Effects of an eight-week stretching program on the passive-elastic properties and function of the calf muscles of older women.
Calf muscle stretching programs are used to increase dorsiflexion range of motion at the ankle, yet the effects of the stretching programs on the passive properties of aged calf muscles and on standing and ambulatory function have not been studied. This initial study examined the effects of an eight-week stretching program on the passive-elastic properties of the calf muscles of older women and on selected functional activities. Nineteen women aged 65-89 years with limited dorsiflexion range of motion first completed a timed agility course, a timed 10-m walk and a standing functional reach test. A dynamometer then moved the right ankle from plantarflexion to maximal dorsiflexion and back to plantarflexion at 5 deg s(-1) to measure calf muscle passive properties. The women were randomly assigned to a group that stretched three-times a week for eight-weeks (n=10) or to a control group (n=9) that did not. The tests were repeated after the stretching program. The stretching group showed increased maximal dorsiflexion range of motion, passive resistive forces (Newtons [N]), and the absorbed and retained passive-elastic energy (deg N) (P<0.05). They also had decreased times for the agility course and the 10-m walk (P<0.05). The functional reach test did not change for either group. The eight-week stretching program most likely increased the maximal length, length extensibility and passive resistive forces of the calf muscles. Adaptations of other ankle and leg structures also may have contributed. The passive adaptations were associated with enhanced performances of ambulatory functional activities.


Osteoinductivity of calcium phosphate mediated by connexin 43.
Recent reports have alluded to the osteoinductive properties of calcium phosphate, yet the cellular processes behind this are not well understood. To gain insight into the molecular mechanisms of this phenomenon, we have conducted a series of in vitro and in vivo experiments using a scaffoldless three dimensional (3D) dental pulp cell (DPC) construct as a physiologically relevant model. We demonstrate that amorphous calcium phosphate (ACP) alters cellular functions and 3D spatial tissue differentiation patterns by increasing local calcium concentration, which modulates connexin 43 (Cx43)-mediated gap junctions. These observations indicate a chemical mechanism for osteoinductivity of calcium phosphates. These results provide new insights for possible roles of mineral phases in bone formation and remodeling. This study also emphasizes the strong effect of scaffold materials on cellular functions and is expected to advance the design of future tissue engineering materials.


Moderate-to-vigorous physical activity and behavioral outcomes in adolescents with attention deficit and hyperactivity disorder: The role of sleep.
Attention deficit and hyperactivity disorder (ADHD) is a neurodevelopmental disorder that has a worldwide prevalence of 7.2%. Individuals with ADHD often have sleep and behavioral problems. This cross-sectional survey aims to investigate the relationships between moderate-to-vigorous physical activity (MVPA), sleep, bullying, and school engagement in adolescents with ADHD. Data were obtained from the 2011-2012 National Survey of Children's Health. A subsample (n = 272) that fit the inclusion criteria was included. Path analysis was used to test the hypothesized model (i.e., MVPA → sleep → bullying/school engagement). The proposed model fit the data well. MVPA was found to be associated with sleep, bullying, and school engagement. In addition, sleep mediated the relationship between MVPA and bullying/school engagement. MVPA and sleep play an important role in understanding behavioral outcomes in adolescents with ADHD. Longitudinal or intervention studies are needed to support the present findings.


Stochastic dynamics in a delayed epidemic system with Markovian switching and media coverage.
A stochastic SIR system with Lévy jumps and distributed delay is developed and employed to study the combined effects of Markovian switching and media coverage on stochastic epidemiological dynamics and outcomes. Stochastic Lyapunov functions are used to prove the existence of a stationary distribution to the positive solution. Sufficient conditions for persistence in mean and the extinction of an infectious disease are also shown.


The interplay of galectins-1, -3, and -9 in the immune-inflammatory response underlying cardiovascular and metabolic disease.
Galectins are β-galactoside-binding proteins that bind and crosslink molecules via their sugar moieties, forming signaling and adhesion networks involved in cellular communication, differentiation, migration, and survival. Galectins are expressed ubiquitously across immune cells, and their function varies with their tissue-specific and subcellular location. Particularly galectin-1, -3, and -9 are highly expressed by inflammatory cells and are involved in the modulation of several innate and adaptive immune responses. Modulation in the expression of these proteins accompany major processes in cardiovascular diseases and metabolic disorders, such as atherosclerosis, thrombosis, obesity, and diabetes, making them attractive therapeutic targets. In this review we consider the broad cellular activities ascribed to galectin-1, -3, and -9, highlighting those linked to the progression of different inflammatory driven pathologies in the context of cardiovascular and metabolic disease, to better understand their mechanism of action and provide new insights into the design of novel therapeutic strategies.


High prevalence of soil-transmitted helminth infections among primary school children, Uttar Pradesh, India, 2015.
Soil-transmitted helminth (STH) infections often affect the poorest and most deprived communities. In order to generate reliable data for planning a school based deworming program, we conducted a survey among primary school children studying in government schools in the Indian state of Uttar Pradesh. The objectives of our survey were to estimate the prevalence and intensity of STH infections. We conducted a cross-sectional survey among children studying in 130 primary schools from 9 agro-climatic zones, during May - August 2015. Information about socio-demographic details, defecation and hand-hygiene practices, and stool samples were collected from the school children. Stool samples were examined using the Kato-Katz method. Stool samples from 6421 school children were examined. The overall weighted prevalence of any STH in the State was 75.6% (95% CI: 71.2-79.5). The prevalence was more than 50% in six of the nine agro-climatic zones. A. lumbricoides was the most prevalent STH (prevalence: 69.6%), followed by hookworm (prevalence: 22.6%) and T. trichura (4.6%). The majority of the STH infections were of low intensity. The practice of open defecation and not washing hands with soap after defecation and residence in kutcha house were significant risk factors of STH infection. STH prevalence among primary school children in Uttar Pradesh was high. Given the WHO guidelines on deworming frequency according to STH prevalence, Govt of Uttar Pradesh needs to implement a school-based deworming program with bi-annual frequency. The findings of our survey would also help monitor the performance of school based deworming programme.


The standardization of NK cell assays for use in studies of biological response modifiers.
This paper deals with the standardization of human natural killer (NK) cell assays for the sequential evaluation of patients with various disease states, or who are being treated with biological response modifiers. The method is described for the calculation of lytic units which results in numbers proportional to effector cell activity. It is shown that normal donors are relatively consistent in their cytotoxicity, making it possible to use a 'bank' of normal controls against which patients data can be normalized. Cryopreserved lymphocytes, as well as fresh lymphocytes, can be used as controls. Under the usual conditions for recovering cryopreserved lymphocytes, NK activity is markedly reduced; but by preincubation of the lymphocytes at 37 degrees C for 5 h or more the activity is recovered. A number of currently used methods for the selection of controls are described and discussed with respect to their practicality and validity. The principle problem with currently used methods is the necessity for a large number of controls so that a uniform distribution of NK activity about the 'true' normal is assured. The method which we advocate in this paper is based on the selection of normal control donors from a group of individuals who have been tested repeatedly over several months or years and whose NK activity relative to normal donors as a whole can be stated with reasonable confidence. These values are then used as correction factors which are applied to the relevant control donor's cytotoxicity every time that that person is used. In any particular experiment the mean of the corrected control lytic unit values is used as the denominator for the calculation of patient NK activity relative to normal. This method can be applied 'retrospectively' if a variety of donors have been used repeatedly. Two 'tests' of the methodology are described, with the following results: (1) the relative NK activity of a randomly selected group of normal women, whose data were handled as if they were a patient population, was approximately one, and (2) complete Freund's adjuvant, administered intradermally to patients with resected lung cancer, caused an increase in natural killer cell activity compared to pretreatment levels. The use of these methods should make it possible to derive meaningful NK results which are comparable from laboratory to laboratory.


DDAH1 promoter -396 4N insertion variant is associated with increased risk of type 2 diabetes in a gender-dependent manner.
Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases, making it a contributing factor for diabetes. Endogenous ADMA is hydrolyzed by dimethylarginine dimethylaminohydrolase 1 (DDAH1), and a DDAH1 promoter -396 4N deletion/insertion polymorphism (DDAH1: -396_-395insGCGT) regulates its transcriptional activity. This study aimed to explore the association between this polymorphism and type 2 diabetes (T2DM). In a case-control study, all participants were genotyped for this polymorphism within two sets of populations (discovery: 1,227 T2DM patients and 1,339 controls; replication: 1,190 patients and 1,651 controls). The disease association was assessed by a unconditional logistic regression model. Homeostasis model assessment calculations were conducted among different genotypes. We identified that DDAH1: -396_-395insGCGT insertion allele was significantly associated with increased risk of T2DM (discovery: adjusted odds ratio [OR] = 1.380, 95% CI = 1.128-1.687, p = .002; replication: OR = 1.231, 95% CI = 1.007-1.504, p = .043). The homeostasis model assessment of insulin resistance was increased in participants carrying Ins/Ins alleles (p = .0452). Interestingly, the insertion allele increased the risk of T2DM in males but not in females (male discovery: OR = 1.528, 95% CI = 1.141-2.047, p = .004; replication: OR = 1.439, 95% CI = 1.083-1.911, p = .012; female discovery: OR = 1.218, 95% CI = 0.913-1.626, p = .18; replication: OR = 1.161, 95% CI = 0.871-1.548, p = .308). The DDAH1: -396_-395insGCGT insertion allele is associated with increased risk of T2DM in a gender-dependent manner, affects males but not females.


Effect of drug-paired exteroceptive stimulus presentations on methamphetamine reinstatement in rats.
The purpose of the present study was to examine the impact of drug-paired cues on methamphetamine reinstatement. Three groups of rats were trained to self-administer 0.1 mg/kg/infusion methamphetamine. Each methamphetamine infusion was accompanied by a 6 s flashing light+tone stimulus (cues). After training, the groups were then given 12, daily extinction sessions either with or without response-contingent drug-paired cues and then tested for 1 mg/kg i.p. methamphetamine priming-induced reinstatement either with or without cues. Methamphetamine priming significantly reinstated drug-appropriate responding regardless of whether response-contingent cues were omitted during both extinction and testing, presented during both extinction and testing, or omitted during extinction but presented during reinstatement testing. The group in which cues were omitted during extinction and presented during reinstatement exhibited significantly greater reinstatement than did the other two groups. A separate group of rats was also tested demonstrating that response-contingent presentation of previously methamphetamine-paired cues alone, without methamphetamine priming, significantly reinstated drug-appropriate responding. These data show that methamphetamine priming produces a robust reinstatement effect which can be influenced by drug-paired cues.


