Cutaneous vascular calcifications in patients with chronic kidney disease and calcific uremic arteriolopathy: a cross-sectional study.
Calcific uremic arteriolopathy is a life-threatening cutaneous condition in patients with chronic kidney disease. Often, clinical diagnosis is accompanied by histopathologic evaluations demonstrating vascular calcium deposits. We aimed to investigate the presence of cutaneous calcifications in non-lesional tissue in patients with chronic kidney disease, and the relation to systemic vascular calcification. We investigated the presence of cutaneous vascular calcifications in non-lesional skin biopsies from patients with current or previous calcific uremic arteriolopathy and patients with different stages of chronic kidney disease without calcific uremic arteriolopathy, and explored their association with vascular calcification in other vascular beds. Systemic vascular calcification was examined by mammography and lumbar X-ray. Thirty-nine adults were enrolled (current or previous calcific uremic arteriolopathy, n = 9; end-stage chronic kidney disease, n = 12; chronic kidney disease stage 3b-4, n = 12; healthy controls, n = 6). All calcific uremic arteriolopathy patients had end-stage kidney disease. Cutaneous vascular calcifications were not present in any of the non-lesional skin punch biopsies. Breast arterial calcification was demonstrated in patients with calcific uremic arteriolopathy (75%) and chronic kidney disease (end-stage 67% and stage 3b-4 25%, respectively), but in none of the controls. All chronic kidney disease patients had systemic calcification on lumbar X-ray (median score 21, 22, and 15 in patients with calcific uremic arteriolopathy, end-stage kidney disease and chronic kidney disease stage 3b-4). The serum calcification propensity was significantly different between groups. Despite a high burden of systemic vascular calcification, cutaneous calcium deposits in non-lesional tissue could not be demonstrated histopathologically in patients with chronic kidney disease (with or without current or previous calcific uremic arteriolopathy). Further studies to determine whether these findings are representative or attributed to other factors are warranted.


Hepatic damage exacerbates cisplatin-induced acute kidney injury in Sprague-Dawley rats.
The objective of this study was to elucidate the effect of hepatic damage on cisplatin (CDDP)-induced acute kidney injury (AKI). Thioacetamide (TAA, 150 mg/kg), a hepatotoxicant, was intraperitoneally (i.p.) injected to male Sprague-Dawley rats for 3 d prior to CDDP (5 mg/kg, i.p.) injection. All animals were sacrificed 5 d after CDDP treatment, and urine or blood was obtained to measure various parameters. No significant changes in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity were observed after CDDP treatment. However, pretreatment with TAA significantly elevated ALT and AST activity. Serum blood urea nitrogen and creatinine levels significantly increased in CDDP-treated group compared to control. In addition, urinary excretion of novel protein-based biomarkers such as neutrophil gelatinase-associated lipocalin, vascular endothelial growth factor, kidney injury molecule-1, and tissue inhibitor of metalloproteinase-1 rose markedly in the CDDP-treated group. In particular, pretreatment with TAA markedly elevated CDDP-induced urinary excretion of protein-based nephrotoxic biomarkers compared with CDDP alone. Hematoxylin and eosin staining demonstrated that pretreatment with TAA following CDDP injection led to more severe tubular damage and apoptosis in rats compared with CDDP alone. Antioxidant status was significantly reduced in kidneys following pretreatment with TAA prior to CDDP. These findings indicate that liver injury enhanced the vulnerability of kidney to CDDP-induced AKI and this phenomenon may be associated with severe apoptotic damage.


Recent advancements in the exploitation of the gut microbiome in the diagnosis and treatment of colorectal cancer.
Over the last few decades it has been established that the complex interaction between the host and the multitude of organisms that compose the intestinal microbiota plays an important role in human metabolic health and disease. Whilst there is no defined consensus on the composition of a healthy microbiome due to confounding factors such as ethnicity, geographical locations, age and sex, there are undoubtably populations of microbes that are consistently dysregulated in gut diseases including colorectal cancer (CRC). In this review, we discuss the most recent advances in the application of the gut microbiota, not just bacteria, and derived microbial compounds in the diagnosis of CRC and the potential to exploit microbes as novel agents in the management and treatment of CRC. We highlight examples of the microbiota, and their derivatives, that have the potential to become standalone diagnostic tools or be used in combination with current screening techniques to improve sensitivity and specificity for earlier CRC diagnoses and provide a perspective on their potential as biotherapeutics with translatability to clinical trials.


Sex differences in the use of implantable cardioverter-defibrillators for primary and secondary prevention of sudden cardiac death.
Previous studies of sex differences in the use of implantable cardioverter-defibrillators (ICDs) predate recent expansions in Medicare coverage and did not provide patient follow-up over multiple years. To examine sex differences in ICD use for primary and secondary prevention of sudden cardiac death. Analysis of a 5% national sample of research-identifiable files obtained from the US Centers for Medicare & Medicaid Services for the period 1991 through 2005. Patients were those aged 65 years or older with Medicare fee-for-service coverage and diagnosed with acute myocardial infarction and either heart failure or cardiomyopathy but no prior cardiac arrest or ventricular tachycardia (ie, the primary prevention cohort [n = 65,917 men and 70,504 women]), or with cardiac arrest or ventricular tachycardia (ie, the secondary prevention cohort [n = 52,252 men and 47,411 women]), from 1999 through 2005. Receipt of ICD therapy and all-cause mortality at 1 year. In the 2005 primary prevention cohort, 32.3 per 1000 men and 8.6 per 1000 women received ICD therapy within 1 year of cohort entry. In multivariate analyses, men were more likely than women to receive ICD therapy (hazard ratio [HR], 3.15; 95% confidence interval [CI], 2.86-3.47). Among men and women alive at 180 days after cohort entry, the hazard of mortality in the subsequent year was not significantly lower among those who received ICD therapy (HR, 1.01; 95% CI, 0.82-1.23). In the 2005 secondary prevention cohort, 102.2 per 1000 men and 38.4 per 1000 women received ICD therapy. Controlling for demographic variables and comorbid conditions, men were more likely than women to receive ICD therapy (HR, 2.44; 95% CI, 2.30-2.59). Among men and women alive at 30 days after cohort entry, the hazard of mortality in the subsequent year was significantly lower among those who received ICD therapy (HR, 0.65; 95% CI, 0.60-0.71). In the Medicare population, women are significantly less likely than men to receive ICD therapy for primary or secondary prevention of sudden cardiac death.


Serum adiponectin predicts fracture risk in individuals with type 2 diabetes: the Fukuoka Diabetes Registry.
Serum adiponectin has been reported to impact upon fracture risk in the general population. Although type 2 diabetes is associated with increased fracture risk, it is unclear whether serum adiponectin predicts fractures in individuals with type 2 diabetes. The aim of the study was to prospectively investigate the relationship between serum adiponectin and fracture risk in individuals with type 2 diabetes. In this study, data was obtained from The Fukuoka Diabetes Registry, a multicentre prospective study designed to investigate the influence of modern treatments on the prognoses of patients with diabetes mellitus. We followed 4869 participants with type 2 diabetes (mean age, 65 years), including 1951 postmenopausal women (defined as self-reported amenorrhea for >1 year) and 2754 men, for a median of 5.3 years. The primary outcomes were fractures at any site and major osteoporotic fractures (MOFs). During the follow-up period, fractures at any site occurred in 682 participants, while MOFs occurred in 277 participants. Age-adjusted HRs (95% CIs) of any fracture and MOFs for 1 SD increment in log e -transformed serum adiponectin were 1.27 (1.15, 1.40) and 1.35 (1.17, 1.55) in postmenopausal women and 1.22 (1.08, 1.38) and 1.40 (1.15, 1.71) in men, respectively. HRs (95% CIs) of MOFs for hyperadiponectinaemia (≥ 20 μg/ml) were 1.72 (1.19, 2.50) in postmenopausal women and 2.19 (1.23, 3.90) in men. The per cent attributable risk of hyperadiponectinaemia for MOFs was as high as being age ≥70 years or female sex. Higher serum adiponectin levels were significantly associated with an increased risk of fractures at any site and with an increased risk of MOFs in individuals with type 2 diabetes, including postmenopausal women.


Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey.
There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.


Relationship quality in higher education and the interplay with student engagement and loyalty.
To date, studies that have investigated the bonds between students and their institution have emphasized the importance of student-staff relationships. Measuring the quality of those relationships (i.e., relationship quality) appears to help with investigating the relational ties students have with their higher education institutions. Growing interest has arisen in further investigating relationship quality in higher education, as it might predict students' involvement with the institution (e.g., student engagement and student loyalty). So far, most studies have used a cross-sectional design, so that causality could not be determined. The aim of this longitudinal study was twofold. First, we investigated the temporal ordering of the relation between the relationship quality dimensions of trust (in benevolence and honesty) and affect (satisfaction, affective commitment, and affective conflict). Second, we examined the ordering of the paths between relationship quality, student engagement, and student loyalty. Our objectives were to gain a deeper understanding of the relationship quality construct in higher education and its later outcomes. Participants (N = 1649) were students from three Dutch higher education institutions who were studying in a technology economics or social sciences program. Longitudinal data from two time points were used to evaluate two types of cross-lagged panel models. In the first analysis, we could not assume measurement invariance for affective conflict over time. Therefore, we tested an alternative model without affective conflict, using the latent variables of trust and affect, the student engagement dimensions and student loyalty. In the second type of model, we investigated the manifest variables of relationship quality, student engagement, and student loyalty. The hypotheses were tested by evaluating simultaneous comparisons between estimates. Results indicated that the relation between relationship quality at Time 1 with student engagement and loyalty at Time 2 was stronger than the reverse ordering in the first model. In the second model, results indicated that cross-lagged relations between trust in benevolence and trust in honesty at Time 1 and affective commitment, affective conflict, and satisfaction at Time 2 were more likely than the reverse ordering. Furthermore, cross-lagged relations from relationship quality at Time 1 to student engagement and student loyalty at Time 2 also supported our hypothesis. This study contributes to the existing higher education literature, indicating that students' trust in the quality of their relationship with faculty/staff is essential for developing students' affective commitment and satisfaction and for avoiding conflict over time. Second, relationship quality factors positively influence students' engagement in their studies and their loyalty towards the institution. A relational approach to establishing (long-lasting) bonds with students appears to be fruitful as an approach for educational psychologists and for practitioners' guidance and strategies. Recommendations are made for future research to further examine relationship quality in higher education in Europe and beyond.


