The long-term relationship between population growth and vegetation cover: an empirical analysis based on the panel data of 21 cities in Guangdong Province, China.
It is generally believed that there is an inverse relationship between population growth and vegetation cover. However, reports about vegetation protection and reforestation around the World have been continuously increasing in recent decades, which seems to indicate that this relationship may not be true. In this paper, we have taken 21 cities in Guangdong Province, China as the study area to test the long-term relationship between population growth and vegetation cover, using an AVHRR NDVI data set and the panel cointegrated regression method. The results show that there is a long-term inverted N-shaped curve relationship between population growth and vegetation cover in the region where there are frequent human activities and the influence of climate change on vegetation cover changes is relatively small. The two turning points of the inverted N-shaped curve for the case of Guangdong Province correspond to 2,200 persons · km(-2) and 3,820 persons · km(-2), and they can provide a reference range for similar regions of the World. It also states that the population urbanization may have a negative impact on the vegetation cover at the early stage, but have a positive impact at the later stage. In addition, the Panel Error Correction Model (PECM) is used to investigate the causality direction between population growth and vegetation cover. The results show that not only will the consuming destruction effect and planting construction effect induced by the population growth have a great impact on vegetation cover changes, but vegetation cover changes in turn will also affect the population growth in the long term.


Conceptualisation of socio-technical integrated information technology solutions to improve incident reporting through Maslow's hierarchy of needs: a qualitative study of junior doctors.
Medical errors are common, especially within the acute healthcare delivery. The identification of systemic factors associated with adverse events and the construction of models to improve the safety of the healthcare system seems straightforward, this process has been proven to be much more difficult in the realism of medical practice due to the failure of the incident reporting system to capture the essential information, especially from the perspective of junior doctors. The failure of incidence reporting system has been related to the lack of socio-technical consideration for both system designs and system implementations. The main reason of non-reporting can be conceptualised through the motivation psychology model: Maslow's hierarchy of needs; in order to achieve a change in the socio-cultural domain for incident reporting. This paper presents a qualitative research methodology approach to generate contextual-rich insights into the socio-cultural and technological factors of incident reporting among junior doctors. The research illuminates the guiding principles for future socio-technical integrated information communication technology designs and implementations. Using Maslow's hierarchy of needs as the conceptual framework, the guiding principles aim to design electronic incident reporting systems which will motivate junior doctors to participate in the process. This research paper aims to make a significant contribution to the fields of socio-technical systems and medical errors management. The design and implementation of the new incident reporting system has great potential to motivate junior doctors to change the culture of incident reporting and to work towards a safer future healthcare system.


Cutting the Stone: Health Defined in the Era of Value-based Care.
The immune system contributes to the maintenance of health by preventing and limiting the clinical consequences of infections by pathogenic microorganisms. During the evolution of Homo sapiens, those with the fittest immune system survived. The immune system of Homo sapiens was further improved and adapted by admixture with Neanderthal genes. Nowadays, the human immune system provides adequate protection against the majority of infections. For some 20 infectious diseases, the immune system needs to be improved by vaccination. Vaccination is the number one value-based healthcare intervention and has resulted in global eradication of smallpox. Eradication of poliomyelitis and measles is within reach. A continuous effort will be required for recently emerged pathogens, such as Ebola and HIV, as well as the most difficult - malaria and tuberculosis.


Evaluating hypoxia during air travel in healthy infants.
Up to a third of ex-preterm infants flying near term exhibit pulse oxygen saturation (SpO2) of less than 85% during air travel. A hypoxia challenge test (HCT) is recommended to evaluate the requirement for in-flight supplemental O2. The validity of the HCT in healthy, term infants has not been reported. This study aimed to characterise the in-flight hypoxia response and the accuracy of the HCT to predict this response in healthy, term infants in the first year of life. Infants (n=24: (15 male)) underwent a HCT prior to commercial air travel during which parents monitored SpO2. Thirty-two flights were undertaken with six infants completing multiple flights. The median in-flight SpO2 nadir was 87% and significantly lower than the HCT SpO2 nadir (92%: p<0.001). Infants on seven flights recorded SpO2<85% with one infant recording a HCT with a SpO2 less than 85%. There was marked variability in the in-flight SpO2 in the six infants who undertook multiple flights, and for three of these infants, the SpO2 nadir was both above and below 85%. We report that in healthy term infants an in-flight SpO2 below 85% is common and can vary considerably between flights and that the HCT poorly predicts the risk of in-flight hypoxia (SpO2<85%). As it is common for healthy term infants to have SpO2 less than 85% during air travel further research is needed to clarify whether this is an appropriate cut-off in this age group.


A new lethal autosomal recessive skeletal dysplasia with associated dysmorphic features.
We report a fetus noted on routine ultrasonography at 21 weeks gestation to have a skeletal dysplasia with reduced ossification of shortened long bones and normal sized ribs. The consanguineous parents elected to continue the pregnancy and spontaneous labour occurred at 33 weeks gestation. The child died in the neonatal period. At necropsy, the main skeletal features were abnormal vertebrae with variation in shape and size, and ossification centres, short angulated long bones with distorted metaphyses and multiple abnormalities and fusions of the phalanges and metacarpals. In addition there was hydrops fetalis, a 'digit like' appendage overlying the left biceps muscle, a small chest with pulmonary hypoplasia and facial dysmorphism. In a subsequent pregnancy the fetus was noted at 13 weeks gestation to have nuchal translucency and bilaterally short femora. The fetus progressively developed hydrops fetalis and intrauterine death occurred at 22 weeks gestation. Post mortem examination revealed features very similar to the previous sibling. We suggest that this a new lethal osteochondrodysplasia syndrome. Recurrence in female siblings and parents who are double first cousins, strongly indicate autosomal recessive inheritance.


Impact of COVID-19 on social determinants of health for adults with cystic fibrosis.
Outcomes in cystic fibrosis are influenced by multiple factors, including social determinants of health. Low socioeconomic status has been shown to be associated with lung function decline, increased exacerbation rates, increased health care utilization, and decreased survival in cystic fibrosis. The COVID-19 pandemic disrupted the US economy, placing people with cystic fibrosis at risk for negative impacts due to changes in social determinants of health. To characterize the impact of COVID-19-related changes in social determinants of health in the adult cystic fibrosis population, a social determinants of health questionnaire was designed and distributed to patients as part of a quality improvement project. Of 132 patients contacted, 76 (57.6%) responses were received. Of these responses, 22 (28.9%) answered yes to at least one question that indicated an undesired change in social determinants of health. Patients with stable employment prior to COVID-19 were more likely to endorse undesired change in all domains of the questionnaire, and the undesired changes were most likely to be related to employment, insurance security, and access to medications. Patients receiving disability were more likely to report hardship related to utilities and food security compared with patients previously employed or unemployed. Of patients endorsing risk of socioeconomic hardship, 21 (95.5%) were contacted by a social worker and provided resources. Utilizing a social determinants of health questionnaire to screen for social instability in the context of COVID-19 is feasible and beneficial for patients with cystic fibrosis. Identifying social issues early during the pandemic and implementing processes to provide resources may help patients with cystic fibrosis mitigate social hardship and maintain access to health care and medications.


The role of neuroimaging in the early diagnosis and evaluation of Parkinson's disease.
The development of imaging biomarkers which target specific sites in the brain represents a significant advance in neurodegenerative diseases and Parkinson's disease with the promise of new and improved approaches for the early and accurate diagnosis of disease as well as novel ways to monitor patients and assess treatment. The 3 major applications of imaging may play a role in Parkinson's disease include: 1) the use of neuroimaging as a biomarker of disease in order to improve the accuracy, timeliness, and reliability of diagnosis; 2) objective monitoring of the progression of disease to provide a molecular phenotype of Parkinson's disease which may illuminate some of the sources of clinical variability; 3) the evaluation of so-called ''disease-modifying'' treatments designed to retard the progression of disease by interfering with pathways thought implicated in the ongoing neuronal loss or replace dopamine-producing cells. Each of these areas has shown a numbers of critical clinical investigations which have better defined the utility of the imaging tools to these tasks. Nonetheless, current unresolved issues around the clinical role of neuroimaging in monitoring patients over time and validation of quantitative imaging measures of dopaminergic function are immediate issues for the field and the subject of current research efforts and the extension of the lessons learned in Parkinson's to other neurodegenerative diseases including Alzheimer's dementia.


Psychometric intelligence dissociates implicit and explicit learning.
The hypothesis that performance on implicit learning tasks is unrelated to psychometric intelligence was examined in a sample of 605 German pupils. Performance in artificial grammar learning, process control, and serial learning did not correlate with various measures of intelligence when participants were given standard implicit instructions. Under an explicit rule discovery instruction, however, a significant relationship between performance on the learning tasks and intelligence appeared. This finding provides support for Reber's hypothesis that implicit learning, in contrast to explicit learning, is independent of intelligence, and confirms thereby the distinction between the 2 modes of learning. However, because there were virtually no correlations among the 3 learning tasks, the assumption of a unitary ability of implicit learning was not supported.


Analysis of risk factors for the increased incidence of gallstone caused by hepatectomy: A retrospective case-control study.
An increased risk of gallstones has been observed in patients undergoing hepatectomy. This study attempted to analyze the risk factors for gallstones after hepatectomy. From January 2013 to December 2016, clinical data of 1,452 eligible patients who underwent hepatectomy were consecutively reviewed. According to the imaging, including gallbladder ultrasound, computerized tomography, and magnetic resonance imaging, all patients were divided into the gallstone group and the nongallstone group. Univariate and multivariate logistic regression analyses were performed to select indicators associated with gallstone formation among patients after hepatectomy. In the total sample of included patients, there were 341 patients with gallstones and 1,147 patients without gallstones. The incidence of gallstones was 23.5% (341/1,452). The incidence of gallstones in the primary liver cancer group was higher than that in the benign liver tumor group (25.7% vs. 18.9%, P = 0.004). Univariate and multivariate logistic regression analyses showed that female gender, high body mass index, tumor located in S5, and severe postoperative complication were factors related to gallstones in patients with benign liver tumors after hepatectomy. In addition, Child-Pugh B, low albumin, liver cirrhosis, and transcatheter arterial chemoembolization (TACE) after recurrence were factors related to gallstones in patients with primary liver cancer after hepatectomy. Hepatectomy increased the risk of gallstones in benign or malignant liver tumors, especially when the tumor was located in S5. TACE further increased the risk of gallstones in patients with postoperative recurrence.


