the nanocarrier. Due to the open state of dendritic structure in acidic pH, the maximum release observed at pH 4.5 (lysosomal pH). In the presence of the sugar decorated carrier, cytotoxicity of retinoblastoma cell line Y79 was enhanced which confirmed that tumor cell uptake was improved. These results suggested that this nanocarrier has the potential for treatment of cancer.


Identification of second and third calcitonin receptor-stimulating peptides in porcine brain.
We identified two cDNAs encoding new calcitonin receptor-stimulating peptides (CRSPs) in porcine hypothalamus cDNA library by cross-hybridization with the CRSP cDNA, and designated the second and third peptides as CRSP-2 and CRSP-3. The putative amino acid sequences of prepro-CRSP-2 and prepro-CRSP-3 showed higher identity with that of prepro-CRSP-1 than that of prepro-calcitonin gene-related peptide (CGRP), respectively, and these three CRSPs are considered to form a new family in the CGRP superfamily. RT-PCR analysis demonstrated that both CRSP-2 and CRSP-3 gene transcripts were expressed mainly in the central nervous system and thyroid gland. Synthetic CRSP-2 and CRSP-3 stimulated cAMP production very weakly in LLC-PK(1) cells compared with CRSP and calcitonin (CT). Furthermore, CRSP-2 and CRSP-3 did not elicit a cAMP elevation at all in the COS-7 cells expressing CT receptor or CT-like receptor with or without one of receptor activity-modifying proteins. These results suggest the presence of still unidentified action mechanisms and functions of the peptides in the CGRP superfamily.


Flex: a new computerized system for mechanical ventilation.
To describe and evaluate a new weaning and decision support system for mechanical ventilation. FLEX is a computerized weaning and decision support system for mechanical ventilation that unlike previous rule-based systems derives many of its rules on the basis of the conditions of individual patients. This system can be used in a wide range of ventilatory modes as well as automatic control of weaning. It incorporates the features of the patented ventilatory mode known as Adaptive Support Ventilation (ASV) along with other new features for control of weaning, and control of patient's oxygenation by adjustment of PEEP and the fraction of inspired oxygen. Ventilator data was collected for 10 patients in medical/surgical ICU at baseline and about 24 hours later. Required data fields for each patient for these two time points were also entered into the FLEX program. Comparison of clinical data and FLEX recommendations were made with regard to minute ventilation, alarms, weaning institution and other variables. At baseline, 7 patients were being treated with AC, the remainder with IMV/PS. There was good agreement between the measured and recommended minute ventilations; variances were seen in some patients being treated with permissive hypercapnea and those with evidence of high oxygen needs or other metabolic derangements. At 24 hours, there was improved correlation between measured minute ventilation and that recommended by FLEX, suggesting that clinical adjustments were in-line with Flex recommendations over time. Furthermore, FLEX made recommendations with regard to FIO(2) and PEEP that would potentially diminish the risk of oxygen toxicity, hypoxemia, and barotrauma in selected patients. FLEX has also been implemented as a closed loop system in an initial set up. A new weaning and decision support system for mechanical ventilation is presented. The recommendations made by the system were found to be in line with clinical determinations. Further refinements in the FLEX predictions can be easily made by including inputs which represent permissive hypercapnea or increased metabolic demand for selected patients.


Compound Probiotics Improve the Diarrhea Rate and Intestinal Microbiota of Newborn Calves.
We evaluated the effects of probiotic compounds on the composition of the gut microbiota. Forty newborn calves were random allocated to the lactic acid bacteria + yeast group (LS group), lactic acid bacteria group (L group), yeast group (S group), and control group (D group). Probiotics containing Lactococcus lactis subsp. lactis, Pediococcus pentosaceus, Lactobacillus plantarum, Saccharomyces cerevisiae, and Kluyveromyces marxianus were fed to calves in the three treatment groups for 15 days. The feeding process lasted 15 days. Fecal samples were collected from all calves at the end of the trial and analyzed using high-throughput 16S rRNA sequencing. Totals of 1,029,260 high-quality reads and 420,010,128 bp of sequences were obtained. Among the four groups, the alpha diversity of gut microbes was significantly higher in newborn cattle in the LS group than in those in the L, S, and D groups. Overall, the dominant phyla were Firmicutes, Actinobacteria, and Bacteroidetes, whereas Bifidobacterium was the most abundant phylum in the gut of cattle in the LS group. Newborn calves from the compound probiotic groups had closely clustered gut bacterial communities and had lower rates of diarrhea. Overall, compound probiotics regulated the intestinal microbiota community structure of newborn calves and improved intestinal health. New information relevant to the prevention of diarrhea is provided by our research in newborn calves.