Mitochondrial Homeostasis and Signaling in Parkinson's Disease.
The loss of dopaminergic (DA) neurons in the substantia nigra leads to a progressive, long-term decline of movement and other non-motor deficits. The symptoms of Parkinson's disease (PD) often appear later in the course of the disease, when most of the functional dopaminergic neurons have been lost. The late onset of the disease, the severity of the illness, and its impact on the global health system demand earlier diagnosis and better targeted therapy. PD etiology and pathogenesis are largely unknown. There are mutations in genes that have been linked to PD and, from these complex phenotypes, mitochondrial dysfunction emerged as central in the pathogenesis and evolution of PD. In fact, several PD-associated genes negatively impact on mitochondria physiology, supporting the notion that dysregulation of mitochondrial signaling and homeostasis is pathogenically relevant. Derangement of mitochondrial homeostatic controls can lead to oxidative stress and neuronal cell death. Restoring deranged signaling cascades to and from mitochondria in PD neurons may then represent a viable opportunity to reset energy metabolism and delay the death of dopaminergic neurons. Here, we will highlight the relevance of dysfunctional mitochondrial homeostasis and signaling in PD, the molecular mechanisms involved, and potential therapeutic approaches to restore mitochondrial activities in damaged neurons.


Robust H infinity synchronization of chaotic Lur'e systems.
This paper is concerned with the robust H(infinity) synchronization problem for a class of chaotic Lur'e systems based on delayed feedback control. The master system is assumed to be subject to an energy bounded input noise. By employing an integral inequality, a delay-dependent condition is obtained under which the chaotic master and slave systems are robustly synchronized with a guaranteed H(infinity) performance. The design of a desired delayed feedback controller can be achieved by solving a linear matrix inequality, and the H(infinity) performance index can be optimized via a convex optimization algorithm. Chua's circuit is used as an example to demonstrate the effectiveness of the developed approach and the improvement over some existing results.


Accuracy in workload measurement: a fact or fallacy?
As the drive within a market-led National Health Service is towards cost-efficiency and through-put, nurses are now more than ever having to 'prove their worth'. This has led to various workload measurement systems being used throughout nursing. Before examining the accuracy of these measurement tools this paper attempts to define workload and investigates how measurement is limited by an unclear definition of what 'nursing' actually is. There is little argument as to some of the beneficial effects of monitoring workload where changes in practice, rostering, skill mix and establishments have occurred. It is, however, necessary to examine the accuracy of workload measurement within the current framework of nursing to see if it is the promised panacea. The issues surrounding patient dependency and professional judgement are discussed and the seeming unacceptability of such 'soft data' to non-nursing personnel. Both the 'bottom-up' and 'top-down' approaches of workload measurement are explored within the context of equity, neutrality and bias. The conclusion is drawn that accuracy in nursing workload measurement is not possible in the current economic climate and that a compromise solution that uses patient dependency as an assessment tool is the best that can be hoped for without limiting nursing to inflexible and restrictive practices.


Teaching psychological processes and psychotherapy to medical students.
Psychiatrists are in a key position to teach medical students about psychotherapy. Whilst at first it may appear a formidable task, it need not be so. It should however, have applicability to the bulk of students, who will not go on to psychiatry training. We outline some potentially useful strategies to help clinicians teach aspects of psychotherapy to students: making it easy and relevant, illustrating the broad applications of psychological concepts, introducing cultural references, as well as appreciating that assessment can drive learning.


Effect of Dietary Minerals on Virulence Attributes of Vibrio cholerae.
Vibrio cholerae is a water-borne pathogen responsible for causing a toxin-mediated profuse diarrhea in humans, leading to severe dehydration and death in unattended patients. With increasing reports of antibiotic resistance in V. cholerae, there is a need for alternate interventional strategies for controlling cholera. A potential new strategy for treating infectious diseases involves targeting bacterial virulence rather than growth, where a pathogen's specific mechanisms critical for causing infection in hosts are inhibited. Since bacterial motility, intestinal colonization and cholera toxin are critical components in V. cholerae pathogenesis, attenuating these virulence factors could potentially control cholera in humans. In this study, the efficacy of sub-inhibitory concentration (SIC, highest concentration not inhibiting bacterial growth) of essential minerals, zinc (Zn), selenium (Se), and manganese (Mn) in reducing V. cholerae motility and adhesion to intestinal epithelial cells (Caco-2), cholera toxin production, and toxin binding to the ganglioside receptor (GM1) was investigated. Additionally, V. cholerae attachment and toxin production in an ex vivo mouse intestine model was determined. Further, the effect of Zn, Se and Mn on V. cholerae virulence genes, ctxAB (toxin production), fliA (motility), tcpA (intestinal colonization), and toxR (master regulon) was determined using real-time quantitative PCR. All three minerals significantly reduced V. cholerae motility, adhesion to Caco-2 cells, and cholera toxin production in vitro, and decreased adhesion and toxin production in mouse intestine ex vivo (P < 0.05). In addition, Zn, Se, and Mn down-regulated the transcription of virulence genes, ctxAB, fliA, and toxR. Results suggest that Zn, Se, and Mn could be potentially used to reduce V. cholerae virulence. However, in vivo studies in an animal model are necessary to validate these results.


Viscoelastic polymer flows and elastic turbulence in three-dimensional porous structures.
Viscoelastic polymer solutions flowing through reservoir rocks have been found to improve oil displacement efficiency when the aqueous-phase shear-rate exceeds a critical value. A possible mechanism for this enhanced recovery is elastic turbulence that causes breakup and mobilization of trapped oil ganglia. Here, we apply nuclear magnetic resonance (NMR) pulsed field gradient (PFG) diffusion measurements in a novel way to detect increased motion of disconnected oil ganglia. The data are acquired directly from a three-dimensional (3D) opaque porous structure (sandstone) when viscoelastic fluctuations are expected to be present in the continuous phase. The measured increase in motion of trapped ganglia provides unequivocal evidence of fluctuations in the flowing phase in a fully complex 3D system. This work provides direct evidence of elastic turbulence in a realistic reservoir rock - a measurement that cannot be readily achieved by conventional laboratory methods. We support the NMR data with optical microscopy studies of fluctuating ganglia in simple two-dimensional (2D) microfluidic networks, with consistent apparent rheological behaviour of the aqueous phase, to provide conclusive evidence of elastic turbulence in the 3D structure and hence validate the proposed flow-fluctuation mechanism for enhanced oil recovery.


Identification and Synthesis of Mycalol Analogues with Improved Potency against Anaplastic Thyroid Carcinoma Cell Lines.
The marine metabolite mycalol (1) has a specific inhibitory activity on cells of anaplastic thyroid carcinoma (ATC), a very aggressive and rare cancer that does not have effective conventional therapy. In this study, we describe six new related analogues (2-7) that differ in the length of the terminal alkyl residue and the presence of acetate or 3S-hydroxybutyrate (3S)-3HB as a substituent at C-19. Despite the structural analogies, some of the new members were significantly more cytotoxic than 1 on cell lines derived from human ATC. Structures inclusive of the 2'R,3R,4S,7R,8S,19R absolute configuration were assigned to 2-7 on the basis of detailed spectroscopic analysis, synthesis of different isomers, and application of ECD and Mosher's methods. This work led to the identification of mycalol-578 (3) as the most potent analogue, with an IC50 of 2.3 μM on FRO cells.


The acute pivot shift: clinical correlation.
The pivot shift test and its various modifications has been well described for evaluation of chronic anterolateral rotatory insufficiency of the knee. Fifty knees with acute traumatic hemarthrosis were examined under general anesthesia to assess the reliability of the pivot shift in the acute injury. The pivot shift test as described by Galway and MacIntosh was employed. No patients with a history of previous knee injuries were included. Arthrotomy or arthroscopy was performed following the examination in all cases. There were 38 knees with positive shifts, 35 with complete anterior cruciate tears, and 3 with significant partial tears or attenuation of the ligament. The 12 knees with negative shift demonstrated five normal anterior cruciates, five partial tears and two complete tears of the anterior cruciate. Both of the complete tears were associated with complete medial collateral ligament tears and were clinically apparent by drawer and Lachman tests. A positive pivot shift in this study was very accurate for significant anterior cruciate tears. A negative pivot shift ruled out complete anterior cruciate ligament tears but did not preclude the presence of a partial tear. Partial tears associated with a negative pivot shift retained ligament competence. We conclude that: (1) the pivot shift is a direct test of cruciate competence; (2) the pivot shift is present acutely in a very high percentage of cases and does not necessarily develop over time; (3) the pivot shift exam performed under general anesthesia is a very reliable test for significant tears of the anterior cruciate; and (4) the arthroscope remains a useful tool in the evaluation of acute traumatic hemarthrosis, but is not always necessary in establishing competence of the anterior cruciate ligament.


The influence of demographic and phenotypic heterogeneity on the prevalence of gestational diabetes mellitus.
In order to explore the influence of demographic and phenotypic characteristics on the prevalence of gestational diabetes mellitus (GDM), data were analyzed from 3744 consecutive patients who underwent universal screening with a 50 g glucose load at 24-28 weeks gestational age. Those with a 1-h plasma glucose greater than or equal to 130 mg/dl underwent a 3-h, 100-g oral glucose tolerance test following dietary preparation. The population was 39.1% White, 37.7% Black, 19.8% Hispanic and 3.4% Oriental/other. The overall prevalence of GDM was 3.5 cases/100. Significant inter-racial differences in maternal age and prepregnant percent ideal body weight (PIBW) were observed, with White patients being older and leaner than Blacks and Hispanics. By multiple logistic regression, Black and Hispanic race, maternal age and PIBW were found to have significant independent effects on the prevalence of GDM. Controlling for age and PIBW, the adjusted relative risk of GDM was significantly higher in Black (1.81, 95% CI 1.13-2.89) and Hispanic (2.45, 95% CI 1.48-4.04) patients compared to White. We conclude that demographic and phenotypic characteristics of populations need to be taken into consideration in future studies of prevalence of GDM, perinatal implications and therapeutic approaches to the disease.


