Cervical cancer screening program integrating Pap smear and HPV DNA testing: a population-based study.
We conducted a population-based cohort study to evaluate the complementary value of HPV testing to Papanicolaou (Pap) smear and the prevalence and genotype distribution of HPV in Taiwan. In this report, we described the design of the whole study and analyzed the cross-sectional results. Female residents (age >or= 30 years) of Taoyuan, Taiwan were invited. After signing informed consent, every participant had a Pap smear and a HPV testing. Patients with Pap >or= atypical squamous cell of undetermined significance (Group I) or those with HPV-positive but normal cytology (Group II) were referred for a colposcopic examination. A total of 10,014 women were eligible. The overall HPV prevalence was 10.8% (95% confidence interval 10.5%-11.4%) in the study population. A total of 37 types of HPV were identified and the leading three were HPV-52, -18 and -58. There was a significant positive correlation of HPV prevalence with older age, postmenopausal status, current-user of oral contraceptives and never-user of hormone replacement therapy. Past users of oral contraceptives and never users of Pap were associated with higher risk of abnormal Pap, while age 40-49 strata had lower risk. Fifty-nine cases of cervical intraepithelial neoplasia (CIN) 2 from Group I and additional 11 from Group II were identified. The improvement of sensitivity with additional HPV testing was 15.3%. Besides, no specific subgroup was found to most benefit from the combined strategy. The value of adding HPV test to conventional Pap smear has to be evaluated after longer-term follow-up of this population-based cohort.


Rapid purification of recombinant listeriolysin O (LLO) from Escherichia coli.
Listeria monocytogenes is an emerging foodborne pathogen that is responsible for about 28% of the food-related deaths in the United States. It causes meningitis, septicaemia and in pregnant women, abortions and stillbirths. It secretes the toxin listeriolysin O (LLO) that allows the bacteria to enter the cytoplasm of host cells, where they can replicate and cause further infection. The rapid and sensitive detection of LLO in food samples is a key to monitoring and prevention of listeriosis. To facilitate the development of an assay for the specific detection of LLO, a source of LLO is essential. We outline a method of producing a large amount of functional LLO by expressing the hlyA gene (encoding LLO) in Escherichia coli and purifying the recombinant LLO using a one-step purification method. Purification of the protein takes only about 4 h. We compared three different expression constructs for the production of the toxin, which tends to interact strongly with a number of column surfaces. The first construct, using an intein fusion system, could not be purified from the column. The second LLO construct contained an N-terminus His tag; it gave a yield of 3.5-8 mg l(-1). The third contained a C-terminus His tag; it gave a yield of 2.5 mg l(-1) LLO. The purified LLO from the latter two constructs retained its activity at 4 degrees C for over a year as determined by bovine red blood cell hemolysis assay. This paper provides a much-needed, high-yield, one-step purification method of recombinant LLO, and is the first to provide evidence of long-term stability of the toxin for further applications.


Determinants of gluten-free diet adoption among individuals without celiac disease or non-celiac gluten sensitivity.
Gluten-free (GF) foods are typically less nutritious and more expensive than their gluten-containing variants, yet people without a diagnosed gluten sensitivity continue to adopt this diet. There is a lack of research about what factors drive people without Celiac disease or non-Celiac gluten sensitivity to follow the GF diet. A nationally representative sample of 2982 US residents without a diagnosed gluten sensitivity were surveyed about their attitudes, perceptions, and experiences with the GF diet. Logistic regression was used to compare respondents who were currently avoiding or had avoided gluten previously (GF consumer) to respondents who had never tried a GF diet (non-GF consumer). Over one-fifth of respondents were GF consumers. Beliefs that a gluten-reduced diet is healthier (OR 1.69; 95% CI [1.30,2.18]), that GF products are more nutritious (OR 1.46, 95% CI [1.11,1.90), and that a GF diet can help clear acne (OR 1.46; 95% CI [1.13,1.88]) were all positively associated with trying a GF diet. Personal research was the most influential source of information associated with trying a GF diet (OR 2.92; 95% CI [1.91,4.52]). This was followed by "healthcare center or health professional" (OR 2.57; 95% CI [1.71,3.90]. Respondents who were never encouraged to try the GF diet were less likely to try the diet (OR 0.33, 95% CI [0.23,0.46]). Positive, but scientifically unsubstantiated, beliefs about the benefits of the GF diet were strongly associated with trying a GF diet, and the source of recommendation to try a GF diet was important.


[Analysis of Gene Variation in Thymoma by Microarray].
Thymoma is the most common malignant tumor in anterior mediastinum, and its specific pathogenesis is still unclear. This limits the study of targeted drugs for thymoma. The aim of the study is to investigate the genes and signal pathways of thymoma, and provide help for the research of thymic tumor pathogenesis using the technology of second-generation genechip to analyze thymoma. From January 2015 to December 2017, we analyzed 31 cases of thymoma by CapitaBio mRNA expression profile genechip technology, and then confirmed the genes by reverse transcription-polymerase chain reaction (RT-PCR). We found some genes with different expression levels between thymoma and surrounding thymus tissue. Among them, six driving genes (FANCI, CAPD3, NCAPG, OXCT1, EPHA1 and MCM2) were significantly abnormal in thymoma. Some specific genes affected by copy-number variation were detected: E2F2, EphA1, CCL25 and MCM2 were significantly up-regulated, while IL-6, CD36, FABP4, SH2D1A and MYOC genes were significantly down-regulated. KEGG database analysis showed that the expression of 10 signaling pathway genes was generally up-regulated or down-regulated, such as systemic lupus erythematosus, viral oncogenes, primary immunodeficiency, cell cycle genes and p53 signaling pathway, which may be related to occurrence of thymoma. We found a variety of genes abnormally expressed in thymoma, which will provide reference for the study of pathogenesis and biomarkers of thymoma in the future.


Techno-economic assessment of emerging CO2 electrolysis technologies.
Recycling of waste CO2 to bulk chemicals has a tremendous potential for the decarbonization of the chemical industry. Quantitative analysis of the prospects of this technology is hindered by the lack of flexible techno-economic assessment (TEA) models that enable evaluation of the processing costs under different deployment scenarios. In this protocol, we explain how to convert literature data into metrics useful for evaluation of the emerging electrolysis technologies, derive TEA models, and illustrate their use with a CO2-to-ethylene example. For complete details on the use and execution of this protocol, please refer to Barecka et al. (2021a).


PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy.
Gastrointestinal (GI) malignancies are the most prevalent tumors worldwide, with increasing incidence and mortality. Although surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy have led to significant advances in the treatment of GI cancer patients, overall survival is still low. Therefore, alternative strategies must be identified to improve patient outcomes. In the tumor microenvironment, tumor cells can escape the host immune response through the interaction of PD-1 and PD-L, which inhibits the function of T cells and tumor-infiltrating lymphocytes while increasing the function of immunosuppressive T regulatory cells. The use of an anti-PD-1/PD-L blockade enables reprogramming of the immune system to efficiently identify and kill tumor cells. In recent years, the efficacy of PD-1/PD-L blockade has been demonstrated in many tumors, and this treatment is expected to be a pan-immunotherapy for tumors. Here, we review the signaling pathway underlying the dysregulation of PD-1/PD-L in tumors, summarize the current clinical data for PD-1/PD-L inhibitors in GI malignancies, and discuss road toward precision immunotherapy in relation to PD-1/PD-L blockade. The preliminary data for PD-1/PD-L inhibitors are encouraging, and the precision immunotherapy of PD-1/PD-L inhibitors will be a viable and pivotal clinical strategy for GI cancer therapy.


Substance-P-containing nerve fibers in the nasal mucosa.
Nerve fibers displaying SP immunoreactivity were detected in the nasal mucosa of several mammals. The fibers were seen around small blood vessels, seromucous glands, and beneath and sometimes within the surface epithelium. In the pterygopalatine ganglion and the trigeminal ganglion, known to innervate the nasal mucosa, SP-positive nerve cell bodies were seen. Sympathetic denervation with 6-hydroxydopamine (6-OHDA) or bilateral cervical sympathectomy did not visibly affect the distribution of SP fibers in the nasal mucosa in mice or rats. The findings are compatible with the view that the bulk of SP fibers to the nasal mucosa derive from the trigeminal ganglion with a possible contribution from the pterygopalatine ganglion.


Phases of Hyperconnectivity and Hypoconnectivity in the Default Mode and Salience Networks Track with Amyloid and Tau in Clinically Normal Individuals.
Alzheimer's disease (AD) is characterized by two hallmark molecular pathologies: amyloid aβ1-42 and Tau neurofibrillary tangles. To date, studies of functional connectivity MRI (fcMRI) in individuals with preclinical AD have relied on associations with in vivo measures of amyloid pathology. With the recent advent of in vivo Tau-PET tracers it is now possible to extend investigations on fcMRI in a sample of cognitively normal elderly humans to regional measures of Tau. We modeled fcMRI measures across four major cortical association networks [default-mode network (DMN), salience network (SAL), dorsal attention network, and frontoparietal control network] as a function of global cortical amyloid [Pittsburgh Compound B (PiB)-PET] and regional Tau (AV1451-PET) in entorhinal, inferior temporal (IT), and inferior parietal cortex. Results showed that the interaction term between PiB and IT AV1451 was significantly associated with connectivity in the DMN and salience. The interaction revealed that amyloid-positive (aβ+) individuals show increased connectivity in the DMN and salience when neocortical Tau levels are low, whereas aβ+ individuals demonstrate decreased connectivity in these networks as a function of elevated Tau-PET signal. This pattern suggests a hyperconnectivity phase followed by a hypoconnectivity phase in the course of preclinical AD.SIGNIFICANCE STATEMENT This article offers a first look at the relationship between Tau-PET imaging with F18-AV1451 and functional connectivity MRI (fcMRI) in the context of amyloid-PET imaging. The results suggest a nonlinear relationship between fcMRI and both Tau-PET and amyloid-PET imaging. The pattern supports recent conjecture that the AD fcMRI trajectory is characterized by periods of both hyperconnectivity and hypoconnectivity. Furthermore, this nonlinear pattern can account for the sometimes conflicting reports of associations between amyloid and fcMRI in individuals with preclinical Alzheimer's disease.