Synergies between agriculture and bioenergy in Latin American countries: A circular economy strategy for bioenergy production in Ecuador.
This study quantifies the synergies between agriculture and bioenergy considering biodiesel production as part of a set of systemic initiatives. We present a case study in Ecuador taking into account the recent government measures aimed at developing the bioenergy sector. Four scenarios have been evaluated through a newly designed systemic scheme of circular-economy initiatives. These scenarios encompass three production pathways covering three energy crops: palm oil (PO), microalgae in open ponds (M1) and microalgae in laminar photobioreactors (M2). We have applied Benefit-Cost Analysis (BCA) methodology considering the Net Present Value (NPV) and the Benefit-Cost Ratio (BCR) as the main evaluation criteria. In terms of private investment, biodiesel production from PO is more attractive than from M2. However, regarding efficiency and effectiveness of public funds, M2 is superior to PO because the public BCR and NPV are higher, and the pressure on agricultural land is lower. Moreover, M2 as part of a systemic approach presents a better carbon balance. These findings show that, under a systemic approach based on circular economy, strategies like the one analyzed in this study are economically feasible and may have a promising future.


Transvaginal ultrasound ovarian diathermy: sheep as an experimental model.
Some techniques of transvaginal ovarian drilling have been previously described. Nevertheless a monopolar transvaginal ovarian cauterization, that use the expertise and safety of transvaginal puncture for oocyte captation seems to be an easier and feasible approach. The aim of this study was to develop a minimally invasive ovarian cauterization technique under transvaginal ultrasound control, and to evaluate the safety of the transvaginal ovarian monopolar cauterization, female sheep at reproductive age were used as an experimental model. An experimental study was performed in a university research center. Seventeen female sheep (15 Corriedale e 2 Suffolk) in reproductive age were submitted to transvaginal ovarian cauterization with a monopolar Valleylab Force 2 electrocautery. Macroscopic and microscopic lesions were assessed. Ovarian size were 1.31 cm2 ± 0,43 (Corriedale) and 3.41 cm2 ± 0,64 (Suffolk). From 30 ovaries from Corriedale sheep punctured, only 3 were cauterized, presenting macroscopic and typical microscopic lesion. In the Suffolk sheep group, only one ovary was cauterized. No lesion could be found in the needle path. This is the first experimental animal model described for ovarian cauterization needle guided by transvaginal ultrasound. The sheep does not seem to be the ideal animal model to study this technique. Another animal model, whose ovaries are better identified by transvaginal ultrasound should be sought for this technique, theoretically less invasive, before it could be offered safely to women with polycystic ovary syndrome.


Pelvic exenteration for vulvar cancer: Postoperative morbidity and oncologic outcome - A single center retrospective analysis.
Pelvic exenteration may be the only curative treatment for some patients with primary advanced or recurrent vulvar cancer but is associated with high morbidity. This study evaluated the clinical outcome of patients treated at a centralized service in Norway. This retrospective study included patients treated with pelvic exenteration for primary locally advanced or recurrent vulvar cancer between 1996 and 2019 at Oslo University Hospital, Norway. Complications were coded according to the contracted Accordion classification. Relapse free survival (RFS), cancer specific survival (CSS) and overall survival (OS) were estimated with the Kaplan Meier method. The 30 patients were followed for a median of 4.94 years (95%CI: 3.37-NR). Exenteration due to primary vulvar cancer was carried out in 16 (53%) patients, 14 (47%) had recurrent vulvar cancer. Free histopathological margins were achieved in 28 (93%) patients. The 90 days morbidity for grade 3 complications was 63%, predominantly wound/surgical flap infections, 7% had no complications. 90 days mortality was 3%. Five-year RFS was 26% (95% CI 8-48%), OS was 50% (95%CI: 29-69%) and CSS was 64% (95% CI 43-79%). There was no significant difference in survival between patients with primary vs recurrent disease. The 3-year CSS for patients with negative lymph nodes and positive lymph nodes was 70% (95% CI 47-84%) and 30% (95% CI 1-72%), respectively. Acceptable oncologic outcomes after pelvic exenteration for primary and recurrent vulvar cancer can be achieved if surgery is centralized. Careful patient selection is imperative due to significant postoperative morbidity and considerable risk of relapse.