Relative spatial frequency tuning and its contrast dependency in human perception.
Several physiological studies in cats and monkeys have reported that the spatial frequency (SF) tuning of visual neurons varies depending on the luminance contrast and size of stimulus. However, comparatively little is known about the effect of changing the stimulus contrast and size on SF tuning in human perception. In the present study, we investigated the effects of stimulus size and luminance contrast on human SF tuning using the subspace-reverse-correlation method. Measuring SF tunings at six different stimulus sizes and three different luminance contrast conditions (90%, 10%, and 1%), we found that human perception exhibits significant stimulus-size-dependent SF tunings. At 90% and 10% contrast, participants exhibited relative SF tuning (cycles/image) rather than absolute SF tuning (cycles/°) at response peak latency. On the other hand, at 1% contrast, the magnitude of the size-dependent-peak SF shift was too small for strictly relative SF tuning. These results show that human SF tuning is not fixed, but varies depending on the stimulus size and contrast. This dependency may contribute to size-invariant object recognition within an appropriate contrast rage.


Patterns of dental caries among school children assessed using Caries Assessment Spectrum and Treatment tool.
The present study aimed to assess and monitor patterns of dental caries among primary and permanent molars using Caries Assessment Spectrum and Treatment (CAST) index and to evaluate integration of CAST tool into patient health information (PHI) system of a Teaching Dental Hospital. Dental records of n = 348 children, aged 7-9-years, attending University Dental Hospital Sharjah, for routine checkup and treatment as part of School Dental Program were assessed and translated into CAST codes. Dental caries prevalence for the second primary and first permanent molars were recorded. Spearman's correlation coefficient was used to assess the correlation of the status between primary and permanent molar. CAST codes 0-2 were observed only in about 3% of primary and almost 5% in permanent dentition. The prevalence of children with diseased first permanent molar (codes 4-7) was almost 67%, while it was over 70% in second primary molars. A strong correlations were observed in the status between second primary and first permanent molars in the lower jaw on both right and left sides, r was 0.694 and 0.643 (P = 0.001), respectively. In the upper jaw, both right and left second primary molars revealed moderate correlation r = 0.435 (P ≤ 0.05) between disease stages with their neighboring permanent first molars. The unweighted kappa value for the intraexaminer reliability was 0.97 for second primary and 0.95 for first permanent molars. Our study recommends the integration of CAST tool in the PHI system where a simple numerical value can express clinical progress, overcome interruptions of treatment, and ensures continuity of patient care in teaching hospitals.


The natural sweetener metabolite steviol inhibits the proliferation of human osteosarcoma U2OS cell line.
Steviol is the colonic metabolite of the natural sweetener steviol glycosides. It does not diffuse to the blood and the half maximal inhibitory concentration of steviol is longer compared with that of current chemotherapy agents, including 5-fluorouracil and doxorubicin. The present study demonstrated that steviol inhibits the proliferation of the human osteosarcoma U2OS cell line in a dose- and time-dependent manner, and that the inhibition rate is comparative with that of doxorubicin and 5-fluorouracil. The mechanism of this anticancer activity is also investigated. The results indicated that steviol inhibits U2OS cells through inducing G1 phase cell cycle arrest, downregulating the ability of colony formation via a mitochondrial apoptotic pathway, which was indicated by an increase of the Bax/Bcl-2 ratio and activation of cyclin-dependent kinase inhibitor 1, tumor protein 53 and cyclin-dependent kinase; whereas a Survivin and Caspase 3-independent mechanism was involved. Considering that steviol appears minimally in the plasma during metabolism, and possesses a median lethal dose of 100-fold greater compared with that of 5-fluorouracil, it may become a potential chemotherapy agent.


Long-Term Saccharin Consumption and Increased Risk of Obesity, Diabetes, Hepatic Dysfunction, and Renal Impairment in Rats.
Background and objectives: This study evaluated the effect of chronic consumption of saccharin on important physiological and biochemical parameters in rats. Materials and Methods: Male Wistar rats were used in this study and were divided into four groups: A control group and three experimental groups (groups 1, 2, and 3) were treated with different doses of saccharin at 2.5, 5, and 10 mg/kg, respectively. Each experimental group received sodium saccharin once per day for 120 days while the control group was treated with distilled water only. In addition to the evaluation of body weight, blood samples [total protein, albumin, glucose, lipid profile, alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatinine, and uric acid] and urine (isoprostane) were collected in zero time, and after 60 and 120 days for biochemical evaluation. Liver (catalase activity) and brain (8-hydroxy-2'-deoxyguanosine, 8-OHdG) tissues were collected at time zero and after 120 days. Results: The data showed that saccharin at 5 mg/kg increased body weight of treated rats after 60 (59%) and 120 (67%) days of treatment. Increased concentration of serum glucose was observed after treatment with saccharin at 5 (75% and 62%) and 10 mg/kg (43% and 40%) following 60 and 120 days, respectively. The concentration of albumin decreased after treatment with saccharin at 2.5 (34% and 36%), 5 (39% and 34%), and 10 mg/kg (15% and 21%) after 60 and 120 days of treatment, respectively. The activity of LDH and uric acid increased proportionally with dosage levels and consumption period. There was an increased concentration of creatinine after treatment with saccharin at 2.5 (125% and 68%), 5 (114% and 45%), and 10 mg/kg (26% and 31%) following 60 and 120 days, respectively. Catalase activity and 8-OHdG increased by 51% and 49%, respectively, following 120 days of treatment with saccharin at 2.5 mg/kg. Elevation in the concentration of isoprostane was observed after treatment with saccharin at all doses. Conclusions: The administration of saccharin throughout the treatment period was correlated with impaired kidney and liver function. Both hyperglycemic and obesity-inducing side effects were observed. There was an increased oxidative status of the liver, as well as exposure to increased oxidative stress demonstrated through the increased levels of isoprostane, uric acid, 8-OHdG, and activity of catalase. Therefore, it is suggested that saccharin is unsafe to be included in the diet.


12-step participation and outcomes over 7 years among adolescent substance use patients with and without psychiatric comorbidity.
This study examines the associations between 12-step participation and outcomes over 7 years among 419 adolescent substance use patients with and without psychiatric comorbidities. Although level of participation decreased over time for both groups, comorbid adolescents participated in 12-step groups at comparable or higher levels across time points. Results from mixed-effects logistic regression models indicated that for both groups, 12-step participation was associated with both alcohol and drug abstinence at follow-ups, increasing the likelihood of either by at least 3 times. Findings highlight the potential benefits of 12-step participation in maintaining long-term recovery for adolescents with and without psychiatric disorders.


Detection of hepatitis G virus (GB virus C) RNA in human saliva.
Using PCR and genomic sequencing, we confirmed the presence of and homology between hepatitis G virus (HGV) (also called GB virus C) RNA in six serum samples and that in two saliva samples obtained from 34 patients with chronic hepatitis C virus infections. Thus, HGV may be found outside the circulatory system.


Excitability modulation by taurine: action on axon membrane permeabilities.
Taurine, a ubiquitous sulfonic amino acid, has been described as a regulator of membrane activity in both normal and pathologic states of nerve and muscle. The common feature of its effects on brain activity and its interaction with muscle, can be summarized in terms of a stabilizing function on excitable membranes. In this paper, we report data on the ionic mechanisms by which taurine modulates membrane behavior of the lobster giant axon. Our data show that taurine increases membrane permeabilities to potassium and chloride but not to sodium. This increase is transient, showing membrane desensitization during taurine application. A reversal potential for the taurine response was observed at about -85 mV, causing the membrane potential to stabilize near the resting level. In addition, taurine causes a reduction of the action potential duration, resulting primarily from an acceleration of the depolarization phase. These ionic actions of taurine may explain its overall inhibitory effects in the central nervous system and in the retina and may account for its antiarrhythmic properties.


Acute hemodialysis in a young man with severe symptomatic hyponatremia and kidney injury.
A 35-year-old man presented with severe hypo-osmolar hyponatremia (serum sodium 99 mmol/L), profound nonoliguric renal failure (serum creatinine 1240 μmol/L), and nephrotic range proteinuria. Computed tomography of the abdomen revealed nephromegaly and no obstruction. The patient was admitted to the intensive care unit (ICU) and conventional hemodialysis was initiated. To avoid rapid sodium correction, we prescribed concurrent dialysate flow, a low dialysate sodium concentration, a small surface area dialyzer, and a low blood flow rate. We infused dextrose 5% water into the venous return line and adjusted the infusion rate according to hourly sodium concentration. The rate of sodium correction was 7.7 mmol/day over the first 3 days of admission. A subsequent renal biopsy revealed focal segmental glomerulosclerosis and interstitial infiltration with extranodal NK/T-cell lymphoma nasal type. The patient died of massive lower gastrointestinal bleeding secondary to lymphomatous involvement day 19 in the ICU. In the setting of acute kidney injury requiring renal replacement therapy and concomitant severe hyponatremia, it is challenging to avoid overcorrection of serum sodium. We describe several key prescription modifications to conventional hemodialysis, factors that affect sodium diffusion at the level of the dialyzer membrane, and the importance of frequent laboratory monitoring.


Serum albumin leads to false-positive results in the XTT and the MTT assay.
Tetrazolium salts like 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) or sodium 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) that form formazans after reduction are widely used to investigate cell viability. Besides cellular enzymes, some constituents of cell media and other substances reduce tetrazolium salts, thereby interfering with these assays. We describe here that different preparations of serum albumin from bovine or human origin can lead to a concentration-dependent increase in the signals of the XTT assay; therefore leading to an overestimation of cell numbers and to an underestimation of potential cytotoxic effects of compounds to be tested. The same effect was seen in the MTT assay with human serum albumin (HSA). We demonstrate that this reductive activity cannot be inactivated by proteolytic digestion, but that it is due to the free cysteine residue in albumin, and is also observed when cysteine or glutathione (GSH) are used. Binding of N-ethylmaleimide (NEM) to the free cysteine residue leads to a decrease of the albumin interference in the XTT assay.