[Prophylaxis and therapy for hip dislocations in patients with infantile cerebral palsy (ICP): motor functional, radiological and clinical results after subcutaneous adductor tenotomy].
The current study assessed the clinical and radiological outcome and motor function improvement after subcutaneous adductor tenotomy in children with cerebral palsy (ICP). It was also analysed if groups with different preoperative hip functions and radiological hip migrations differed in their final clinical, radiological and motor function outcome. A prospective study of 91 children with infantile cerebral palsy (ICP, mean age 4.9 years, range: 1.1 - 15.8) with 141 hip dislocations or subluxations analysed preoperatively the hip abduction and radiologically the migration percentage (MP). Depending on the preoperative status, all patients were grouped into 3 abduction and 3 MP groups. Additionally, the motor function was classified according to the Rancho los Amigos scale. A subcutaneous adductor tenotomy was performed mono- or bilaterally and all patients were treated for 4 - 6 weeks with a hip abduction splint. Patients were assessed annually for 4 years; clinical and radiological results and the motor function were analysed according to their preoperative status. The mean hip abduction was preoperatively 30.3 +/- 1.2 degrees and was significantly improved to 50.3 +/- 1.3 degrees 1 year and to 43.3 +/- 2.2 degrees 4 years post surgery. The preoperative mean MP was preoperatively 42.3 +/- 1.3 % and was significantly improved to 34.6 % 1 year and to 31.9 % 4 years post surgery. After 4 years, 41 % had undergone a motor function improvement and 52 % no change in motor function. After 4 years, patients with a hip abduction <or= 20 degrees showed the most improvement; other abduction groups also improved significantly but to a lesser extent. The 4-year MP was significantly and to a relatively large extent improved in the groups with a preoperative MP between 25 % and 50 % and above 50 %. With a preoperative MP <or= 25 %, there was a significant but only slight improvement. The motor function was improved when the preoperative hip abduction was most restricted and the preoperative MP was high. CONCLUSION The subcutaneous adductor tenotomy in hip dislocation and subluxation of children with cerebral palsy is a safe procedure that can treat and prevent hip dislocation/subluxation in 76 % of the cases. In appropriately selected patients, the number of individuals that are "freely walking" and "walking with aid" can be doubled. MP and hip abduction are both predictors of therapy outcome.


A Study of Dyslipidemia and Its Clinical Implications in Childhood Nephrotic Syndrome.
Nephrotic syndrome in children is characterized by dyslipidemia, which is an indirect risk factor for cardiovascular diseases, progressive glomerulosclerosis, and related complications. The objective is to determine the range of lipid profile abnormalities in relation to onset, relapse, and remission, as well as to determine if there is any relationship between dyslipidemia and the frequency of relapses. One hundred and two diagnosed cases of nephrotic syndrome in the age group of less than 12 years were included, out of which 64 patients belonged to the first episode of nephrotic syndrome and 38 patients were relapse cases. Steroid-resistant nephrotic syndrome cases or patients with a history of diabetes mellitus, hypothyroidism, familial hypercholesterolemia, children with chronic kidney disease, and edema due to other causes were excluded from the study. There was a statistically significant increase in lipid parameters except for high-density lipoprotein (HDL) cholesterol at the disease onset when compared to remission in cases of the first episode as well as relapse cases of nephrotic syndrome. There was a positive correlation between relapse frequency and dyslipidemia. Dyslipidaemia was also associated with low serum albumin, with a p-value <0.001, which is statistically significant. Dyslipidemia is significantly higher in relapse cases of nephrotic syndrome and remains higher even during remission. Dyslipidemia is a directly associated risk factor for atherosclerosis and coronary heart disease (CAD), along with progressive glomerulosclerosis. Early identification and treatment of hyperlipidemia is therefore justified so that along with longevity, we can also improve the quality of life of children suffering from nephrotic syndrome.


Aspergillus fumigatus MADS-Box Transcription Factor rlmA Is Required for Regulation of the Cell Wall Integrity and Virulence.
The Cell Wall Integrity (CWI) pathway is the primary signaling cascade that controls the de novo synthesis of the fungal cell wall, and in Saccharomyces cerevisiae this event is highly dependent on the RLM1 transcription factor. Here, we investigated the function of RlmA in the fungal pathogen Aspergillus fumigatus We show that the ΔrlmA strain exhibits an altered cell wall organization in addition to defects related to vegetative growth and tolerance to cell wall-perturbing agents. A genetic analysis indicated that rlmA is positioned downstream of the pkcA and mpkA genes in the CWI pathway. As a consequence, rlmA loss-of-function leads to the altered expression of genes encoding cell wall-related proteins. RlmA positively regulates the phosphorylation of MpkA and is induced at both protein and transcriptional levels during cell wall stress. The rlmA was also involved in tolerance to oxidative damage and transcriptional regulation of genes related to oxidative stress adaptation. Moreover, the ΔrlmA strain had attenuated virulence in a neutropenic murine model of invasive pulmonary aspergillosis. Our results suggest that RlmA functions as a transcription factor in the A. fumigatus CWI pathway, acting downstream of PkcA-MpkA signaling and contributing to the virulence of this fungus.


Language from police body camera footage shows racial disparities in officer respect.
Using footage from body-worn cameras, we analyze the respectfulness of police officer language toward white and black community members during routine traffic stops. We develop computational linguistic methods that extract levels of respect automatically from transcripts, informed by a thin-slicing study of participant ratings of officer utterances. We find that officers speak with consistently less respect toward black versus white community members, even after controlling for the race of the officer, the severity of the infraction, the location of the stop, and the outcome of the stop. Such disparities in common, everyday interactions between police and the communities they serve have important implications for procedural justice and the building of police-community trust.


Synthesis of a Glycosylphosphatidylinositol Anchor Derived from Leishmania donovani That Can Be Functionalized by Cu-Catalyzed Azide-Alkyne Cycloadditions.
A flexible assembly strategy has been developed for the synthesis of Leishmania donovani GPI anchors that bear a clickable alkyne tag. This strategy is based on the use of the 2-naphthylmethyl (Nap) ethers and levulinoyl (Lev) ester for permanent protection of hydroxyls. Removal of seven Nap ethers by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone made it possible to prepare GPIs having an alkyne functionality that could be modified by Cu(I)-catalyzed [3 + 2] cycloadditions to install tags for imaging studies.


Preparation of a hydrophobic polythiophene film to improve protein adsorption and proliferation of PC 12 cells.
High quality films of polythiophene with different alkyl side chains were successfully synthesized by a novel method in the presence of sodium dodecylbenzenesulonate (SDBS) under N2 atmosphere on the PTFE (polytetrafluorethylene) substrate. The as-prepared films were characterized by scanning electron microscopy (SEM), conductivity measurement, and water contact angle measurement. The morphologies of the films were homogeneous with micro-/nanostructures, and their conductivities were high enough for biomedical applications. Hydrophobicity of the films could be adjusted easily by inducing alkyl side chains with different length, which could control protein adsorption in succession. Hydrophobic polythiophene film with a long alkyl side chain had a higher ability of protein adsorption and PC 12 cell proliferation. The biocompatibility study of the synthesized films in vitro proved that the synthesized films were not cytotoxic to two cell lines used and could support cell attachment and proliferation well. Polythiophenes films prepared by in-situ deposition will be good candidates for biomedical applications.


Methylation alterations of the MyoD1 upstream region are predictive of subclassification of human rhabdomyosarcomas.
MyoD1 expression is a distinguishing characteristic of rhabdomyosarcoma. In this study, distinct methylation alterations were identified in the 5' flanking region of the MyoD1 gene from the two major subtypes, ie, alveolar and embryonal rhabdomyosarcoma. The MyoD1 methylation patterns of 26 rhabdomyosarcomas were compared with that of normal skeletal muscle and nonmuscle specimens by Southern blot analysis using methylation-sensitive restriction enzymes HhaI and HpaII. A 5-kb region immediately upstream of the MyoD1 coding sequence was found to be methylated in adult muscle and all nonmuscle tissues tested. The MyoD1 upstream region was unmethylated in the majority of the alveolar rhabdomyosarcomas (13 of 15, 87%) examined in this study. In contrast, 10 of 11 (91%) embryonal rhabdomyosarcomas showed a methylation pattern that was also observed in fetal muscle cells, in which the CpG sites in the MyoD1 upstream region were partially methylated. Our data suggest that the methylation status of the MyoD1 upstream CpG sites may be related to rhabdomyosarcoma tumorigenesis and may have valuable implications for its differential diagnosis.


Statistical reliability of a relative standard deviation of chromatographic peak area estimated by a chemometric tool based on the FUMI theory.
In pharmaceutical analysis using a high-performance liquid chromatography (HPLC) system, repeatability assessment is significant to obtain reliable and precise quantitative results. The purpose of the present study is to experimentally show the statistical reliability of a relative standard deviation (RSD) of peak area estimated by a chemometric tool based on probability theory, called the function of mutual information (FUMI) theory, which stochastically provided an RSD of peak area and SD of baseline areas with width k (s(k)) from noises and a signal on a single chromatogram. An ultra-high-performance liquid chromatography with ultraviolet detection (UHPLC-UV) for determining ergosterol was applied as an example of the repeatability assessment. In addition, the statistical reliability of an RSD of peak area in the UHPLC-UV system was certified according to a chi-square (χ2) distribution. The 712 values of s(k) were experimentally obtained from a data series of 1001 points in the noise regions of 712 chromatograms. The histogram of χ2 of s(k) was well-fitted to the χ2 distribution curve (freedom degree, ν = 50), indicating that the statistical reliability of an RSD of the peak area in the UHPLC-UV estimated by the FUMI theory (n = 1) was equivalent to that estimated by 50 runs of chromatographic measurements.