cis- and trans-acting elements involved in regulation of aniA, the gene encoding the major anaerobically induced outer membrane protein in Neisseria gonorrhoeae.
AniA (formerly Pan1) is the major anaerobically induced outer membrane protein in Neisseria gonorrhoeae. AniA has been shown to be a major antigen in patients with gonococcal disease, and we have been studying its regulation in order to understand the gonococcal response to anaerobiosis and its potential role in virulence. This study presents a genetic analysis of aniA regulation. Through deletion analysis of the upstream region, we have determined the minimal promoter region necessary for aniA expression. This 130-bp region contains a sigma 70-type promoter and an FNR (fumarate and nitrate reductase regulator protein) binding site, both of which are absolutely required for anaerobic expression. Also located in the minimal promoter region are three T-rich direct repeats and several potential NarP binding sites. This 80-bp region is required for induction by nitrite. By site-directed mutagenesis of promoter sequences, we have determined that the transcription of aniA is initiated only from the sigma 70-type promoter. The gearbox promoter, previously believed to be the major promoter, does not appear to be active during anaerobiosis. The gonococcal FNR and NarP homologs are involved in the regulation of aniA, and we demonstrate that placing aniA under the control of the tac promoter compensates for the inability of a gonococcal fnr mutant to grow anaerobically.


Nitric oxide enhances increase in cytosolic Ca(2+) and promotes nicotine-triggered MAPK pathway in PC12 cells.
The purpose of this study was to investigate the roles of neuronal nitric oxide synthase (nNOS), Ca(2+)/calmodulin (CaM)-dependent protein kinases (CaMKs), and protein kinase C (PKC) in nicotine-induced extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) activation. Treatment with nicotine stimulated ERK1/2 and p38 MAPK phosphorylation in the PC12 cells expressing nNOS (NPC12 cells) as compared with that in control PC12 cells. An inhibitor of L-type voltage-sensitive Ca(2+) channel suppressed the nicotine-induced phosphorylation of p38 MAPK. The inhibition of CaMK-kinase, the upstream activator of CaMKI and CaMKIV, did not inhibit the enhanced their phosphorylation. ERK1/2 phosphorylation was attenuated by inhibitors of p38 MAPK, PKC, and MAPK-kinase 1/2, indicating the involvement of these protein kinases upstream of ERK1/2. Furthermore, we found that nNOS expression enhances the nicotine-induced increase in the intracellular concentration of Ca(2+), using the Ca(2+)-sensitive fluorescent probe Fura2. These data suggest that NO promotes nicotine-triggered Ca(2+) transient in PC12 cells to activate possibly CaMKII, leading to sequential phosphorylation of p38 MAPK and ERK1/2.


Recurrences during a 10-year follow-up after first renal stone episode.
Each of 92 patients in a Swedish district served by only one hospital had been treated for their first renal stone in 1977 and was evaluated 10 years later. Recurrent stone formation during the observation period was observed in 26% of the patients, with no difference between men and women. Of all the patients who had sought medical advice in 1977 because of urinary stone colic, 51% were experiencing their first stone episode. Ten years later 37% of the original patients were still classified as single stone formers. The recorded recurrence rate was lower than that previously reported in the literature.


Disentangling the coupling relationships between functional denitrifiers and nitrogen transformation during cattle-manure and biochar composting: A novel perspective.
This study explored the coupling relationships between denitrifiers and N-transformation using multi-level (DNA, RNA and enzyme) and multi-aspect (abundance, diversity, structure, key community, network pattern, and functional module) analyses during cattle-manure (CM) and biochar (CMB) composting. Amino sugar-N (ASN, 0.914) and hydrolysable unknown-N (-0.724) were main organic-N components mediating NH4+-N in CM and CMB, respectively. Biochar lowered nirK, nirS, and nosZ genes copies, up-regulated nir gene transcripts, and inhibited nitrite reductase (NIR) activity. For nirK-denitrifiers, Luteimonas was predominant taxa influencing NO2--N and amino acid-N (AAN). Unclassified_k_norank_d_Bacteria and unclassified_p_Proteobacteria regulated NO3--N and ASN, respectively. These three genera played crucial roles in mediating NIR activity and nosZ/nirK. For nirS-denitrifiers, Paracoccus and Pseudomonas mediated NH4+-N and AAN, respectively, and they were vital genera regulating NO3--N, ASN and NIR activity. Furthermore, nirK-denitrifiers was major contributor to denitrification. Overall, functional denitrifiers might simultaneously participate in multiple N-transformation processes.