Repeat Cold Snare Polypectomy Can Be Performed for Recurrent Benign Lesions After Cold Snare Polypectomy.
Recurrence after cold snare polypectomy (CSP) sometimes occurs. We assessed the feasibility of repeat CSP for recurrence after CSP. We retrospectively reviewed recurrent lesions after CSP which were resected by repeat CSP from 2016 to 2021 in our institution and analyzed clinical outcomes of repeat CSP, comparing those of non-recurrent 454 lesions receiving standard CSP in 2016 and follow-up colonoscopy. We also analyzed the recurrent rate among cases receiving follow-up in both groups. Indication of repeat CSP was lesions diagnosed as benign tumors of ≤ 10 mm. We analyzed 80 lesions receiving repeat CSP. The polyp size (mean ± standard deviation: SD) was 4.1 ± 2.3 mm (range 2-10 mm). The right-sided colon and non-polypoid morphology rates were 66.3% and 43.8%, respectively. Histopathological diagnosis was 66 adenomas, 12 sessile serrated lesions (SSLs), 1 SSL with dysplasia, and 1 high-grade dysplasia. The procedure time (min, mean ± SD) of repeat CSP was 0.9 ± 0.8. Regarding the comparison of repeat CSP/ standard CSP group, the en bloc resection and histopathological complete resection rates were 78.8%/ 98.0% (p < 0.001) and 43.8%/59.6% (p = 0.007) and the rates of perioperative hemorrhage requiring endoscopic clipping were 1.3%/ 1.0% (p = 0.646). There were no postoperative hemorrhage and perforation in both groups (p = 1.0). Among lesions receiving follow-up colonoscopy, the mean recurrence rates (number, median follow-up period: interquartile) of repeat CSP and standard CSP group were 2.0% (1/50, 12 months: 12-24) versus 0.7% (3/454, 12 months: 12-24) (p = 0.862). Repeat CSP for benign recurrent lesions after CSP was safe and feasible.


Predicting Cirrhosis and Poor Outcomes of Bile Drainage Surgery for Biliary Atresia: A Multicentric Observational Study in Japan.
To identify patients with biliary atresia (BA) with extremely poor outcomes of bile drainage surgery using the infant BA liver fibrosis (iBALF) score, a liver fibrosis marker based on standard blood analysis. Although primary liver transplantation (LTx) is beginning to be considered as an alternative to bile drainage surgery in patients with BA, those most likely to benefit from this procedure have not yet been identified. The medical records of 380 patients with BA with bile drainage surgery between 2015 and 2019 were collected for retrospective analysis from 60 participating hospitals. To predict native liver survival at age 1 year, a receiver-operating characteristic curve was drawn for the iBALF score. The cutoff value was determined as the point indicating >99% sensitivity. The median age at surgery was 56 days (range: 4-183 d), and native liver survival at age 1 year was achieved in 258 (67.9%) patients. An iBALF score of 5.27 was chosen as the cutoff, and 18 patients (4.7%) were found to have an iBALF score >5.27; of these, only two (95% confidence interval [CI]: 1.4-34.7%) had native liver survival at age 1 year, indicating a significantly poorer outcome than in the other patients (95% CI: 65.7-75.4%). Moreover, patients with an iBALF score >5.27 had significantly higher mortality and younger age at salvage LTx. Patients with BA having a preoperative iBALF score >5.27 had extremely poor outcomes of bile drainage surgery and may be considered as candidates for primary LTx.


Radiographic pseudochondrocalcinosis in early failure of a cemented total knee replacement.
We observed a case of early-onset osteolysis in a cemented total knee arthroplasty. Preoperative radiographs suggested numerous radiopaque particles covering the polyethylene insert. Findings at the time of revision confirmed the presence of small radiopaque polymethylmethacrylate particles on the bearing surface of the tibial insert, presumably leading to early failure of the knee arthroplasty.


Optimum gravity vector and vertical acceleration estimation using a tri-axial accelerometer for falls and normal activities.
This study aims to determine an optimum estimate for the gravitational vector and vertical acceleration profiles using a body-worn tri-axial accelerometer during falls and normal activities of daily living (ADL), validated using a camera based motion analysis system. Five young healthy subjects performed a number of simulated falls and normal ADL while trunk kinematics were measured by both an optical motion analysis system and a tri-axial accelerometer. Through low-pass filtering of the trunk tri-axial accelerometer signal between 1 Hz and 2.7 Hz using a 1(st) order or higher, Butterworth IIR filter, accurate gravity vector profile can be obtained using the method described here. A high mean correlation (≥ 0.83: Coefficient of Multiple Correlations) and low mean percentage error (≤ 2.06 m/s(2)) were found between the vertical acceleration profile generated from the tri-axial accelerometer based sensor to those from the optical motion capture system. This proposed system enables optimum gravity vector and vertical acceleration profiles to be measured from the trunk during falls and normal ADL.


Mineral element levels in wild edible mushrooms from Yunnan, China.
Ten species of wild edible mushrooms (Boletus griseus, Boletus speciosus, Lactarius hygrophoroides, Leucopaxillus giganteus, Macrocybe gigantea, Melanoleuca arcuata, Morchella deliciosa, Mycena haematopus, Pulveroboletus ravenelii, and Tricholoma matsutake) collected from Yunnan province of China, were analyzed for ten mineral elements (calcium, chromium, cobalt, copper, iron, magnesium, manganese, potassium, sodium, and zinc) contents using ICP-AES. The minimum and maximum element contents of mushrooms were determined as milligrams per kilograms dry weight for Ca (38-470), Cr (0.45-6.3), Co (0.29-2.3), Cu (13-58), Fe (22-510), Mg (84-550), Mn (1.4-70), K (1,300-4,600), Na (190-670), and Zn (16-160). The mushrooms species with the highest levels of mineral elements were B. griseus for K and Na, P. ravenelii for Cu, M. deliciosa for Mn, L. giganteus for Cr and Fe, M. gigantea for Ca, Mg and Zn, T. matsutake for Co. These results demonstrate that the mineral element contents in mushrooms are considerably species dependent and affected by environmental factors.


Uveitis associated with sarcoidosis and angiotensin converting enzyme.
Sarcoid uveitis is usually a presumptive diagnosis based on the simultaneous presence of uveitis and clinicoradiographic or histologic findings of sarcoidosis. The elevation of serum ACE in some patients with granulomatous uveitis is strongly presumptive of sarcoid uveitis even in the absence of these findings. Serum ACE may prove to be a useful indicator of ocular sarcoid in the absence of otherwise undetectable systemic disease.


Palifermin: new drug. Prevention of oral mucositis: inappropriate evaluation.
(1) Patients treated with high-dose chemotherapy combined with total body irradiation (myeloablative therapy) often develop oral mucositis. Prevention is based mainly on sucking ice during chemotherapy. (2) Palifermin is a growth factor marketed for the prevention of severe oral mucositis in adults with malignant haemopathies who are receiving myeloablative therapy followed by peripheral stem cell autografting. (3) Palifermin has not been compared with sucking ice, despite the efficacy of this simple treatment. (4) In a randomised placebo-controlled double-blind trial involving 212 adult patients treated with high-dose chemotherapy and total body irradiation, palifermin reduced the incidence of severe oral mucositis (63% versus 98%) and its duration (about 3 days versus 9 days). The myeloablative regimen used in this trial is not that commonly used in Europe. The efficacy of palifermin during less aggressive regimens, which cause less severe oral mucositis, is not known. (5) The main adverse events noted in clinical trials were erythema and cutaneous oedema. It is not known whether palifermin increases the long-term risk of cancer. (6) Treatment with palifermin is expensive, 4800.00 euros in France); the optimal dosing schedule is not known and the unit dose chosen by the manufacturer is wastefully large. (7) In practice, it remains to be demonstrated that palifermin is more effective than simply sucking ice.


Behavioral economics and drug choice: effects of unit price on cocaine self-administration by monkeys.
The application of microeconomic theory to the experimental analysis of behavior has been termed behavioral economics. There has been an increasing interest in applying the concepts of behavioral economics to the study of drug self-administration. In a previously published experiment (Nader and Woolverton, 1992), rhesus monkeys (N = 3) were trained in a discrete-trials choice procedure and allowed to choose between intravenous injections of cocaine (0.03-1.0 mg/kg/injection) and food presentation (1 or 4 pellets; 1 g/pellet) during daily 7-h experimental sessions. When cocaine or food was available under a fixed-ratio (FR) 30 schedule, cocaine intake increased in a dose-related manner for all monkeys. When the response requirement (FR) for cocaine was differentially increased by doubling or quadrupling, the frequency of cocaine choice decreased, shifting the cocaine dose-response function to the right. The present paper is a reanalysis of data from that experiment. Several mathematical models, differentially incorporating the effects of FR, dose and number of food pellets, were compared. When cocaine consumption was analyzed using a multiple linear regression analysis with FR, dose and number of pellets as separate main effects (model I), the R2 was 0.82. When FR and dose were combined into one factor, unit price (UP, responses/mg/kg), and cocaine consumption was analyzed as a linear function of UP (model IIA), the R2 was 0.54. When cocaine consumption was analyzed as a curvilinear, negatively accelerated function of UP (model IIB), the R2 was 0.53. The difference between models I and IIA was statistically significant while models IIA and IIB were not different.(ABSTRACT TRUNCATED AT 250 WORDS)


β2-adrenergic receptor expression in patients receiving bevacizumab therapy for metastatic melanoma.
Vascular endothelial growth factor (VEGF) was initially known as vascular permeability factor and identified as a driver of tumour angiogenesis. Recently, its role in supporting an immunosuppressive tumour microenvironment was demonstrated, and anti-VEGF treatment combined with immune checkpoint blockade is currently investigated. Further, beta-adrenergic signalling as a modifier of cancer hallmarks like immune response, angiogenesis and metastasis gained increased attention during past years. Focusing on the aspect of immunosuppression in upregulated beta-adrenergic signalling, we investigated predictive markers in patients with metastatic melanoma who received bevacizumab monotherapy, a specific VEGF-A binding antibody. We explored the expression of beta-2 adrenergic receptor (β2-AR), interleukin 6-receptor (IL6-R), cyclooxygenase 2 (COX2) and VEGF-A by immunohistochemistry in melanoma to assess the correlation between these proteins in melanoma cells and response to treatment. Strong β2-AR expression in metastases was associated with clinical benefit of bevacizumab. Furthermore, expression of the latter was positively linked to expression of VEGF-A and COX2. β2-AR expression in melanoma metastasis appears to distinguish a subgroup of patients that might benefit from anti-VEGF treatment. Our results strengthen further exploration of anti-VEGF therapy in combination with immune checkpoint blockade in clinical studies and the investigation of β2-AR as predictive marker.