Sirtuin 7 mitigates renal ferroptosis, fibrosis and injury in hypertensive mice by facilitating the KLF15/Nrf2 signaling.
Hypertension is one of the leading causes of chronic kidney disease characterized with renal fibrosis. This study aimed to investigate roles and mechanisms of sirtuin 7 (SIRT7) in hypertensive renal injury. Mini-pumps were implanted to male C57BL/6 mice to deliver angiotensin (Ang) Ⅱ (1.5 mg/kg/d) or saline for 2 weeks. Ang Ⅱ infusion resulted in marked increases in systolic blood pressure levels, renal ferroptosis and interstitial fibrosis in hypertensive mice, concomitantly with downregulated SIRT7 and Krüppel-like factor 15 (KLF15) levels. Notably, administration of recombinant adeno-associated virus-SIRT7 or ferroptosis inhibitor ferrostatin-1 effectively mitigated Ang Ⅱ-triggered renal ferroptosis, epithelial-mesenchymal transition (EMT), interstitial fibrosis, renal functional and structural injury in hypertensive mice by blunting the KIM-1/NOX4 signaling and enforcing the KLF15/Nrf2 and xCT/GPX4 signaling, respectively. In primary cultured mouse renal tubular epithelial cells (TECs), Ang Ⅱ pretreatment led to repressed SIRT7 expression and augmented ferroptosis as well as partial EMT, which were substantially antagonized by rhSIRT7 or ferrostatin-1 administration. Additionally, both Nrf2 inhibitor ML385 and KLF15 siRNA strikingly abolished the rhSIRT7-mediated beneficial roles in mouse renal TECs in response to Ang Ⅱ with reduced expression of Nrf2, xCT and GPX4. More importantly, ML385 administration remarkably amplified Ang Ⅱ-mediated ROS generation, lipid peroxidation and ferroptosis in renal TECs, which were significantly reversed by ferrostatin-1. In conclusion, SIRT7 alleviates renal ferroptosis, lipid peroxidation, and partial EMT under hypertensive status by facilitating the KLF15/Nrf2 signaling, thereby mitigating renal fibrosis, injury and dysfunction. Targeting SIRT7 signaling serves as a promising strategy for hypertension and hypertensive renal injury.


Can Dislocation Rates Be Decreased Using the Anterior Approach in Patients With Lumbar Spondylosis or Lumbar Instrumented Fusion?
Although spinopelvic stiffness is known to contribute to instability following total hip arthroplasty (THA), it is unknown whether use of an anterior surgical approach is associated with decreased postoperative instability rates in patients with lumbar spondylosis or fusion. A retrospective review was performed of 1750 patients who underwent primary THA at our institution over an 8-year time period. Radiographic and chart review was performed evaluating for dislocations. Lumbar and pelvic radiographs were used to identify the presence of spondylosis and/or instrumented fusion. Patients were then divided into non-spondylosis and spondylosis or fusion groups to compare dislocation rates by surgical approach. In total, 54.4% of THA patients had an anterior approach (n = 952) and 54.6% had lumbar spondylosis or instrumented fusion (n = 956). There were 29 dislocations in total (1.7%), with less occurring in anterior approach patients (0.6% vs 2.9%, P < .001). In the patients without lumbar spondylosis, there were less dislocations in the anterior approach group (0.2% vs 1.7%, P = .048). Likewise, in patients with lumbar spondylosis or fusion, there were less dislocations in the anterior approach group (1.0% vs 3.8%, P = .004). Using logistic regression, there was a 4.1× increased risk of dislocation with a posterior approach vs an anterior approach in the spondylosis or fusion group (P = .011). Patients with lumbar spondylosis or fusion have high rates of instability. At our institution, we found that utilization of an anterior surgical approach substantially mitigated this risk.


Comparison of the cytotoxic and inflammatory responses of titanium particles with different methods for endotoxin removal in RAW264.7 macrophages.
It is generally accepted that periprosthetic bone resorption is initiated through aseptic inflammation aggravated by wear particles that are generated from artificial joint. However, some studies have demonstrated that "endotoxin-free" wear particles are almost completely unable to stimulate the macrophage-mediated production of proinflammatory cytokines. Here, we compare the titanium particles with different methods of endotoxin removal. The results indicated that different titanium particle preparation dosages did not significantly change particle size, morphology, and chemical composition. But it could cause variations in the endotoxin concentration of titanium particles and inflammatory responses in RAW264.7 macrophages. The particles with higher endotoxin levels correlated with more extensive inflammatory responses. When testing endotoxins using the supernatant of particle suspensions, it would lead to false negative results compared with testing the particle themselves. And when using the particles themselves, all the particles should be removed by centrifugation to avoid particle interference before the absorbance value was determined. Therefore, we suggest that research concerning wear particles should completely describe the endotoxin testing process, including endotoxin removal from particles and the details of endotoxin testing. Moreover, future research should focus on the surface of wear particles (the potential role of adherent endotoxin) rather than the particles themselves.


Characteristics of asbestos fibers in lung tissue from occupational and environmental asbestos exposure of lung cancer patients in Busan, Korea.
The Asbestos Injury Relief Act in Korea requires that asbestos exposure be assessed through clinical examination and chest computed tomography (CT). However, a more specific measurement of asbestos characteristics in the lung tissue may be appropriate. We aimed to investigate the asbestos burden and characterize asbestos fibers in patients with lung cancer and ultimately assess the relationship between occupational and environmental asbestos exposure and lung cancer in Korea. We evaluated 37 lung cancer patients (LCPs) from Busan. The factors affecting asbestos burden in LCPs were analyzed using a multiple regression analysis. History of asbestos exposure (environmental/occupational), male sex, and old age were the main factors affecting asbestos burden in lung tissues of LCPs. These factors had an approximate 37% adjusted coefficient of determination. There was a significant difference in the length of asbestos fibers (4.06-37.6 µm vs. 4.26-91.7 µm) and aspect ratio (4.5-151.9 vs. 5.6-735.6) between those who were occupationally exposed to asbestos and those who were environmentally exposed (P < 0.01). Therefore, both environmental/occupational exposure to asbestos should be strongly managed to reduce the risk of lung cancer, and exposure should be assessed according to the characteristics of asbestos fibers in the lung tissue.


[Incorporation of 1-6-14C-glucose into lipid fractions of the liver and brain of rats with different alcohol motivation].
Specific radioactivity of total phospholipids, cholesterol and lysophosphatidyl choline was decreased in liver tissue of rats consuming ethanol as compared with the animals preferring water. In brain of rats with alcohol motivation incorporation of 1-6-14C-glucose into cardiolipin was decreased, while the label incorporated into triacylglycerols, sulfatides II and cerebrosides I at the increased rate.


Failure to pace following high dose antiarrhythmic therapy--reversal with isoproterenol.
A patient with resistant ventricular tachycardia treated with a combination of antiarrhythmic agents is described. Sudden onset of a wide complex ventricular rhythm with periods of asystole and failure to achieve transvenous pacing were observed, presumably due to antiarrhythmic drug toxicity. Inability to pace was reversed by the infusion of isoproterenol.


The UK Public Health Skills and Career Framework--could it help to make public health the business of every workforce?
There is growing recognition of the impact of the wider determinants of health and health inequalities, and an acknowledgement that addressing these root causes of ill health requires public health to be everyone's business and responsibility. Therefore, equipping the whole of the public health workforce and a wide range of other disciplines with the knowledge and skills to have a positive influence on health is a priority. The UK is implementing a competence-based skills framework that addresses this dual need. The aim of this paper is to describe how the UK Public Health Skills and Career Framework was developed, and to invite discussion on its potential usefulness as a tool for facilitating a shared approach to strengthening public health competence within and across countries.


[Critical evaluation of the searching technic of the polarization-sensitive neurons of insects].
The demerit of the light stimulator used by the authors was the presence of lenses between the eye and the observed light source. Apart from the image of the aperture diaphragm, the images of some details and reflections were formed. The terminal lens of the stimulator and the eye optics can divide the main and secondary images of the retina. Therefore the reactions of insect neurons to polarized light described previously could be explored also as the responses to flickers in secondary images.


Repositioning medication for cardiovascular and cerebrovascular disease to delay the onset and prevent progression of Alzheimer's disease.
Alzheimer's disease (AD) is a complex, progressive, neurodegenerative disorder. As with other common chronic diseases, multiple risk factors contribute to the onset and progression of AD. Many researchers have evaluated the epidemiologic and pathophysiological association between AD, cardiovascular diseases (CVDs), and cerebrovascular diseases (CBVDs), including commonly reported risk factors such as diabetes, hypertension, and dyslipidemia. Relevant therapies of CVDs/CBVDs for the attenuation of AD have also been empirically investigated. Considering the challenges of new drug development, in terms of cost and time, multifactorial approaches such as therapeutic repositioning of CVD/CBVD medication should be explored to delay the onset and progression of AD. Thus, in this review, we discuss our current understanding of the association between cardiovascular risk factors and AD, as revealed by clinical and non-clinical studies, as well as the therapeutic implications of CVD/CBVD medication that may attenuate AD. Furthermore, we discuss future directions by evaluating ongoing trials in the field.


Periostin attenuates oxygen and glucose deprivation-induced death of mouse neural stem cells via inhibition of p38 MAPK activation.
Promoting neural stem cells (NSCs) survival in the harsh niche is essential to cell replacement therapy for various central nervous system diseases. As an integral component of the extracellular matrix, Periostin (POSTN) has been shown to protect various cell types from hypoxia-ischemia damage. This study aimed to investigate the neuroprotective effects of POSTN on NSCs injury induced by oxygen and glucose deprivation (OGD). Under challenge with OGD, cell viability significantly decreased in cultured mouse NSCs, and supplement POSTN rescued cell viability in a concentration-dependent manner, as shown by CCK-8. TUNEL and propidium iodide/Hoechst staining showed that POSTN pretreatment protected NSCs against OGD-induced apoptosis. Western blot assay demonstrated that POSTN pretreatment inhibited cleavage of caspase-3 and restored the balance of Bcl-2/Bax. And pretreatment with cilengitide (an inhibitor of POSTN receptors) abolished the protective effect of POSTN. Further investigation demonstrated that supplement POSTN inhibited phosphorylation of p38 in a concentration-dependent manner. Moreover, the neuroprotective effect of POSTN was hampered by anisomycin, an activator of p38. We conclude that POSTN pretreatment in cultured mouse NSCs mitigated OGD-induced cell death, and inhibition of the p38 MAPK pathway might be one of the underlying mechanisms. Our findings may provide a novel strategy for enhancing both endogenous and exogenous NSCs survival after ischemia and hypoxia injury.