Treatment, survival, and costs of oropharyngeal cancer care in the elderly.
To examine associations between treatment, survival, and costs in elderly patients with oropharyngeal squamous cell cancer (OPSCC). Retrospective cross-sectional analysis of Surveillance, Epidemiology, and End Results-Medicare data. We evaluated 666 patients diagnosed with OPSCC from 2004 to 2007 using cross-tabulations, multivariate logistic and generalized linear regression modeling, and survival analysis. The majority of patients were nonsmokers (79%), had advanced-stage disease (59%), and received chemoradiation (38%) or radiation (28%). Surgery with postoperative radiation (hazard ratio [HR]: 0.33 [95% CI: 0.20-0.53]) and chemoradiation (HR: 0.45 [95% CI: 0.29-0.71]) were associated with improved survival, whereas stage IV disease was associated with poorer survival (HR: 1.95 [95% CI: 1.13-3.38]). Additional cancer-directed treatment after primary treatment was more likely following chemoradiation (odds ratio [OR]: 3.44 [95% CI: 1.78-6.63]). Salvage surgery was performed in 25% of patients undergoing subsequent additional cancer-directed treatment, and was associated with high-volume hospitals (OR: 2.81 [95% CI: 1.07-7.74]). Additional radiation (HR: 0.47 [95% CI: 0.31-0.72]) and salvage surgery (HR: 0.61 [95% CI: 0.38-0.99]) were associated with improved overall survival when performed >6 months following initial treatment, whereas salvage neck dissection alone was not significantly associated with survival after controlling for time to salvage (HR: 0.38 [95% CI: 0.05-2.78]). Treatment and 5-year overall costs were highest for chemoradiation, surgery with postoperative radiation, and additional cancer-directed treatment. Multimodality treatment in elderly OPSCC patients was associated with improved survival and increased costs. Chemoradiation was associated with an increased likelihood of additional cancer-directed treatment. Salvage surgery was centralized at high-volume hospitals, and was associated with improved survival when performed >6 months after last initial treatment date, but was performed in <20% of patients undergoing additional treatment. 2c. Laryngoscope, 128:1103-1112, 2018.


TRPV2 channel-based therapies in the cardiovascular field. Molecular underpinnings of clinically relevant therapies.
The transient receptor potential (TRP) ion channel family is composed of twenty-seven channel proteins that are ubiquitously expressed in the human body. The TRPV (vanilloid) subfamily has been a recent target of investigation within the cardiovascular field. TRPV1, which is sensitive to heat as well as vanilloids, is the best characterized TRPV channel and is the namesake for the subfamily that includes six members. Research into the function of TRPV2 has suggested that it plays an important role in cardiovascular function. Over the last twenty years a greater understanding of the differences among the TRPV channels has allowed for more precise experimentation and has opened various translational opportunities. TRPV2 has been found to be a both a mechanosensor and a mediator of calcium handling and has been found to play important roles in healthy and diseased cardiomyocytes. These roles have been translated into clinical studies in patients with muscular dystrophy (both agonism and antagonism) as well as in patients with cardiomyopathy and heart failure with reduced ejection fraction. Its role as a structural protein has also been elucidated, though the clinical significance of this finding has yet to be established. Despite the clinical progress that has been made there is still a need for large, prospective randomized studies with TRPV2 channel agonists and antagonists in order to bring these basic and translational science findings to the bedside.


Nutrition and indigenous health in New Zealand.
Within New Zealand, Maori experience a greater burden than non-Maori from childhood communicable diseases and from adult non-communicable diseases, for which malnutrition is recognised to have an important role in causality. The nutritional status of Maori is poorer than non-Maori. A larger proportion of Maori newborns are small for gestational age. Weight gain during the first 2 years of life is then more rapid than for non-Maori, and the proportion of Maori that are obese is higher than non-Maori through childhood and into adulthood. Across the age range from infancy to women of childbearing age, iron deficiency is more prevalent, and vitamin D status is poorer in Maori than non-Maori. Over the past two decades, the nutritional status of Maori has improved at birth and during childhood. The proportion of Maori infants small for gestational age and the mean body mass of Maori children aged 2-14 years have decreased. These improvements have been larger than in non-Maori. Further reduction in disparities in nutritional status between Maori and non-Maori must be a priority if the health status of New Zealand's population is to improve. The interventions must address the role that poverty plays in malnutrition, need to be rooted in local food systems and be community driven. If population health status is to improve, New Zealand must secure access to nutritious food for pregnant women, infants and children living in low-income families.