Effect of recirculation of 99mTc-Sn colloid in estimating mean transit time of soft-tissue vascular anomalies by direct puncture scintigraphy: a simulation analysis.
We have reported direct puncture scintigraphy, a novel method to estimate mean transit time (MTT) of soft-tissue vascular anomaly. In the examination, 99mTc-Sn colloid is infused percutaneously into the lesion, and MTT is calculated using the time-activity curve for the lesion. Recirculation of 99mTc-Sn colloid is neglected in computing MTT, and this may cause error. The aim of this study was to assess this error by simulation analysis. Data simulating direct puncture scintigraphy were produced for lesions with various blood volumes and various blood flows, considering recirculation and blood clearance of 99mTc-Sn colloid, and MTT was estimated by the same method used in the patient examination. Although MTT was overestimated in large lesions with intermediate or long MTT, the error was small except in extremely large lesions. It was suggested that recirculation of 99mTc-Sn colloid does not cause a serious problem in the clinical use of direct puncture scintigraphy.


Effects of PGC-1alpha on TNF-alpha-induced MCP-1 and VCAM-1 expression and NF-kappaB activation in human aortic smooth muscle and endothelial cells.
Increased oxidative stress in vascular cells is implicated in the pathogenesis of atherosclerosis. Reactive oxygen species (ROS) induce vascular inflammation via the proinflammatory cytokine/NF-kappaB pathway. Several lines of evidence suggest that peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1alpha) is an important regulator of intracellular ROS levels. However, no studies have examined the effects of PGC-1alpha on this process. We investigated the effects of PGC-1alpha on inflammatory molecule expression and activity of the redox-sensitive transcription factor, NF-kappaB, in vascular cells. PGC-1alpha expressed in human aortic smooth (HASMCs) and endothelial cells (HAECs) is upregulated by AMP-activated protein kinase activators, including metformin, rosiglitazone and alpha-lipoic acid. Tumor necrosis factor-alpha (TNF-alpha), a major proinflammatory factor in the development of vascular inflammation, stimulates intracellular ROS production through an increase in both mitochondrial ROS and NAD(P)H oxidase activity. Adenovirus-mediated overexpression of the PGC-1alpha gene in HASMCs and HAECs leads to a significant reduction in intracellular and mitochondrial ROS production as well as NAD(P)H oxidase activity. Consequently, NF-kappaB activity and MCP-1 and VCAM-1 induced by TNF-alpha are suppressed. Our data support the possibility that agents stimulating PGC-1alpha expression in the vasculature aid in preventing the development of atherosclerosis.


[Idiopathic chondrolysis of the hip].
Between 1993-2003 the authors treated 5 girls with idiopathic chondrolysis of the hip joint. Their mean age at first symptoms were 9 years (range 6-11 years). In all initial symptoms were pain and a hip flexion contracture of a mean 33 degrees (range 30-40 degrees). All were treated with multiple stationary rehabilitation including traction, range of motion exercises, analgetic physical therapy and longlasting walking with crutches. At the follow up examination only one hip was I 10 degree. Remaining 4 children were painfree. In 2 of them an acetabular protrusion, hip joint space narrowing and degenerative changes were observed on anteroposterior radiographs and clinically the hips were stiff in functional position. In the remaining 2 children, the hip range of motion was limited, with 30 and 90 degree of flexion, but joint space became wider on radiographs. Results were bad, because we do not know neither effective causative non symptomatic methods of treatment. Maybe the new technics of treatment, like arthrodiastasis, will bring better results.


Consideration of family history of cancer in medical routine: a survey in the primary care setting in Germany.
Family history of cancer (FHC) is important in the context of cancer prevention and risk counselling, but there is a lack of information about its consideration in medical routine. We aimed to characterize how FHC is assessed and taken into account in the primary care setting in Germany. We conducted a mail survey among 285 office-based physicians in south-west Germany. We sent a questionnaire to randomly selected general practitioners, dermatologists, gastroenterologists, gynaecologists, urologists and pulmonologists, asking about collection of information on FHC and implications for preventive counselling. A total of 207 physicians returned the questionnaire (response rate 73%), of whom 71% reported asking for FHC routinely, 17% reported using a standardized tool to collect the information and 35% reported regularly updating it. Implications of a positive FHC for counselling were heterogeneous, with priority on recommendations for screening. Referral to genetic counselling was considered by 34% of physicians, mainly gastroenterologists and gynaecologists. In the primary care setting in Germany, FHC is considered an important topic, but there is a lack of standardization in collecting the information and heterogeneity on the implications for counselling. Options to improve this situation, such as the implementation of standardized tools or centralized counselling systems, are needed.


Heat flux of driven granular mixtures at low density: Stability analysis of the homogeneous steady state.
The Navier-Stokes order hydrodynamic equations for a low-density driven granular mixture obtained previously [Khalil and Garzó, Phys. Rev. E 88, 052201 (2013)PLEEE81539-375510.1103/PhysRevE.88.052201] from the Chapman-Enskog solution to the Boltzmann equation are considered further. The four transport coefficients associated with the heat flux are obtained in terms of the mass ratio, the size ratio, composition, coefficients of restitution, and the driven parameters of the model. Their quantitative variation on the control parameters of the system is demonstrated by considering the leading terms in a Sonine polynomial expansion to solve the exact integral equations. As an application of these results, the stability of the homogeneous steady state is studied. In contrast to the results obtained in undriven granular mixtures, the stability analysis of the linearized Navier-Stokes hydrodynamic equations shows that the transversal and longitudinal modes are (linearly) stable with respect to long enough wavelength excitations. This conclusion agrees with a previous analysis made for single granular gases.


Cardiovascular disease knowledge and risk perception among underserved individuals at increased risk of cardiovascular disease.
Cardiovascular disease (CVD) risk factor awareness and knowledge are believed to be prerequisites for adopting healthy lifestyle behaviors. The purpose of this study was to examine knowledge of CVD risk factors and risk perception among individuals with high CVD risk. The sample consisted of inner city and rural medically underserved patients at high risk of CVD. To be eligible for the trial, subjects were required to have a 10% or greater CVD risk on the Framingham risk score. Knowledge of CVD was assessed with a 29-item questionnaire created for this study. Subjects also rated their perception of risk as compared with individuals of their own sex and age. Data were collected from 465 subjects (mean [SD] age, 60.5 [10.1] years; mean [SD] Framingham risk score, 17.3% [9.5%]). The mean (SD) CVD knowledge score was 63.7% (14.6%), and mean (SD) level of risk perception was 0.35 (1.4). Men and women had similar Framingham risk scores, but women perceived their risk to be significantly higher than that of their male counterparts. Women were also more knowledgeable than men about CVD. Urban participants had significantly higher actual risks than did their rural counterparts (18.2% [10.7%] vs 16.0% [8.9%], respectively; P = .01) but were significantly less knowledgeable about heart disease and also perceived their risk to be lower. These results indicate a low perception of risk and cardiovascular knowledge especially among men and inner city residents. Innovative educational strategies are needed to increase risk factor knowledge and awareness among at-risk individuals.


Accumulation of transposable elements in the genome of Drosophila melanogaster is associated with a decrease in fitness.
Replicates of the two isogenic laboratory strains of Drosophila melanogaster, 2b and Harwich, contain different average transposable element (TE) copy numbers in the same genetic background. These lines were used to analyze the correlation between TE copy number and fitness. Assuming a weak deleterious effect of each TE insertion, a decrease in fitness is expected with an increase in genomic TE copy number. Higher rates of ectopic exchanges and, consequently, chromosomal rearrangements resulting in early embryonic death are also predicted from an increase in TE copy number. Therefore egg hatchability is expected to decrease as the genomic TE copy number increases. In 2b, where replicate lines have diverged up by 90 TE copies per haploid genome, a negative correlation between the number of TE insertions and both fitness and egg hatchability were found. Neither correlation was significant for the Harwich replicates, which have only diverged by 30 TE copies. The average deleterious effect of a TE insertion on fitness and its components was estimated as 0.004. Both homozygous and heterozygous TE insertions were shown to have deleterious effects on fitness and its components.


[Research on control effect of sulfoxaflor and flonicamid on Lonicera japonica].
The study was aimed to determine the efficacy of two pesticides in the control of aphids in Lonicera japonica, and study the applicability of pesticides in L. japonica. The number of insects was counted before and 2, 3, 7 and 10 days after the application of pesticide in the test area within different dosage groups. The method was 5-point sampling method. Five aphids on the L. japonica branches were selected, then the number of insects was recorded. The effect of the two pesticides on the control rate of aphid was more than 80% at 1 d after application. The results showed that the two pesticides had good efficacy. After 7 days and 10 days, the control effect was 100%. After 1 day of spraying, the effect of the two pesticides on the control of L. japonica aphids was more than 80%, which was higher than that of the control agent. The results showed that the two pesticides had good and fast effect. After 7 days and 10 days of spraying, the control effect was 100%. The control effect of two kinds pesticides for aphid sprayed in recommended dose on the L. japonica is good and showed no hytotoxicity.


[A hepatocellular carcinoma showing sarcomatous features and an extensive metastasis].
A 47-year-old female was admitted for a right hypochondrial pain and was diagnosed as having a hepatic tumor with a cystic lesion. After a right and a caudal lobectomy, she died of hepatic failure due to a tumoral recurrence. At autopsy, a cystic tumoral nodule, 15 x 7 cm in size, and numerous other nodules were revealed in the liver. Metastases were seen in both lungs, the left kidney, the colon, the mesenterium, the peritoneum, the diaphragm, and the para-pancreatic lymph nodes. The hepatic tumors consisted of four types of tumor cells: spindle, round, mixed (spindle and round cells), and cells with pseudoalveolar features. All tumor cells showed a positive immunohistochemical reaction to polyclonal keratin, low molecular monoclonal keratin, alpha 1 anti-trypsin, vimentin and to actin in their cytoplasms. This is considered a very rare case.


Cloning and characterization of ZAP36, an annexin-like, zymogen granule membrane associated protein, in exocrine pancreas.
ZAP36, a zymogen granule membrane associated protein with 36 kDa, was cloned from both canine and rat pancreas. ZAP36 is found to be a novel member of annexin IV, and showed an apical localization in exocrine pancreas and an ubiquitous expression in epithelial tissues. ZAP36 may be involved in exocytosis in apical regions of polarized cells.