Parent-adolescent emotion-related behavior during conflict in a clinical sample.
Parents and adolescents often have conflict. Previous research has been inconsistent regarding the association between some parent behaviors during this conflict and adolescent symptoms. This study examines parents' behaviors during a conflict resolution discussion in a clinical sample, and the relationship between parents' behaviors and adolescents' depression and anxiety symptoms. Depression and anxiety symptoms were self-reported by 22 adolescents of ages 13-17 who were diagnosed with depression. They also participated in an observed conflict resolution task with one parent. Using observationally coded data, we utilized two linear multiple regressions to assess how parent and adolescent emotion-related behaviors related to adolescents' depression and anxiety symptoms. Adolescents' conflict behaviors were not associated with their psychopathology symptoms. Parent conflict behaviors of support and withdrawal were both negatively associated with adolescent depression and anxiety, with parent contempt marginally associated with adolescent depression. In this clinical sample, parents of adolescents with low mood or anxiety demonstrated some reduced negative parenting behaviors (i.e., contempt and withdrawal), but also reduced positive parenting behavior (i.e., support). The results suggest that when some negative parenting behaviors are reduced, this may inadvertently reinforce depressive behaviors. The results also indicate the importance of increasing supportive parent behaviors.


Ultrasonically activated gas-filled micropores release hemoglobin and antigens from human erythrocytes in vitro.
Antigen release from human type B red blood cells was investigated by sensitive capillary-tube assay techniques after subjecting 3% suspensions to a controlled form of ultrasonic cavitation. Cells were kept suspended during the 1,000-sec exposures by an orbital motion of the sample chamber. Several spatial peak intensities of continuous 1.7 MHz ultrasound were applied to the samples which included gas-filled 4-microns diameter micropores in hydrophobic membranes. Free hemoglobin, indicating hemolysis, and free antigenic material, indicating solubilization of antigens, were found in the supernates of suspensions exposed to 90 mW/cm2 or 180 mW/cm2, respectively, or greater intensities. None of the free antigenic material could be attributed to antigen loss by surviving cells. For these conditions, the antigen release effect of ultrasound appears to be a byproduct of cavitation-induced cell lysis.


Overview of formative, process, and outcome evaluation methods used in the VERB campaign.
Evaluation was an integral part of the VERB campaign. This paper describes the array of evaluation methods used to support the development, implementation, and assessment of campaign activities. The evaluation of VERB consisted of formative, process, and outcome evaluations and involved both qualitative and quantitative methods. Formative evaluation allowed staff to test ideas for messages and to gauge their appropriateness for the intended audiences. Process evaluation allowed staff to test and monitor the fidelity of the campaign's implementation to objectives and to make changes while the campaign was under way. Outcome evaluation allowed staff to determine the campaign's effects on the target audience. Because a comprehensive approach was used, which included formative and process evaluation, the VERB team's ability to interpret the results of the outcome evaluation was enhanced.


The role of cellular motility in the invasion of human neuroblastoma cells with or without N-myc amplification and expression.
Patients who have neuroblastomas with N-myc amplification that are extremely invasive and result in distant metastases tend to have a very poor prognosis. The authors reported previously that N-mycamplification and expression might be closely related to the invasiveness of human neuroblastoma cells. However, the role of cellular motility has not yet been clarified in the invasion of neuroblastoma cells. The aim of this study was, therefore, to elucidate the role of cellular motility in the invasion of neuroblastoma cells. Six human neuroblastoma cell lines were used for an invasion assay in vitro using polycarbonate filters coated with basement membrane Matrigel. The amplification and expression of N-myc oncogene was examined by Southern and Northern blotting, respectively. The cellular motility was quantified by computerized image analysis on the morphology of cultured cells. IMR-32, GOTO, and DZ, all of which had N-myc amplification, showed a high degree of invasiveness and a high cellular motility, whereas NB-69 and SK-N-SH without N-myc amplification showed an extremely low degree of invasiveness and cellular motility. ST without N-myc amplification, which was established from an aggressive tumor, showed an exceptionally high degree of motility and invasiveness. A transcriptional reduction of the N-myc gene by retinoic acid (RA) decreased the motility, which thus resulted in a marked decline of invasiveness in IMR-32 and GOTO. The cellular motility correlated with the invasive capacity of human neuroblastoma cells, which thus indicated that cellular motility may play an important role in invasion.


Heteroscedasticity of retention factor and adequate modeling in micellar liquid chromatography.
The two concepts of micelle formation (pseudo-phase and mass-action) could be the basis of retention models in micellar liquid chromatography (MLC). The separation of 4-hydroxybenzoic acid esters and seven polyaromatic hydrocarbons were performed to study the repeatability of retention factor in MLC. The full two factor experimental design was used for studying the dependence of retention factor variance on mobile phase composition (sodium dodecylsulfate, 1-butanol). The experimentally observed heteroscedasticity and perturbations after linearization were taken into account by using statistical weights obtained on the basis of errors propagation law and the modeling of retention by non-weighted and weighted least squares method was performed. The mechanistical retention models based on pseudo-phase and mass-action concepts of micelle formation were compared by fitting quality and prediction capability and high robustness of bilogarithmic dependence was observed. The significance of retention factor heteroscedasticity for retention hydrophobicity relationships was shown.


Radiotherapy-induced uterine cacinosarcoma: A case report and review of the literature.
Radiation therapy is a very effective treatment modality for cervical cancer, but unfortunately, ionizing radiation is associated with many side effects, including secondary cancer formation. We report a case of carcinosarcoma of the uterus in a woman with a history of pelvic irradiation for cervical carcinoma. A review of the literature was performed to present the incidence, optimal management, and prognosis for post-radiation uterine carcinosarcoma.


Handedness and familial sinistrality in a Japanese student population.
A handedness questionnaire consisting of thirteen items was administered to 4282 Japanese senior high school students. Information on the occurrence of left-handedness in their family as well as on forced conversion of hand usage in their childhood was obtained. Results indicated that incidence of non-right-handedness was 7.2%, with that of males being greater than that of females. The proportion of converted right-handers was greater in females than in males. When the frequency of converted right-handers was added to that of present non-right-handers, the average for non-right-handedness increased to 11%. Non-right-handers, particularly females, had familial sinistrality more frequently than right-handers. Item analysis revealed that the incidence of individuals who always use left hand for writing and eating was only 0.7% and 1.7%, respectively. This suggests that social pressure for right-hand writing and eating remains high in Japan.


Long-term follow-up and survival after Ultraflex stent insertion in the management of complex malignant airway stenoses.
Despite being commercially available for a few years now, the literature regarding the outcome of Ultraflex stent insertion in complex malignant airway stenoses is sparse. To assess long-term complications and survival in patients with complex malignant airway stenoses treated with insertion of nitinol stents. 60 consecutive patients with Ultraflex stent insertion for malignant airway stenoses were included. Follow-up was obtained in all patients. 62 Ultraflex stents (covered = 51, uncovered = 11) were implanted in 60 patients. Diagnoses were bronchial carcinoma (n = 50), esophageal carcinoma (n = 3) and metastases (n = 7). Stents were inserted in the trachea (n = 5), main bronchi/intermediate bronchus (n = 22), from main bronchi/intermediate bronchus to lobar bronchi (n = 28) or in the lobar bronchi themselves (n = 7). Successful reopening of the stenoses and relief were achieved in all patients. There was no procedure-related mortality. Complications included mucous plugging in 8%, stenosing granulation tissue in 5%, tumor ingrowth in 5% and stent migration in 5% of patients. Using Kaplan-Meier estimates, the overall mean survival was 160 days (standard error: 30). Median survival was 91 days. The overall 3- and 6-month survival were 52 and 20%, respectively. Death (n = 59, 98%) was attributed mainly to disease progression with cachexia and metastases, pneumonia (n = 5, 10%), and hemoptysis (n = 1, 2%). Ultraflex stents have a low complication rate and can be effectively used in complex malignant airway stenoses with marked asymmetry or irregularity, angulation or changing diameters.


Secular trends in cholesterol lipoproteins and triglycerides and prevalence of dyslipidemias in an urban Indian population.
Coronary heart disease is increasing in urban Indian subjects and lipid abnormalities are important risk factors. To determine secular trends in prevalence of various lipid abnormalities we performed studies in an urban Indian population. Successive epidemiological Jaipur Heart Watch (JHW) studies were performed in Western India in urban locations. The studies evaluated adults > or = 20 years for multiple coronary risk factors using standardized methodology (JHW-1, 1993-94, n = 2212; JHW-2, 1999-2001, n = 1123; JHW-3, 2002-03, n = 458, and JHW-4 2004-2005, n = 1127). For the present analyses data of subjects 20-59 years (n = 4136, men 2341, women 1795) have been included. In successive studies, fasting measurements for cholesterol lipoproteins (total cholesterol, LDL cholesterol, HDL cholesterol) and triglycerides were performed in 193, 454, 179 and 252 men (n = 1078) and 83, 472, 195, 248 women (n = 998) respectively (total 2076). Age-group specific levels of various cholesterol lipoproteins, triglycerides and their ratios were determined. Prevalence of various dyslipidemias (total cholesterol > or = 200 mg/dl, LDL cholesterol > or = 130 mg/dl, non-HDL cholesterol > or = 160 mg/dl, triglycerides > or = 150 mg/dl, low HDL cholesterol <40 mg/dl, high cholesterol remnants > or = 25 mg/dl, and high total:HDL cholesterol ratio > or = 5.0, and > or = 4.0 were also determined. Significance of secular trends in prevalence of dyslipidemias was determined using linear-curve estimation regression. Association of changing trends in prevalence of dyslipidemias with trends in educational status, obesity and truncal obesity (high waist:hip ratio) were determined using two-line regression analysis. Mean levels of various lipoproteins increased sharply from JHW-1 to JHW-2 and then gradually in JHW-3 and JHW-4. Age-adjusted mean values (mg/dl) in JHW-1, JHW-2, JHW-3 and JHW-4 studies respectively showed a significant increase in total cholesterol (174.9 +/- 45, 196.0 +/- 42, 187.5 +/- 38, 193.5 +/- 39, 2-stage least-squares regression R = 0.11, p < 0.001), LDL cholesterol (106.2 +/- 40, 127.6 +/- 39, 122.6 +/- 44, 119.2 +/- 31, R = 0.11, p < 0.001), non-HDL cholesterol (131.3 +/- 43, 156.4 +/- 43, 150.1 +/- 41, 150.9 +/- 32, R = 0.12, p < 0.001), remnant cholesterol (25.1 +/- 11, 28.9 +/- 14, 26.0 +/- 11, 31.7 +/- 14, R = 0.06, p = 0.001), total:HDL cholesterol ratio (4.26 +/- 1.3, 5.18 +/- 1.7, 5.21 +/- 1.7, 4.69 +/- 1.2, R = 0.10, p < 0.001) and triglycerides (125.6 +/- 53, 144.5 +/- 71, 130.1 +/- 57, 158.7 +/- 72, R = 0.06, p = 0.001) and decrease in HDL cholesterol (43.6 +/- 14, 39.7 +/- 8, 37.3 +/- 6, 42.5 +/- 6, R = 0.04, p = 0.027). Trends in age-adjusted prevalence (%) of dyslipidemias in JHW-1, JHW-2, JHW-3 and JHW-4 studies respectively showed insignificant changes in high total cholesterol (26.3, 35.1, 25.6, 26.0, linear curve-estimation coefficient multiple R = 0.034), high LDL cholesterol > or = 130 mg/dl (24.2, 36.2, 31.0, 22.2, R = 0.062), and high low HDL cholesterol < 40 mg/dl (46.2, 53.3, 55.4, 33.7, R = 0.136). Increase was observed in prevalence of high non-HDL cholesterol (23.0, 33.5, 27.4, 26.6, R = 0.026), high remnant cholesterol (40.1, 40.3, 30.1, 60.6, R = 0.143), high total:HDL cholesterol ratio > or = 5.0 (22.2, 47.6, 53.2, 26.3, R = 0.031) and > or = 4.0 (58.6, 72.5, 70.1, 62.0, R = 0.006), and high triglycerides (25.7, 28.2, 17.5, 34.2, R = 0.047). Greater correlation of increasing non-HDL cholesterol, remnant cholesterol, triglycerides and total:HDL cholesterol ratio was observed with increasing truncal obesity than generalized obesity (two-line regression analysis p < 0.05). Greater educational level, as marker of socioeconomic status, correlated significantly with increasing obesity (r2 men 0.98, women 0.99), and truncal obesity (r2 men 0.71, women 0.90). In an urban Indian population, trends reveal increase in mean total-, non-HDL-, remnant-, and total:HDL cholesterol, and triglycerides and decline in HDL cholesterol levels. Prevalence of subjects with high total cholesterol did not change significantly while those with high non-HDL cholesterol, cholesterol remnants, triglycerides and total-HDL cholesterol ratio increased. Increasing dyslipidemias correlate significantly with increasing truncal obesity and obesity.