Inhibitory action of salicylideneamino-2-thiophenol on NF-κB signaling cascade and cyclooxygenase-2 in HNE-treated endothelial cells.
In the present study, the anti-inflammatory effect of salicylideneamino-2-thiophenol (SAL-2), a derivative of salicylate, on a potent oxidant 4-hydroxynonenal (HNE)-induced oxidative stress was investigated using rat prostate endothelial (YPEN-1) cells. We focused on anti-inflammatory activity of SAL-2 which was determined by its ability to suppress COX-2 and iNOS gene expression through suppression of NF-κB and redox regulation. We found that SAL-2 effectively inhibited HNE-induced reactive species generation, while upregulated GSH/GSSG ratio. Prostagrandin (PG) E2 production stimulated by arachidonic acid was suppressed by SAL-2. SAL-2 also downregulated COX-2 and iNOS expression induced by HNE, but salicylate did not. We found that SAL-2 inhibited HNE-mediated IKK phosphorylation, IκBα degradation and nuclear translocation of p65 which are linked to NF-κB activation. Furthermore, SAL-2 inhibited HNE-induced activation of mitogen-activated protein kinases. Collectively, SAL-2 inhibited COX-2 and iNOS gene expression through suppression of NF-κB leading to the inhibition of PGE2 synthesis. Based on these data, we propose that with its combined effect on strong anti-oxidant and anti-inflammatory action, SAL-2 can be a potent anti-inflammatory agent for treatment of inflammatory-related diseases.


Transforming growth factor β1 antagonizes the transcription, expression and vascular signaling of guanylyl cyclase/natriuretic peptide receptor A - role of δEF1.
The objective of this study was to determine the role of transforming growth factor β1 (TGF-β1) in transcriptional regulation and function of the guanylyl cyclase A/natriuretic peptide receptor A gene (Npr1) and whether cross-talk exists between these two hormonal systems in target cells. After treatment of primary cultured rat thoracic aortic vascular smooth muscle cells and mouse mesangial cells with TGF-β1, the Npr1 promoter construct containing a δ-crystallin enhancer binding factor 1 (δEF1) site showed 85% reduction in luciferase activity in a time- and dose-dependent manner. TGF-β1 also significantly attenuated luciferase activity of the Npr1 promoter by 62%, and decreased atrial natriuretic peptide-mediated relaxation of mouse denuded aortic rings ex vivo. Treatment of cells with TGF-β1 increased the protein levels of δEF1 by 2.4-2.8-fold, and also significantly enhanced the phosphorylation of Smad 2/3, but markedly reduced Npr1 mRNA and receptor protein levels. Over-expression of δEF1 showed a reduction in Npr1 promoter activity by 75%, while deletion or site-directed mutagenesis of δEF1 sites in the Npr1 promoter eliminated the TGF-β1-mediated repression of Npr1 transcription. TGF-β1 significantly increased the expression of α-smooth muscle actin and collagen type I α2 in rat thoracic aortic vascular smooth muscle cells, which was markedly attenuated by atrial natriuretic peptide in cells over-expressing natriuretic peptide receptor A. Together, the present results suggest that an antagonistic cascade exists between the TGF-β1/Smad/δEF1 pathways and Npr1 expression and receptor signaling that is relevant to renal and vascular remodeling, and may be critical in the regulation of blood pressure and cardiovascular homeostasis.


Climate change and animals in Saudi Arabia.
Global warming is occurring at an alarming rate and predictions are that air temperature (T a) will continue to increase during this century. Increases in T a as a result of unabated production of greenhouse gases in our atmosphere pose a threat to the distribution and abundance of wildlife populations worldwide. Although all the animals worldwide will likely be affected by global warming, diurnal animals in the deserts will be particularly threatened in the future because T as are already high, and animals have limited access to water. It is expected that Saudi Arabia will experience a 3-5 °C in T a over the next century. For predicting the consequences of global warming for animals, it is important to understand how individual species will respond to higher air temperatures. We think that populations will not have sufficient time to make evolutionary adjustments to higher T a, and therefore they will be forced to alter their distribution patterns, or make phenotypic adjustments in their ability to cope with high T a. This report examines how increases in T a might affect body temperature (T b) in the animals of arid regions. We chose three taxonomic groups, mammals, birds, and reptiles (Arabian oryx, Arabian spiny-tailed lizard, vultures, and hoopoe larks) from Saudi Arabia, an area in which T a often reaches 45 °C during midday in summer. When T a exceeds T b, animals must resort to behavioral and physiological methods to control their T b; failure to do so results in death. The observations of this study show that in many cases T b is already close to the upper lethal limit of around 47° C in these species and therefore allowing their T b to increase as T a increases are not an option. We conclude that global warming will have a detrimental impact on a wide range of desert animals, but in reality we know little about the ability of most animals to cope with change in T a. The data presented should serve as base-line information on T b of animals in the Kingdom for future scientists in Saudi Arabia as they explore the impact of global warming on animal species.


Second primary cancers of the head and neck following treatment of initial primary head and neck cancers.
The risk of a second primary cancer arising in the head and neck, following surgical or radiation treatment of an initial primary cancer in the head and neck, was evaluated for 2,151 patients whose first cancers were diagnosed and treated at UCLA between 1955 and 1979. Based on follow-up data ranging from 5 to 30 years, the rate of development of second cancers of the head and neck was in excess of 2.5 per 1000 person-years at risk. There was no statistically significant difference in the frequency or post-treatment interval of second primary cancers related to the type of treatment of the first cancer, whether that was surgery, radiation therapy, or surgery plus radiation therapy.