Priming effects of activity-stress ulcer in rats.
The activity-stress ulcer procedure consists of housing rats in running-wheel activity cages while at the same time, restricting their food intake to 1 hr per day. Male Wistar rats which had been habituated with ad lib feeding to the running-wheel cage environment for 3 days prior to the restricted feeding phase, developed significantly more gastric glandular ulcers and exhibited greater levels of running activity when compared to rats which had been given no habituation experience. Control rats housed in standard laboratory cages but which received the same restricted feeding regimen, developed significantly less stress pathology. Since allowing to rats access to the running-wheel during habituation resulted in enhanced stress pathology, this manipulation is referred to as a "priming effect." A possible explanation for such a "priming effect" is discussed in terms of procedures which may increase running wheel activity and decreases survival time during the restricted feeding phase of the activity-stress ulcer procedure.


Choosing wisely in infectious serology: the merits of triaging send-away tests.
Over-utilisation of pathology requests can incur unnecessary costs and be detrimental to patient care. The choosing wisely campaign has helped to reduce the use of tests with limited or no value. This report describes the estimated benefits and costs of implementing a triage process of infectious serology requests in a single mixed hospital and community laboratory. Data analysis of triaging of send away infectious serology was conducted from 1 November 2016 to 31 October 2017. A total of 618 tests were triaged over a 1-year period. Of these 379 (61.3%) were declined. The total gross savings was $45,066. The total cost for implementing this change was estimated to be $4220 per year. The total saving was $40,846.37. There was significant cost saving secondary to this intervention, with other more difficult to measure tangible benefits including fostering communication between laboratory staff and clinicians.


Mechanistic and structural insights into the bifunctional enzyme PaaY from Acinetobacter baumannii.
PaaY is a thioesterase that enables toxic metabolites to be degraded through the bacterial phenylacetic acid (PA) pathway. The Acinetobacter baumannii gene FQU82_01591 encodes PaaY, which we demonstrate to possess γ-carbonic anhydrase activity in addition to thioesterase activity. The crystal structure of AbPaaY in complex with bicarbonate reveals a homotrimer with a canonical γ-carbonic anhydrase active site. Thioesterase activity assays demonstrate a preference for lauroyl-CoA as a substrate. The AbPaaY trimer structure shows a unique domain-swapped C-termini, which increases the stability of the enzyme in vitro and decreases its susceptibility to proteolysis in vivo. The domain-swapped C-termini impact thioesterase substrate specificity and enzyme efficacy without affecting carbonic anhydrase activity. AbPaaY knockout reduced the growth of Acinetobacter in media containing PA, decreased biofilm formation, and impaired hydrogen peroxide resistance. Collectively, AbPaaY is a bifunctional enzyme that plays a key role in the metabolism, growth, and stress response mechanisms of A. baumannii.


Utilizing Actionable Data Analytics to Support Patient Navigation Enrollment and Retention Within Federally Qualified Health Centers.
Emergency departments (EDs) have become the primary source of care for increasing number of patients, leading to treatment of nonemergent cases, which divert resources from true emergency situations and represent poor cost-effectiveness for treating such cases. There is evidence that suggests that patient navigation (PN) integrated into the ED and other case management techniques can help reduce the number of primary care-related ED visits and these navigation programs are more cost-effective than the ED visits themselves. The Greater New Orleans Community Health Connection Primary Care Capacity Project Quality Improvement Initiative (GNOPQii) is a pilot project aimed at improving the efficiency of PN for patients who have had avoidable ED encounters or inpatient readmissions through applied data and technology program. Partnering Federally Qualified Health Centers were equipped with actionable ED utilization data to integrate with their own patient clinical data to track patient ED activity. The pilot design also included the use of patient navigators to address the nonclinical cultural and behavioral barriers to care. As part of the overall evaluation, comparisons of data utilization and PN services pre- and post-GNOPQii were conducted. A total of 337 referrals were made, and 145 patients were enrolled into the GNOPQii pilot program. The direct services needed the most by patients were transportation and medication resources. Of those who enrolled (N = 145), 63 patients graduated, meaning program compliance and 90 days without visits to the ED, resulting in a 43% success rate. If an estimated $1898 savings for every nonemergency ED encounter replaced by an office-based encounter is applied to our results, the GNOPQii program contributed to a minimum of $119 574.00 savings even if only 1 deterred ED visit per graduate is assumed. Future research is needed to systematically test the efficacy of GNOPQii in reducing nonemergent ED visits.


Breast milk odor via olfactometer for tube-fed, premature infants.
Human newborns use odor cues to orient to their source of nutrition. However, tube-fed, premature infants have restricted chemosensory experience. New methods of introducing breast milk odor to tube-fed premature infants will permit empiric tests of the effect of controlled exposure to nutrient odor. We therefore developed an infant olfactometer and piloted its use in 7 tube-fed, premature infants in the neonatal intensive care unit. Since nonnutritive sucking shortens the amount of time required to wean from tube-feeding, we tested the effect of breast milk odor on nonnutritive sucking. Six out of 7 subjects responded to breast milk odor with an increase in number of sucks. Statistical analysis supported the hypothesis that breast milk odor reinforces nonnutritive sucking. These results indicate the feasibility and potential of this experimental approach, and warrant further study of the effect of controlled nutrient odor exposure on feeding behavior of premature infants.


Endemic goitre and iodine metabolism in schoolchildren from the Daunia uplands (province of Foggia, Italy).
A study of endemic goitre was carried out in the western part of the province of Foggia (Daunia's pre-Appennines). About 50% of a total of 2719 children aged 6-15 years examined in the agricultural and hill towns of Accadia, Bovino, Candela, Deliceto and Sant'Agata di Puglia (500 to 800 m above sea level), presented a thyroid enlargement (usually of Grade 1). Urinary creatinine values were normal, while urinary iodine was low: 37.7 +/- 28.39 mug/g creatinine (mean +/- SD for 319 subjects). Serum levels of thyroid hormones were normal: T4 = 7.89 +/- 2.61 mug/dl; T3 = 114.72 +/- 40 ng/dl; T3 (T4 X 100) = 0.166 +/- 0.09. Subjects with Grade 2 thyroid enlargement had significant lower urinary iodine and serum T4, and higher T3 and T3/T4 ratio than children without goitre (Grade 0). Serum thyrotropin was rather high (3.79 +/- 4.17 muU/ml), but bore no straight relation to the thyroid size; in subjects with Grade 2 thyroids there was an inverse relationship between plasma T4 and TSH levels. Drinking water iodine was generally low (2-3 mug/l), though some richer sources (18, 38, 66 mug/l) were noted. Iodine contents of locally produced foodstuffs were below those found in food on Turin markets.


Cation dependencies and turnover rates of the human K⁺-dependent Na⁺-Ca²⁺ exchangers NCKX1, NCKX2, NCKX3 and NCKX4.
The Solute Carrier Family 24 (SLC24) belongs to the CaCA super family of Ca(2+)/cation antiporters and codes for five different K(+)- dependent Na(+)- Ca(2+) exchangers (NCKX1-5). NCKX proteins play a critical role in Ca(2+) homeostasis in a wide variety of biological processes such as vision, olfaction, enamel formation, Melanocortin-4-receptor-dependent satiety and skin pigmentation. NCKX transcripts are widely found throughout the brain. In this study we examine the differences between NCKX1-4 in terms of cation dependencies. We measured changes to Ca(2+) influx via the reverse exchange mode while manipulating external Ca(2+) or K(+) or internal Na(+) concentrations (External Ca(2+) Dependence, External K(+) Dependence and Internal Na(+) Dependence respectively); we also looked at the effect of external Na(+)/Ca(2+) competition and 3' 4'-Dichlorobenzamil on the transport of ions in HEK 293 cell lines. A fluorescence based assay was used to determine differences in transport kinetics of the four membrane spanning exchangers using the Michaelis-Menten constant (Km). Our results show that there are no significant differences between the NCKX isoforms to explain the variation in the specific expression pattern of these exchangers.


Estrogen-receptor immunoreactivity in hamster brain: preoptic area, hypothalamus and amygdala.
The distribution of estrogen-receptor containing cells in the preoptic area, hypothalamus and amygdala of female Syrian hamster brain was studied by immunocytochemical methods. Dense populations of estrogen-receptor immunoreactive (ER-IR) cells were found in the medial preoptic area, the bed nucleus of the stria terminalis, amygdala, ventral and lateral parts of the hypothalamus, and the arcuate nucleus. Injection of estradiol caused a decrease in estrogen-receptor immunoreactivity (ERIR) containing cells within one hour, a decrease that may reflect a change in the ability of the occupied estrogen receptor to bind the particular antibody (H222) used rather than down-regulation of the estrogen receptor. Our findings on the distribution of estrogen-receptor containing cells in these areas using an immunocytochemical technique are consistent with and extend the findings of others using autoradiographic and in vitro binding techniques to study estrogen receptor distribution in hamster brain.


Physicians' learning strategies.
This article examines the two categories of learning strategies that physicians use in clinical practice. The strategies are similar in their overall architectures and differ (1) according to nature of the clinical problem that precipitated the need to learn, and (2) the ways in which learning resources are used.


Proposal of a Nutritional Quality Index (NQI) to Evaluate the Nutritional Supplementation of Sportspeople.
Numerous supplements are used by sportspeople. They are not always appropriate for the individual or the sports activity and may do more harm than good. Vitamin and mineral supplements are unnecessary if the energy intake is sufficient to maintain body weight and derives from a diet with an adequate variety of foods. The study objectives were to evaluate the main nutrients used as supplements in sports and to propose a nutritional quality index (NQI) that enables sportspeople to optimize their use of supplements and detect and remedy possible nutritional deficits. A nutritional study was performed in 485 sportspeople recruited from Centros Andaluces de Medicina del Deporte, (CAMD). All completed socio-demographic, food frequency, and lifestyle questionnaires. The nutritional quality of their diet and need for supplementation were evaluated by scoring their dietary intake with and without supplementation, yielding two NQI scores (scales of 0-21 points) for each participant. A superior mean NQI score was obtained when the supplements taken by participants were not included (16. 28 (SD of 3.52)) than when they were included (15.47 (SD: 3.08)), attributable to an excessive intake of some nutrients through supplementation. These results indicate that sportspeople with a varied and balanced diet do not need supplements, which appear to offer no performance benefits and may pose a health risk.


Health educators' perceptions of a sexual health intervention for homeless adolescents.
The purpose of this qualitative descriptive study was to explore the perceptions and experiences of health educators in providing a brief, street-based intervention to homeless adolescents. Qualitative data were collected via e-mail from a purposive sample of 13 male and female health educators who provided the intervention and analyzed using manifest and latent content analysis techniques. Five categories with two or more subcategories were identified in the data and included how the educators' views changed, how they felt homeless youth were similar to and different from other adolescents, positive aspects and challenges of providing the intervention, and suggestions for future interventionists working with this population. The health educators' practice was strengthened over the course of providing the intervention through their positive experiences, changes in their perceptions, some of which were biased, and ability to confront the challenges that accompany working with this vulnerable population. Health educators who work with this population should learn about the culture of homeless youth and characteristics of homeless youth that may influence their participation in a sexual health intervention. Moreover, they need to be non-judgmental, practice the intervention, be aware of their biases, and remain flexible.