Effect of potassium depolarization on phosphate-activated glutaminase activity in primary cultures of cerebellar granule neurons and astroglial cells during development.
The cerebellar granule cells are believed to be glutamatergic neurons. During the normal development of granule cells grown in a chemically defined medium, the specific activity of phosphate-activated glutaminase increased from 60 at 3 days to 150 (nmol/h/mg protein) at 15 days in vitro. Treatment with 25 mM K+ for the last 2 days elevated glutaminase activity in an age-dependent manner: about 100% at 3 and 6 days, 75% at 10 days, and 40% at 15 days in vitro. The enhancement of glutaminase in granule cells was dose-dependent. The half-maximal effect was obtained at about 20 mM K+, whereas the maximum concentration, which produced about a 2.5-fold increase in 3-day-old cultures was about 40 mM K+. The voltage-sensitive Na+ channel inhibitor tetrodotoxin had no effect on the depolarization-induced activity in granule cells. However, the increase in glutaminase by 25 mM K+ was significantly blocked by both organic (nifedipine) and inorganic (Ni2+ and Mg2+) calcium antagonists, indicating that elevation in activity may be mediated through transmembrane Ca2+ entry into granule cells. In contrast to neurons, in cultured cerebellar astrocytes, the activity of glutaminase slightly decreased during development, and treatment with 25 mM K+ had no significant effect on this enzyme activity. The present findings, together with previous observations, would indicate that depolarization with K+, which is believed to mimic in vivo presynaptic stimulation, could be one of the mechanisms that selectively controls the development and function of neurons, when measured in terms of the activity of the enzymes involved in the synthesis of cell-specific neurotransmitters.


Parental stress of Korean immigrants in the U.S.: Meeting Child and Youth's educational needs amid the COVID-19 pandemic.
This study investigates Korean immigrants' parental stress amid the COVID-19 pandemic, especially when they experience difficulties trying to meet their children's educational needs. Korean immigrant parents residing in the U.S. were invited to complete an online survey through purposive sampling. The final sample included a total of 341 Korean immigrant parents from 42 U.S. states. Three models of Ordinary Least Squares (OLS) regressions were conducted to examine the associations between parent-reported difficulties meeting the children's educational needs, parental stress, and the immigrant parents' resilience and social support. Findings indicate that parents' difficulties meeting their children's educational needs in general as well as language barriers were associated with increased parental stress. Moreover, parents' resilience and social support also significantly decreased parental stress levels. Implications for practice, policy, and future research are presented.


Percutaneous Image-Guided Cryoablation of Challenging Mediastinal Lesions Using Large-Volume Hydrodissection: Technical Considerations and Outcomes.
This study was designed to describe the technique of percutaneous image-guided cryoablation with large-volume hydrodissection for the treatment of challenging mediastinal lesions. Between March 2014 and June 2015, three patients (mean age 62.7 years) with four neoplastic anterior mediastinal lesions underwent five cryoablation procedures using large-volume hydrodissection. Procedures were performed under general anaesthesia using CT guidance. Lesion characteristics, hydrodissection and cryoablation data, technical success, complications, and clinical outcomes were assessed using retrospective chart review. Lesions (mean size 2.7 cm; range 2-4.3 cm) were in contact with great vessels (n = 13), trachea (n = 3), and mediastinal nerves (n = 6). Hydrodissection was performed intercostally (n = 4), suprasternally (n = 2), transsternally (n = 1), or via the sternoclavicular joint (n = 1) using 1-3 spinal needles over 13.4 (range 7-26) minutes; 450 ml of dilute contrast was injected (range 300-600 ml) and increased mean lesion-collateral structure distance from 1.9 to 7.7 mm. Vulnerable mediastinal nerves were identified in four of five procedures. Technical success was 100 %, with one immediate complication (recurrent laryngeal nerve injury). Mean follow-up period was 15 months. One lesion demonstrated residual disease on restaging PET-CT and was retreated to achieve complete ablation. At last follow-up, two patients remained disease-free, and one patient developed distant disease after 1 year without local recurrence. Cryoablation using large-volume hydrodissection is a feasible technique, enabling safe and effective treatment of challenging mediastinal lesions.


Variation of biophysical parameters of the skin with age, gender, and body region.
Understanding the physiological, chemical, and biophysical characteristics of the skin helps us to arrange a proper approach to the management of skin diseases. The aim of this study was to measure 6 biophysical characteristics of normal skin (sebum content, hydration, transepidermal water loss (TEWL), erythema index, melanin index, and elasticity) in a normal population and assess the effect of sex, age, and body location on them. Fifty healthy volunteers in 5 age groups (5 males and females in each) were enrolled in this study. A multifunctional skin physiology monitor (Courage & Khazaka electronic GmbH, Germany) was used to measure skin sebum content, hydration, TEWL, erythema index, melanin index, and elasticity in 8 different locations of the body. There were significant differences between the hydration, melanin index, and elasticity of different age groups. Regarding the locations, forehead had the highest melanin index, where as palm had the lowest value. The mean values of erythema index and melanin index and TEWL were significantly higher in males and anatomic location was a significant independent factor for all of 6 measured parameters. Several biophysical properties of the skin vary among different gender, age groups, and body locations.


Simple fibre optic spectrophotometric cell for pH determination.
A simple, inexpensive fibre optic spectrophotometric cell has been developed for clinical use. The system may employ one of two indicator reagents for the measurement: phenol red and BDH universal indicator. The spectrophotometer uses two ultrabright LED sources and a PIN diode photodetector. The fibre is of the plastic type with a core diameter of 1.0 mm. Two alternative analytical methods are available: electronic or computer processing. In the case of phenol red the measuring range using computer processing is between 6.0 and 8.0 pH units, with an accuracy of 0.015 pH units. The range for electronic circuit processing is from 6.8 to 8.0 pH units with an accuracy of 0.02 pH units. Using a BDH universal indicator, the range for computer processing is between 5.5 and 8.5 pH units with an accuracy of 0.05 pH units, while with electronic processing the range is between 6.0 and 8.0 pH units with an accuracy of 0.03 pH units. A description of the optoelectronics, an analysis of the indicator reagents and the calibration procedure are presented here, together with some example results.


Multiparametric Prostate Magnetic Resonance Imaging at 3 T: Failure of Magnetic Resonance Spectroscopy to Provide Added Value.
To assess the effect of proton magnetic resonance spectroscopy imaging (MRSI) on the accuracy of multiparametric magnetic resonance imaging (mpMRI) at 3 T for prostate cancer detection. Thirty-four patients with prostate cancer were included in this retrospective study. All patients underwent preoperative mpMRI on a 3-T scanner before radical prostatectomy. Magnetic resonance imaging evaluation was based on the prostate imaging-reporting and data system classification system. The accuracy of mpMRI with and without MRSI was determined using receiver operating characteristic analysis, with histology as the reference standard. Multiparametric MRI including MRSI had a sensitivity of 57.0% and a specificity of 89.2% for sextant-based cancer detection. Multiparametric MRI without MRSI had a sensitivity of 58.1% and a specificity of 87.4%. There was no significant difference regarding the accuracy of mpMRI with and without MRSI (P = 0.48). The addition of MRSI does not improve the accuracy of 3 T mpMRI for sextant localization of prostate cancer.


Novel synthetic bisbenzimidazole that targets angiogenesis in Ehrlich ascites carcinoma bearing mice.
Cancer is a leading cause of death in developed countries and second cause in developing countries. Herein we are reporting the synthesis of novel bisbenzimidazole derivatives and their anticancer properties. Among the newly synthesized bisbenzimidazoles, 3-(4-flurophenylsulfonyl)-1,7-dimethyl-2-propyl-1H,3H-2,5-bibenzo[d]imidazole (FDPB) presented as a potent antiproliferative agent against HeLa, HCT116 and A549 cells with selectivity over normal Vero cells (IC50 >50 μM). Additionally, we evaluated the efficacy of lead compound against Ehrlich ascites tumor (EAT) bearing mice for its antitumor and antiangiogenic properties. Our lead compound significantly reduced the cell viability, body weight, ascites volume and downregulated the formation of neovasculature and production of Vascular Endothelial Growth Factor (VEGF).