Pulmonary comorbidities in psoriasis are associated with a high risk of respiratory failure.
To identify respiratory comorbidities associated with a high risk of developing respiratory failure in subjects with psoriasis. This was a cross-sectional analysis of data from subjects enrolled in the UK Biobank cohort. All diagnoses were self-reported. The risk of each respiratory comorbidity was compared by logistic regression models adjusting for age, sex, weight, diabetes mellitus, and smoking history; the risk of comorbid respiratory failure for each pulmonary comorbidity was also compared. Of the 472,782 Caucasian subjects in the database, 3,285 self-reported a diagnosis of psoriasis. More men and smokers reported psoriasis and were older, had higher weight and body mass index, and lower pulmonary function than non-psoriatic subjects. Those with psoriasis were at significantly higher risk for multiple pulmonary comorbidities compared to those without psoriasis. Furthermore, those with psoriasis had a higher risk for respiratory failure accompanied by asthma and airflow limitation than non-psoriatic subjects. Subjects with psoriasis and pulmonary comorbidities, such as asthma and airflow limitation, are at increased risk for respiratory failure. Common immunopathological links implicating a 'skin-lung axis' may underlie psoriasis and pulmonary comorbidities.


18F-FDG PET/CT and 68Ga-DOTATATE PET/CT Findings in a Patient With Primary Renal Well-Differentiated Neuroendocrine Tumor.
Primary renal well-differentiated neuroendocrine tumors (WDNETs), also called renal carcinoids, are extremely rare. Since first described in 1966, approximately 100 cases have been reported in the literature. However, there have been no cases shown by PET/CT to date. We presented a patient with primary renal WDNET who had undergone both 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT for diagnosis and staging. This case illustrated that 68Ga-DOTATATE PET/CT scanning could play a role in the diagnosis, staging, and follow-up of primary renal WDNETs.


Targeting Cytochrome P450 (CYP) 1B1 Enzyme with Four Series of A-Ring Substituted Estrane Derivatives: Design, Synthesis, Inhibitory Activity, and Selectivity.
Cytochrome P450 (CYP) 1B1 is involved in the bioactivation of procarcinogens and drug resistance. To obtain selective CYP1B1 inhibitors over CYP1A1, we synthesized four series of estrane derivatives: (1) 12 estrone (E1)- and 17β-estradiol (E2)-derivatives bearing a 3- or a 4-pyridinyl core at C2, C3, or C4, (2) eight estrane derivatives with different sulfur groups at C3, (3) 19 E1- and E2-derivatives bearing distinct aryls at C2, and (4) five D-ring derivatives. E2-derivatives were more active than oxidized E1-analogues, thus highlighting the key role of 17β-OH for interaction with CYP1B1. 2-(4-Fluorophenyl)-E2 was the best CYP1B1 inhibitor (IC50 = 0.24 μM), with a selectivity index (SI) of 20 over CYP1A1. Furthermore, the addition of a C17α-ethynyl group as D-ring modification improved the selectivity index to 25 with only a slight loss of activity (IC50 = 0.37 μM). Our docking results showed that these compounds fit better into the CYP1B1 binding site than that of CYP1A1.


Assessing field vulnerability to phosphorus loss in Beijing agricultural area using Revised Field Phosphorus Ranking Scheme.
Guanting Reservoir, one of the drinking water supply sources of Beijing, suffers from water eutrophication. It is mainly supplied by Guishui River. Thus, to investigate the reasons of phosphorus (P) loss and improve the P management strategies in Guishui River watershed are important for the safety of drinking water in this region. In this study, a Revised Field P Ranking Scheme (PRS) was developed to reflect the field vulnerability of P loss at the field scale based on the Field PRS. In this new scheme, six factors are included, and each one was assigned a relative weight and a determination method. The affecting factors were classified into transport factors and source factors, and, the standards of environmental quality on surface water and soil erosion classification and degradation of the China were used in this scheme. By the new scheme, thirty-four fields in the Guishui River were categorized as "low", "medium" or "high" potential for P loss into the runoff. The results showed that the P loss risks of orchard and vegetable fields were higher than that of corn and soybean fields. The source factors were the main factors to affect P loss from the study area. In the study area, controlling P input and improving P usage efficiency are critical to decrease P loss. Based on the results, it was suggested that more attention should be paid on the fields of vegetable and orchard since they have extremely high usage rate of P and high soil test of P. Compared with P surplus by field measurements, the Revised Field PRS was more suitable for reflecting the characteristics of fields, and had higher potential capacity to identify critical source areas of P loss than PRS.