Direct effect of gonadotropins on decidualization of human endometrial stroma cells.
Decidualization of stromal cells isolated from proliferative human endometrium was achieved by adding to the culture medium human gonadotropins (FSH, FSH + LH, hCG). In addition to changes in the morphology of the stromal cells to the decidual phenotype, decidualization was evident from the expression of prolactin (PRL), demonstrated immunocytochemically, by Western blotting analysis, and by measuring its output into the medium through solid phase enzyme immunoassay. Gonadotropins also induced cAMP formation in the endometrial stromal cells under the same experimental conditions. This finding suggests that the mechanism by which gonadotropins promote decidualization of human endometrial stromal cells in vitro involves the introduction of cAMP, a compound that we have found to elicit the expression of PRL in this system. PRL is likely to be a key intermediate in the process of decidualization since it is by itself capable of inducing differentiation of the endometrial stromal cells to the decidual phenotype. Awareness of direct actions of gonadotropins on the endometrial cells and, in particular, of the decidualizing effects of FSH (Metrodin), FSH+LH (Pergonal) and hCG may contribute to the understanding of physiologic as well as pathophysiologic conditions relevant to endometrial functions and fertility.


The minimal important difference of St.George's respiratory questionnaire in subjects with chronic pulmonary aspergillosis.
The estimates of the minimal important difference (MID) for the Saint George's respiratory questionnaire (SGRQ) score in CPA remain unknown. We performed a retrospective analysis on treatment-naïve CPA subjects (n = 148) treated with six-month oral itraconazole therapy and completed SGRQ at baseline and six months. The study's objective was to estimate the MID for SGRQ. We used an anchor-based method to determine the MID and found the MID for SGRQ of 7.3.


LRRC8A is essential for volume-regulated anion channel in smooth muscle cells contributing to cerebrovascular remodeling during hypertension.
Recent studies revealed LRRC8A to be an essential component of volume-regulated anion channel (VRAC), which regulates cellular volume homeostasis. However, evidence for the contribution of LRRC8A-dependent VRAC activity in vascular smooth muscle cells (VSMCs) is still lacking, and the relevant functional role of LRRC8A in VSMCs remains unknown. The primary goal of this study was to elucidate the role of LRRC8A in VRAC activity in VSMCs and the functional role of LRRC8A in cerebrovascular remodeling during hypertension. siRNA-mediated knockdown and adenovirus-mediated overexpression of LRRC8A were used to elucidate the electrophysiological properties of LRRC8A in basilar smooth muscle cells (BASMCs). A smooth muscle-specific overexpressing transgenic mouse model was used to investigate the functional role of LRRC8A in cerebrovascular remodeling. LRRC8A is essential for volume-regulated chloride current (ICl, Vol ) in BASMCs. Overexpression of LRRC8A induced a voltage-dependent Cl- current independently of hypotonic stimulation. LRRC8A regulated BASMCs proliferation through activation of WNK1/PI3K-p85/AKT axis. Smooth muscle-specific upregulation of LRRC8A aggravated Angiotensin II-induced cerebrovascular remodeling in mice. LRRC8A is an essential component of VRAC and is required for cell volume homeostasis during osmotic challenge in BASMCs. Smooth muscle specific overexpression of LRRC8A increases BASMCs proliferation and substantially aggravates basilar artery remodeling, revealing a potential therapeutic target for vascular remodeling in hypertension.


Getting key players to work together and defending against diversion--Oregon.
In this report, the author, Executive Vice President of the American Cancer Society in Oregon, reviews the key factors in the crafting of the coalition leading to passage of a tobacco tax in Oregon. Mr. North also emphasizes the importance of institutionalizing the coalition after passage to provide the required leadership for future efforts.


[Changes in lipid composition and carbohydrate composition of Aspergillus niger conidia during germination].
Data on the lipid composition and carbohydrate composition of Aspergillus niger conidia make it possible to characterize the individual germination stages and differentiate between the conidia capable of germination and those that lost the germination capacity. The following criteria are proposed: the ratio of phosphatidylcholine and phosphatidylethanolamine, the ratio of mannitol and arabitol, and the levels of sterols and free fatty acids. The role of these compounds in the biochemical background of cell transition from dormancy to active metabolism and their use as indices of the quality of inocula in biotechnological processes are discussed.


The effect of ligation or separation between the intrauterine device horn and adjacent ovary on implantation in the hamster.
The purpose of this study was to determine whether the luteolytic action of an intrauterine device (IUD) is suppressed following interruption of the continuity between the IUD uterine horn and the adjacent ovary. After several estrous cycles, a silk IUD was placed in the cervical end of one uterine horn of adult hamsters. The animals were then mated, and on day 6 of gestation the ovary and oviduct contralateral to the IUD were removed and a ligature was placed between the IUD horn and the adjacent ovary. The hamsters were killed on day 9 or day 13 of gestation. Fetal development in the contralateral horn was suppressed on day 13 but not on day 9. In the second study the animals were treated as in the first study except that the communication between the IUD horn and the adjacent ovary was severed completely. The hamsters were killed on day 9 or day 13. On both days 9 and 13 normal fetal development was observed in the control horn; no implantation sites were present in the IUD side. In the control (non-IUD) animals of each study, normal fetuses were present in both uterine horns. The study demonstrates that luteolysis does not occur if there is complete disruption of the communication between the IUD horn and ovary. The study also demonstrates that, since implantation did not occur in the IUD horn with a normally functioning ipsilateral ovary, the luteolytic action of the device is not the prime factor in suppressing implantation in the hamster.


Covered versus uncovered metal stents for malignant gastric outlet obstruction: a systematic review and meta-analysis.
Self-expandable metal stents (SEMSs) are used for palliation of malignant gastric outlet obstruction (GOO). Studies comparing covered SEMSs (C-SEMSs) and uncovered SEMSs (U-SEMSs) have led to inconclusive results. We compared efficacy and safety of C-SEMSs versus U-SEMSs in patients with GOO. We searched MEDLINE, EMBASE, and Cochrane Library from 2000 to 2019 to identify available studies comparing C-SEMSs versus U-SEMSs in patients with GOO. Primary outcomes were stent survival and patient survival, whereas secondary outcomes were clinical and technical success, Gastric Outlet Obstruction Score System (GOOSS) score after the procedure, overall adverse events, reintervention rate, dysfunction rate, stent occlusion, and stent migration. Overall, 7 randomized controlled trials and 9 observational studies were identified that included 1741 patients. C-SEMSs were associated with higher stent survival (hazard ratio, .68; 95% confidence interval [CI], .48-.96), whereas patient survival did not statistically significantly differ between C-SEMS and U-SEMS groups (hazard ratio, .96; 95% CI, .75-1.23). Clinical and technical success were not statistically different between groups (odds ratios, 1.1 [95% CI, .76-1.61] and .69 [95% CI, .21-2.3], respectively). There were no differences in terms of overall adverse events, reintervention rate, dysfunction rate, and GOOSS rate ≥2 after SEMS placement. U-SEMSs were associated with a higher rate of occlusion (odds ratio, .34; 95% CI, .21-.53) and C-SEMSs with a higher rate of migration (odds ratio, 4.28; 95% CI, 2.79-6.57). C-SEMSs were associated with higher stent survival (time between stent deployment and stent dysfunction) compared with U-SEMSs, whereas no differences in terms of patient survival (time between stent deployment and patient's death) emerged. However, U-SEMSs were associated with higher risk of occlusion and C-SEMSs with higher risk of migration. Further studies using new C-SEMSs with an antimigration system are needed.


Polyphenol-rich extract of Ocimum gratissimum leaves prevented toxic effects of cyclophosphamide on the kidney function of Wistar rats.
Cyclophosphamide (CP) is one of the potent and low cost chemotherapy used in clinical setting against a variety of tumors. However, its association with nephrotoxicity limits its therapeutic use. Ocimum gratissimum leaf is a medicinal plant with numerous pharmacological and therapeutic efficacies, such as antioxidant, anti-inflammation, and anti-apoptotic properties. The present study was designed to evaluate the protective effect of Ocimum gratissimum (OG) against CP-induced kidney dysfunction in rats. Rats were pre-treated with 400 mg/kg b.w. of leave extract of Ocimum gratissimum (Ocimum G.) for 4 days and then 50 mg/kg b.w. of CP was co-administered from day 5 to day 7 along with Ocimum G. Markers of renal function and oxidative stress, food and water intake, electrolytes, aldosterone, leukocytes infiltration, inflammation and histopathological alteration were evaluated. Obvious renal inflammation and kidney injuries were observed in CP treated groups. However, administration of leave extract of Ocimum G. prevented oxidative stress, kidney injuries, attenuated inflammation, increased aldosterone production and reduced sodium ion and water loss in rats. The plasma creatinine, urea and urine albumin concentration were normalized after the administration of Ocimum G. extract in rats treated with CP. Ocimum G. also decreased the plasma concentrations of Interleukin-(IL)-6, C-reactive protein and activity of myeloperoxidase and malondialdehyde in CP treated rats. Ocimum G. prevented kidney injury and enhanced renal function via inhibiting inflammation and oxidant-induced CP toxicity. The efficacy of Ocimum G. is related to the presence of various phytochemicals in the plant.


Measuring mast seeding behavior: relationships among population variation, individual variation and synchrony.
Mast seeding, or masting, is the variable production of flowers, seeds, or fruit across years more or less synchronously by individuals within a population. A critical issue is the extent to which temporal variation in seed production over a collection of individuals can be viewed as arising from a combination of individual variation and synchrony among individuals. Studies of masting typically quantify such variation in terms of the coefficient of variation (CV). In this paper we examine mathematically how the population CV relates to the mean individual CV and synchrony, concluding that the relationship is a complex one which cannot isolate an overall measure of synchrony, and involves additional factors, principally the number of plants sampled and the mean productivity per plant. Our development suggests some simple approximate relationships of population CV to individual variability, synchrony and the number of individuals. These were found to fit quite well when applied to data from 59 studies which included seed production at the individual level.