Exploring food insecurity among young mothers (15-24 years).
The purpose of this study was to explore the experience of food insecurity of young mothers (15-24 years) and identify strategies used to manage food-insecure periods. This exploratory study used the U.S. Household Food Security Survey Module, cognitive interviewing, and individual interviews. Sixteen out of 21 young mothers indicated that they fluctuated between low food insecurity (reduced desirability of diet), and all 21 participants reported some days of food insufficiency (anxiety over shortage of food). All the women reported that their children had only marginal food insecurity due to extensive strategies. Nutrition counseling must include food insecurity assessment.


Reliance on external cues for movement initiation in Parkinson's disease. Evidence from movement-related potentials.
The aim of this study was to investigate the neurophysiological mechanisms underlying Parkinson's disease patients' increased reliance on external cues for the initiation of movement. Lateralized movement-related cortical potentials were recorded in a noise-compatibility task with seven patients and seven age-matched control subjects. In this two-choice task, visual stimuli containing incompatible target and distractor elements, which simultaneously instructed for responses from both hands, initially caused activation of the motor cortex controlling the wrong response hand. The incorrect response activation was of higher amplitude in patients than in control subjects, causing a longer response delay relative to response times when target and distractors instructed the same hand. In addition, hand-specific motor cortex activation started earlier in patients than in control subjects. These results indicate that visual stimuli exerted an earlier and stronger influence on movement initiation in patients than in control subjects. We hypothesize that information from sensory stimuli relevant for the generation of a response can have rapid access to motor structures in Parkinson's disease patients, thereby facilitating the initiation of movement. The findings may reflect a compensatory mechanism, but could also be related to excitability changes in the motor cortex intrinsic to the pathophysiology of Parkinson's disease.


Silica Polymerization from Supersaturated Dilute Aqueous Solutions in the Presence of Alkaline Earth Salts.
The early stages of silica polymerization in aqueous solution proceed according to a mechanism based on three steps: nucleation, particle growth, and agglomeration of the particles. Application of time-resolved static and dynamic light scattering as a powerful in situ technique in combination with spectrophotometric analysis of the monomer consumption based on the molybdenum blue method was carried out to further investigate this 3-step process. Experiments were carried out at four different initial silicic acid contents covering a range between 350 and 750 ppm in the presence of either 10 mM NaCl or 5 mM of a mixture of CaCl2 and MgCl2. The process in all cases was initiated with a drop of pH to 7. Addition of the salts made possible an analysis of the impact of an electrolyte on the process. Independent of the presence or absence of salt, particle growth in step two proceeded as a monomer-addition process without being interfered significantly by Ostwald-ripening. The growing particles were compact with a homogeneous density. The size of the particles approached final values between 5 and 20 nm with the actual value increasing with decreasing initial silicic acid content. Above a certain concentration of initial silica content, which depends on the level of added salt, particle-particle interactions caused agglomeration. The presence of electrolyte shifted this level from ∼2000 ppm to a range between 500 and 750 ppm. The resulting agglomerates had a fractal dimension of 2. Independent of the conditions, particle growth could be described with a simple nucleation and growth model.


Acute recreational drug toxicity: Comparison of self-reports and results of immunoassay and additional analytical methods in a multicenter European case series.
The aim of the study was to compare self-reported and analytically confirmed substance use in cases of acute recreational drug toxicity.We performed a retrospective analysis of emergency department presentations of acute recreational drug toxicity over 2 years (October 2013 to September 2015) within the European Drug Emergencies Network Plus project.Among the 10,956 cases of acute recreational drug toxicity during the study period, 831 could be included. Between the self-reported substance use and the toxicological results, the highest agreement was found for heroin (86.1%) and cocaine (74.1%), whereas inhalants, poppers, and magic mushrooms were self-reported but not analytically detected. Cathinones and other new psychoactive substances (NPS) could be detected using additional analytical methods. Among cases with both immunoassay (IA) and confirmation with mass spectrometry (MS), the results were consistent for methadone (100%) and cocaine (95.5%) and less consistent for amphetamines (81.8%). In cases with a positive IA for amphetamines (n = 54), MS confirmed the presence of 3,4-methylenedioxymethamphetamine (MDMA), amphetamine, methamphetamine, and NPS in 37, 20, 10, and 6 cases, respectively, also revealing use of more than 1 substance in some cases. MS yielded positive results in 21 cases with a negative IA for amphetamines, including amphetamine, MDMA, methamphetamine, and NPS, in 14, 7, 2, and 2 cases, respectively.In conclusion, the highest agreement was found between self-reports and analytical findings for heroin and cocaine. The diagnosis of NPS use was mainly based on self-report. The IAs accurately identified methadone and cocaine, and MS had advantages for the detection of NPS and amphetamine derivatives.


Lichtenstein inguinal herniorraphy under local infiltration anaesthesia as rapid outpatient procedure.
In Scandinavian countries the use of local anaesthesia combined with fast patient's discharge is still uncommon in inguinal herniorraphy. To report the feasibility, safety, costs and long-term outcome in terms of pain and recurrence after 101 open inguinal herniorraphies operated under local anesthesia as rapid outpatient procedure. All patients were selected and operated using Lichtenstein polypropylene mesh herniorraphy by the same senior surgeon and one nurse. The incidence of pain and recurrences were asked by questionnaire after the mean follow-up of 2 years. The rate of clinically important wound hematomas (n = 3) and infections (n = 1) were low as well as the number of recurrences (n = 1). Although 23% of the patients felt later some pain sensations in the inguinal region, only 2 patients needed occasionally pain-relieving drugs. Over 90 per cent of the patients were very satisfied with the operation. Lichtenstein inguinal hernioplasty under local infiltration anaesthesia is rapid, well-tolerated, simple and inexpensive operation, which gives excellent results.


Microwave-vacuum extraction cum drying of tomato slices: Optimization and functional characterization.
Fruits and vegetables have shorter shelf life due to their perishable nature. Tomato, being a nutritionally rich fruit needs to be preserved for a longer period. In this context, this study was designed to dry the tomato slices through microwave-vacuum drying. This process was optimized for moisture ratio and drying rate using response surface methodology (RSM). The process was investigated at different power levels (30, 50, 80, and 100 W), pressure (0, 15, 20, and 25 inHg), and time (0, 4, 6, and 10 min) using Box-Behnken design. Results indicated that color, energy efficiency, and drying characteristics were significantly affected by changing power, vacuum levels, and processing time. Besides, nine mathematical models were applied on experimental data to deeply understand the moisture ratio of tomato slices. Amongst, Midilli model was found best to describe the drying process at 100 W and 25 inHg supported by R 2 (0.9989), RMSE (0.001), and X 2 (1.34e-4). This study was focused on finding the optimal combinations of power, vacuum pressure, and time for better drying and reduced wastage of the fruit owing to its perishable nature. From all the microwave powers, higher microwave power and vacuum level showed better energy consumption, energy efficiencies, color retention, and rehydration capacity.


Ageing is associated with brown adipose tissue remodelling and loss of white fat browning in female C57BL/6 mice.
Fat storage changes throughout life and affects body metabolism. Ageing impact on brown (BAT) and white adipose tissue (WAT) deserves attention, especially in females, because they are less prone to age-induced weight gain. While in male mice the impact of ageing on adipose tissue remodelling is well characterized, the effects in female mice remain largely unclear. Thus, we investigated BAT and WAT remodelling during ageing in female C57BL/6 mice. At 3 months, body weight was 24 ± 0.3 g (mean±SD), and it increased from 6 to 9 months of age (+20%, P < 0.0001). Oral glucose tolerance test showed no disturbance of glucose metabolism. All WAT depots became heavier, and white adipocytes hypertrophied. The subcutaneous and visceral WAT had clusters of beige cells in younger mice, but they were progressively lost by ageing, indicating loss of WAT browning. Older mice had hypertrophied classic brown adipocytes that had larger cytoplasmic lipid droplets than younger mice. Pearson's correlation showed that WAT mass has a weak correlate with BAT mass, although white adipocyte diameter has a strong correlation with classic brown adipocyte size. In conclusion, our results indicate that female C57BL/6 mice have a progressive age-dependent loss of subcutaneous and visceral WAT browning, and this process runs in parallel with BAT morphological changes towards a fat storer phenotype, independent of cycling or disturbances in glucose metabolism.


Low‑level mechanical vibration enhances osteoblastogenesis via a canonical Wnt signaling‑associated mechanism.
Osteoporosis is a skeletal metabolic disease characterized by reduced bone mass and a high susceptibility to fractures, in which osteoblasts and osteoclasts are highly involved in the abnormal bone remodeling processes. Recently, low‑magnitude, high‑frequency whole‑body vibration has been demonstrated to significantly reduce osteopenia experimentally and clinically. However, the underlying mechanism regarding how osteoblastic activity is altered when bone tissues adapt to mechanical vibration remains elusive. The current study systematically investigated the effect and potential molecular signaling mechanisms in mediating the effects of mechanical vibration (0.5 gn, 45 Hz) on primary osteoblasts in vitro. The results of the present study demonstrated that low‑level mechanical stimulation promoted osteoblastic proliferation and extracellular matrix mineralization. In addition, it was also revealed that mechanical vibration induced improved cytoskeleton arrangement in primary osteoblasts. Furthermore, mechanical vibration resulted in significantly increased gene expression of alkaline phosphatase, bone morphogenetic protein 2 and osteoprotegerin, and suppressed sclerostin gene expression, as determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analyses. Mechanical vibration was observed to upregulate gene and protein expression levels of osteogenesis‑associated biomarkers, including osteocalcin and Runt‑related transcription factor 2. In addition, RT‑qPCR and western blotting analysis demonstrated that mechanical vibration promoted gene and protein expression of canonical Wnt signaling genes, including Wnt3a, low‑density lipoprotein receptor‑related protein 6 and β‑catenin. In conclusion, the present study demonstrated that mechanical vibration stimulates osteoblastic activities and may function through a potential canonical Wnt signaling‑associated mechanism. These findings provided novel information that improves the understanding of the molecular mechanisms involved in osteoblastic activities in response to mechanical vibration, which may facilitate the scientific application of mechanical vibration for the treatment of osteoporosis in the clinic.