Selenium in foods: evaluation of atomic absorption spectrometric techniques involving hydrogen selenide generation and carbon furnace atomization.
The performance of hydrogen selenide generation- and carbon furnace atomization-atomic absorption spectrometry, with a semiautomated trace metal accessory and a carbon rod atomizer, respectively, was evaluated for the determination of selenium in foods. Samples were digested with nitric, perchloric, and sulfuric acids for both procedures. Hydrogen selenide was generated with stannous chloride/potassium iodide/zinc from 20 ml aliquots in a hydrochloric-sulfuric acid medium and directed into an argon-hydrogen-entrained air flame. Sample matrix interferences in the carbon furnace technique were minimized by isolating selenium by precipitation with ascorbic acid and redissolution in nitric-perchloric acid prior to taking 5 mul aliquots for estimation; precision was significantly improved by incorporating 5000 mug nickel/ml into analytical solutions. For the hydrogen selenide and carbon furnace techniques, respectively, the following data were obtained for untreated standard solutions: sensitivity, 0.13 and 10.0 ng/ml; absolute sensitivity, 2.6 and 0.05 ng; detection limit, 0.4 and 90 ng/ml; absolute detection limit, 7 and 0.45 ng. The detection limit and absolute detection limit for samples were 2.5 ng/ml and 50 ng, respectively, for the hydrogen selenide method, and 25 ng/ml and 0.13 ng, respectively, for the carbon furnace method. Taking into consideration these figures and the practical aspects of both methods, the overall performance of the hydrogen selenide method was superior.


Autographa californica multiple nucleopolyhedrovirus nucleocapsid assembly is interrupted upon deletion of the 38K gene.
38K (ac98) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is a highly conserved baculovirus gene whose function is unknown. To determine the role of 38K in the baculovirus life cycle, a 38K knockout bacmid containing the AcMNPV genome was generated through homologous recombination in Escherichia coli. Furthermore, a 38K repair bacmid was constructed by transposing the 38K open reading frame with its native promoter region into the polyhedrin locus of the 38K knockout bacmid. After transfection of these viruses into Spodoptera frugiperda cells, the 38K knockout bacmid led to a defect in production of infectious budded virus, while the 38K repair bacmid rescued this defect, allowing budded-virus titers to reach wild-type levels. Slot blot analysis indicated that 38K deletion did not affect the levels of viral DNA replication. Subsequent immunoelectron-microscopic analysis revealed that masses of electron-lucent tubular structures containing the capsid protein VP39 were present in cells transfected with 38K knockout bacmids, suggesting that nucleocapsid assembly was interrupted. In contrast, the production of normal nucleocapsids was restored when the 38K knockout bacmid was rescued with a copy of 38K. Recombinant virus that expresses 38K fused to green fluorescent protein as a visual marker was constructed to monitor protein transport and localization within the nucleus during infection. Fluorescence was first detected along the cytoplasmic periphery of the nucleus and subsequently localized to the center of the nucleus. These results demonstrate that 38K plays a role in nucleocapsid assembly and is essential for viral replication in the AcMNPV life cycle.


The effect of cisplatin-based neoadjuvant chemotherapy on the renal function of patients undergoing radical cystectomy.
Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both. We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context. We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m2) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m2). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m2), and the proportion of those with stage ≥3 CKD increased from 37% to 51%. Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.


Recurrent wheezing, allergic rhinitis, and maternal asthma as predictors of asthma in children.
Background: Early prediction of asthma is crucial for asthma prevention. Objective: We estimated the odds ratio (OR) of recurrent wheezing during the first 3 years of life, atopic rhinitis, and maternal asthma for asthma in school-age children (ages ≥ 6 years). Methods: This case-control study was conducted in Salvador, Brazil. Medical records of children diagnosed with asthma (cases) and of children screened for pulmonary illnesses and without asthma (controls) were reviewed. Information was retrieved and registered in standardized forms. Results: We included 125 subjects (cases) and 375 controls, whose median (percentile 25th-percentile 75th) age was 8.1 years (6.6-10.0 years) and 9.2 years (7.0-11.9 years), respectively. The subjects (cases) and the controls had at least three episodes of wheezing during the first 3 years of life (69.7% and 1.4%, respectively), a maternal history of asthma (36.0% and 4.0%, respectively), and atopic rhinitis (95.9% and 35.1%, respectively). The adjusted OR of three or more episodes of wheezing during the first 3 years of life was OR 132.5 (95% confidence interval [CI], 36.8-477.1), of a personal history of atopic rhinitis was OR 21.3 (95% CI, 5.3-85.0), and of maternal asthma was OR 10.2 (95% CI, 3.1-33.6) for asthma in a logistic regression (which also included age, gender, and maternal history of allergic rhinitis [OR insignificant for these factors]). Conclusion: Children with a history of three or more episodes of wheezing during the first 3 years of life were at least 37 times more likely to develop asthma than children without this history. A maternal history of asthma and a personal history of atopic rhinitis are also predictors of asthma in children.


Schistosomus Reflexus Syndrome in Olive Ridley Sea Turtles ( Lepidochelys olivacea).
The olive ridley sea turtle ( Lepidochelys olivacea), considered the most abundant sea turtle species, is listed as vulnerable on the International Union for Conservation of Nature Red List. The most important nesting areas are located in the Eastern Pacific, and congenital malformations have been previously reported in this species. The present study was conducted in a single population at El Verde beach, one of the most important nesting beaches for the species in the northwestern Mexican Pacific. The study was based on embryos that had been incubated in a controlled environment. Schistosomus reflexus syndrome (SRS) was observed in 124 of 20 257 olive ridley embryos (0.6%), comprising 124 of 400 (31%) cases of congenital malformations over a 7-month period. Affected embryos had malformations of the carapace, bridge, or plastron, resulting in exposure of the abdominal or thoracic viscera, as well as spinal malformation and abnormal positioning of limbs adjacent to the head with subsequent ankylosis. SRS phenotypes (although lethal) varied from mild to severe, although most cases were severe. SRS was mostly associated with congenital malformations in the neck (short neck, 80%), tail (anury, 38%), and flippers (different types of dysmelias, 53%). In most cases of severe SRS, ankyloses were present. Documenting these findings could be important to identify the cause of the developmental defects, and identification of the cause of the defects may be of significance to the population and to our efforts to manage this and other populations at risk.


Endogenous stages of Eimeria tuskegeensis (Protozoa: Eimeriidae) in the cotton rat, Sigmodon hispidus.
Endogenous stages of Eimeria tuskegeensis were studied in experimentally infected cotton rats, Sigmodon hispidus. Almost all parasites were located on the basilar side of the nucleus in epithelial cells on the sides and tips of villi of the small intestine. The endogenous cycle consisted of three generations of schizogony followed by gametogony. First-, second-, third-generation schizonts could be distinguished by time of appearance, size and shape of the schizont, and number, size, shape, and arrangement of merozoites. Immature gametogonous stages appeared to 84 hr postinoculation (PI) and developed into mature microgametocytes and macrogametes by 96 hr PI. Microgametocytes had a mono-centric type of development. Intermediate macrogametes had small, basophilic wall-forming bodies and mature macrogametes had large, eosinophilic wall-forming bodies. It was not possible to determine whether these were two distinct types of wall-forming bodies or whether they were different stages of a single type. Two nuclei were seen in the host's epithelial cells parasitized by schizonts, microgematocytes, macrogametes, and oocysts. This binucleate condition was apparently parasite-induced.


[Inhibition of telomerase with hTERT antisense enhances TNF-alpha-induced apoptosis in prostate cancer cells PC3].
To investigate the inhibiting effect of telomerase with hTERT antisense on TNF-alpha-induced apoptosis in prostate cancer cells PC3. Antisense phosphorothioate oligodeoxynucleotide (AS PS-ODN) was synthesized and purified. Telomerase activity was measured by telomeric repeat amplification protocol (TRAP) and telomerase PCR-ELISA Kit, cell viability was determined by MTT assay, and cell apoptosis was observed by morphological method and determined by flow cytometry. AS PS-ODN could significantly inhibit the telomerase activity and increase the susceptibility of TNF-alpha-induced apoptosis of PC3 cells. Inhibition of telomerase with hTERT antisense can enhance TNF-alpha-induced apoptosis in prostate cancer cells.


The effects of Phyllanthus niruri aqueous extract on the activation of murine lymphocytes and bone marrow-derived macrophages.
Phyllanthus niruri L. (Euphorbiaceae) is acclaimed world-wide for its versatile ethnomedicinal uses. It features in recipes used by some herbalists to manage different diseases, including claims of efficacy against many life-threatening infections, such as HIV/AIDS and hepatitis. In order to understand the mechanisms and the involvement of the immune system in mediating these activities, the effects of the aqueous extract of P. niruri on the activation of murine lymphocytes and macrophages were investigated. The study showed that the extract of P. niruri is a potent murine lymphocytes mitogen, inducing significant (p < 0.01) increases in the expression of surface activation maker (CD69) and proliferation of B and T lymphocytes. The production of interferon-gamma (IFN- gamma) and interleukine-4 (IL-4) by P. niruri extract-stimulated naïve splenocytes cultures was also significantly (p < 0.05) increased in a concentration-dependent manner. Various indices of activation and functions murine bone marrow-derived macrophages were significantly (p < 0.05) enhanced by pre-treatment with the extract, including phagocytosis, lysosomal enzymes activity, and TNF-alpha release. Phyllanthus niruri extract was also shown to modulate nitric oxide release by macrophages. These activities suggest that stimulation of the immune system by the extracts of P. niruri could be partly responsible for the ethnomedicinal applications in the management of infectious diseases.