Penetrating Trauma to the Ureter, Bladder, and Urethra.
We describe the epidemiology, diagnosis, and management of adult civilian penetrating trauma to the ureter, bladder, and urethra. Trauma is a significant source of death and morbidity. Genitourinary injuries are present in 10% of penetrating trauma cases. Prompt recognition and appropriate management of genitourinary injuries, which are often masked or overlooked due to concomitant injuries, is essential to minimize morbidity. Penetrating trauma most commonly results from gunshot wounds or stab wounds. Compared to blunt trauma, these typically require surgical exploration. An understanding of anatomy and a high index of suspicion are necessary for prompt recognition of genitourinary injuries.


Treatment of contaminated greywater using pelletised mine water sludge.
Precipitated sludge (ochre) obtained from a mine water treatment plant was considered as an adsorbent substance for pollutants, since ochre is relatively free from problematic levels of toxic elements, which could impair on the quality of water to be treated. Artificially created ochre pellets from mixing Portland cement with raw ochre sludge were utilised to remediate either high (HC) or low (LC) contaminated synthetic greywater (SGW) in mesocosm-scale stabilisation ponds at 2-day and 7-day contact times under real weather conditions in Salford. After a specific retention time, treated SGW was agitated before sampling to evaluate pollutant removal mechanisms (other than sedimentation) such as adsorption by ochre pellets, before replacing the treated water with new inflow SGW. The results showed that cement-ochre pellets have a high ability to adsorb ortho-phosphate-phosphorous (PO4-P) significantly (p < 0.05) by 70.7% and 56.0% at 7-day contact time for HC-SGW and LC-SGW, respectively. After the experiment, an analysis revealed that elements such as boron (B), cadmium (Cd), magnesium (Mg), manganese (Mn), nickel (Ni) and zinc (Zn) accumulated significantly (p < 0.05) within the ochre pellets. The notable accumulation of Cd within ochre pellets reflects the significant (p < 0.05) remediation of greywater during the first 35 and 20 successive times of treatment for HC-SGW at 2- and 7-day contact times, respectively. Cadmium was still adsorbed significantly (p < 0.05) during the treatment of LC-SGW. However, the calcium (Ca) content decreased significantly (p < 0.05) within ochre pellets treating both types of greywaters due to mobilisation. The corresponding increases of Ca in greywater were significant (p < 0.05).


Fibers immunoreactive for nerve growth factor receptor in adult rat cortex and hippocampus mimic the innervation pattern of AChE-positive fibers.
Numerous reports have indicated that nerve growth factor (NGF) exerts neurotrophic effects on the cholinergic neurons of the basal forebrain. Receptors for NGF (NGFR) have been demonstrated on cholinergic perikarya in the medial septum, diagonal band of Broca, and basal nucleus of Meynert. These neurons provide the major cholinergic innervation to the cerebral cortex and hippocampus, and previous studies have shown that their terminal plexuses also possess NGFR. However, these studies have shown only isolated examples of immunoreactive fibers. In the present paper we confirm and extend the observation of the presence of NGFR immunoreactivity in the hippocampus and cortex of adult rat by showing the entire plexus and demonstrating that the plexus is strikingly similar to the pattern of cholinergic innervation. Fibers stained for acetylcholinesterase (AChE) and NGFR immunoreactivity were found in all layers of the parietal cortex. Within the hippocampus, fibers were observed in all regions, but were most dense in the strata oriens, pyramidale, and radiatum of hippocampal subfields CA1 and CA3. Particularly intense staining was found throughout the dentate gyrus. Partial transections of the fimbria-fornix, which disrupt fibers projecting from the medial septum to the hippocampus, concomitantly abolish the innervation pattern of both NGFR and AChE. These results provide additional evidence that NGFR are associated with septohippocampal and basocortical cholinergic fibers.


A decision tool for whole-body CT in major trauma that safely reduces unnecessary scanning and associated radiation risks: An initial exploratory analysis.
Whole-body CT (WBCT) has become routine practice in the assessment of major trauma patients. Whilst this may be associated with increased survival, several studies report high rates of negative scans. As no national guideline exists, selection criteria for WBCT vary widely. This study aims to (1) produce a scoring system that improves patient selection for WBCT (2) quantify patient radiation doses and their concomitant risk of malignancy. Clinical notes were reviewed for all patients undergoing a WBCT for trauma over a 21-month period at a UK major trauma centre. Clinical and radiological findings were categorised according to body region. Univariate analysis was performed using Chi-squared testing, followed by multivariable logistic regression. Secondary regression analysis of patients with significant injuries that the model did not identify was performed. The model was optimised and used to develop a scoring system. Sensitivity and specificity were calculated using the same dataset as was used to derive the models. Radiation exposure was determined and the excess lifetime risk of malignancy calculated. 255 patients were included, with a mean age of 45 years. 16% of scans were positive for polytrauma, 42% demonstrated some injury and 42% showed no injury. The regression model identified independent predictors of polytrauma to be (1) clinical signs in more than one body region, (2) reduced Glasgow Coma Score, (3) haemodynamic abnormality, (4) respiratory abnormality, (5) mechanism of injury. The final model had a sensitivity of 95% (95% CI 86-99%) and specificity of 59% (95% CI 52-66%) for significant CT findings. Mean radiation exposure was 31.8 mSv, conferring a median excess malignancy risk of 1 in 474. After including neurological deficit, our scoring system had a sensitivity of 97% (95% CI 88-99%) and specificity of 56% (95% CI 49-64%) for significant injury. We propose this is used to stratify the use of trauma radiographs, focused CT and WBCT for major trauma patients. Although not intended to replace clinical judgement, our scoring system adds an objective component to decision-making. We believe this will safely reduce the number of unnecessary CT scans performed on a relatively young cohort of patients.


Metformin Use and Pancreatic Cancer Survival among Non-Hispanic White and African American U.S. Veterans with Diabetes Mellitus.
The effect of metformin use on survival among patients with pancreatic ductal adenocarcinoma (PDAC) is controversial. Furthermore, there are no data on African American patients. To address these, we analyzed data from the United States Veterans Health Administration (VHA). A population-based retrospective cohort study evaluating overall survival among 3,811 patients with PDAC with preexisting diabetes mellitus, diagnosed with PDAC within the VHA between 1998 and 2013. We calculated HRs and 95% confidence intervals (CI) using multivariable adjusted time-varying Cox proportional hazards regression to control for immortal time bias and confounders. Metformin use was not associated with overall survival in the complete analyses (HR = 1.05; 95% CI, 0.92-1.14; P = 0.28). However, among patients who were metformin naïve at the time of PDAC diagnosis (N = 1,158), metformin use was associated with improved overall survival in non-Hispanic white patients (HR = 0.78; 95% CI, 0.61-0.99; P = 0.04), but not African American patients (HR = 1.20; 95% CI, 0.75-1.93; P = 0.45). The survival benefit among non-Hispanic whites was limited to patients with metastatic disease (HR = 0.67; 95% CI, 0.44-1.01; P = 0.06). Among African American patients with metastatic disease, HR was 1.30 (95% CI, 0.77-2.53; P = 0.28). There was a suggestion of heterogeneity by race in patients with metastatic disease (P heterogeneity = 0.05). We observed no associations between metformin use and survival in patients with PDAC, but there appears to be a survival benefit among non-Hispanic white patients who were metformin naïve at the time of PDAC diagnosis. If confirmed in other studies, our findings suggest that metformin as an adjunctive treatment for PDAC may not improve survival among African American patients.


Gene Flow and Genetic Structure Reveal Reduced Diversity between Generations of a Tropical Tree, Manilkara multifida Penn., in Atlantic Forest Fragments.
The Atlantic Forest remnants in southern Bahia, Brazil, contain large tree species that have suffered disturbances in recent decades. Anthropogenic activities have led to a decrease in the population of many tree species and a loss of alleles that can maintain the evolutionary fitness of their populations. This study assessed patterns of genetic diversity, spatial genetic structure, and genetic structure among Manilkara multifida Penn. populations, comparing the genetic parameters of adult and juvenile trees. In particular, we collected leaves from adults and juveniles of M. multifida in two protected areas, the Veracel Station (EVC) and the Una Biological Reserve (UBR), located in threatened Atlantic Forest fragments. We observed a substantial decay in genetic variability between generations in both areas i.e., adults' HO values were higher (EVC = 0.720, UBR = 0.736) than juveniles' (EVC = 0.463 and UBR = 0.560). Both juveniles and adults showed genetic structure between the two areas (θ = 0.017 for adults and θ = 0.109 for juveniles). Additionally, forest fragments indicated an unexpectedly short gene flow. Our results, therefore, highlight the pervasive effects of historical deforestation and other human disturbances on the genetic diversity of M. multifida populations within a key conservation region of the Atlantic Forest biodiversity hotspot.


Curse or blessing? The relationship between sustainable development plans for resource cities and corporate sustainability - Evidence from China.
In recent years, the sustainable development of resource cities has become a challenge for all countries. It aims to transform the traditional monolithic economic model and find a way to develop the city's economy and environment in harmony. In this context, we uncover the relationship between sustainable development plan of resource-based cities (SDPRC) and corporate sustainable performance and examine possible pathways for action. Using a difference-in-differences (DID) model and a series of robustness tests, our study reveals the following. First, SDPRC enhances corporate sustainability. Second, possible mechanisms for SDPRC are explored. SDPRC achieves corporate sustainability by optimal resource allocation and increasing green innovation outputs. Third, urban heterogeneity is explored and it is found that SDPRC only has a positive impact on the sustainable performance in growth and mature cities, but not in declining and regenerating cities. Finally, firm heterogeneity was examined, with SDPRC having a more positive impact on the sustainable performance of state-owned firms, large firms and heavily polluting firms. This study sheds light on the impact of SDPRC at the firm level and provides new theoretical insights for urban planning policy reform in developing countries such as China.


Interstitial glucose concentration in insulin-resistant human skeletal muscle: influence of one bout of exercise and of local perfusion with insulin or vanadate.
The present study investigated the changes occurring in interstitial metabolite concentrations and blood flow in insulin-resistant human skeletal muscle during the post-exercise recovery period following a single 2-h bout of one-legged exercise. In addition, the effect of microdialysis perfusion with insulin or the insulin-mimetic trace element vanadate was explored. Eight microdialysis catheters, four in each leg, were inserted in the quadriceps femoris muscle of nine insulin-resistant obese male subjects 2 h following exercise. Two catheters in each leg were perfused at 0.2 microl/min for metabolite determinations and two at 1.33 microl/min for the determination of blood flow. Samples were collected until 9 h after the end of exercise had passed. The interstitial glucose concentration (mean +/- SD) was significantly lower in the exercised (2.8 +/- 1.3 mM) than in the rested leg (3.7 +/- 0.9 mM), P = 0.001, a difference that lasted at least 8 h after the exercise bout. On the other hand, blood flow was not different in the two legs. Microdialysis perfusion with insulin (14 mU/ml) or sodium metavanadate (100 mM) decreased the interstitial glucose concentration (P = 0.001) in both the exercised and rested leg. With vanadate, this decrease was similar in the exercised (-69%) and the rested leg (-71%), whereas insulin had a larger effect in the exercised leg (-29 vs. -6.9%), P = 0.05. This study shows that the interstitial glucose concentration in insulin-resistant skeletal muscle is markedly decreased for several hours following a single exercise session. This is in accordance with recent findings in healthy subjects. This change is accompanied by an increased insulin effect on the interstitial glucose concentration. The effect of vanadate was not decreased in insulin-resistant human skeletal muscle and was not augmented by exercise.