Traditional Medicines and Kidney Disease in Low- and Middle-Income Countries: Opportunities and Challenges.
Traditional medicines are a principal form of health care for many populations, particularly in low- and middle-income countries, and they have gained attention as an important means of health care coverage globally. In the context of kidney diseases, the challenges and opportunities presented by traditional medicine practices are among the most important considerations for developing effective and sustainable public health strategies. However, little is known about the practices of traditional medicines in relation to kidney diseases, especially concerning benefits and harms. Kidney diseases may be caused, treated, prevented, improved, or worsened by traditional medicines depending on the setting, the person, and the types, modes, and frequencies of traditional medicine use. Given the profound knowledge gaps, nephrology practitioners and researchers may be uniquely positioned to facilitate more optimal public health strategies through recognition and careful investigation of traditional medicine practices. Effective implementation of such strategies also will require local partnerships, including engaging practitioners and users of traditional medicines. As such, practitioners and researchers investigating kidney diseases may be uniquely positioned to bridge the cultural, social, historical, and biologic differences between biomedicine and traditional medicine, and they have opportunities to lead efforts in developing public health strategies that are sensitive to these differences.


Treatment of Helicobacter pylori Is Not Associated With Future Clostridium difficile Infection.
Helicobacter pylori (HP) infection is associated with many gastrointestinal disorders, including gastric cancer, and consensus guidelines recommend eradication after detection. There is a theoretical, yet uninvestigated, concern that HP treatment could increase the risk of Clostridium difficile infection (CDI). Using the data from a large cohort of patients with HP, we investigated whether HP eradication is associated with CDI. A retrospective cohort study within the Veterans Health Administration on 38,535 patients (median age 61.8 years; 91.8% men) with detected HP between January 1, 1994, and December 31, 2018 was conducted. Primary outcome was a positive laboratory test for CDI within 3 months of HP detection. Multivariable logistic regression evaluated the following: patient demographics, previous CDI, recent hospitalization, and whether the patient received HP eradication therapy (by antibiotic and regimen, and including proton pump therapy). Secondary analysis of those treated evaluated whether eradication of HP was associated with CDI. Among 38,535 patients, 28,818 (74.8%) were treated for HP and 284 (0.74%) developed CDI. In multivariable analysis, prominent factors included hospital discharge within 12 weeks (odds ratio [OR] 2.15; 95% confidence interval [CI]: 1.22-3.77) and 4 weeks (OR 3.46; 95% CI: 2.18-5.48), P < 0.001, and previous CDI (OR 12.5; 95% CI: 9.21-17.0, P < 0.001). Treatment of HP was not associated with future CDI. In secondary analysis of those treated, confirmation of eradication was not associated with future CDI (OR 1.49; 95% CI: 0.67-3.29). In a large study of US patients with HP, we demonstrate that neither treatment nor eradication of HP is associated with CDI. Previous C. difficile infection and recent hospital discharge, established risk factors for CDI, are strongly associated. These findings suggest that treatment should be continued to be prescribed when HP is detected (http://links.lww.com/AJG/B507).


A new selective suicide inhibitor of peripheral DOPA decarboxylase.
Although the present study is based on a small number of patients, our clinical data clearly show that DFMD is as effective as other peripheral decarboxylase inhibitors in potentiating the action of L-DOPA. In 3 patients, we observed an improvement above that with previous therapy. This may suggest that in some patients DFMD is either more effective than other decarboxylase inhibitors or that it has its own effect. Subjective complaints with DFMD were frequent and 9 of the 10 patients preferred their previous therapy. In 5 patients, we observed an increase in blood pressure while on DFMD plus L-DOPA and 2 had EEG changes. These effects appear to be drug-related. Because of its side effects, DFMD cannot be considered in this form as a useful adjuvant in Parkinson therapy. However, further studies are necessary for the development of selective inhibitors.


Analysis of some selected catechins and caffeine in green tea by high performance liquid chromatography.
Green tea seems to have a positive impact on health due to the catechins-found as flavanols. Thus, the present study was aimed to develop a low cost reversed phase high performance liquid chromatographic (HPLC) method for simultaneous determination of flavanol contents, namely catechin (C), epicatechin (EC), epigallocatechin (EGC), epicatechin 3-gallate (ECG) and epigallocatechin 3-gallate (EGCG) and caffeine in 29 commercial green tea samples available in a Saudi Arabian local market. A C-18 reversed-phase column, acetonitrile-trifluoroacetic acid as a mobile phase, coupled with UV detector at 205 nm, was successfully used for precise analysis of the tested analytes in boiled water of digested tea leaves. The average values of N (No. of theoretical plates), HETP (height equivalent of theoretical plates) and R(s) (separation factor) (at 10 μg ml(-1) of the catechins EC, EGC, EGCG and ECG) were 2.6×10(3)±1.2×10(3), 1.7×10(-3)±4.7×10(-4) cm and 1.7±5.53×10(-2), respectively. The developed HPLC method demonstrated excellent performance, with low limits of detection (LOD) and quantification (LOQ) of the tested catechins of 0.004-0.05 μg ml(-1) and 0.01-0.17 μg ml(-1), respectively, and recovery percentages of 96-101%. The influence of infusion time (5-30 min) and temperature on the content of the flavanols was investigated by HPLC. After a 5 min infusion of the tea leaves, the average concentrations of caffeine, catechin, EC, EGC, ECG and EGCG were found to be in the ranges 0.086-2.23, 0.113-2.94, 0.58-10.22, 0.19-24.9, 0.22-13.9 and 1.01-43.3 mg g(-1), respectively. The contents of caffeine and catechins followed the sequence: EGCG>EGC>ECG>EC>C>caffeine. The method was applied satisfactorily for the analysis of (+)-catechin, even at trace and ultra trace concentrations of catechins. The method was rapid, accurate, reproducible and ideal for routine analysis.


Retrospective, Registry-based, Cohort Investigation of Clinical Outcomes in Patients with Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma in Finland.
Most cases of keratinocyte cancer can be treated effectively with surgery. However, survival is reduced in patients with advanced disease. This retrospective cohort study evaluated overall survival of patients with invasive keratinocyte cancers, and high-risk features for progression of the disease and mortality in Finnish patients in a real-world setting. A total of 43,143 patients with keratinocyte cancer types of basal cell carcinoma and 10,380 with cutaneous squamous cell carcinoma were identified nationwide. More detailed patient records were available for a subset of patients (basal cell carcinoma n = 5,020 and cutaneous squamous cell carcinoma n = 1,482) from a regional database. Fifty percent of patients with advanced cutaneous squamous cell carcinoma died approximately 4.5 years after diagnosis. Multivariable models suggested that risk factors for keratinocyte cancer progression were male sex, presence of comorbidities, immunosuppression, and pre-cancerous lesions, while risk factors for disease-specific mortality were advanced disease stage with immunosuppression, other malignancies, and consecutive surgical excisions. These results suggest that identifying patient and tumour factors associated with poor disease outcome could be important when determining appropriate treatment and follow-up; however, further studies are necessary.


The effect of pelvic floor training on sexual function of treated patients.
The aim of this study was to determine the effects of improvements in urinary incontinence resulting from pelvic floor rehabilitation on the sexual function of patients. The study involved 42 clinic patients who received pelvic floor rehabilitation treatment. Their sexual histories were obtained through face-to-face interviews. Pelvic muscle strength was measured with a perineometer. Improvement in incontinence was measured with the pad test. Seventeen women reported decreased sexual desire before the treatment; 5 of these indicated improvement after treatment. Nine of 17 women who experienced dyspareunia prior to treatment reported an improvement afterwards, and four women reported complete relief from pain. Five of 15 women who complained of difficulty in reaching climax before the treatment experienced improvement in this area. In conclusion, an improvement in sexual desire, performance during coitus and achievement of orgasm were observed in women who received pelvic floor muscle rehabilitation. No change was seen in the arousal and resolution stages of sexual activity.


Intra-strain variability of Cryptococcus neoformans can be detected on phloxin B medium.
A method was devised for easy detection of intra-strain variability of the human pathogenic yeast Cryptococcus neoformans. Cultivation of strains on a medium containing Phloxin B resulted in different coloured colonies. Generally, colonies were either pink or red; however there were also several colony-colour segregant in which both colours could be observed. A number of these segregants were isolated and analysed. Virulence factors such as the cell and capsule sizes were measured; further temperature sensitivity, growth rates, mating-types and melanin production were also studied. Segregants were examined by random amplified polymorphic DNA (RAPD) fingerprinting and electrophoretic karyotyping by pulsed-field gel electrophoresis (CHEF). They showed both phenotypic and genotypic differences. The main differences appeared in phenotypic characters and RAPD patterns; while the chromosomal patterns remained unchanged. Reversion frequency analysis revealed that the reason for this segregation could be due to phenotypic switching. The physiological reason for the colour changes was also investigated and was attributed to the differential ability of the cells to accumulate Phloxin B either into their capsules or into their cells. The method described here is potentially applicable for the detection of strain heterogeneity in both basic and clinical microbiology laboratories.


Targeting the SUMO pathway as a novel treatment for anaplastic thyroid cancer.
Cancer stem cells (CSCs) are expanded in anaplastic thyroid cancer (ATC) and standard treatment approaches have failed to improve survival, suggesting a need to specifically target the CSC population. Recent studies in breast and colorectal cancer demonstrated that inhibition of the SUMO pathway repressed CD44 and cleared the CSC population, mediated through SUMO-unconjugated TFAP2A. We sought to evaluate effects of inhibiting the SUMO pathway in ATC. ATC cell lines and primary ATC tumor samples were evaluated. The SUMO pathway was inhibited by knockdown of PIAS1 and use of SUMO inhibitors anacardic acid and PYR-41. The expression of TFAP2A in primary ATC was examined by immunohistochemistry. All ATC cell lines expressed TFAP2A but only 8505C expressed SUMO-conjugated TFAP2A. In 8505C only, inhibition of the SUMO pathway by knockdown of PIAS1 or treatment with SUMO inhibitors repressed expression of CD44 with a concomitant loss of SUMO-conjugated TFAP2A. The effect of SUMO inhibition on CD44 expression was dependent upon TFAP2A. Treatment with SUMO inhibitors resulted in a statistically improved tumor-free survival in mice harboring 8505C xenografts. An examination of primary ATC tissue determined that TFAP2A was expressed in 4 of 11 tumors surveyed. We conclude that inhibition of the SUMO pathway repressed the CSC population, delaying the outgrowth of tumor xenografts in ATC. The effect of SUMO inhibition was dependent upon expression of SUMO-conjugated TFAP2A, which may serve as a molecular marker for therapeutic effects of SUMO inhibitors. The findings provide pre-clinical evidence for development of SUMO inhibitors for the treatment of ATC.