Angioscopic Ulcerated Plaques in the Femoropopliteal Artery Associated with Impaired Infrapopliteal Runoff.
To determine the correlation between upstream atherosclerosis in the femoropopliteal arteries, assessed using angioscopy, and impaired infrapopliteal runoff. Thirty-one patients with peripheral arterial disease who underwent endovascular therapy and angioscopy were prospectively included. Yellow plaque color scores were semiquantitatively determined as 0, 1, 2, or 3. Irregular plaques with rough surfaces, similar to gastric ulcers, were defined as ulcerated plaques (UPs). Angioscopic data were correlated with angiographic runoff scores (ARS). UPs were detected in 74.2% of enrolled diseased legs using angioscopy. Mural thrombi were more commonly observed in the femoropopliteal artery in patients with UPs than in those without UPs (91.3% vs 37.5%, respectively; P = .006) and were frequently found on the UPs (21/23 patients with UPs). Univariate and multivariate linear regression analyses revealed that the presence of UPs was positively and independently associated with a poor ARS and that oral anticoagulant use was independently associated with a preferable ARS (standardized β = 0.462, P = .004 and standardized β = -0.411, P = .009, respectively, in the multivariate analysis). UPs, associated with mural thrombi and diagnosed by angioscopic examination, were demonstrated to be one of the factors associated with poor infrapopliteal runoff.


Mechanisms of FGF gradient formation during embryogenesis.
Fibroblast growth factors (FGFs) have long been attributed to influence morphogenesis in embryonic development. Signaling by FGF morphogen encodes positional identity of tissues by creating a concentration gradient over the developing embryo. Various mechanisms that influence the development of such gradient have been elucidated in the recent past. These mechanisms of FGF gradient formation present either as an extracellular control over FGF ligand diffusion or as a subcellular control of FGF propagation and signaling. In this review, we describe our current understanding of FGF as a morphogen, the extracellular control of FGF gradient formation by heparan sulfate proteoglycans (HSPGs) and mechanisms of intracellular regulation of FGF signaling that influence gradient formation.


Personalized genomic medicine with a patchwork, partially owned genome.
"His book was known as the Book of Sand, because neither the book nor the sand have any beginning or end." - Jorge Luis BorgesThe human genome is a three billion-letter recipe for the genesis of a human being, directing development from a single-celled embryo to the trillions of adult cells. Since the sequencing of the human genome was announced in 2001, researchers have an increased ability to discern the genetic basis for diseases. This reference genome has opened the door to genomic medicine, aimed at detecting and understanding all genetic variations of the human genome that contribute to the manifestation and progression of disease. The overarching vision of genomic (or "personalized") medicine is to custom-tailor each treatment for maximum effectiveness in an individual patient. Detecting the variation in a patient's deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein structures is no longer an insurmountable hurdle. Today, the challenge for genomic medicine lies in contextualizing those myriad genetic variations in terms of their functional consequences for a person's health and development throughout life and in terms of that patient's susceptibility to disease and differential clinical responses to medication. Additionally, several recent developments have complicated our understanding of the nominal human genome and, thereby, altered the progression of genomic medicine. In this brief review, we shall focus on these developments and examine how they are changing our understanding of our genome.


Pectoralis major flap for head and neck reconstruction in era of free flaps.
The aim of this study was to evaluate factors affecting the selection of pectoralis major flap in the era of free tissue reconstruction for post ablative head and neck defects and flap associated complications. The records of patients who underwent various reconstructive procedures between July 2009 and December 2010 were retrospectively analysed. 147 reconstructive procedures including 79 free flaps and 58 pectoralis major flaps were performed. Pectoralis major flap was selected for reconstruction in 21 patients (36%) due to resource constrains, in 12 (20%) patients for associated medical comorbidities, in 11 (19%) undergoing extended/salvage neck dissections, and in 5 patients with vessel depleted neck and free flap failure salvage surgery. None of the flaps was lost, 41% of patients had flap related complications. Most complications were self-limiting and were managed conservatively. Data from this study suggest that pectoralis major flap is a reliable option for head and neck reconstruction and has a major role even in this era of free flaps. The selection of pectoralis major flap over free flap was influenced by patient factors in most cases. Resource constraints remain a major deciding factor in a developing country setting.


Downregulation of mitochondrial complex I induces ROS production in colorectal cancer subtypes that differently controls migration.
Colorectal cancer (CRC) can be classified into four molecular subtypes (CMS) among which CMS1 is associated with the best prognosis, while CMS4, the mesenchymal subtype, has the worst outcome. Although mitochondria are considered to be hubs of numerous signaling pathways, the study of mitochondrial metabolism has been neglected for many years. Mitochondrial Complex I (CI) plays a dual role, both in energy and reactive oxygen species (ROS) production. However, the possible contribution of CI to tumorigenesis in cancer remains unclear. The purpose of this study was to investigate the CI under the prism of the CMS classification of CRC in ex vivo models. Biochemical dosages, bioenergetics analysis and western-blot were used to characterize CI expression, function and redox balance in LoVo and MDST8 cell lines, belonging to CMS1 and CMS4 subgroups, respectively. Cell proliferation and migration were assessed by xCELLigence technology. Overproduction or scavenging of mitochondrial ROS (mtROS) were performed to analyze the effect of mtROS on proliferation, migration, and mesenchymal markers. Focal adhesion kinase (FAK) and its activation were analyzed by immunofluorescence. We assessed the distribution of two CI scores in CRC cohorts according to CMS classification and their relevance for patient survival. We found that CI is downregulated in CMS4 cells and is associated with elevated mtROS. We establish for the first time that in these migrating cells, mtROS production is maintained at optimal levels not only through changes in CI activity but also by inactivation/acetylation of superoxide dismutase 2 (SOD2), a major mitochondrial antioxidant enzyme. We show that promoting or scavenging mtROS both mitigate CMS4 cells' migration. Our results also point to a mtROS-mediated focal adhesion kinase (FAK) activation, which likely sustains their migratory phenotype. Using cohorts of CRC patients, we document that the expression of CI is downregulated in the CMS4 subgroup, and that low CI expression is associated with poor prognosis. Patients' datasets reveal an inverse correlation between CI and the epithelial-mesenchymal transition (EMT) pathway. We showed that inhibition of CI contributes to heighten mtROS, which likely foster MDST8 migration and might account for the specific EMT signature of CMS4 tumors. These data reveal a novel role of mitochondrial CI in CRC, with biological consequences that may be targeted with anti- or pro-oxidant drugs in clinical practice.


Radiation qualities of x-ray beams in cooperative clinical trials.
X-ray beams are usually described by "MV" numbers which represent accelerating potentials (AP) and approximations to the maximum energies in the photon spectra. However, these numbers do not uniquely specify the properties of the beams. Current high energy photon dosimetry protocols specify radiation quality in terms of a measured ionization ratio which is equivalent to the ratio of the tissue-maximum ratios at depths 10 cm and 20 cm, for field size 10 cm X 10 cm [TMR)20(10]. For convenience, the American Association of Physicists in Medicine introduced a new parameter, known as the Nominal Accelerating Potential (NAP), which was derived from (TMR)20(10) and features values in MV units that are similar to those of the conventional accelerating potentials. (TMR)20(10) and Nominal Accelerating Potential may be considered to be expressions of the penetrating powers of x-ray beams. We determined (TMR)20(10) and Nominal Accelerating Potential for 460 treatment machines with stated accelerating potentials from 4 MV to 25 MV in the Quality Assurance Review Center's files of machine data from institutions that participate in cooperative clinical trials. The results demonstrate appreciable variability of the two parameters at each stated accelerating potential, with overlapping of adjacent groups of machines. It is concluded that the manufacturers' MV numbers do not reliably identify x-ray beams in terms of their depth dose properties. To promote standardization and consistency of energy specification in clinical trials as well as in general practice, we propose that x-ray beams be designated by their Nominal Accelerating Potential values as an adjunct to the use of (TMR)20(10) in radiation therapy.


Maternal, fetal and placental regulation of placental iron trafficking.
The human placenta is a highly specialized organ that is responsible for housing, protecting, and nourishing the fetus across gestation. The placenta is essential as it functions among other things as the liver, lungs, and gut while also playing key immunological and endocrine roles. The structure and transport capacity of this temporary organ must evolve as gestation progresses while also adapting to possible alterations in maternal nutrient availability. All nutrients needed by the developing fetus must cross the human placenta. Iron (Fe) is one such nutrient that is both integral to placental function and to successful pregnancy outcomes. Iron deficiency is among the most common nutrient deficiencies globally and pregnant women are particularly vulnerable. Data on the partitioning of Fe between the mother, placenta and fetus are evolving yet many unanswered questions remain. Hepcidin, erythroferrone and erythropoietin are regulatory hormones that are integral to iron homeostasis. The mother, fetus and placenta independently produce these hormones, but the relative function of these hormones varies in each of the maternal, placental, and fetal compartments. This review will summarize basic aspects of Fe physiology in pregnant women and the maternal, fetal, and placental adaptations that occur to maintain Fe homeostasis at this key life stage.


The evolving story of AtzT, a periplasmic binding protein.
Atrazine is an s-triazine-based herbicide that is used in many countries around the world in many millions of tons per year. A small number of organisms, such as Pseudomonas sp. strain ADP, have evolved to use this modified s-triazine as a food source, and the various genes required to metabolize atrazine can be found on a single plasmid. The atomic structures of seven of the eight proteins involved in the breakdown of atrazine by Pseudomonas sp. strain ADP have been determined by X-ray crystallography, but the structures of the proteins required by the cell to import atrazine for use as an energy source are still lacking. The structure of AtzT, a periplasmic binding protein that may be involved in the transport of a derivative of atrazine, 2-hydroxyatrazine, into the cell for mineralization, has now been determined. The structure was determined by SAD phasing using an ethylmercury phosphate derivative that diffracted X-rays to beyond 1.9 Å resolution. `Native' (guanine-bound) and 2-hydroxyatrazine-bound structures were also determined to high resolution (1.67 and 1.65 Å, respectively), showing that 2-hydroxyatrazine binds in a similar way to the purportedly native ligand. Structural similarities led to the belief that it may be possible to evolve AtzT from a purine-binding protein to a protein that can bind and detect atrazine in the environment.


Identification of the hypervirulent lineages of Neisseria meningitidis, the ST-8 and ST-11 complexes, by using monoclonal antibodies specific to NmeDI.
Most cases of serogroup C meningococcal disease are caused by the clonal lineages ST-8 and ST-11. The gene encoding the putative restriction-modification system NmeDI is specific to these lineages. We report here a monoclonal antibody directed against the NmeDI endonuclease as a tool for their rapid and spe-cific identification.