Intra-thyroid thyroglossal duct cyst as a differential diagnosis of thyroid nodule.
An intra-thyroid thyroglossal duct cyst (ITTDC) presented as a congenital anterior neck mass in a 10-year-old male. Diagnosis, work-up, management approach, and differential diagnosis of thyroid nodules are discussed, as well as distinguishing features between thyroglossal duct cyst (TDC) and branchial cleft cyst (BCC). This is the fourth case of ITTDC reported in the pediatric population, and ITTDC should remain in the differential diagnosis of pediatric neck mass.


Inhibition of phosphatidylinositol-specific phospholipase C by phosphonate substrate analogues.
Non-hydrolysable analogues of phosphatidylinositol were synthesized and tested as inhibitors of phosphatidylinositol-specific phospholipase C from Bacillus cereus. In these molecules, the phosphodiester bond of phosphatidylinositol hydrolyzed by the phospholipase was replaced by a phosphonate linkage and a simpler hydrophobic group replaced the diacylglycerol moiety. One of the phosphonates also contained a carboxylate functional group suitable for matrix attachment. All three synthetic phosphonates inhibited the phospholipase C activity in a concentration-dependent manner, with the analogue most closely resembling the structure of the natural substrate, phosphatidylinositol, being the most potent inhibitor. The data indicate that phosphonate analogues of phosphatidylinositol may be useful for study of phospholipase C and other proteins interacting with myo-inositol phospholipids.


Patients' and health professionals' understanding of and preferences for graphical presentation styles for individual-level EORTC QLQ-C30 scores.
To investigate patients' and health professionals' understanding of and preferences for different graphical presentation styles for individual-level EORTC QLQ-C30 scores. We recruited cancer patients (any treatment and diagnosis) in four European countries and health professionals in the Netherlands. Using a questionnaire, we assessed objective and self-rated understanding of QLQ-C30 scores and preferences for five presentation styles (bar and line charts, with or without color coding, and a heat map). In total, 548 patients and 227 health professionals participated. Eighty-three percent of patients and 85 % of professionals self-rated the graphs as very or quite easy to understand; this did not differ between graphical presentation styles. The mean percentage of correct answers to questions objectively assessing understanding was 59 % in patients, 78 % in medical specialists, and 74 % in other health professionals. Objective understanding did not differ between graphical formats in patients. For non-colored charts, 49.8 % of patients did not have a preference. Colored bar charts (39 %) were preferred over heat maps (20 %) and colored line charts (12 %). Medical specialists preferred heat maps (46 %) followed by non-colored bar charts (19 %), whereas these charts were equally valued by other health professionals (both 32 %). The substantial discrepancy between participants' high self-rated and relatively low objective understanding of graphical presentation of PRO results highlights the need to provide sufficient guidance when presenting such results. It may be appropriate to adapt the presentation of PRO results to individual preferences. This could be facilitated when PROs are administered and presented to patients and health professionals electronically.


Biochemical confirmation of recombination within the B-G subregion of the chicken major histocompatibility complex.
Analysis of the B-G antigens of eight chicken major histocompatibility complex (B) system recombinant haplotypes by high resolution two-dimensional gel electrophoresis has provided evidence for the transfer of the complete B-G subregion in seven cases. In the eighth, a partial duplication within the B-G subregion appears to have occurred. In this recombinant, the entire array of polypeptides associated with one parental allele, B-G23, is expressed together with nearly the entire array of B-G polypeptides of the other parental haplotype, B2. This compound polypeptide pattern corroborates the serological evidence for a partial duplication within the B-G subregion and provides indirect evidence for the existence of multiple loci within B-G and for a means by which polymorphism may be introduced into the chicken major histocompatibility complex.


Spinal Cord Subependymoma: A Subanalysis of the Neurospinal Society of Japan's Multicenter Study of Intramedullary Spinal Cord Tumors.
This study aimed to analyze the clinical characteristics, treatment strategies, and surgical outcomes of subependymoma patients from the 2022 Neurospinal Society of Japan multicenter intramedullary spinal cord tumor study. Twenty-six patients with spinal cord subependymoma who were included in the index study of 1,033 patients were retrospectively analyzed. Mean patient age was 49.4 years. Seventeen patients were men and 9 were women. Sensory disturbance was reported in 22 patients and motor weakness in 18. Median duration of symptoms was 24 months. The tumor was eccentrically located in 19 patients (73.1%) and unilateral in 17 (65.4%). Gross total resection was achieved in 6 patients (23.1%). The same rate for ependymoma patients in the index study was significantly higher (74.8%). Median follow-up was 40.5 months (interquartile range, 18-68 months). In 2 patients who underwent only partial resection, reoperation was required owing to progression 68 and 90 months after surgery, respectively. No recurrence occurred in patients who underwent gross total resection. Five patients experienced neurological worsening after surgery. Although spinal cord subependymoma can be difficult to distinguish from other intramedullary spinal cord lesions before surgery, it is characterized by an indolent clinical course and eccentric location. Surgical treatment should prioritize functional preservation because the prognosis is good even after subtotal resection.


Effects of adrenalectomy and hypercorticism on the ACTH content of the anterior and posterior pituitary in rats with inherited diabetes insipidus (Brattleboro strain).
The effects of adrenalectomy (Adx) and hypercorticism on the ACTH content in the anterior (AH) and the neurointermediate lobe (NIL) of the pituitary in Long Evans (+/+), heterozygous (+/DI) and homozygous (DI/DI) Brattleboro rats were determined using dispersed adrenal cells bioassay. Adx decreased the NIL-ACTH content in +/DI and DI/DI rats and left it unchanged in the +/+ rats. Adx increased the AH-ACTH content in the three groups. Hypercorticism had a delayed decreasing effect both in the AH and in the NIL in all rats, with one exception for the NIL in DI/DI rats. Conversely to what appeared in Wistar rats, in Long Evans and Brattleboro rats the corticosterone administered in drinking water was unable to reduce the increase in AH-ACTH activity. These data suggest that Brattleboro, and, to a lesser extent, Long Evans rats from which the former are derived present some particularities in the regulation of their corticotropic function at the AH and the NIL level. We also observed that NaCl (0.9%) added to drinking water and hypercorticism are two factors able to increase diabetes insipidus in homozygous rats without modifying the water intake in Long Evans and heterozygous rats.


The effects of a single dose of amphetamine and iprindole on the serotonergic system of the rat brain.
Rats treated with iprindole (IPR) (10 mg/kg, i.p.) were given a single dose (15 mg/kg, i.p.) of amphetamine (AMP). Marked decreases in the activity of tryptophan hydroxylase (TPH) were observed in both the cerebral cortex and neostriatum after 6 hr, with maximum depression observed at 24 hr. Enzyme activity had returned to control levels in neostriatum after 3 days and in cerebral cortex after 7 days. Levels of serotonin (5-HT) in both the cerebral cortex and neostriatum were significantly lowered at 24 hr but had recovered by 72 hr. Levels of tryptophan (TRP) in the cortex were significantly elevated after 6 hr, recovering by 24 hr. In the neostriatum, the activity of tyrosine hydroxylase (TH) was significantly depressed by 24 hr and remained so for 7 days. Concentrations of dopamine (DA) were decreased at all times examined. This study clarifies the differences previously observed in the response of the serotonergic system to amphetamine or methamphetamine (METH) in iprindole-treated rats.


Genetic design of conditional D-glutamate auxotrophy for Bacillus subtilis: use of a vector-borne poly-gamma-glutamate synthetic system.
Bacillus subtilis possesses two glutamate racemase isozymes, RacE and YrpC. For the first time, we succeeded in constructing glutamate racemase-gene disruptants of B. subtilis. Phenotypic analysis of their D-glutamate auxotrophy indicated that the RacE-type glutamate racemase is important for ensuring maximum growth rate but dispensable. The YrpC-type glutamate racemase probably operates as an anaplerotic enzyme for RacE, especially under liquid culture conditions. We found novel applicability of RacE-less mutants inheriting only a marginal activity for endogenous D-glutamate supply, viz. the employment for the in vivo identification of D-glutamate-consuming systems. In fact, the genetic induction of a poly-gamma-glutamate synthetic system led a RacE-less mutant to severe growth suppression, which was overcome in the presence of a high concentration of exogenous D-glutamate. The results indicate that a significant amount of D-glutamate is consumed during poly-glutamate biosynthesis. To our knowledge, this is the first report of conditional D-glutamate auxotrophy for B. subtilis.


Lung tissue phantom mimicking pulmonary optical properties, relative humidity, and temperature: a tool to analyze the changes in oxygen gas absorption for different inflated volumes.
Gas in scattering media absorption spectroscopy (GASMAS) enables noninvasive gas sensing in the body. It is developing as a tool for diagnosis and monitoring of respiratory conditions in neonates. Phantom models with relevant features to the clinical translation of GASMAS technology are necessary to understand technical challenges and potential applications of this technique. State-of-the-art phantoms designed for this purpose have focused on the optical properties and anthropomorphic geometry of the thorax, contributing to the source-detector placement, design, and optimization. Lung phantom mimicking the alveolar anatomy has not been included in the existent models due to the inherent complexity of the tissue. We present a simplified model that recreates inflated alveoli embedded in lung phantom. The goal of this study was to build a lung model with air-filled structures mimicking inflated alveoli surrounded by optical phantom with accurate optical properties (μa = 0.50 cm - 1 and μs'=5.4 cm-1) and physiological parameters [37°C and 100% relative humidity (RH)], and to control the air volume within the phantom to demonstrate the feasibility of GASMAS in sensing changes in pulmonary air volume. The lung model was built using a capillary structure with analogous size to alveolar units. Part of the capillaries were filled with liquid lung optical phantom to recreate scattering and absorption, whereas empty capillaries mimicked air filled alveoli. The capillary array was placed inside a custom-made chamber that maintained pulmonary temperature and RH. The geometry of the chamber permitted the placement of the laser head and detector of a GASMAS bench top system (MicroLab Dual O2 / H2O), to test the changes in volume of the lung model in transmittance geometry. The lung tissue model with air volume range from 6.89 × 10 - 7 m3 to 1.80 × 10 - 3 m3 was built. Two measurement sets, with 10 different capillary configurations each, were arranged to increase or decrease progressively (in steps of 3.93 × 10 - 8 m3) the air volume in the lung model. The respective GASMAS data acquisition was performed for both data sets. The maximum absorption signal was obtained for configurations with the highest number of air-filled capillaries and decreased progressively when the air spaces were replaced by capillaries filled with liquid optical phantom. Further studies are necessary to define the minimum and maximum volume of air that can be measured with GASMAS-based devices for different source-detector geometries. The optical properties and the structure of tissue from the respiratory zone have been modeled using a simplified capillary array immersed in a controlled environment chamber at pulmonary temperature and RH. The feasibility of measuring volume changes with GASMAS technique has been proven, stating a new possible application of GASMAS technology in respiratory treatment and diagnostics.