Modeling type 2 diabetes in rats by administering tacrolimus.
The prevalence of diabetes is rapidly increasing. The current number of diagnosed cases is ~422 million, expected to reach ~640 million by 2040. Type 2 diabetes, which constitutes ~95% of the cases, is characterized by insulin resistance and a progressive loss of β-cell function. Despite intense research efforts, no treatments are yet able to cure the disease or halt its progression. Since all existing animal models of type 2 diabetes have serious drawbacks, one is needed that represents the complete pathogenesis, is low cost and non-obese, and can be developed relatively quickly. The aim of this study was to evaluate a low-cost, non-obese model of type 2 diabetes engendered by administering a daily high dose of tacrolimus (an immunosuppressant) to Wistar rats for 4 weeks. The biochemical and antioxidant markers were measured at basal and after the 4-week tacrolimus treatment. At week 4, the values of these parameters closely resembled those observed in human type 2 diabetes, including fasting blood glucose at 141.5 mg/dL, blood glucose greater than 200 mg/dL at 120 min of the glucose tolerance test, blood glucose at varied levels in the insulin tolerance test, and elevated levels of cholesterol and triglyceride. The tacrolimus treatment produced hypoinsulinemia and sustained hyperglycemia, probably explained by the alteration found in pancreatic β-cell function and morphology. This model should certainly be instrumental for evaluating possible type 2 diabetes treatments, and for designing new immunosuppressants that do not cause pancreatic damage, type 2 diabetes, or new-onset diabetes after transplantation (NODAT).


A combined streaming-potential optical reflectometer for studying adsorption at the water/solid surface.
A novel in-situ streaming-potential optical reflectometry apparatus (SPOR) was constructed and utilized to probe the molecular architecture of aqueous adsorbates on a negatively charged silica surface. By combining optical reflectometry and electrokinetic streaming potentials, we measure simultaneously the adsorption density, gamma, and zeta potential, zeta, in a rectangular flow cell constructed with one transparent wall. Both dynamic and equilibrium measurements are possible, allowing the study of sorption kinetics and reversibility. Using SPOR, we investigate the adsorption of a classic nonionic surfactant (pentaethylene glycol monododecyl ether, C12E5), a simple cationic surfactant (hexadecyl trimethylammonium bromide, CTAB) of opposite charge to that of the substrate surface, and two cationic polyelectrolytes (poly(2-(dimethylamino)ethyl methacrylate), PDAEMA; (poly(propyl methacrylate) trimethylammonium chloride, MAPTAC). For the polyethylene oxide nonionic surfactant, bilayer adsorption is established above the critical micelle concentration (cmc) both from the adsorption amounts and from the interpretation of the observed zeta potentials. Near adsorption saturation, CTAB also forms bilayer structures on silica. Here, however, we observe a strong charge reversal of the surface. The SPOR data, along with Gouy-Chapman theory, permit assessment of the net ionization fraction of the CTAB bilayer at 10% so that most of the adsorbed CTAB molecules are counterion complexed. The adsorption of both C12E5 and CTAB is reversible. The adsorption of the cationic polymers, however, is completely irreversible to a solvent wash. As with CTAB, both PDAEMA and MAPTAC demonstrate strong charge reversal. For the polyelectrolyte molecules, however, the adsorbed layer is thin and flat. Here also, a Gouy-Chapman analysis shows that less than 20% of the adsorbed layer is ionized. Furthermore, the amount of charge reversal is inversely proportional to the Debye length in agreement with available theory. SPOR provides a new tool for elucidating aqueous adsorbate molecular structure at solid surfaces.


The structure of prion: is it enough for interpreting the diverse phenotypes of prion diseases?
Prion diseases, or transmissible spongiform encephalopathies, are neurodegenerative diseases, which affect human and many species of animals with 100% fatality rate. The most accepted etiology for prion disease is 'prion', which arises from the conversion from cellular PrP(C) to the pathological PrP(Sc). This review discussed the characteristic structure of PrP, including PRNP gene, PrP(C), PrP(Sc), PrP amyloid, and prion strains.


Enhanced recovery pathway versus standard care in patients undergoing video-assisted thoracoscopic lobectomy.
The objective of this study was to compare outcomes after video-assisted thoracoscopic lobectomy or segmentectomy before and after introduction of an enhanced recovery program. Data from 600 patients undergoing video-assisted lobectomy or segmentectomy between April 2014 and January 2017 were analyzed. A comparative analysis was performed between patients undergoing operation before (365 patients) and after (235 patients) the start of the enhanced recovery program. The incidence of cardiopulmonary complications and 30-day and 90-day mortality, postoperative length of stay, and 30-day and 90-day hospital readmission rates were evaluated. Risk-adjusted cardiopulmonary morbidity and 30-day mortality were calculated for each group and compared. The 2 groups had a similar postoperative length of stay (enhanced recovery pathway median 5 days vs pre-enhanced recovery pathway 4, P = .44), cardiopulmonary complication rates (enhanced recovery pathway 22.6% vs pre-enhanced recovery pathway 22.4%, P = .98), 30-day mortality rates (enhanced recovery pathway 3.8% vs pre-enhanced recovery pathway 2.2%, P = .31), and 90-day mortality rates (enhanced recovery pathway 4.7% vs pre-enhanced recovery pathway 3.0%, P = .37). No differences were noted in terms of 30-day (enhanced recovery pathway 7.2% vs pre-enhanced recovery pathway 7.4%, P = .94) or 90-day readmission rates (enhanced recovery pathway 9.8% vs pre-enhanced recovery pathway 12.3%, P = .34). The risk-adjusted cardiopulmonary morbidity rates were similar in the 2 periods (P = .76), whereas the risk-adjusted 30-day mortality was higher in the enhanced recovery pathway period compared with the pre-enhanced recovery pathway mortality (P = .0004). We found no benefit conferred by the enhanced recovery program on outcomes such as cardiopulmonary complications, 30- and 90-day mortality, length of stay, and readmissions. Enhanced recovery program elements may be insufficiently different than previous standards of perioperative care to confer detectable benefits in our settings.


Combined Probe Strategy to Increase the Enzymatic Digestion Rate and Accelerate the Renal Radioactivity Clearance of Peptide Radiotracers.
High and sustained renal radioactivity accumulation is a major challenge in peptide-based radionuclide imaging and therapy. However, neutral endopeptidase (NEP)-based enzymatic hydrolysis to release and excrete the radioactive fragments has been proven to be an effective and promising way to reduce renal accumulation. Despite the improvement, the effect is still far from being satisfactory. To further reduce kidney uptake, we studied the relationship between the enzymatic reaction rate and the substrate concentration and came up with a combined probe strategy. Model compounds Boc-MVK-Dde and Boc-MFK-Dde were used for an in vitro enzymatic digestion study. NOTA-Exendin 4 and NOTA-MVK-Exendin 4 were labeled with 64Cu for in vivo dose-dependent micro-positron emission tomography (PET) studies. Groups 1 and 2 were injected with 0.2 and 0.8 nmol of 64Cu-NOTA-Exendin 4, respectively. Groups 3-6 were injected with 0.2, 0.8, 1.0, and 1.4 nmol of 64Cu-NOTA-MVK-Exendin 4, respectively. Groups 7 and 8 were co-injected with 0.2 nmol of 64Cu-NOTA-MVK-Exendin 4 and NOTA-MVK-PEG5K (1.3 and 2.6 nmol). The radioactivity uptakes were determined and compared within and among the groups. The in vitro cleavage study for both Boc-MVK-Dde and Boc-MFK-Dde indicated that within a certain concentration range, the enzyme digestion rate increased with increasing substrate concentration. The microPET images showed that the renal clearance could be accelerated significantly by increasing the injection dose of 64Cu-NOTA-MVK-Exendin 4, with the kidney uptakes being 60.98, 43.01, and 16.10 % ID/g at 1 h for groups 3, 4 and 5, respectively. Unfortunately, the tumor uptakes were also significantly inhibited as the injected dose of the tracer increased. However, with the co-injection of NOTA-MVK-PEG5K, the renal accumulation was significantly decreased without hampering the tumor uptake. As a result, the tumor-to-kidney ratios were significantly improved, which were 1.93, 3.47, 1.74, and 3.38 times that of group 3 at 1, 4, 24, and 48 h, respectively. The enzymatic reaction rate of NEP is dependent on the concentration of the substrates both in vitro and in vivo. The combined probe strategy developed in this study can dramatically reduce the renal accumulation of a peptide radioligand without affecting the tumor uptake, which shows great potential in peptide-based radiotheranostics.


Experiences of substitute decision makers in making decisions for older persons diagnosed with major neurocognitive disorder at end of life: a qualitative systematic review protocol.
The objective of this systematic review is to identify and synthesize the best available qualitative evidence on how substitute decision makers (SDMs) are affected by and experience making decisions at end of life (EOL) for older persons diagnosed with major neurocognitive disorder (major NCD) (dementia). Addressing the objective will provide an understanding of SDMs' experiences of making decisions for older persons diagnosed with major NCD at EOL, in order to tailor supportive education and interventions and potentially decrease inopportune outcomes.Specifically, the review questions are as follows.


[Clinical and treatment profiles of patients affected by acute coronary syndromes derived from administrative databases in the ASSL 10 Veneto orientale].
This paper presents a revision of services provided to patient over two years following a myocardial infarction (MI) based on data derived from administrative databases. The study aims to evaluate the burden and the resources consumed by these patients, as well as the adherence to clinical guidelines. All patient hospitalised for myocardial infarction in the cardiology unit of the hospital of San Donà di Piave (Venice, Italy) were identified. The clinical record was reviewed to reconstruct clinical history. Then from the Local Health Unit n. 10 all information regarding these patient were collected and analysed after record linkage. The patients with MI were 236. Of these, 20 died during the first hospitalization, 2 were lost to the follow up and 40 died within the two years period. The 214 patients who were alive after the first hospitalization produced 447 ordinary and 57 day hospital hospitalization. Specialist services were 23.250, and of these 17.583 were evaluated as being related to the cardiac disease. The value of drug prescribed over the two year period was Euro 553.108. The number of prescriptions belonging to the anatomic ATC class C were 29.076, received by 210 people. The mean pro capita estimated cost was Euro 22.058 in the first year, and Euro 6.226 in the second year. The characteristics of the sample population of our patients with MI were similar to those described in the literature. Follow up showed a sharp decrease of care and services received by patients during the second year after the acute event. In addition, a large part of services was not related to the cardiac diseases. Only a limited number of patients followed a rehabilitation programme. The estimated pro capita overall cost was very relevant in the first year, and the difference with the cost of the second year suggests a fall over time of the relevance attributed by the patients to the cardiac problems.