High urea induces anxiety disorders associated with chronic kidney disease by promoting abnormal proliferation of OPC in amygdala.
Chronic kidney disease (CKD) with anxiety disorder is of a great concern due to its high morbidity and mortality. Urea, as an important toxin in CKD, is not only a pathological factor for complications in patients with CKD, but also is accumulated in the brain of aging and neurodegenerative diseases. However, the pathological role and underlying regulatory mechanism of urea in CKD related mood disorders have not been well established. We previously reported a depression phenotype in mice with abnormal urea metabolism. Since patients with depression are more likely to suffer from anxiety, we speculate that high urea may be an important factor causing anxiety in CKD patients. In adenine-induced CKD mouse model and UT-B-/- mouse model, multiple behavioral studies confirmed that high urea induces anxiety-like behavior. Single-cell transcriptome revealed that down-regulation of Egr1 induced compensatory proliferation of oligodendrocyte progenitor cells (OPC). Myelin-related signaling pathways of oligodendrocytes (OL) were change significant in the urea accumulation amygdala. The study showed that high urea downregulated Egr1 with subsequent upregulation of ERK pathways in OPCs. These data indicate that the pathological role and molecular mechanism of high urea in CKD-related anxiety, and provide objective serological indicator and a potential new drug target for the prevention and treatment of anxiety in CKD patients.


Zymogram and life-history studies on trypanosomes of the subgenus Megatrypanum.
Of 13 Swedish dairy cows examined, 12 (92.3%) were found to be infected with trypanosomes by cultivation of blood samples. Of the two species of tabanid fly caught close to the cattle, 33.3% of the Tabanus bromius and 8.6% of the Haematopota pluvialis were also found to be infected with trypanosomes on dissection. Isoenzyme patterns of trypanosome isolates from one H. pluvialis and from six cattle were identical, incriminating this fly species as a vector of the trypanosome. Comparison of these isolates with other Megatrypanum isolates indicated that the Swedish parasites were a form of Trypanosoma theileri and that T. theileri and the badger parasite T. pestanai are closely related. An isolate of a Megatrypanum from a buffalo (Syncerus caffer) in Kenya was entirely different from T. theileri.


Dissociation of covert and overt spatial attention during prehension movements: selective interference effects.
In four experiments, the influence of distractor objects on the temporal evolution of the reach-to-grasp movement toward a target object (an apple) was examined. In the first experiment, the distractor was another apple, which moved laterally behind the target and occasionally changed direction toward the target, thus becoming the to-be-grasped object. In the second and third experiments, the distractor was a stationary piece of fruit, which sometimes became the to-be-grasped object because of a change in illumination. The fourth experiment was a combination of the first two experiments. In all cases, selective interference effects on the transport and manipulation components were observed only when attention to the distractor was covert rather than overt. It is proposed that covert visuospatial attention selects information about distracting but potentially important stimuli, such that a registration of significance is accomplished without the need to process all available information.


Targeting of the antivascular drug combretastatin to irradiated tumors results in tumor growth delay.
The aim of the study is to evaluate the effects of targeting the antivascular drug combretastatin to irradiated mouse melanomas. Combretastatin was incorporated into liposomes with surfaces modified by the addition of cyclo(Arg-Gly-Asp-D-Phe-Cys) (RGD) to create an immunoliposome (IL). This addition of RGD allows the liposome to be preferentially targeted to alphavbeta3, an integrin up-regulated in the vasculature of irradiated tumors. C57BL mice bearing a transplanted B16-F10 melanoma were randomly assigned to one of the following treatment groups: untreated, a single dose of 5-Gy radiation (IR), IL (14.5 mg/kg of combretastatin), 5-Gy radiation plus IL, and a systemic administration of free drug (81.0 mg/kg of combretastatin). In this transplanted tumor model, there was no significant increase in the volume of the IL + IR (5 Gy) treated tumors during the initial 6 days posttreatment; all other treatment groups exhibited exponential growth curves after day 3. The IL + IR (5 Gy) treatment resulted in a 5.1-day tumor growth delay compared to untreated controls. These findings indicate that preferential targeting of antivascular drugs to irradiated tumors results in significant tumor growth delay.


Inhibitory effect of ethanol on the 5-hydroxytryptamine-induced Bezold-Jarisch reflex--involvement of peripheral 5-HT3 receptors.
The influence of ethanol (0.5, 1.0 and 2.0 g/kg i.p.) on the Bezold-Jarisch reflex in urethane-anaesthetized rats was studied. 5-Hydroxytryptamine (serotonin; 5-HT; 1, 3, 10 and 30 micrograms/kg i.v.) and capsaicin (1, 3 and 10 micrograms/kg i.v.) reflexly decreased heart rate in a dose-dependent manner. The 5-HT3 receptor antagonist ondansetron 10 micrograms/kg i.v. abolished the 5-HT- but not the capsaicin-stimulated bradycardia, indicating that 5-HT and capsaicin acted via different trigger mechanisms (5-HT3 receptor-dependent and -independent, respectively). Ethanol at 1.0 and 2.0 g/kg i.p. inhibited in a dose-dependent manner (by 20-45%) the 5-HT- but not the capsaicin-stimulated decrease in heart rate. Our results demonstrate that the inhibitory effect of ethanol on the 5-HT3 receptor-mediated Bezold-Jarisch reflex may be related to the direct effect of ethanol on 5-HT3 receptors on sensory vagal nerves in the heart.


Vitamin E status of cattle and sheep. 1: A background review.
The role of tocopherol in animal health, and its inter-relationship with selenium and polyunsaturated fatty acids, are reviewed.


Hypogammaglobulinemia in a renal transplant recipient with antiglomerular basement membrane disease.
A thirty-six-year-old woman developed antiglomerular basement membrane disease, necessitating bilateral nephrectomies. Subsequent to cadaveric renal transplant and 8 years of immunosuppressive treatment with prednisone and azathioprine, the patient developed multiple life-threatening infections. Quantitative immunoglobulins revealed IgG = 9, IgA less than 6.7, and IgM = 33. Lymphocyte population studies revealed absence of B-lymphocytes. It is suspected that prednisone or azathioprine may have caused a defect in B cell differentiation. In patients who are taking immunosuppressive medications and develop multiple infections, it is indicated to evaluate immunoglobulin and/or B lymphocyte status.


A DFT study to investigate the physical, electrical, optical properties and thermodynamic functions of boron nanoclusters (MxB2n0; x=1,2, n=3,4,5).
First Principle DFT calculations employing the B3LYP/LanL2DZ/SDD level of theory were used to analyze the various characteristics of boron nanoclusters (B6, B8, and B10). These pure structures were further doped with four transition metals (Ta, Ti, Tc, and V) to examine the enhancement of the pure structures' structural, electrical, and optical features. To study structural stability, we have estimated cohesion energy and imaginary frequencies. Cohesion energies were entirely negative, with a range of -3.37 eV to -8.07 eV, and most constructions had no imaginary frequencies, indicating their structural occurrences. The calculated adsorption energy suggests that the order of stability of the pristine boron nanoclusters is B10>B8>B6, and TcB10 and Tc2B10 are the more stable structures. Mulliken charge, DOS, HOMO-LUMO, and the HOMO-LUMO gap have all been examined in-depth to provide insight into electrical characteristics. UV-Vis and CD measurements show the doped boron nanoclusters have excellent optical properties. Aside from calculating thermodynamic functions, we have also calculated the global DFT parameters, which give us a deep quantum mechanical understanding of the optimized structure for further research and applications in the field of science and technology.


Consumption rates and the evolution of diet-induced plasticity in the head morphology of Melanoplus femurrubrum (Orthoptera: Acrididae).
Phenotypic plasticity may be an ecologically important evolutionary response to natural selection in multiple environments. I have determined the effect of diet-induced developmental plasticity in the head size of grasshoppers (Melanoplus femurrubrum) onfeeding performance on two types of plants. Full-sib families were divided and raised on either red clover, Trifolium repens, or rye grass, Lolium perenne. In three different stages of ontogeny, grasshoppers raised on rye grass had significantly larger heads, relative to body size, than full-sibs raised on clover. A principal components analysis indicated that two to five relative head size characters covaried as a block in their plastic response to the feeding environment. Regressions of adjusted consumption rates (mg/sec) against relative head size revealed that larger head sizes, induced by the rye grass diet, enhanced consumption rates of rye grass, but not clover. Unexpectedly, a similar positive association was observed between head size and consumption rate for grasshoppers raised on clover when they were feeding on clover. These results support the inference that grasshoppers exhibit adaptive phenotypic plasticity. However, the unexpected influence of head size on consumption rates of clover indicates that the functional relationship between head morphology and feeding performance is complex and that variation in this relationship among plant environments is not sufficient to explain the evolution of diet-induced phenotypic plasticity.


Precancerous histopathologic lesions of upper gastrointestinal tract among dyspeptic patients upon endoscopic evaluations.
Gastric cancer is one of the most important causes of morbidity and mortality worldwide which is influenced by different risk factors. This study aimed to investigate the effects of various factors associated with precancerous lesions among dyspeptic patients. Among dyspeptic patients admitted to gastrointestinal clinics in Ilam city, west of Iran, 1123 were investigated during 2008 to 2011. All patients were evaluated by endoscopy and their biopsy samples were examined for histological differentiations and their pathology reports were classified according to Sydney criteria. One thousand out of 1123 admitted dyspeptic patients were finally analyzed. The mean age of participants was 48 years (ranged 21-84 years), and 64.8% of patients were male. The frequency of patients with atrophy, metaplasia, or both was 14.4%, adenocarcinoma 1.2%, and polyp hyperplasia 0.7%, respectively. The highest frequency was related to those with chronic gastritis accompanied by Helicobacter pylori infection with a figure of 80.8%. The frequency of precancerous lesions among smokers compared to non-smokers was higher significantly (p < 0.03). Though non-significant, BMI was associated with the higher risk of premalignant lesions among dyspeptic patients by an increasing manner. Chronic gastritis accompanied with H. pylori infection was revealed as the most prevalent variable among dyspeptic patients. Also, higher BMI compared to normal and smokers compared to non-smokers were more involved by precancerous lesions.