Cloning of the gene encoding Trop-2, a cell-surface glycoprotein expressed by human carcinomas.
We have cloned by expression the cDNA encoding Trop-2, a cell-surface glycoprotein expressed by most human carcinomas. Formal proof of the identity of the clone is the hybridization to DNA and RNA from genomic TROP2 transfectants. TROP2 is a single-copy gene in human cells, hybridizes to a single 1.8-kb mRNA from expressing sources and encodes a 35,709 Da type-1 transmembrane protein with a single transmembrane domain. TROP2 is essentially identical to GA733-1. Thus, we have proven that GA733-1, for which a protein product had not been identified, is a functional gene. TROP2 is also homologous to TROP1/KSA/GA733-2, confirming the serological similarities between the 2 molecules. The homology between the Trop-1 and Trop-2 peptides is clustered in 2 extracytoplasmic domains and in the transmembrane/cytoplasmic region. Twelve cysteines and a potential cytoplasmic tyrosine phosphorylation site are also conserved. Trop-1 and Trop-2 are homologous to serum IGF-II-binding proteins and appear as signal transducers. Thus, they likely represent novel cell-surface receptors and may play a role in regulating the growth of carcinoma cells. On the other hand, we have found no evidence for a role of Trop-2 and Trop-1 as homophilic adhesion molecules.


Incorporation of graphene oxide as a coupling agent in a 3D printed polylactic acid/hardystonite nanocomposite scaffold for bone tissue regeneration applications.
3D printing fabrication has become a dominant approach for the creation of tissue engineering constructs as it is accurate, fast, reproducible and can produce patient-specific templates. In this study, 3D printing is applied to create nanocomposite scaffold of polylactic acid (PLA)/hardystonite (HT)-graphene oxide (GO). GO is utilized as a coupling agent of alkaline treated HT nanoparticles within PLA matrix. The addition of HT-GO nanoparticles of up to 30 wt% to PLA matrix was found to increase the degradability from 7.33 ± 0.66 to 16.03 ± 1.47 % during 28 days. Also, the addition of 20 wt% of HT-GO nanoparticles to PLA scaffold (PLA/20HTGO sample) significantly increased the compressive strength (from 7.65 ± 0.86 to 14.66 ± 1.01 MPa) and elastic modulus (from 94.46 ± 18.03 to 189.15 ± 10.87 MPa). The apatite formation on the surface of nanocomposite scaffolds in simulated body fluid within 28 days confirmed the excellent bioactivity of nanocomposite scaffolds. The MG63 cell adhesion and proliferation and, also, the rat bone marrow mesenchymal stem cells osteogenic differentiation were highly stimulated on the PLA/20HTGO scaffold. According to the sum of results obtained in the current study, the optimized PLA/20HTGO nanocomposite scaffold is highly promising for hard tissue engineering applications.


The effect of age on peripheral stem cell mobilization in healthy donors, single center experience.
Peripheral stem cell transplantation is used as a life-saving therapeutic option in hematological malignancies. As previously established, most hematological malignancies are seen in the elderly population. Therefore, possible HLA-identical sibling donors of elderly patients are generally of an advanced age. In this study, we aimed to evaluate the effect of old age on stem cell mobilization and quality in older adult healthy sibling donors. Between 2006 and 2014, we evaluated 38 healthy donors aged ≥55 years. The granulocyte-colony stimulating factor (G-CSF) analogs were used at a dose of 5 µg/kg/day and administered subcutaneously twice a day for five days. CD34+ cells were estimated in the peripheral blood before collection of the apheresis product. The National Marrow Donor Program selects healthy unrelated donors if they are younger than 60 years. Therefore, we compared the product quality in donors over the age of 60 to that in donors aged 60 years or less. We collected sufficient products from all the donors with one to three apheresis procedures. No serious complication was detected in all donors. Reaching the target CD34+ cell count in one day were detected in 83% of younger and 79% of older donors (P = NS). Collected CD34+ cells x10e6/recipient body weight (kg) was same and 5.1 in the groups (P = NS). There were no correlation between the donor age and these parameters. Healthy donor apheresis in older adults can be performed effectively and possible donors should be evaluated regardless of their age. J. Clin. Apheresis 32:16-20, 2017. © 2016 Wiley Periodicals, Inc.