Simultaneous quantification of abemaciclib and its active metabolites in human and mouse plasma by UHPLC-MS/MS.
Abemaciclib is the third cyclin-dependent kinase 4 and 6 inhibitor approved for the treatment of advanced or metastatic breast cancer. In humans, abemaciclib is extensively metabolized by CYP3A4 with the formation of three active metabolites: N-desethylabemaciclib (M2), hydroxyabemaciclib (M20) and hydroxy-N-desethylabemaciclib (M18). These metabolites showed similar potency compared to the parent drug and were significantly abundant in plasma circulation. Thus, M2, M20, and M18 may contribute to the clinical activity of abemaciclib. For this reason, an UHPLC-MS/MS method for the simultaneous quantification of abemaciclib and its active metabolites in human and mouse plasma was developed and validated to support further clinical or preclinical investigations on this drug. Samples were processed by protein precipitation with acetonitrile, followed by supernatant dilution and filtration. Chromatographic separation was performed on a Kinetex C18 column (150 × 2.1 mm ID, 2.6 μm) using gradient elution with 10 mM ammonium bicarbonate in water (eluent A) and in methanol-water (9:1, v/v, eluent B). This method was selective, linear, accurate and precise within the range of 1-600 ng/mL for abemaciclib, 0.5-300 ng/mL for M2 and M20, and 0.2-120 ng/mL for M18. Furthermore, stability of the analytes in human and mouse plasma samples in several conditions was demonstrated. Finally, this assay was successfully used in a preclinical pharmacokinetic study, where abemaciclib and its active metabolites were identified and quantified. Inter-species differences between human and mouse samples were encountered, especially in the formation of M20, where isomers of this compound were detected in mouse plasma, but not in human plasma. This was confirmed by high resolution-mass spectrometry (HR-MS) measurements.


Cell Sorting of Neural Stem and Progenitor Cells from the Adult Mouse Subventricular Zone and Live-imaging of their Cell Cycle Dynamics.
Neural stem cells (NSCs) in the subventricular zone of the lateral ventricles (SVZ) sustain olfactory neurogenesis throughout life in the mammalian brain. They successively generate transit amplifying cells (TACs) and neuroblasts that differentiate into neurons once they integrate the olfactory bulbs. Emerging fluorescent activated cell sorting (FACS) techniques have allowed the isolation of NSCs as well as their progeny and have started to shed light on gene regulatory networks in adult neurogenic niches. We report here a cell sorting technique that allows to follow and distinguish the cell cycle dynamics of the above-mentioned cell populations from the adult SVZ with a LeX/EGFR/CD24 triple staining. Isolated cells are then plated as adherent cells to explore in details their cell cycle progression by time-lapse video microscopy. To this end, we use transgenic Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) mice in which cells are red-fluorescent during G1 phase due to a G1 specific red-Cdt1 reporter. This method has recently revealed that proliferating NSCs progressively lengthen their G1 phase during aging, leading to neurogenesis impairment. This method is easily transposable to other systems and could be of great interest for the study of the cell cycle dynamics of brain cells in the context of brain pathologies.


The yeast noncoding RNA interaction network.
This article describes the creation of the first expert manually curated noncoding RNA interaction networks for S. cerevisiae The RNA-RNA and RNA-protein interaction networks have been carefully extracted from the experimental literature and made available through the IntAct database (www.ebi.ac.uk/intact). We provide an initial network analysis and compare their properties to the much larger protein-protein interaction network. We find that the proteins that bind to ncRNAs in the network contain only a small proportion of classical RNA binding domains. We also see an enrichment of WD40 domains suggesting their direct involvement in ncRNA interactions. We discuss the challenges in collecting noncoding RNA interaction data and the opportunities for worldwide collaboration to fill the unmet need for this data.


[The oxLDL/β2GPI/anti-β2GPI antibody complex promotes A7r5 chemotaxis, migration and lipid accumulation].
Objective To explore the effect of the oxidized low-density lipoprotein/β2 -glycoprotein I/β2 glycoprotein I antibody (oxLDL/β2GPI/β2GPI-Ab) complex on the migration, chemotaxis and lipid accumulation of rat thoracic aortic smooth muscle A7r5 cell line, and unveil the role of Toll-like receptor 4 (TLR4) pathway during the process. Methods A7r5 cells were cultured in vitro with or without the pretreatment of TAK-242, a TLR4 inhibitor. Then the cells were stimulated by oxLDL, oxLDL/β2GPI complex, β2GPI, β2GPI-Ab, β2GPI/β2GPI-Ab complex or oxLDL/β2GPI/β2GPI-Ab complex. Total RNA was extracted from the cells and the mRNA levels of monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and acetyl-CoA acetyltransferase 1 (ACAT1) were evaluated by real-time quantitative PCR. The cell supernatants were collected, and the protein levels of MCP-1 and MMP-9 were determined by ELISA. The migration of A7r5 was observed through wound-healing test. A7r5 cells pretreated with or without TAK-242 were stimulated by oxLDL or oxLDL/β2GPI/β2GPI-Ab complex, and the content of total cholesterol (TC) and free cholesterol (FC) in them were measured by corresponding test kits. Then the level of intracellular cholesterol ester (CE) was calculated. Results The oxLDL/β2GPI/β2GPI-Ab complex promoted the migration and cholesterol accumulation, and up-regulated the expressions of MCP-1, MMP-9 and ACAT1 in A7r5 cells. In addition, the application of TLR4 inhibitor, TAK-242, suppressed these effects. Conclusion oxLDL/β2GPI/β2GPI-Ab complex contributes to the process of atherosclerosis through promoting the migration, chemotaxis and lipid accumulation of a7r5 in a TLR4-dependent manner.


The viral oncoprotein HBx of Hepatitis B virus promotes the growth of hepatocellular carcinoma through cooperating with the cellular oncoprotein RMP.
The smallest gene HBx of Hepatitis B virus (HBV) is recognized as an important viral oncogene (V-oncogene) in the hepatocarcinogenesis. Our previous work demonstrated that RMP is a cellular oncogene (C-oncogene) required for the proliferation of hepatocellular carcinoma (HCC) cells. Here we presented the collaboration between V-oncogene HBx and C-oncogene RMP in the development of HCC. The coexpression of HBx and RMP resulted in the cooperative effect of antiapoptosis and proliferation of HCC cells. In vivo, overexpression of RMP accelerated the growth of HBx-induced xenograft tumors in nude mice and vice versa HBx promoted the growth of RMP-driven xenograft tumors. Although HBx didn't regulate the expression of RMP, HBx and RMP interact with each other and collocalized in the cytoplasm of HCC cells. HBx and RMP collaboratively inhibited the expression of apoptotic factors and promoted the expression of antiapoptotic factors. This finding suggests that HBV may induce, or at least partially contributes to the carcinogenesis of HCC, through its V-oncoprotein HBx interacting with the C-oncoprotein RMP.


Dairy products and bone health: how strong is the scientific evidence?
The relevance of dairy produce for the diminishment of osteoporotic risk is still a matter of scientific debate due to the outcome of a few single observational studies. This review will address the most robust point estimate on the role of dairy products, as reported in systematic reviews and meta-analyses on randomised controlled trials in the case of bone mineralisation or prospective studies in the case of fracture risk. Plain dairy products or those fortified with Ca and/or vitamin D improve total body bone mineral content (BMC) by 45-50 g over 1 year when the daily baseline Ca intake is lower than 750 mg in Caucasians and Chinese girls. In Caucasian and Chinese women, Ca from (fortified) dairy products increases bone mineral density (BMD) by 0·7-1·8 % over 2 years dependent on the site of measurement. Despite the results on BMC, there are currently no studies that have investigated the potential of dairy products to reduce fracture risk in children. In adult Caucasian women, daily intake of 200-250 ml of milk is associated with a reduction in fracture risk of 5 % or higher. In conclusion, the role of dairy products for BMC or BMD has been sufficiently established in Chinese and Caucasian girls and women. In Caucasian women, drinking milk also reduces fracture risk. More research on the role of dairy products within the context of bone health-promoting diets is needed in specific ethnicities, other than Chinese and Caucasians, and in men.


Evidence of altered secondary lymphoid-tissue chemokine responsiveness in Balb/c mice infected with Schistosoma mansoni.
To determine the extent to which splenic T cells were affected by Schistosoma mansoni infection, we investigated the ability of the T cells to produce interferon (IFN)-gamma, as well as their chemotactic ability 7 wk PI. In this study, we report that splenic T cells from Balb/c mice with S. mansoni infections were capable of producing levels of IFN-gamma comparable with splenic T cells from naive mice. However, the T cells exhibited altered chemotactic activity, as evidenced by an inability to respond to secondary lymphoid-tissue chemokine (SLC/CCL21). Although no difference in chemokine expression was found between the spleens of infected versus control mice, chemokine production was greater in the livers of infected versus control mice. Collectively, these data indicate that Balb/c mice with 7-wk S. mansoni infection possess splenic T cells with altered chemotactic activity and that the alterations may be a consequence of the granulomatous response in the liver.


Exposure to low-dose radiation in occupational settings and ischaemic heart disease: a systematic review and meta-analysis.
Ionising radiation is a human carcinogen, but the evidence is less clear that exposure to low-dose ionising radiation (LDIR) increases the risk of adverse cardiovascular outcomes. We synthesised the literature of chronic occupational exposure to LDIR and cardiovascular disease, particularly for ischaemic heart disease (IHD).The literature search was conducted using three databases including studies published between 1990 and 2022. A quality assessment of the studies was completed using the Office of Health and Assessment and Translation Risk of Bias Rating Tool. We conducted meta-analyses for IHD mortality using random effects models using measures of excess relative risk per sievert (ERR/Sv) obtained from internal cohort comparisons, as well as with standardised mortality ratios (SMRs) from external cohort comparisons.We identified 2189 articles, and of these, 26 provided data on IHD and were retained. Most studies were classified as having a 'moderate' level of risk of bias. Fourteen and 10 studies reporting external radiation doses were included in meta-analyses using SMR and ERR/Sv, respectively. The meta-summary SMR was 0.81 (95% CI 0.74 to 0.89) with evidence of reduced risk but high heterogeneity across studies. For internal cohort measures, the summary ERR/Sv for a lagged exposure of 10 years was 0.10 (95% CI 0.01 to 0.20) with low heterogeneity. The subgroup analysis by lagged exposure time showed the strongest association were for the 15 and 20 years lag.Our findings suggest that occupational exposure to LDIR increases the risk IHD mortality and highlight the relevance of internal cohort comparisons.