Use of early phase online vision for grip configuration is modulated according to movement duration in prehension.
Our previous study (Hum Mov Sci 25:349-371, 2006) investigated whether and how online vision in the early phase of movement influences the control of reach-to-grasp movements (movement duration: approximately 1000 ms). We used liquid-crystal shutter goggles to manipulate the duration of available online vision during the movement and specified that online vision during the early phase influences grasping movements. The current study examined the effect of online early phase vision on the grip configuration according to the movement duration and compared it between two different movement durations (approximately 500 and 1000 ms). We found that non-availability of early phase online vision affected the grip configuration (i.e., inducing a larger peak grip aperture) even in the shorter movement duration. The influential period for online vision for grasping control shifts to an earlier time when movement time is shorter (i.e., from approximately 214 to 106 ms after movement onset), indicating a flexible mechanism for grip configuration according to the movement duration and the available online vision.


Similar responses by macrophages from young and old mice infected with Mycobacterium tuberculosis.
The growth of four isolates of Mycobacterium tuberculosis was compared in cultures of bone marrow-derived macrophages generated from young (3 months) and old (24 months) female C57BL/6 mice. In all four cases, no differences were seen in the course of the in vitro infection over a 10-day culture period. Macrophages from both young and old mice secreted similar levels of nitric oxide if treated with interferon gamma (IFN) 24 h prior to infection. Expression of mRNA encoding an array of early response genes in the two sets of cultures was also generally similar. These data indicate that the capacity of macrophages to respond to infection with a virulent intracellular bacterial infection does not seem to be influenced by the increasing age of the host.


Lentiviral vector-mediated gene transfer in embryonic stem cells.
The major limitations in gene transduction to embryonic stem (ES) cells are (1) low efficiency of gene delivery and (2) suppression of gene expression after integration into the host genome. A human immunodeficiency virus type I (HIV-1)-based lentiviral vector has been demonstrated to be an excellent tool for stable and efficient gene expression in ES cells. Here, we introduce a protocol for lentiviral vector-mediated transgene expression in murine ES cells. Using lentiviral vectors expressing LacZ, green fluorescent protein, and Cre recombinase, we demonstrate the efficiency and utility of the vectors in ES cell study.


Quantifying the contribution of direct runoff and baseflow to nitrogen loading in the Western Lake Erie Basins.
Soluble nitrogen is highly mobile in soil and susceptible to leaching. It is important to identify nitrogen transport pathways so that the sources can be efficiently targeted in environment management. This study quantified the contribution of direct runoff and baseflow to nitrate + nitrite loading by separating flow and nitrate + nitrite concentration measurements into two periods depending on whether only baseflow was present or not using baseflow separation methods. When both direct runoff and baseflow were present in streamflow, their nitrate + nitrite concentrations were assumed based on the hydrological reasoning that baseflow does not change rapidly, and streamflow mostly consists of direct runoff within a rainfall event. For this study, we obtained and investigated daily flow and nitrate + nitrite concentration observations made at the outlets of 22 watersheds located in the Western Lake Erie area. Results showed that baseflow was responsible for 26 to 77% of the nitrate + nitrite loads. The relative nitrate + nitrite load contributions of direct runoff and baseflow substantially varied with the sizes of drainage areas and agricultural land uses. Increases in drainage areas tend to prolong the travel time of surface runoff and thus help its reinfiltration into soil, which then could increase the baseflow contribution. In addition, the artificial drainage networks common in the agricultural fields of the study areas would promote the drainage of nutrient-laden excess water from soils. Such findings suggest the need for environmental management customized considering nitrogen transport pathways.


Introduction to glass microstructuring techniques.
In this chapter an overview of manufacturing methods, leading to the fabrication of microstructures in glass substrates, is presented. Glass is a material of excellent optical properties, a very good electric insulator, biocompatible and chemically stable. In addition to its intrinsic qualities, glass can be processed with the use of manufacturing methods originating from the microelectronic industry. In this text two complete manufacturing protocols are described, each composed of standard microfabrication steps; namely, the deposition of masking layers, photolithographic patterning and pattern transfer via wet or dry etching. As a result, a set of building blocks is provided, allowing the manufacture of various microfluidic components that are frequently used in the domain of micro-total analysis system technology.


Western-type diet differentially modulates osteoblast, osteoclast, and lipoblast differentiation and activation in a background of APOE deficiency.
During the past few years, considerable evidence has uncovered a strong relationship between fat and bone metabolism. Consequently, alterations in plasma lipid metabolic pathways strongly affect bone mass and quality. We recently showed that the deficiency of apolipoprotein A-1 (APOA1), a central regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, results in reduced bone mass in C57BL/6 mice. It is documented that apolipoprotein E (APOE), a lipoprotein know for its atheroprotective functions and de novo biogenesis of HDL-C, is associated with the accumulation of fat in the liver and other organs and regulates bone mass in mice. We further studied the mechanism of APOE in bone metabolism using well-characterized APOE knockout mice. We found that bone mass was remarkably reduced in APOE deficient mice fed Western-type diet (WTD) compared to wild type counterparts. Static (microCT-based) and dynamic histomorphometry showed that the reduced bone mass in APOΕ-/- mice is attributed to both decreased osteoblastic bone synthesis and elevated osteoclastic bone resorption. Interestingly, histologic analysis of femoral sections revealed a significant reduction in the number of bone marrow lipoblasts in APOΕ-/- compared to wild type mice under WTD. Analyses of whole bone marrow cells obtained from femora of both animal groups showed that APOE null mice had significantly reduced levels of the osteoblastic (RUNX2 and Osterix) and lipoblastic (PPARγ and CEBPα) cardinal regulators. Additionally, the modulators of bone remodeling RANK, RANKL, and cathepsin K were greatly increased, while OPG and the OPG/RANKL ratio were remarkably decreased in APOΕ-/- mice fed WTD, compared to their wild-type counterparts. These findings suggest that APOE deficiency challenged with WTD reduces osteoblastic and lipoblastic differentiation and activity, whereas it enhances osteoclastic function, ultimately resulting in reduced bone mass, in mice.


Haploidentical hematopoietic stem cell transplantation in children with high-risk hematologic malignancies: outcomes with two different strategies for GvHD prevention. Ex vivo T-cell depletion and post-transplant cyclophosphamide: 10 years of experience at a single center.
Forty patients with high-risk hematologic malignancies, median age 9 years, underwent haploidentical-HSCT from April 2005 to April 2015. Seventeen patients were transplanted with CD3-depleted PBSCs by negative selection (TCD group) following a reduced-intensity conditioning regimen (RIC), and 23 patients received T-cell-replete PBSCs followed by post-transplantation cyclophosphamide (PT-Cy group) after myeloablative conditioning (n=16) or RIC (n=7). Outcomes are reported for the TCD and PT-Cy recipients, respectively. Engraftment was achieved in 88% versus 100%. Median time to neutrophils>500/μL was 10 days versus 15 days. Platelets>20 000/μL occurred at a median of 16 days versus 20 days, respectively. Transplant-related mortality (TRM) was 24% versus 26% at 1 year. The cumulative incidence (CI) of grade III-IV acute GvHD was 7% versus 5%, and chronic GvHD 9% versus 53% (P=0.029). Relapse at 2 years was 31% versus 24%. Actuarial overall survival rates at 2 years were 47% versus 48%. Causes of death were infections (n=3), sinusoidal obstructive syndrome (n=4), acute GvHD (n=2) and relapse (n=9). These results indicate that haploidentical-HSCT is feasible in Uruguay. The TRM rate is of concern and should be the focus of continuing attention. Chronic GvHD risk was higher in the PT-Cy approach, so modifications are justified.


Excess S-adenosylmethionine inhibits methylation via catabolism to adenine.
The global dietary supplement market is valued at over USD 100 billion. One popular dietary supplement, S-adenosylmethionine, is marketed to improve joints, liver health and emotional well-being in the US since 1999, and has been a prescription drug in Europe to treat depression and arthritis since 1975, but recent studies questioned its efficacy. In our body, S-adenosylmethionine is critical for the methylation of nucleic acids, proteins and many other targets. The marketing of SAM implies that more S-adenosylmethionine is better since it would stimulate methylations and improve health. Previously, we have shown that methylation reactions regulate biological rhythms in many organisms. Here, using biological rhythms to assess the effects of exogenous S-adenosylmethionine, we reveal that excess S-adenosylmethionine disrupts rhythms and, rather than promoting methylation, is catabolized to adenine and methylthioadenosine, toxic methylation inhibitors. These findings further our understanding of methyl metabolism and question the safety of S-adenosylmethionine as a supplement.


Midazolam via the intranasal route: an effective rescue medication for severe epilepsy in adults with learning disability.
People with a learning disability are often disadvantaged due to the nature of their disability. Up to a third are likely to have concomitant epilepsy which adds to the health loss experienced by this group. It is important to manage their epilepsy in such a way as to limit the debilitating effects of both the illness and the medication. Rectal diazepam remains the gold standard rescue medication for prolonged, recurrent seizures or seizures associated with hypoxia. Some of the drawbacks are highlighted in this paper and we go on to explore a novel means of treating these seizures. Midazolam, via the intranasal route, has been used extensively in children, mostly as a sedative but also in the treatment of epilepsy. We present two cases, both are adults with a learning disability, who have benefited significantly from the use of intranasal midazolam. Ongoing research into the safe use of this form of treatment, training of staff and carers and the impact on the individual is being conducted.


Nucleotide sequence of cDNA encoding subunit VIII of cytochrome c oxidase from rat heart.
In this study, the complete cDNA of subunit VIII-h of rat cytochrome c oxidase is presented. A rat skeletal muscle cDNA library was screened with a 132 bp fragment of the cDNA of rat COX subunit VIII-h. Four positive clones were sequenced in both directions.