Cryptorchidism and semen quality: a TEM and molecular study.
Cryptorchidism is a pathological condition defined as the failure of the testis to descend into the scrotum, the location of the cryptorchid testis can be in the inguinal canal or in the prescrotal and abdominal area, sometimes resulting in atrophic seminiferous tubules. The aim of this study was to analyze semen quality of men who underwent orchidopexy for unilateral or bilateral cryptorchidism during childhood. Semen quality was investigated by light microscopy to evaluate sperm concentration and motility. Sperm morphology was performed by transmission electron microscope (TEM), and the data were mathematically elaborated. The presence of Y microdeletions was investigated by polymerase chain reaction. The effect of cryptorchidism on meiosis was explored by fluorescence in situ hybridization (FISH). The incidence of azoospermia was higher in the group with bilateral compared with unilateral cryptorchidism, and semen parameters were better in the unilateral group. Sperm pathologies detected by TEM indicated a severe deterioration of sperm quality in both groups. Necrosis and apoptosis appeared to be the most frequent pathologies, and their values reached statistical significance compared with those from fertile controls. The presence of chromosome Y microdeletions in patients with cryptorchidism and severe spermatogenetic defects is controversial. No microdeletions were found in this study. FISH values indicated that the mean percentage of gonosome disomies and diploidies were generally out of normal range, indicating a severe disturbance of meiotic segregation. The effects induced by cryptorchidism resolved in childhood seem to include a spermatogenetic impairment, leading to recommendation of detailed ultrastructural and chromosomal sperm analyses before undertaking assisted reproductive techniques.


The use of pneumatic retinopexy to delay surgical repair of a retinal detachment associated with the ganciclovir intraocular device.
Rhegmatogenous retinal detachments are associated with cytomegalovirus (CMV) retinitis and the use of the ganciclovir intraocular device. Pars plana vitrectomy with silicone oil tamponade is the preferred technique to repair such detachments. The authors describe the use of pneumatic retinopexy as part of a treatment strategy in the management of multiple retinal detachments in a patient with CMV retinitis treated with ganciclovir implants. Pneumatic retinopexy may benefit patients when the causative retinal break is superior and is located in an area of retina uninvolved with CMV infection, because it can be used to delay surgical intervention.


Top3α is required during the convergent migration step of double Holliday junction dissolution.
Although Blm and Top3α are known to form a minimal dissolvasome that can uniquely undo a double Holliday junction structure, the details of the mechanism remain unknown. It was originally suggested that Blm acts first to create a hemicatenane structure from branch migration of the junctions, followed by Top3α performing strand passage to decatenate the interlocking single strands. Recent evidence suggests that Top3α may also be important for assisting in the migration of the junctions. Using a mismatch-dHJ substrate (MM-DHJS) and eukaryotic Top1 (in place of Top3α), we show that the presence of a topoisomerase is required for Blm to substantially migrate a topologically constrained Holliday junction. When investigated by electron microscopy, these migrated structures did not resemble a hemicatenane. However, when Blm is together with Top3α, the dissolution reaction is processive with no pausing at a partially migrated structure. Potential mechanisms are discussed.


The herbal decoction modified Danggui Buxue Tang attenuates immune-mediated bone marrow failure by regulating the differentiation of T lymphocytes in an immune-induced aplastic anemia mouse model.
Angelicae Sinensis, Radix Astragali and Rhizoma Coptidis are all herbs of modified Danggui Buxue Tang (DGBX) and are extensively applied herbs in traditional Chinese medicine for the treatment of anemia and inflammation. In this study, immune-induced AA mice were used as an animal model, and the immunosuppressive agent, Ciclosporin A (CsA), was used as a positive control. Multiple pro-inflammatory cytokines were examined by bead-based multiplex flow cytometry. The T-cell subsets were assessed using a fluorescence-activated cell sorter (FACS). Western blot analysis was used to estimate the protein expression levels of specific transcription factors for T helper cells (Th1, Th2 and Th17) and key molecules of the Janus-activated kinase (Jak)/signal transducer and activator of transcription (Stat3) signaling pathway. DGBX treatment could significantly increase the production of whole blood cells in peripheral blood (PB); inhibit the expansion of Th1 and Th17 cells; increase the differentiation of Th2 and Tregs cells; regulate the expression levels of T-bet, GATA-3, RORγ and proinflammatory cytokines; and decrease the expression levels of key molecules in the Jak/Stat signaling pathway. These results indicate that DGBX can regulate the differentiation of T lymphocytes, resulting in immunosuppressive and hematogenic functions on AA mice. DGBX might be a good candidate for inclusion in a randomized study for AA with more data on the possible side effects and doses used in humans. Ultimately, it may be used for applications of traditional medicine against AA in modern complementary and alternative immunosuppressive therapeutics.


Characterization of a regulatory network of peptide antibiotic detoxification modules in Lactobacillus casei BL23.
Two-component systems (TCS) are major signal transduction pathways that allow bacteria to detect and respond to environmental and intracellular changes. A group of TCS has been shown to be involved in the response against antimicrobial peptides (AMPs). These TCS are characterized by the possession of intramembrane-sensing histidine kinases, and they are usually associated with ABC transporters of the peptide-7 exporter family (Pep7E). Lactobacillus casei BL23 encodes two TCS belonging to this group (TCS09 and TCS12) that are located next to two ABC transporters (ABC09 and ABC12), as well as a third Pep7E ABC transporter not genetically associated with any TCS (orphan ABC). This study addressed the involvement of modules TCS09/ABC09 and TCS12/ABC12 in AMP resistance. Results showed that both systems contribute to L. casei resistance to AMPs, and that each TCS constitutes a functional unit with its corresponding ABC transporter. Analysis of transcriptional levels showed that module 09 is required for the induction of ABC09 expression in response to nisin. In contrast, module 12 controls a wider regulon that encompasses the orphan ABC, the dlt operon (d-alanylation of teichoid acids), and the mprF gene (l-lysinylation of phospholipids), thereby controlling properties of the cell envelope. Furthermore, the characterization of a dltA mutant showed that Dlt plays a major role in AMP resistance in L. casei. This is the first report on the regulation of the response of L. casei to AMPs, giving insight into its ability to adapt to the challenging environments that it encounters as a probiotic microorganism.


[Carcinoid tumor of the duodenal papilla].
Carcinoid tumor of the duodenal papilla is very rare. The authors report the case of a 17 years old male with a carcinoid tumor at this site in whom a partial pancreatoduodenectomy was performed and who is well and asymptomatic 13 years after the surgical intervention. A review of literature of this unusual condition and a discussion about the treatment are presented.


Induction of reactive oxygen species-stimulated distinctive autophagy by chelerythrine in non-small cell lung cancer cells.
Chelerythrine (CHE), a natural benzo[c]phenanthridine alkaloid, shows anti-cancer effect through a number of mechanisms. Herein, the effect and mechanism of the CHE-induced autophagy, a type II programmed cell death, in non-small cell lung cancer (NSCLC) cells were studied for the first time. CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a concentration-dependent manner in NSCLC A549 and NCI-H1299 cells. In addition, CHE triggered the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II). The CHE-induced expression of LC3-II was further increased in the combination treatment with chloroquine (CQ), an autophagy inhibitor, and large amounts of red-puncta were observed in the CHE-treated A549 cells with stable expression of mRFP-EGFP-LC3, indicating that CHE induces autophagy flux. Silence of beclin 1 reversed the CHE-induced expression of LC3-II. Inhibition of autophagy remarkably reversed the CHE-induced cell viability decrease and apoptosis in NCI-H1299 cells but not in A549 cells. Furthermore, CHE triggered reactive oxygen species (ROS) generation in both cell lines. A decreased level of ROS through pretreatment with N-acetyl-L-cysteine reversed the CHE-induced cell viability decrease, apoptosis, and autophagy. Taken together, CHE induced distinctive autophagy in A549 (accompanied autophagy) and NCI-H1299 (pro-death autophagy) cells and a decreased level of ROS reversed the effect of CHE in NSCLC cells in terms of cell viability, apoptosis, and autophagy.


Predictive factors for deterioration from hydrocephalus after subarachnoid hemorrhage.
We studied the predictive factors for deterioration from hydrocephalus that developed during the first 28 days after admission in 660 patients following aneurysmal subarachnoid hemorrhage (SAH). Deterioration from hydrocephalus was defined as deterioration of consciousness with no detectable cause other than hydrocephalus confirmed by a repeat CT with a bicaudate index exceeding the 95th percentile for age. Deterioration from hydrocephalus occurred in 143 (22%) of the 660 patients. The variables included in the analysis were sex, age, loss of consciousness at ictus, sum score on the Glasgow Coma Scale on admission, sum score of cisternal blood and presence of ventricular blood on initial CT, hydrocephalus on initial CT, confirmed aneurysm, rebleeding, delayed cerebral ischemia, and treatment with tranexamic acid for 4 (short-term treatment) or 28 (long-term treatment) days. In a multivariate analysis with the Cox proportional hazards model incorporating fixed and time-dependent covariates, sum score of cisternal blood on initial CT (hazard ratio 3.15, p < 0.000001), presence of ventricular blood on initial CT (hazard ratio 1.66, p = 0.004), hydrocephalus on initial CT (hazard ratio 3.37, p < 0.000001), and long-term treatment with tranexamic acid (hazard ratio 2.40, p < 0.000001) were significantly related with the development of hydrocephalus. We conclude that a high amount of blood after SAH and delay of the resorption of cisternal and ventricular blood caused by long-term treatment with tranexamic acid increases the risk of deterioration from hydrocephalus after SAH.