Ductular proliferation and hepatic secretory function in experimental fascioliasis.
Proliferation of bile duct-like epithelial cells is a common feature of extrahepatic biliary obstruction and it is also present in other forms of liver disease. Experimental infestation with Fasciola hepatica induces hyperplasia of ductular cells together with different functional alterations, such as hypercholeresis, in the rat. We have investigated the contribution of ductular biliary secretion to the hypercholeretic phenomenon in rats with experimental fascioliasis. Infestation was induced by oral administration of 20 metacercariae of F. hepatica. Twelve weeks later, histological study of the liver showed a hyperplastic reaction with proliferation of bile duct-like structures. Basal bile flow in infested animals was significantly higher than that of control animals (+17%), while biliary secretion of bile acids did not significantly differ between both groups. Bile flow increase was associated in parasitized animals with a significantly lower [14C]mannitol bile:plasma ratio (-23%). Intravenous secretin administration (0.3 CU/100 g body wt min) induced a significant increase in the biliary concentration of bicarbonate (+21%) and an enhancement of bile flow (+21%) only in the animals with ductular proliferation. Taurocholate infusion (0.5 nmol/100 g body wt min) produced a similar bile flow increase both in control rats and in rats with proliferated biliary ductules. These results indicate that proliferated bile ductules and ducts spontaneously secrete bile in response to infestation by F. hepatica and that secretin-stimulated bile flow originates at the proliferated biliary structures.


The application value of early postoperative pain management (EPPM) combined with skin temperature monitoring (STM) after flap repair of soft tissue defects in the lower limbs: a non-randomized controlled trial.
Flap repair is often required when repairing soft tissue defects in the lower limbs. Although early postoperative pain management (EPPM) can improve postoperative comfort and rest efficiency, and reduce the probability of complications, it cannot detect tissue blood circulation disorders in time. The purpose of this study was to explore the application value of EPPM combined with skin temperature monitoring (STM) after flap repair of soft tissue defects in the lower limbs. We retrospectively collected the data of 101 patients who underwent lower limb soft tissue defect flap repair, which were divided into the EPPM group (n=50 cases) and the EPPM-STM group (n=51 cases). The EPPM group was given early postoperative pain management, and the EPPM-STM group was given additional skin temperature monitoring on the basis of the EPPM group. The clinical effect, reoperation rate, flap survival rate, pain score, postoperative quality of life and mental resilience, and complications were analyzed and compared. The average healing time of the EPPM-STM group was significantly lower compared with the EPPM group, and the serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) levels were significantly lower after the intervention (t=7.418, 3.447, 7.472; P<0.001, =0.001, <0.001). Compared with the EPPM group, the reoperation rate and complication rate in the EPPM-STM group were significantly lower, and the flap survival rate was significantly higher (χ2=6.966, 7.358; P=0.008, 0.007). The pain scores of the EPPM-STM group were significantly lower than those of the EPPM group after intervention (At 3 days: t=4.723; P<0.001. At 5 days: t=5.261; P<0.001), while the mental resilience and quality of life scores were significantly higher (t=-12.942, -9.975; P<0.001, <0.001). Logistic regression analysis showed that the postoperative management methods and the area of the flap defect were independent risk factors that affected the survival of the flap (t=7.358, 4.819; P=0.007, 0.028). EPPM combined with STM can increase the speed of postoperative healing, increase the survival rate of skin flaps, reduce the rate of reoperation and complications, and improve the quality of life and mental resilience of patients who undergo flap repair.


Generalized and Robust Least Squares Regression.
As a simple yet effective method, least squares regression (LSR) is extensively applied for data regression and classification. Combined with sparse representation, LSR can be extended to feature selection (FS) as well, in which l1 regularization is often applied in embedded FS algorithms. However, because the loss function is in the form of squared error, LSR and its variants are sensitive to noises, which significantly degrades the effectiveness and performance of classification and FS. To cope with the problem, we propose a generalized and robust LSR (GRLSR) for classification and FS, which is made up of arbitrary concave loss function and the l2,p -norm regularization term. Meanwhile, an iterative algorithm is applied to efficiently deal with the nonconvex minimization problem, in which an additional weight to suppress the effect of noises is added to each data point. The weights can be automatically assigned according to the error of the samples. When the error is large, the value of the corresponding weight is small. It is this mechanism that allows GRLSR to reduce the impact of noises and outliers. According to the different formulations of the concave loss function, four specific methods are proposed to clarify the essence of the framework. Comprehensive experiments on corrupted datasets have proven the advantage of the proposed method.


[Skeletal muscle reaction to the loading limit. III. Changes in the contractile apparatus].
A description is given of the changes in the contractile apparatus of the skeletal muscle following extreme long-term exercise. In detail, they include Z-stripe dehiscences, myofibril disintegrations and destructions of single sarcomer . These findings are known from myopathology . A characteristic feature is their subsarcolemmic localisation. The pathogenesis is discussed. In connection with the alterations of the sarcolemma and the mitochondria as well as the increased endo- and exocytosis of the muscle fibre, the cause is seen in a local intracellular catabolism. At the same time, the possible importance to the effluence of enzymes, especially of creatine phosphokinase, is pointed out.


Bilevel tumescent anesthetic infiltration for hair transplantation.
A dual level of tumescent anesthetic infiltration has been found to expedite hair graft or strip harvesting for hair transplantation, reducing bleeding, and increasing the exit angle of the hairs, thereby promoting increased survivorship of hair shafts and bulbs. To acquaint the readership with this variation of anesthetic tumescent technique in hair transplantation. Patients were utilized for this study during international teaching exchanges. Larger multiport infiltrators were used for the deep infiltration; smaller and more narrow infiltrators were used for the more superficial anesthetic administration. Subcutaneous compression and a bilevel vasoconstriction in both donor and recipient sites resulted in an increased upwardly angled exit angle of the hairs to be harvested, an increased separation of individual hair shafts, and reduced bleeding. Placement of the correct incisional angle of instruments inserted into the donor site was facilitated. Utilization of a bilevel tumescent anesthetic infiltration technique is a superior method of anesthesia for hair transplant harvesting and transplanting. Bleeding at both occipital donor and frontal recipient sites was negligible.


[Acute chloroquine intoxication--rare, but always serious: case reports and literature review].
Chloroquine is a derivative of 4-aminoquinoline, which is used in the malaria prophylaxis and treatment and the therapy of some connective tissue diseases. Its narrow therapeutic index causes that the medicine is relatively toxic, especially in the case of an overdose or an acute intoxication. In the recent study two cases of the acute chloroquine poisoning, hospitalized in the Toxicology Department in Kraków, were described and one of them was fatal. The first case was 16-year-old girl who ingested 5 g of chloroquine phosphate in the suicidal attempt. After about 2 hours general seizures appeared followed by ventricular fibrillation and cardiac arrest. After near 2-hour-lasted reanimation procedures she was resuscitated, but 14 hours later another cardiac arrest appeared because of the bradyasystole. Despite the institution of advanced reanimation methods including external pacemaker and electrostimulation, spontaneous circulation did not return and the patient was declared dead. Postmortem toxicological examination of blood, vitreous humour, bile and liver revealed extremely high concentrations of chloroquine (252.15 mg/l in blood). The second case was the 15-year-old girl who ingested 7.5 g of chloroquine phosphate. She developed significant hypotension requiring intravenous infusions of fluids and catecholamines and respiratory distress positively treated with endotracheal intubation and mechanical ventilation. In both cases a considerable hypokalemia and prolonged QTc interval were observed. According to the literature, a clinical picture, diagnosis and recommended therapy of an acute chloroquine poisoning were reviewed.


Virulence factors, antimicrobial susceptibility and molecular characterization of Streptococcus agalactiae isolated from pregnant women.
Forty-one Streptococcus agalactiae isolates collected from pregnant women at 35-37 weeks of gestation were analysed for their capsular types, antimicrobial resistance determinants, distribution of virulence factors and genetic relatedness using PCR and multiplex PCR. Capsular type III was predominant (65.8%), followed by capsular type II (14.6%), Ib (7.3%), and V(4.9%). All isolates were susceptible to penicillin, vancomycin, linezolid and quinupristin-dalfopristin. Resistance to tetracycline, erythromycin and clindamycin were found in 97.6%, 24.4%, and 14.6% of isolates, respectively. The most common antimicrobial resistance gene was tetM found in 97.6% of the isolates followed by ermTR and ermB found in 12% and 7.3% of isolates, respectively. The most common virulence gene was hly (100%), followed by scpB (97.6%), bca (97.6%), rib (53.65%) and bac (4.9%). The insertion sequence IS1548 was found in 63.4% of isolates. By multi locus variable number of tandem repeat analysis (MLVA) typing, 30 different allelic profiles or MLVA types (MTs) were identified. The most frequent was the MT1 (5/41, 12.2%) and followed by MT2 (4/41, 9.75%). Our data revealed that population structure of these isolates is highly diverse and indicates different MLVA types.