The expression of lactate transporters (MCT1 and MCT4) in heart and muscle.
It is now known that lactate traverses the plasma membrane of many tissues, including heart and muscle, via a stereo-specific, pH-dependent monocarboxylate transport (MCT) system. In the past few years a family of MCTs (MCT1-MCT7) has been cloned. Transcripts of MCT1 and MCT4 are detectable in rat and human skeletal muscle and in the heart. However, only skeletal muscle expresses both the MCT1 and MCT4 proteins, whereas rat heart expresses the MCTI, but not the MCT4 protein. The kinetic activities of MCT1(Km=3.5 mM) and MCT4 (Km= 17-34 mM) are quite different. Among rat muscles, MCT1 expression is highly correlated with the oxidative fiber composition of the muscle, and other indices of oxidative metabolism. Lactate uptake from the circulation is also highly correlated with the MCT1 content of muscles. MCT4 is confined to fast-twitch (fast glycolytic and fast oxidative glycolytic) muscle fibers, in which MCT4 content is correlated with indices of anaerobic metabolism. Collectively, these data suggest that MCT1 and MCT4 are primarily responsible for lactate uptake from the circulation and lactate extrusion out of muscle, respectively. Exercise training can increase the expression of both MCT1 and MCT4 in human muscle, although the extent of this up-regulation may be related to the intensity of training. In the rat heart, MCT1 expression is induced more easily by exercise training than in rat skeletai muscle. It appears that MCT1 and MCT4 expression are regulated in a tissue-specific and isoform-specific manner. Therefore, skeletal muscle lactate concentrations are not only regulated by the rate of glycolysis, but also by the efficiency of trans-sarcolemmal lactate transport, a process that is regulated by the quantity of available MCT proteins.


Incidence and severity of SARS-CoV-2 reinfection, a multicenter cohort study in Shanghai, China.
During March 2022 to January 2023, two Omicron waves hit Shanghai and caused a massive number of reinfections. To better understand the incidence and clinical characteristics of SARS-CoV-2 reinfection in Shanghai, China, we conducted a multicenter cohort study. COVID-19 patients first infected with BA.2 (March 1, 2022-May 23, 2022) who were quarantined in Huashan Hospital, Renji Hospital, and Shanghai Jing'an Central Hospital were followed up for reinfection from June 1, 2022 to January 31, 2023. Of 897 primary infections, 148 (16.5%) experienced reinfection. Incidence rate of reinfection was 0.66 cases per 1000 person-days. Female gender (adjusted odds ratio [aOR]= 2.19, 95% confidence interval [CI]: 1.29-3.83) was a risk factor for reinfection. The four most common symptoms of reinfections during the circulation of BA.5 sublineages were cough (62.59%), sore throat (54.42%), fatigue (48.98%), and fever (42.57%). Having received a booster vaccination was not associated with reduced severity of reinfection in comparison with not having received booster vaccination. After matched 1:1 by age and sex, we found that reinfections with BA.5 sublineages had significantly lower occurrence and severity of fever, fatigue, sore throat, and cough, as compared to primary infections with BA.5 sublineages. SARS-CoV-2 Omicron reinfections were less severe than Omicron primary infections during the circulation of the same subvariant. Protection offered by both vaccination and previous infection was poor against SARS-CoV-2 reinfection.


Prevalence and management of severe intrapartum hypertension in patients with preeclampsia at an urban tertiary care medical center.
Data on management of severe intrapartum hypertension is lacking. The aim of this study is to explore the proportion of timely interventions in severe, persistent intrapartum hypertension treatment by exploring the prevalence and management of intrapartum hypertension trends. This was a retrospective case-control study of pregnant women who delivered at the University of Chicago between January 2015 and March 2017. Patients with severe preeclampsia who underwent labor (either induced or spontaneous) were stratified into two groups: severe intrapartum hypertension and no severe intrapartum hypertension. Type of treatment and timing to treatment of severe hypertensive episodes were explored as well as prevalence of maternal adverse outcomes. A total of 95 patients with severe preeclampsia in labor were identified. In patients with persistent severe intrapartum hypertension (n = 52), 15 (28.9%) received treatment. Patients experiencing greater than three episodes of blood pressure elevation were more likely to receive treatment as compared to those with fewer episodes. There was no significant difference in severe maternal morbidity (SMM) between those treated within 60 min compared to those untreated or treated after 60 min (16.7% vs 27.5%; p = 0.71). Management protocols of intrapartum hypertensive episodes are variable or not universally implemented. Inadequately treated episodes of severe intrapartum hypertension trend towards higher rates of SMM.


Application of systems principles in consultation-liaison psychiatry.
The application of systems principles in a hospital setting, its value as a diagnostic tool in assessing problem behavior and its use in planning intervention are described. Examples from different treatment settings are used to demonstrate the applications.