An assay for uracil in human DNA at baseline: effect of marginal vitamin B6 deficiency.
Improvements are made to our gas-chromatography-mass-spectrometry-based assay for quantifying low levels of DNA-uracil. Folate deficiency leads to increased deoxyuridine monophosphate/thymidylate (dUMP/dTMP) ratios and uracil misincorporation into DNA, which may increase cancer risk. Vitamin B6 (B6) deficiency might also result in increased DNA-uracil because B6 is a cofactor for serine hydroxymethyltransferase, which catalyzes the methylation of tetrahydrofolate (THF) to methylene-THF, the folate form that is required to convert dUMP to dTMP. However, the low baseline levels of DNA-uracil in healthy human lymphocytes are difficult to measure accurately. This version of the assay (Uracil assay V3) has an approximately 10-fold increase in signal strength over the previous method and a 10-fold lower detection limit (0.2 pg uracil). Five micrograms of DNA, the amount in about 1 ml of human blood, is a suitable amount for this assay. Using this improved assay, DNA-uracil was measured in lymphocytes from 12 healthy smoking or nonsmoking young men and women who consumed a B6-restricted diet (0.7 mg B6/day, or approximately half the recommended dietary allowance) for 28 days. DNA-uracil concentration was not significantly related to B6 status or smoking. More severe and/or prolonged B6 deficiency may be necessary to detect significant changes in DNA-uracil in humans. The average concentration of DNA-uracil in these subjects was found to be approximately 3,000 uracils per diploid lymphocyte, which is comparable to steady state levels of one of the oxidative adducts of DNA, 8-oxoguanine.


Microfingerprinting analysis of human Ia molecules favours a three loci model.
Alpha subunits from DC1 Ia molecules, when compared with DR alpha subunits, are shown to possess distinctive features revealed by differences in microfingerprinting patterns after peptic digestion. Alpha chains from BR4X7 molecules differ from DC1 alpha chains and are more similar to DR alpha chains. Since DC1 and BR4X7 beta chains (which carry the HLA-controlled alloantigenic determinants) associate with different alpha subunits, it is considered unlikely that they are controlled by alleles at the same locus. The proposed model implies the existence of three tightly linked HLA loci controlling the beta subunits of DR, DC and BR molecules respectively.


Transnational Support of Asian Indian Elderly in India: Examining Patterns of Exchanges.
Using a mixed methods approach, the provision of support exchanges between family members across national borders was examined. Specifically, this project examined transnational support among Asian Indian elderly residing in India whose children resided outside India. Seventy adults participated in this project in the cities of Bangalore and Mumbai. Individuals participated in either a focus group meeting or completed a survey to examine their transnational family support experiences. Most seniors were educated, of middle-income category or higher, socially active, enjoyed good health, and were not keen to live in multigeneration households. Survey findings suggest that transnational care is reciprocal in nature and that communication technology has enhanced intergenerational contact. The older adults' report of support exchanges provided and received between generations showed significant differences on certain types of support. Undoubtedly, in today's rapidly growing global economy, a great deal of emotional support, communication, and exchanges takes place between adults and their elderly parents across national borders.


The efficiency of ECT: II. Correlation of specific treatment variables to response rate in unilateral ECT.
Determining the most efficient use of electroconvulsive therapy (ECT) for treating depression hinges on defining the crucial variable(s) related to the maximal efficacy of an individual seizure. In this study, we examined the relationships of several treatment variables to antidepressant effect of 109 individual unilaterally induced seizures. The seizures occurred during the maximal response phase of 39 courses of ECT judged to have been effective. The patients were divided according to whether or not they were receiving antidepressants during ECT. The variables were treatment number, seizure length, and type of seizure end point. In the total group, earlier treatments were significantly related to antidepressant effect. Seizure length and type of seizure end point appeared to be of little consequence. Further studies of ECT should focus particularly on the effects of the first treatment in order to define optimal ECT efficiency.


High-school adolescents' motivation to rugby participation and selection criteria for inclusion in school rugby teams: coaches' perspective (the SCRuM project).
Despite increasing rugby popularity among schoolboys' worldwide, specific factors influencing their motivation to participate in rugby remain unclear. Therefore, this study was conducted in two parts with a dual purpose of exploring perceptions of rugby coaches on (i) factors motivating schoolboys to engage in competitive rugby, and (ii) criteria for selecting schoolboy rugby players for possible inclusion in school rugby teams. A qualitative study targeting Zimbabwean high school-based rugby coaches purposively-recruited during the 2017 Dairiboard Zimbabwe Rugby School Festival was conducted. Using the conventional approach to content analysis, the 22 recruited male coaches (median age = 45.5 years) felt that playing rugby is a choice largely influenced by either intrinsic or extrinsic motives for schoolboys. Additionally, coaches considered players' characteristics (performance during training, attitude, physical qualities and skills) and match-related factors when selecting schoolboys for possible inclusion in school rugby teams. To effectively promote competitive rugby participation among schoolboys and promote sustainable and effective talent identification programmes in Zimbabwe, more recognition should be paid to factors motivating schoolboys to participate in rugby and also on the factors coaches consider when assembling school rugby teams which indirectly informs on what coaches think should be trained among schoolboy rugby players.


A new SEMA7A variant found in Native Americans with alloantibody.
John Milton Hagen (JMH) antigens are carried by Semaphorin 7A that plays important roles in the nervous system and the immune responses. Its role on the erythrocytes is unclear. Over the years, few samples were referred to our Immunohaematology Reference Laboratory to elucidate their JMH status. Seven blood samples with antibodies compatible with JMH1-negative red cells were studied at the molecular level to identify polymorphisms and explain the JMH diversity observed. Four samples were of Native American background and three were Caucasians. Molecular analyses of the SEMA7A were undertaken, and soluble form of recombinant Sema7A proteins was produced to characterize the antibodies. Sequencing of the cDNA showed a polymorphism in SEMA7A exon 9 at position 1040 (G>T) in the four Native American samples. Caucasians had a normal sequence. This polymorphism precludes a change at position 347 where an Arg is replaced by a Leu. Plasma was assayed in ELISA on wild-type Sema7AArg347 and variant Sema7ALeu347 proteins. Results clearly indicated a specific recognition of the antibody produced by the Native Americans for the wild-type Sema7AArg347 protein and not the variant one. A new SEMA7A variant was identified in this study. The antibody present in the Native American plasma samples should be considered as an alloantibody because it recognizes the wild-type protein.


Inhibition of glucose-stimulated insulin release from beta TC3 cells and rodent islets by an analog of FK506.
Immunosuppression is currently used for allotransplantation, and is being evaluated for the treatment of insulin-dependent diabetes mellitus and other autoimmune diseases. However, most available agents have a number of side effects that limit their use in clinical situations. It has been shown previously, for example, that cyclosporine may inhibit insulin release from islet tumor cells and rat islets. We have studied the effects of an analog of a newer agent (FK506) termed L-683,590 on insulin secretion by an islet tumor line, beta TC3, and rat islets, and compared the effects of this drug to those of cyclosporine, since both cause similar immunosuppression. L-683,590 and cyclosporine inhibited insulin release by beta TC3 cells by about 50% and 80%, respectively, at doses that inhibit lymphokine production by T cells. The inhibition by L-683,590 and cyclosporine was more pronounced at higher glucose levels, and was not simply attributable to a general toxic effect of the drugs on the cells. Insulin release during long-term (> 48 hr) cultures of isolated rat islets was also inhibited by the drugs. However, there was no effect of either agent on insulin release by islets during the first 4 hr following a glucose stimulus. Both drugs caused reduced levels of insulin mRNA (by 56 +/- 8.1% and 66 +/- 16% in the presence of L-683,590 and cyclosporine, respectively), accounting for reduced rates of insulin biosynthesis that were also seen. Our studies indicate that: (1) both cyclosporine and L-683,590 inhibit insulin release by beta TC3 cells and cultured rat islets after 48 hr (cyclosporine is a more potent inhibitor); (2) neither drug inhibits the release of insulin during the first 4 hr following a glucose stimulus; and (3) their mechanisms of action appear to be similar--both drugs cause reduced levels of insulin mRNA. Although the toxicity of FK506 on human islets in vivo is still unknown, it may be of particular importance in individuals with impaired beta cell function, such as patients with new-onset insulin-dependent diabetes or patients with non-insulin-dependent diabetes mellitus.


Australian indigenous children with low cognitive ability: Family and cultural participation.
Family and cultural inclusion are essential for the healthy development of young Australian Indigenous peoples with low cognitive ability. To date, this issue has received limited research attention. A secondary analysis of data collected in Wave 4 of Footprints in Time, Australia's Longitudinal Study of Indigenous Children, was conducted to help address this research gap. The study results indicated that in some areas, Indigenous children with low cognitive ability are at a higher risk of social exclusion than their peers. We discuss the policy implications of these findings with regards to addressing Indigenous disadvantage.


"Boldness" in the domestic dog differs among breeds and breed groups.
"Boldness" in dogs is believed to be one end of the shy-bold axis, representing a super-trait. Several personality traits fall under the influence of this super-trait. Previous studies on boldness in dogs have found differences among breeds, but grouping breeds on the basis of behavioural similarities has been elusive. This study investigated differences in the expression of boldness among dog breeds, kennel club breed groups, and sub-groups of kennel club breed groups by way of a survey on dog personality circulated among Australian dog-training clubs and internet forums and lists. Breed had a significant effect on boldness (F=1.63, numDF=111, denDF=272, p<0.001), as did breed group (F=10.66, numDF=8, denDF=772, p<0.001). Herding and gundog groups were broken into sub-groups based on historic breed purpose. Retrievers were significantly bolder than flushing and pointing breeds (Reg. Coef.=2.148; S.E.=0.593; p<0.001), and tending and loose-eyed herding breeds were bolder than heading and cattle-herding breeds (Reg. Coef.=1.744; S.E.=0.866; p=0.045 and Reg. Coef.=1.842; S.E.=0.693; p=0.0084, respectively). This study supports the existence of the shy-bold continuum in dogs. Differences in boldness among groups and sub-groups suggest that behavioural tendencies may be influenced by historical purpose regardless of whether that purpose still factors in selective breeding.


The movement of a nerve in a magnetic field: application to MRI Lorentz effect imaging.
Direct detection of neural activity with MRI would be a breakthrough innovation in brain imaging. A Lorentz force method has been proposed to image nerve activity using MRI; a force between the action currents and the static MRI magnetic field causes the nerve to move. In the presence of a magnetic field gradient, this will cause the spins to precess at a different frequency, affecting the MRI signal. Previous mathematical modeling suggests that this effect is too small to explain the experimental data, but that model was limited because the action currents were assumed to be independent of position along the nerve and because the magnetic field was assumed to be perpendicular to the nerve. In this paper, we calculate the nerve displacement analytically without these two assumptions. Using realistic parameter values, the nerve motion is <5 nm, which induced a phase shift in the MRI signal of <0.02°. Therefore, our results suggest that Lorentz force imaging is beyond the capabilities of current technology.