Histamine synthesis by mouse T lymphocytes through induced histidine decarboxylase.
When spleen cells of C57BL/6 mice or mast cell-deficient W/Wv mice were cultured, their histidine decarboxylase (HDC) activity increased with increases in the histamine concentration in the cells and the medium. Addition of concanavalin A (Con A) or Escherichia coli lipopolysaccharide (LPS) enhanced the increase. The removal of adherent cells reduced both the control HDC activity and the response to the mitogens. Purified T lymphocytes responded to Con A but not to LPS. Neither Con A nor LPS had any effect on B lymphocytes. Treatment of T cells with anti-Thy-1.2 and complement completely abrogated the induction of HDC. Histamine synthesis dependent on Con A by T cells was stimulated by the addition of conditioned medium from peritoneal adherent cells activated with LPS. The addition of recombinant interleukin-1 (rIL-1) or peritoneal adherent cells fixed with paraformaldehyde significantly enhanced HDC induction dependent on Con A in T cells. These results suggest that histamine is synthesized by T lymphocytes through HDC and that the reaction was enhanced by a soluble factor(s) released from macrophages.


Imaging for spine tumors and new applications.
Discuss intramedullary, intradural/extramedullary, and extradural spinal tumors including imaging characteristics with emphasis on MR and advances in treatment. Literature and institutional review. Spinal tumors: intramedullary, intradural/extramedullary, and extradural, comprise a wide range of histological tumors with an even wider range of clinical symptoms and prognostic features. They are relatively rare and if left untreated, can cause serious neurological deficits and disability. An accurate diagnosis is therefore crucial in determining prognosis and directing therapy. Magnetic resonance imaging (MRI) has revolutionized the diagnosis of intraspinal tumors, allowing for early detection and improved anatomical localization. Magnetic resonance has also become an integral part in staging of both primary and metastatic neoplasms of the spine for guiding therapy and is an excellent modality for follow-up. Advances in MRI (perfusion and molecular imaging) may help refine and describe these neoplasms for accurate treatment and prognosis in the future. Surveillance protocols and role of magnetic resonance are not well established. Magnetic resonance plays an integral role in evaluation of spinal tumors with increasing role in staging and treatment.


Antihypertensive activity of OPC-13340, a new potent and long-acting dihydropyridine calcium antagonist, in rats.
The antihypertensive action of OPC-13340, a new dihydropyridine, was studied in rats and compared with the action of nicardipine and other dihydropyridines. OPC-13340 showed more potent and longer hypotensive action than nicardipine when administered either intravenously (i.v.) or orally in normotensive and hypertensive rats. Among 6 compounds tested, (OPC-13340, nifedipine, nitrendipine, nisoldipine, nicardipine and diltiazem), OPC-13340 was the most potent and long-acting when administered orally to spontaneously hypertensive rats (SHR). Tachycardia after administration of OPC-13340 was less or diminished earlier than that of nicardipine. Oral administration of OPC-13340 (3 mg/kg) once daily for 13 days did not cause any rebound phenomena in SHR. The compound inhibited Ca- or K-induced contractions in isolated rat aorta and shortened action potential duration in guinea pig papillary muscle, suggesting Ca channel blocking action. OPC-13340 might be useful as a drug for once-daily therapy of essential hypertension.


Spatiotemporal aggregation for temporally extensive international microdata.
We describe a strategy for regionalizing subnational administrative units in conjunction with harmonizing changes in unit boundaries over time that can be applied to provide small-area geographic identifiers for census microdata. The availability of small-area identifiers blends the flexibility of individual microdata with the spatial specificity of aggregate data. Regionalizing microdata by administrative units poses a number of challenges, such as the need to aggregate individual scale data in a way that ensures confidentiality and issues arising from changing spatial boundaries over time. We describe a regionalization and harmonization strategy that creates units that satisfy spatial and other constraints while maximizing the number of units in a way that supports policy and research use. We describe this regionalization strategy for three test cases of Malawi, Brazil, and the United States. We test different algorithms and develop a semi-automated strategy for regionalization that meets data restrictions, computation, and data demands from end users.


Differences in sodium and D-glucose transport between hamster and rat lungs.
The purpose of this study was to characterize phloridzin- and amiloride-sensitive transport across blood-gas barrier of hamster and rat lungs. Air spaces of isolated perfused lungs were instilled with a solution containing 22Na or L-[3H]glucose, D-[14C]glucose, and fluorescein isothiocyanate-labeled dextran. Apparent permeability-surface area products (PS) were calculated. Phloridzin (Na(+)-dependent D-glucose transport inhibitor) had no effect on D-glucose or sodium transport out of air spaces in hamster lungs. In contrast, in rat lungs, phloridzin decreased PS for D-glucose by 89% and that for Na by 28%. Trapping of 14CO2 in vascular samples was measured to estimate metabolism. Unlabeled air space D-glucose increased appearance of perfused D-[14C]glucose in air spaces of rat lungs. We conclude that Na(+)-dependent D-glucose transport is important for D-glucose uptake in rat lungs but not in hamster lungs. In hamster lungs, amiloride (Na+ transport inhibitor) also decreased PS for sodium, but drugs known to stimulate sodium transport in rat lungs had no effect. Thus, species differences in active transport processes exist in the distal air spaces of mammalian lungs.


Astrocyte morphology is confined by cortical functional boundaries in mammals ranging from mice to human.
Cortical blood flow can be modulated by local activity across a range of species; from barrel-specific blood flow in the rodent somatosensory cortex to the human cortex, where BOLD-fMRI reveals numerous functional borders. However, it appears that the distribution of blood capillaries largely ignores these functional boundaries. Here we report that, by contrast, astrocytes, a major player in blood-flow control, show a striking morphological sensitivity to functional borders. Specifically, we show that astrocyte processes are structurally confined by barrel boundaries in the mouse, by the border of primary auditory cortex in the rat and by layers IIIa/b and Cytochrome Oxidase (CO)-blobs boundaries in the human primary visual cortex. Thus, astrocytes which are critical elements in neuro-hemodynamic coupling show a significant anatomical segregation along functional boundaries across different mammalian species. These results may open a new anatomical marker for delineating functional borders across species, including post-mortem human brains.


Conceptualization and measurement of doing family caregiving well.
To review progress in the conceptualization and measurement of five concepts related to doing family caregiving well: caregiving mastery, self-efficacy, competence, preparedness, and quality. Families are increasingly involved in providing complex care to ill or aged family members at home. Their ability to do caregiving well is vitally important and a focus of nursing practice in many clinical settings. Concepts were organized into two groups: those that refer to caregivers' perceptions of how well they are providing care and those that refer to professional assessment of the quality of care provided. Family caregiving literature from nursing, gerontology, psychology, and social work, 1987-1996. There is growing interest in doing family caregiving well. However, research in this area is limited by the current state of development of ideas and measures. Two issues that should be addressed to advance research are the perspective taken on doing caregiving well and change over time in doing caregiving well.


Capitellidae (Annelida: Polychaeta) from the Pacific Coast of Costa Rica.
Eleven species of Capitellidae (Annelida: Polychaeta) belonging to eight genera are reported from the subtidal and intertidal of the Pacific Coast of Costa Rica. Three species, Mediomastus ambiseta, M. californiensis and Notomastus hemipodus, are found in highest abundances and are widespread in subtidal and intertidal environments. A taxonomic key to these species is included.


FOXP3-stained image analysis for follicular lymphoma: Optimal adaptive thresholding with maximal nucleus coverage.
Immunohistochemical detection of FOXP3 antigen is a usable marker for detection of regulatory T lymphocytes (TR) in formalin fixed and paraffin embedded sections of different types of tumor tissue. TR plays a major role in homeostasis of normal immune systems where they prevent auto reactivity of the immune system towards the host. This beneficial effect of TR is frequently "hijacked" by malignant cells where tumor-infiltrating regulatory T cells are recruited by the malignant nuclei to inhibit the beneficial immune response of the host against the tumor cells. In the majority of human solid tumors, an increased number of tumor-infiltrating FOXP3 positive TR is associated with worse outcome. However, in follicular lymphoma (FL) the impact of the number and distribution of TR on the outcome still remains controversial. In this study, we present a novel method to detect and enumerate nuclei from FOXP3 stained images of FL biopsies. The proposed method defines a new adaptive thresholding procedure, namely the optimal adaptive thresholding (OAT) method, which aims to minimize under-segmented and over-segmented nuclei for coarse segmentation. Next, we integrate a parameter free elliptical arc and line segment detector (ELSD) as additional information to refine segmentation results and to split most of the merged nuclei. Finally, we utilize a state-of-the-art super-pixel method, Simple Linear Iterative Clustering (SLIC) to split the rest of the merged nuclei. Our dataset consists of 13 region-of-interest images containing 769 negative and 88 positive nuclei. Three expert pathologists evaluated the method and reported sensitivity values in detecting negative and positive nuclei ranging from 83-100% and 90-95%, and precision values of 98-100% and 99-100%, respectively. The proposed solution can be used to investigate the impact of FOXP3 positive nuclei on the outcome and prognosis in FL.


Specificity of an Na+ -dependent taurocholate transport site in isolated rat hepatocytes.
The structural specificity of the taurocholate uptake mechanism was studied by determining the ability of 100 microM structural analogues of taurocholate to inhibit the uptake of 5 microM [14C]-taurocholate into freshly isolated rat hepatocytes. Taurocholate was a more potent inhibitor than cholate. The fewer the number of hydroxyl groups, the more potent the inhibitors. Neither hydroxyl group orientation (alpha or beta) nor esterification with formic acid strongly influenced inhibitory potency. Replacement of hydroxyl groups with keto groups, however, diminished inhibitory potency. These facts suggested that distortion of the sterol backbone may be an important factor in diminishing inhibitory potency. Charge on the nonsteroid moiety affected potency. Both neutral and negatively charged compounds inhibited more strongly than positively charged compounds. As important as charge, however, was length of the nonsteroidal moiety. Inhibitory potency increased progressively as length beyond C-17 increased up to 11 A. Inhibitory potency was reduced again, however, with an extremely long end group of 18 A. The inhibitors do not act as cytotoxins since cellular oxygen consumption was not diminished by any of them. Furthermore, inhibition was specific for the taurocholate uptake mechanism. The three most potent inhibitory compounds inhibited L-alanine uptake little or not at all. The kinetics of inhibition, determined for three selected compounds, were consistent with competitive inhibition. The structural specificity of the rat hepatocyte sodium-dependent taurocholate uptake site is similar to that of the guinea pig ileum uptake site.