Neonatal tolerance under breastfeeding influence.
Diseases due to defect in tolerance induction such as allergy, celiac disease, or Type 1 Diabetes develop mostly in childhood indicating the necessity of early intervention for primary prevention. Epidemiological studies report that breastfeeding could protect from these diseases. However, data are controversial and the mechanisms unclear. Experimental data suggest that breastfeeding-induced protection might rely on tolerance induction as long as some criteria are fulfilled. Thus, the tolerogenic potential of breast milk would depend on maternal exposure to common environmental and dietary antigens and the efficiency of antigen transfer across mammary epithelium. Induction of tolerance upon breast milk-mediated antigen transfer will also depend on the presence of immunomodulatory factors in breast milk and of its impact on neonatal gut and immune system maturation. The better understanding of maternal influence on tolerance induction through breastfeeding should allow the development of new strategies to prevent immune-mediated diseases.


Policing Tumorigenesis within the Skin: Good Outs Bad.
Recently published in Nature, Brown et al. (2017) shed new light on how the skin handles the activation of oncogenic pathways in the stem cell compartment and how wild-type cells limit the proliferation of mutant cells to maintain proper tissue homeostasis.


Analysis of spatial and temporal changes in human interference in important ecological function areas in China: the Gansu section of Qilian Mountain National Park as an example.
The disturbance characteristics and driving factors of human activity intensity in national parks are important factors affecting environmental change in ecological function areas. In-depth analysis of these must be the basis of improving the ecological environment in northwest China. This study selected data related to human activities from 2000 to 2020 to analyze the comprehensive impact of human interference on national park development and found that the NDVI (Normalized Difference Vegetation Index) of Qilian Mountain National Park showed an increasing trend and that the NPP (net primary productivity) showed spatial distribution characteristics of decreasing from east to west during the study period. This showed that human interference in and around the national park was changing significantly and that the high value area was gradually shifting southward. In the first decade, economic and social development was slow; related industries such as industry, tourism, and modern agriculture were not introduced on a large scale; and the ecological environment was in relatively good condition, with relatively weak human interference. However, in the second decade, human interference was prominent, with deeper ecological damage, but rapid economic development. Infrastructure development, population urbanization, and traditional production and living practices were the main factors driving changes in human interference. The Chinese government's proposed green building policy will further reduce the ecological impact of human activities while ensuring economic development. Building upon this, the present paper puts forth a "zero-disturbance" framework for national parks, aiming to offer recommendations for the future development of such parks.


Oxytocin-ergometrine co-administration does not reduce blood loss at caesarean delivery for labour arrest.
To determine if intravenous infusion of a combination of oxytocin and ergometrine maleate is better than oxytocin alone to decrease blood loss at caesarean delivery for labour arrest. Prospective, double-blinded, randomised controlled trial. Mount Sinai Hospital, Toronto, Canada. Women undergoing caesarean deliveries for labour arrest. Forty-eight women were randomised to receive infusion of either ergometrine maleate 0.25 mg + oxytocin 20 iu or oxytocin 20 iu alone, diluted in 1 l of lactated Ringer's Solution, immediately after delivery of the infant. Unsatisfactory uterine contractions after delivery were treated with additional boluses of the study solution or rescue carboprost. Blood loss was estimated based on the haematocrit values before and 48 hours after delivery. The primary outcome was the estimated blood loss, while the secondary outcomes included the use of additional uterotonics, need for blood transfusion and the incidence of adverse effects. The estimated blood loss was similar in the oxytocin-ergometrine and oxytocin-only groups; 1218 +/- 716 ml and 1299 +/- 774 ml, respectively (P = 0.72). Significantly fewer women required additional boluses of the study drug in the oxytocin-ergometrine group (21 and 57%; P = 0.01). Nausea (42 and 9%; P = 0.01) and vomiting (25 and 4%; P = 0.05) were significantly more prevalent in the oxytocin-ergometrine group. In women undergoing caesarean delivery for labour arrest, the co-administration of ergometrine with oxytocin does not reduce intraoperative blood loss, despite apparently superior uterine contraction.


Purification and characterization of acetylcholinesterase in Rhynchophorus ferrugineus (Olivier) (Coleoptera: Curculionidae).
Red palm weevil (RPW), Rhynchophorus ferrugineus, is one of the most destructive pests of cultivated palm trees. The application of synthetic insecticides is currently a main strategy for RPW control. In this study we estimated the distribution of acetylcholinesterase (AChE), as a detoxifying enzyme and the target site of inhibition by insecticides, using ASChI as substrate in different organs of the pest including whole gut, cuticle, fat body, head and haemolymph. The activity ranged from 314.9 to 3868 U in individual organs while the specific activity ranged from 99 to 340.8 U/mg proteins; the cuticle had the highest enzyme level. During larval development, the 11th instar larvae had the highest enzyme content with 5630 U in the cuticle, with a specific activity of 140 U/mg protein. The two major AChE isoenzymes were purified by chromatography on gel filtration and ion exchange columns. They had specific activities of 3504.3 and 2979 U/mg protein, molecular weights of 33 and 54 kDa and activation energies of 8.3 and 4.4 kcal/mol, respectively. Both isoenzymes had monomeric forms, optimum activity at pH 8.0 and 40 °C, were completely inhibited by Hg2+ and Cu2 and showed similar trends towards the inhibitors eserine, BW284C51 and iso-OMPA. The catalytic properties were compared with those previously recorded for different insect species. This work will pave the way for more studies for improving the understanding of insecticide resistance and developing the field application of synthetic insecticides for controlling R. ferrugineus to ensure successful application.


Community patterns of nectivorous adult parasitoids (Diptera, Bombyliidae) on their resources.
Highly diverse assemblages of nectivorous bee flies (Diptera: bombyliidae) occur at desert sites in California presenting an opportunity to investigate the ecology of this little-known group. This study compared communities of adult bee flies visiting flowers at two sites, one in the Mojave Desert (Darwin Plateau) and one in the Great Basin (Mono Basin), during periods of higher and lower resource abundance. The range of resources used by single species varied inversely with the number of species present, with the greatest number of species and smallest niche breadths occurring at the Darwin Plateau. Adult bee flies did not visit flower resources at random. Rather the two major divisions of the family exhibited contrasting patterns of specialization on plant species. Results of this study support the hypothesis that resources were limiting for adult bee flies in the period of lower food abundance at the Darwin Plateau and not limiting at the Mono Basin during this study. Bee flies at the Mono Basin exhibited lower densities per flower (despite higher densities per unit area), lower frequency of feeding, a lower degree of specialization, and less pronounced phenological changes than bee flies at the Darwin Plateau. The data suggest that episodes of population regulation in the non-parasitic (i.e. adult) stage, due to short supply of the adults' food, contribute to determining the structure of parasitoid communities.


Roles of periodic breathing and isocapnic buffering period during exercise in heart failure.
In heart failure, exercise - induced periodic breathing and end tidal carbon dioxide pressure value during the isocapnic buffering period are two features identified at cardiopulmonary exercise testing strictly related to sympathetic activation. In the present review we analysed the physiology behind periodic breathing and the isocapnic buffering period and present the relevant prognostic value of both periodic breathing and the presence/absence of the identifiable isocapnic buffering period.


The effect of sodium nitroprusside on the uptake and efflux of 45Ca from rabbit and rat vessels.
In this study we investigated if sodium nitroprusside (NaNP), a vasodilator with direct action on smooth muscle, would have any effect on calcium kinetics in blood vessels. The effect of NaNP, in 0.1-10 micrometer concentration, was studied in vitro on the uptake of 45Ca with the lanthanum method and on the efflux of 45Ca. The drug failed to alter the uptake of 'La-resistant' 45Ca in rabbit mesenteric artery and vein. This was true even if Ca2+ uptake was increased in the vessels by 60 mM KCl. The efflux of 45Ca on the other hand was enhanced from rabbit mesenteric vein and from rat aorta exposed to NaNP, in a dose-related way. The present study, like our previous one on other vasodilators, indicates that NaNP has en effect on vascular calcium kinetics but this is the first time that a relationship could be established between the dose of the drug and the effect on 45Ca efflux.


Noradrenergic innervation of serotoninergic neurons in the myenteric plexus.
The monoaminergic innervation of the guinea pig small intestine was investigated to determine if there is an anatomical basis for the hypothesis that serotoninergic and noradrenergic neurons physiologically interact in the enteric nervous system. Initial rates of uptake of tritiated 5-hydroxytryptamine (3H-5-HT) or norepinephrine (3H-NE) by segments of guinea pig small intestine were measured in order to estimate the regional density of the serotoninergic and noradrenergic innervation. No change was found in the uptake of 3H-5-HT as a function of distance between duodenum and ileum, whereas the relative uptake of 3H-NE declined. The pattern of serotoninergic elements demonstrated radioautographically was compared with that obtained by visualizing 5-HT immunoreactivity. Both methods revealed that a small number of serotoninergic neurons, located in 35.3% +/- 1.5% of myenteric ganglia, give rise to many fibers that form thick bundles in interganglionic connectives. Moreover, there was a pronounced heterogeneity in the serotoninergic innervation of individual myenteric neurons and ganglia. In material fixed with aldehydes and postfixed with NaMnO4, noradrenergic axon terminals were identified by their characteristic small dense-cored vesicles. Following incubation with 3H-NE only terminals with small dense-cored vesicles were radioautographically labeled, confirming that these terminals are noradrenergic. When 3H-5-HT was substituted for 3H-NE, noradrenergic terminals were not labeled, showing that nonspecific uptake of 3H-5-HT into noradrenergic axons did not occur in the presence of 5-hydroxydopamine. The combination of aldehyde-NaMnO4 fixation with the radioautographic localization of 3H-5-HT thus permitted the simultaneous identification of serotoninergic and noradrenergic neural elements. Serotoninergic varicosities were found to differ from noradrenergic varicosities in the size, appearance, and packing density of their synaptic vesicles. In addition, recognizable but rudimentary pre- and postsynaptic membrane specializations were associated with serotoninergic but not noradrenergic varicosities. Most serotoninergic neuronal cell bodies were contacted both by serotoninergic synapses and noradrenergic varicosities. Similar appositions of noradrenergic varicosities with nonserotoninergic neurons appeared to be rare. In view of earlier observations that sympathetic nerves affect the release of 5-HT from stimulated enteric serotoninergic neurons, it seems likely that the noradrenergic appositions with serotoninergic neurons are the anatomical substrate for this effect.(ABSTRACT TRUNCATED AT 400 WORDS)