Cr(VI) and doxorubicin adsorptive capture by a novel bionanocomposite of Ti-MOF@TiO2 incorporated with watermelon biochar and chitosan hydrogel.
Biodegradable polymers, biochars and metal organic frameworks (MOFs) have manifested as top prospects for elimination of harmful pollutants. In the current study, Ti-MOF was synthesized and decorated with TiO2 nanoparticles, then embedded into watermelon peel biochar and functionalized with chitosan hydrogel to produce Ti-MOF@TiO2@WMPB@CTH. Various instruments were employed to assure the effective production of the bionanocomposite. The HR-TEM and SEM studies referred to excellent surface porosity and homogeneity of Ti-MOF@TiO2@WMPB@CTH bionanocomposite, with 51.02-74.23 nm. Based on the BET analysis, the mesoporous structure has a significant surface area of 366.04 m2 g-1 and a considerable total pore volume of 11.38 × 10-2 cm3 g-1, with a mean pore size of 12.434 nm. Removal of doxorubicin (DOX) and hexavalent chromium (Cr(VI)) was examined under various experimentations. Pseudo-second order kinetic models in addition to Langmuir isotherm offered the best fitting. Thermodynamic experiments of the two contaminants demonstrated spontaneous and endothermic interactions. After five subsequent adsorption and desorption cycles, Ti-MOF@TiO2@WMPB@CTH bionanocomposite demonstrated an exceptional recyclability for the elimination of DOX and Cr(VI) ions, reaching 97.96 % and 95.28 %, respectively. Finally, the newly designed Ti-MOF@TiO2@WMPB@CTH bionanocomposite demonstrated a high removing efficiency of Cr(VI) ions and DOX from samples of real water.


Primary sclerosing cholangitis is protective against nonalcoholic fatty liver disease in inflammatory bowel disease.
Nonalcoholic fatty liver disease (NAFLD) occurs with higher prevalence in patients with inflammatory bowel disease (IBD) relative to the general population, and susceptibility is related to the metabolic syndrome, as well as higher prevalence of bowel resection and gut microbiotal factors. Liver complications, including NAFLD and primary sclerosing cholangitis (PSC), contribute to treatment and prognosis of patients with IBD. However, the potential interplay of NAFLD and PSC is not well understood. We retrospectively assessed severity of steatosis and steatohepatitis in liver specimens from 49 patients with IBD only, 44 with IBD and comorbid PSC, and 30 with IBD and PSC after liver transplantation. Patients with IBD had higher prevalence of at least grade 1 steatosis (59%) than IBD and PSC (11%), or IBD and PSC posttransplant (3%) (P < .001). The average severity of steatosis was 25% ± 8% (95% confidence interval) for IBD only, 3% ± 1% for comorbid IBD and PSC, and 1% ± 1% for IBD and PSC posttransplant (P < .001). Steatohepatitis was significantly higher in IBD only (12%) than in IBD and PSC ± transplant (0%) (P = .01). Despite these differences in susceptibility to NAFLD, the 3 populations had statistically indistinguishable average body mass index and total cholesterol and prevalence of hypertension, diabetes, and alcohol use. Multivariate regression modeling revealed body mass index, hypertension, and diabetes as significant correlates to NAFLD severity in all studied populations. In conclusion, patients with comorbid IBD and PSC have significantly less susceptibility to NAFLD than those with IBD alone, despite similar prevalence of major NAFLD risk factors.


An updated review of pediatric autoimmune neuropsychiatric disorders associated with Streptococcus/pediatric acute-onset neuropsychiatric syndrome, also known as idiopathic autoimmune encephalitis: What the allergist should know.
Pediatric acute-onset neuropsychiatric syndrome, further subcategorized as pediatric autoimmune neuropsychiatric disorders associated with streptococcus, is a form of idiopathic autoimmune encephalitis (IAE). Poststreptococcal autoimmunity seen in Idiopathic autoimmune encephalitis manifests as various neuropsychiatric symptoms such as obsessive rituals, tics, anxiety, depression, and many others. Idiopathic autoimmune encephalitis has clinically heterogeneous phenotypes that make accurate diagnosing difficult, although diagnostic testing such as the Cunningham Panel increases the likelihood of finding effective treatments. Current recommended treatments include psychiatric medication, behavioral intervention, antibiotics, anti-inflammatory therapy, and immunomodulating therapy. To provide an updated review on the diagnosis, management, and treatment of pediatric autoimmune neuropsychiatric disorder associated with streptococcus and pediatric autoimmune neuropsychiatric syndrome, also referred to as IAE. Information from 47 sources was used to outline current knowledge of IAE pathophysiology, clinical manifestations, and epidemiology, and to outline diagnostic recommendations and current treatment guidelines. Gaps in knowledge, in addition to current controversy, were also outlined to provide a thorough background of this condition and future needs for IAE research. Owing to the complexity and variability in ways patients with IAE may present to the allergist/immunologist office, an interdisciplinary approach is imperative to provide patients with the best medical care. Still, more research is needed to further elucidate the mechanism(s) and optimal treatment algorithm for IAE to facilitate broader recognition and acceptance of this condition by the medical community.


Silkworm carotenoprotein as an efficient carotenoid extractor, solubilizer and transporter.
Found in many organisms, water-soluble carotenoproteins are prospective antioxidant nanocarriers for biomedical applications. Yet, the toolkit of characterized carotenoproteins is rather limited: such proteins are either too specific binders of only few different carotenoids, or their ability to transfer carotenoids to various acceptor systems is unknown. Here, by focusing on a recently characterized recombinant ~27-kDa Carotenoid-Binding Protein from Bombyx mori (BmCBP) [Slonimskiy et al., International Journal of Biological Macromolecules 214 (2022): 664-671], we analyze its carotenoid-binding repertoire and potential as a carotenoid delivery module. We show that BmCBP forms productive complexes with both hydroxyl- and ketocarotenoids - lutein, zeaxanthin, astaxanthin, canthaxanthin and a smaller antioxidant, aporhodoxanthinone, but not with β-carotene or retinal, which defines its broad ligand specificity toward xanthophylls valuable to human health. Moreover, the His-tagged BmCBP apoform is capable of cost-efficient and scalable enrichment of xanthophylls from various crude methanolic herbal extracts. Upon carotenoid binding, BmCBP remains monomeric and shows a remarkable ability to dynamically shuttle carotenoids to biological membrane models and to unrelated carotenoproteins, which in particular makes from the cyanobacterial Orange Carotenoid Protein a blue-light controlled photoswitch. Furthermore, administration of BmCBP loaded by zeaxanthin stimulates fibroblast growth, which is attractive for cell- and tissue-based assays.


The cytotoxic effect of mistletoe lectins I, II and III on sensitive and multidrug resistant human colon cancer cell lines in vitro.
Multidrug resistance glycoprotein1 (MDR-1) eliminates amphiphilic chemotherapeutic agents out of tumour cells leading to therapeutic failures. The aim of this study was to investigate the cytotoxic effect of mistletoe lectins (MLs) I, II and III on the sensitive human colon cancer cell line HT 29(mdr-), its multidrug resistant variant HT 29(mdr+), the variant HT 29(SF1m) transfected with the MDR-1 gene and its sensitive control cell line HT 29(deltaSF). Both cell proliferation and ML binding pattern were analysed. Marked quantitative differences concerning the cytotoxic effect of the three MLs on the different cell lines were observed. All MLs showed the greatest cytotoxicity towards the HT 29(mdr+) cells, in which multidrug resistance (MDR) was induced by increasing concentrations of a MDR inducing agent. In contrast, MDR-1 and mock-transfected cells showed almost the same sensitivity towards the three MLs as the control cells (HT 29(mdr-)). FACS analysis showed that the HT 29(mdr+) cells were the cells with the highest density of ML binding sites. Thus, higher sensitivity of HT 29(mdr+) cells are not caused by the overexpression of MDR-1, but are caused by the general changes of the cellular glycosylation during the acquisition of the MDR phenotype.


Simultaneous determination of disopyramide and its mono-N-dealkyl metabolite in plasma and urine by high-performance liquid chromatography.
A high-performance liquid chromatographic procedure is described for the determination of disopyramide and its mono-N-dealkyl metabolite which offers simplicity of extraction with excellent selectivity, sensitivity and reproducibility. The drug and metabolite, following basic diethyl ether extraction and back-extraction with acetic acid, are injected into a reversed-phase high-performance liquid chromatographic column and the absorbance of the eluate measured at 254 nm. Detectability limits of 0.05 micrograms/ml were obtained with both compounds, and studies of the reproducibility, precision, recovery, stability during storage and effect of time in separating plasma from erythrocytes are described. Applications of this high-performance liquid chromatographic procedure to plasma samples from patients on disopyramide therapy and to plasma and urine from a healthy dog administered single doses are reported.


Menarche stories: reminiscences of college students from Lithuania, Malaysia, Sudan, and the United States.
Women college students in four countries were invited to write the story of their first menstruation in as much detail as memory allowed. Stories were received from 26 Lithuanians, 27 Americans, 20 Malaysians, and 23 Sudanese. The stories were read and their contents analyzed for the presence or absence of information on such topics as emotional reaction, preparedness, sources of information about menstruation, changes in body image, and celebrations of this rite of passage. Similarities and differences among the groups are discussed, and passages from particularly interesting stories are quoted.


Characteristics and severity of COVID-19 among Sudanese patients during the waves of the pandemic.
COVID-19 is associated with marked morbidity and mortality. COVID-19 symptoms ranged from mild symptoms to severe pneumonia requiring admission to intensive care unit. Imperial College reported that, this second wave in Khartoum is expected to be similar to the first wave. The aim of our study was to study the characteristics and severity of COVID-19 among Sudanese patients during the waves of the pandemic. A hospital-based analytical Cross-Sectional study assessed the characteristics of COVID-19 patients who attended Imperial Hospital since November 2020, Khartoum, Sudan. Data were collected, retrospectively, from the medical records of COVID-19 patients. The characteristics of the patients were recorded. The statistical package for social sciences (SPSS-23) was used to describe and analyze the data. Descriptive statistics and chi-square test were used; tests were considered statistically significant when p < 0.05. Of the 138 participants, 75.4% were aged above 60 years. Males were 61.6%. Severe cases were 37.7%, with higher rate in the third wave (p = 0.000). Duration of hospitalization was ≤ 5 days in 60.9% of the cases, majority were from the 2nd wave (p = 0.001). Comorbidities of COVID-19 patients were more among non-severe cases (p = 0.001). COVID-19 symptoms were more prevalent in non-severe cases. Complications were more in severe cases (p = 0.000). Odds ratio of having ischemic stroke was 6.833 [95%CI: 2.092-22.321] based on COVID-19 severity. The elderly population were the majority. More males were getting admitted. Atypical symptoms were reported beside the common symptoms. Wider multi-center studies are recommended in order to complete the big picture of COVID-19 in Sudan.