A Comparison of Kenyan Biomphalaria pfeifferi and B. Sudanica as Vectors for Schistosoma mansoni, Including a Discussion of the Need to Better Understand the Effects of Snail Breeding Systems on Transmission.
In Kenya, schistosomes infect an estimated 6 million people with >30 million people at risk of infection. We compared compatibility with, and ability to support and perpetuate, Schistosoma mansoni of Biomphalaria pfeifferi and Biomphalaria sudanica, 2 prominent freshwater snail species involved in schistosomiasis transmission in Kenya. Field-derived B. pfeifferi (from a stream in Mwea, central Kenya) and B. sudanica (from Nawa, Lake Victoria, in western Kenya) were exposed to S. mansoni miracidia isolated from fecal samples of naturally infected humans from Mwea or Nawa. Juvenile (<6 mm shell diameter), young adult (6-9 mm), and adult snails (>9 mm) were each exposed to a single miracidium. Schistosoma mansoni developed faster and consistently had higher infection rates (39.6-80.7%) in B. pfeifferi than in B. sudanica (2.4-21.5%), regardless of the source of S. mansoni or the size of the snails used. Schistosoma mansoni from Nawa produced higher infection rates in both B. pfeifferi and B. sudanica than did S. mansoni from Mwea. Mean daily cercariae production was greater for B. pfeifferi exposed to sympatric than allopatric S. mansoni (583-1,686 vs. 392-1,232), and mean daily cercariae production among B. sudanica were consistently low (50-590) with no significant differences between sympatric or allopatric combinations. Both non-miracidia-exposed and miracidia-exposed B. pfeifferi had higher mortality rates than for B. sudanica, but mean survival time of shedding snails (9.3-13.7 wk) did not differ significantly between the 2 species. A small proportion (1.5%) of the cercariae shedding B. pfeifferi survived up to 40 wk post-exposure. Biomphalaria pfeifferi was more likely to become infected and to shed more cercariae than B. sudanica, suggesting that the risk per individual snail of perpetuating transmission in Kenyan streams or lacustrine habitats may differ considerably. High infection rates exhibited by the preferential self-fertilizing B. pfeifferi relative to the out-crossing B. sudanica point to the need to investigate further the role of host breeding systems in influencing transmission of schistosomiasis by snail hosts.


The role of electrical stimulation therapy in ophthalmic diseases.
Electrical stimulation therapy (EST) involves the use of a low-intensity electrical current in the treatment of neuromuscular conditions. During the recent two decades, EST has emerged as a potential neuroprotective strategy in certain ophthalmic diseases, aided by a lack of effective management for these conditions. The aim of this review is to summarize and discuss current available evidence for the use of EST in ophthalmic diseases in the laboratory setting and in human trials. The compilation and review of published English-language reports on the use of EST in human ophthalmic disease and animal models of ophthalmic disease. From published reports, research work on the use of EST in ophthalmic diseases began in the last 20 years. Different methods of electrical stimulation have been devised, with varying levels of invasiveness. Results from human trials have favored earlier and repeated treatment after insults to the optic nerve, while EST has shown transient effectiveness in degenerative diseases of photoreceptors. Patients also reported no serious adverse effects from EST in the clinical trials. Results from animal studies have further confirmed survival benefits of EST in retinal cell survival, with the underlying mechanism likely multifactorial, but involving Müller cell modulation. Results from human and animal studies have demonstrated the relevance and potential effectiveness of EST in ophthalmic disease. However, optimal disease and species-specific stimulation settings need to be defined.


Constructing a philosophy of chiropractic: evolving worldviews and premodern roots().
The philosophy of chiropractic can be framed as an attempt to correct the problems inherited from the Western Enlightenment. Its origins can be found in the long tradition of Western philosophy. The purpose of this article is to describe in a broad context chiropractic's roots in premodernity and establish the structural and hermeneutical differences between chiropractic's original philosophical ideas and those of premodern philosophers. The worldview or cultural mindset the philosophy arose from must be situated in the context of its time, the birth of the unique postmodern worldview, aperspectival consciousness, and the modern sense of self. This is accomplished by exploring several metatheories about the development of the self through history, with an emphasis on the premodern roots to the chiropractic terms; Universal Intelligence and Innate Intelligence. By contextualizing the philosophy of chiropractic in terms of a structural genealogy of the self and of ideas, a new approach to philosophy in chiropractic emerges. Without accounting for chiropractic's origins as a reflection of the unique time, place, and culture, in terms of the evolution of worldviews through history, any approach to construct or reconstruct a philosophy of chiropractic will potentially miss the seminal feature of chiropractic's emergence.


Sequential Presentation Protects Working Memory From Catastrophic Interference.
Neural network models of memory are notorious for catastrophic interference: Old items are forgotten as new items are memorized (French, 1999; McCloskey & Cohen, 1989). While working memory (WM) in human adults shows severe capacity limitations, these capacity limitations do not reflect neural network style catastrophic interference. However, our ability to quickly apprehend the numerosity of small sets of objects (i.e., subitizing) does show catastrophic capacity limitations, and this subitizing capacity and WM might reflect a common capacity. Accordingly, computational investigations (Knops, Piazza, Sengupta, Eger & Melcher, 2014; Sengupta, Surampudi & Melcher, 2014) suggest that mutual inhibition among neurons can explain both kinds of capacity limitations as well as why our ability to estimate the numerosity of larger sets is limited according to a Weber ratio signature. Based on simulations with a saliency map-like network and mathematical proofs, we provide three results. First, mutual inhibition among neurons leads to catastrophic interference when items are presented simultaneously. The network can remember a limited number of items, but when more items are presented, the network forgets all of them. Second, if memory items are presented sequentially rather than simultaneously, the network remembers the most recent items rather than forgetting all of them. Hence, the tendency in WM tasks to sequentially attend even to simultaneously presented items might not only reflect attentional limitations, but also an adaptive strategy to avoid catastrophic interference. Third, the mean activation level in the network can be used to estimate the number of items in small sets, but it does not accurately reflect the number of items in larger sets. Rather, we suggest that the Weber ratio signature of large number discrimination emerges naturally from the interaction between the limited precision of a numeric estimation system and a multiplicative gain control mechanism.


A continuity model for research consultation in family medicine.
This paper describes a model of individualized research consultation designed to assist family physician faculty members to develop research skills. The consultative relationship described here is a one-to-one helping relationship between a client (a family physician researcher) and a research consultant that is directed toward enabling the client to complete a research project and ultimately to function as an independent researcher. The continuity model stresses a relatively longterm, intensive relationship--a departure from the typical consultation in which the consultant renders advice and then exits. Within this continuity model, the consultant is involved at regular intervals throughout the duration of the research project and is committed to its completion. The principal role of the consultant is that of educator, within which the consultant may at various times act as reflective listener, agent of change, role model, "linker" to resources, and informational expert.


Sex as an obligation and interpersonal communication among Norwegian heterosexual couples.
This study examines the prevalence of having sex as a means of satisfying one's partner among a random sample of 398 heterosexual couples with non-problematic, mild or manifest reduced sexual desire. Data collection was carried out by questionnaires. Two of three women and one of five men with manifest distressing reduced sexual desire had had obligatory sex. Among women with symptoms of mild reduced sexual desire, there was an association between obligatory sex and lack of acknowledgement of one's sexual needs, as well as a lack of communication with one's partner regarding how to be sexually pleased. In men with manifest reduced sexual desire there was an association between obligatory sex and discussion of one's sexual needs, and sexual fantasies with the partner. Thus, men with desire problems seem to communicate with their partner about their sexuality, whereas women seem not to talk with their partner about their sexual needs.


Correlates of fatigue in survivors of breast cancer.
The purpose of this report is to describe variables associated with fatigue for disease-free survivors of breast cancer. On the basis of Mishel's theory of illness uncertainty and the antecedents of uncertainty, a cross-sectional, descriptive, correlational design was used to examine (a) the relationship of fatigue with cancer-related variables and the presence of concurrent illness and (b) whether fatigue and educational level explained a significant proportion of the variation in illness uncertainty. The Mishel Uncertainty in Illness Scale (MUIS) and a single fatigue item on the McCorkle & Young Symptom Distress Scale were used as variable measures. Data were collected from 109 women 1 to 6 years after treatment for Stage I to III breast cancer with no known metastasis. Findings showed that low to moderate fatigue persisted for women, which was related significantly to the presence of concurrent illness. When concurrent illness was taken into account, fatigue was significantly related to treatment with chemotherapy, irrespective of length of time since treatment, age, disease stage, or tamoxifen use. Finally, fatigue and education level explained a significant level of the variation in illness uncertainty. Nurses can identify and assist women who are at risk for fatigue and illness uncertainty after treatment for breast cancer ends.


Rebooting the generally recognized as safe (GRAS) approach for food additive safety in the US.
The US Food and Drug Administration (FDA) has premarket review authority over food additives, but a food manufacturer may, according to the legislation, intentionally add a substance to human food or animal food without their premarket review or approval if the substance is generally recognized, among qualified experts, to be safe under the conditions of its intended use. Generally recognized as safe (GRAS) implies that the current scientific community agrees on the adequacy of how data is generated. This system has come under public pressure because of doubts as to its efficiency and the FDA's recent GRAS rule is part of the response. The FDA guidance for testing food additives, known as the "Redbook", is about two decades old. Work toward a new "Redbook" is on the way, but the US Grocery Manufacturer Association (GMA) also has initiated the development of an independent standard on how to perform GRAS determinations. This review of the current guidance shows a very rigorous system for higher concern levels, but also many waiving options. Opportunities and challenges for safety evaluations of food additives are discussed. Where scientific progress has allowed improving existing and adapting new methods, these should be adopted to improve product safety and animal welfare. The continuous adaptation of such improved methods is therefore needed. Especially, there are opportunities to embrace developments within the toxicity testing for the 21st century movement and evidence-based toxicology approaches. Also, the growing understanding of the limitations of traditional tests needs to be considered.