E3 Ubiquitin Ligase Riplet Is Expressed in T Cells and Suppresses T Cell-Mediated Antitumor Immune Responses.
The E3 ubiquitin ligase Riplet mediates retinoic acid-inducible gene-I polyubiquitination and is essential for viral-induced expression of type I IFNs in dendritic cells and macrophages. The function of Riplet in innate immunity has been well demonstrated; however, its role in adaptive immunity during the antitumor immune response is unclear. In this study, we examined the role of Riplet in the T cell-mediated antitumor immune response. Riplet was expressed in T cells and upregulated in CD8+ T cells in response to TCR-mediated stimulation. Furthermore, PR domain containing 1, eomesodermin, and killer cell lectin-like receptor G1 expression was increased in effector CD8+ T cells by Riplet knockout in vitro, which suggests that Riplet is involved in the effector function of CD8+ T cells. Our results indicated that Riplet deficiency augmented the antitumor response of MO4 (OVA-expressing melanoma)-bearing mice treated with OVA peptide-pulsed dendritic cells. Moreover, both CD4+ and CD8+ T cells played important roles in Riplet-mediated augmentation of the antitumor immune response. In tumor-draining lymph nodes, the Th1 response was promoted, and the induction of OVA-specific CD8+ T cells and IFN-γ production were enhanced by Riplet deficiency. Furthermore, the IFN-γ response and OVA-specific cytotoxicity of CD8+ T cells in tumor tissue were augmented by Riplet deficiency. The expression of Cxcl9fluorescence-minus-one and Cxcl10 mRNA was also enhanced in the tumor microenvironment by Riplet knockout, consistent with the augmented recruitment of CTLs. Overall, we clarified a function of Riplet in T cells, which is to suppress the antitumor immune response through modulating Th1 and CTLs.


Arsenic and cadmium exposure in children living near a smelter complex in San Luis Potosí, Mexico.
The main purpose of this study was to assess environmental contamination by arsenic and cadmium in a smelter community (San Luis Potosí City, México) and its possible contribution to an increased body burden of these elements in children. Arsenic and cadmium were found in the environment (air, soil, and household dust, and tap water) as well as in the urine and hair from children. The study was undertaken in three zones: Morales, an urban area close to the smelter complex; Graciano, an urban area 7 km away from the complex; and Mexquitic, a small rural town 25 km away. The environmental study showed that Morales is the most contaminated of the zones studied. The range of arsenic levels in soil (117-1396 ppm), dust (515-2625 ppm), and air (0.13-1.45 micrograms/m3) in the exposed area (Morales) was higher than those in the control areas. Cadmium concentrations were also higher in Morales. Estimates of the arsenic ingestion rate in Morales (1.0-19.8 micrograms/kg/day) were equal to or higher than the reference dose of 1 microgram/kg/day calculated by the Environmental Protection Agency. The range of arsenic levels in urine (69-594 micrograms/g creatinine) and hair (1.4-57.3 micrograms/g) and that of cadmium in hair (0.25-3.5 micrograms/g) indicated that environmental exposure has resulted in an increased body burden of these elements in children, suggesting that children living in Morales are at high risk of suffering adverse health effects if exposure continues.


Surpassing the subitizing threshold: appetitive-aversive conditioning improves discrimination of numerosities in honeybees.
Animals including humans, fish and honeybees have demonstrated a quantity discrimination threshold at four objects, often known as subitizing elements. Discrimination between numerosities at or above the subitizing range is considered a complex capacity. In the current study, we trained and tested two groups of bees on their ability to differentiate between quantities (4 versus 5 through to 4 versus 8) when trained with different conditioning procedures. Bees trained with appetitive (reward) differential conditioning demonstrated no significant learning of this task, and limited discrimination above the subitizing range. In contrast, bees trained using appetitive-aversive (reward-aversion) differential conditioning demonstrated significant learning and subsequent discrimination of all tested comparisons from 4 versus 5 to 4 versus 8. Our results show conditioning procedure is vital to performance on numerically challenging tasks, and may inform future research on numerical abilities in other animals.


Tea pigments induce cell-cycle arrest and apoptosis in HepG2 cells.
To investigate the molecular mechanisms by which tea pigments exert preventive effects on liver carcinogenesis. HepG2 cells were seeded at a density of 5X10(5)/well in six-well culture dishes and incubated overnight. The cells then were treated with various concentrations of tea pigments over 3 d, harvested by trypsinization, and counted using a hemocytometer. Flow cytometric analysis was performed by a flow cytometer after propidium iodide labeling. Bcl-2 and p21(WAF1) proteins were determined by Western blotting. In addition, DNA laddering assay was performed on treated and untreated cultured HepG2 cells. Tea pigments inhibited the growth of HepG2 cells in a dose-dependent manner. Flow-cytometric analysis showed that tea pigments arrested cell cycle progression at G1 phase. DNA laddering was used to investigate apoptotic cell death, and the result showed that 100 mg/L of tea pigments caused typical DNA laddering. Our study also showed that tea pigments induced upregulation of p21(WAF1) protein and downregulation of Bcl-2 protein. Tea pigments induce cell-cycle arrest and apoptosis. Tea pigments may be used as an ideal chemopreventive agent.


Formal and informal support needs of young women with BRCA mutations.
This qualitative investigation aims to identify the salient support concerns of young women with BRCA mutations, a frequently understudied population with unique developmental, psychosocial, and family needs. Twenty-three unaffected BRCA gene alteration carriers aged 21 to 36 completed illness genograms and open-ended interviews. Transcripts were analyzed using the Listening Guide to highlight key themes, relationships, and meaning structures. Results reveal existing social support networks composed of family, partners, friends, and coworkers are often inadequate and formal services unavailable or underutilized. These findings suggest an important role for clinicians in reducing isolation, bolstering existing support networks, and designing innovative, targeted interventions that address the challenges specific to this age group. Interventions, such as the multifamily support group, should be integrated into genetic counseling protocols to mitigate the risk of distress.


A qualitative study on the intersectional social determinants for indigenous people who become infected with HIV in their youth.
Indigenous young people are currently highly overrepresented in the HIV epidemic in Canada, especially in the Prairie Provinces, such as Manitoba. Understanding HIV-vulnerability in Indigenous peoples must begin with understanding that social determinants are intersectional and linked to the historical legacy of European colonization. In this paper findings that detail the influence of the intersectional social determinants on Indigenous people who become infected with HIV in their youth are presented. The qualitative research design of phenomenology was used as it afforded the opportunity to understand Indigenous young people from their frames of reference and experiences of reality, resulting in a phenomenological understanding of their perspectives and experiences of the early years of living with HIV. A total of 21 Indigenous young people took part open-ended interviews. The stories that the Indigenous young people shared revealed their deeply interconnected social worlds, and how social determinants including abuse, trauma, being part of the child welfare system, and housing and food security were connected throughout various stages of their lives. Such stages included childhood, adolescence and young adulthood (the time of HIV infection), and later adulthood for older participants with the social determinants having multiple influences on their health trajectories. The findings highlight the need for policies and programs that are broadly focused, addressing multiple social determinants together. Overall, there needs to be more emphasis on the multiple social determinants in the life situations of all Indigenous youth. Reducing the health and social disparities in Indigenous youth is key to reducing the number of young Indigenous people diagnosed with HIV. The findings also shed light on the importance of listening to young Indigenous people who have experienced HIV diagnosis and life following diagnosis.


Migrants, workers and refugees: the political economy of population movements in the Middle East.
The author investigates causes and consequences of migratory movements in the Middle East. "Two factors--integration into the world labor market and the fragility of integration within the separate states--largely explain why conflicts in the Middle East have in recent years produced the greatest refugee flows of any region in the world.... The crisis of the secular nation-state in the Middle East will continue as states become either politically or economically more dependent on outside protection or assistance. The challenge by Islamist movements is also likely to undermine national cohesion by politicizing religious identity."


Protective effects of dexmedetomidine on cerebral ischemia/reperfusion injury via the microRNA-214/ROCK1/NF-κB axis.
Cerebral ischemia/reperfusion injury (CIRI) is a complication of surgical procedure associated with high mortality. The protective effect of dexmedetomidine (DEX) on CIRI has been explored in previous works, yet the underlying molecular mechanism remains unclear. Our study explored the protective effect of DEX and its regulatory mechanism on CIRI. A CIRI rat model was established using middle cerebral artery occlusion (MCAO). Neurological deficit scores for rats received MCAO modeling or DEX treatment were measured. Cerebral infarction area of rats was detected by TTC staining, while damage of neurons in hippocampal regions of rats was determined by hematoxylin-eosin (HE) staining. Apoptosis rate of neurons in hippocampal regions was examined by TUNEL staining. The dual-luciferase assay was performed to detect the binding of microRNA-214 (miR-214) to Rho-associated kinase 1 (ROCK1). DEX treatment significantly reduced infarction area of MCAO rats and elevated miR-214 expression. Injection of miR-214 inhibitor attenuated the effect of DEX in MCAO rats by increasing the area of cerebral infarction in rats and apoptosis rate of hippocampal neurons. ROCK1 was targeted and negatively regulated by miR-214. The overexpression of ROCK1 led to activation of NF-κB to aggravate CIRI. Therapeutic effects of DEX on CIRI was elicited by overexpressing miR-214 and impairing ROCK1 expression and NF-κB activation. Our finding might provide novel insights into the molecular mechanism of DEX in rats with CIRI.


Laparoscopic versus Open Surgery for Colorectal Cancer: A Retrospective Analysis of 163 Patients in a Single Institution.
Background. The present study aimed to compare the clinical outcomes of laparoscopic versus open surgery for colorectal cancers. Materials and Methods. The medical records from a total of 163 patients who underwent surgery for colorectal cancers were retrospectively analyzed. Patient's demographic data, operative details and postoperative early outcomes, outpatient follow-up, pathologic results, and stages of the cancer were reviewed from the database. Results. The patients who underwent laparoscopic surgery showed significant advantages due to the minimally invasive nature of the surgery compared with those who underwent open surgery, namely, less blood loss, faster postoperative recovery, and shorter postoperative hospital stay (P < 0.05). However, laparoscopic surgery for colorectal cancer resulted in a longer operative time compared with open surgery (P < 0.05). There were no statistically significant differences between groups for medical complications (P > 0.05). Open surgery resulted in more incisional infections and postoperative ileus compared with laparoscopic surgery (P < 0.05). There were no differences in the pathologic parameters between two groups (P < 0.05). Conclusions. These findings indicated that laparoscopic surgery for colorectal cancer had the clear advantages of a minimally invasive surgery and relative disadvantage with longer surgery time and exhibited similar pathologic parameters compared with open surgery.