1D basin modeling and hydrocarbon generation potential of the Late Carboniferous Limburg Group formations, Northwest European Basin, Netherlands.
The Carboniferous rock samples of the Limburg Group formations were studied to investigate the source rock characteristics and the hydrocarbon generative potential. The source rock samples have been collected representing four rock units from three different wells. These samples were analyzed using Rock-Eval pyrolysis results and measured vitrinite reflectance values, and also by generating a one-dimensional basin model of K1 Field. The total organic carbon in these samples varies from 0.31 to 83.56% with a mean of 37.68%, suggesting that Limburg Group formations have excellent potential as a source of hydrocarbons. Kerogen in the Limburg Group formations is type II-III and type III, generate gas prominently. The outcomes of thermal maturation by Tmax and measured vitrinite reflectance reveal that the examined Limburg source rocks are located in the mature zone. The burial and thermal history models show irregular trend patterns due to uplift, erosion, and non-deposition events that took place in the K1 field (where the structural element is Cleaver Bank High). For the Maurits Formation, the oil generation took place at 2011 m at 230.1Ma ago and the top of the gas window was encountered 217.8Ma ago at 2535 m, whereas for the Hospital Ground Formation, the top of the oil window was encountered 186.8Ma ago at 2404 m and the gas generation took place at 2404 m at 161.9Ma ago.


A new protopanaxadiol-type ginsenoside from the roots of Panax notoginseng.
A new protopanaxadiol-type ginsenoside, 6-O-β-d-glucopyranosyl-20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol-3-one (1), along with three known compounds, was isolated from the roots of Panax notoginseng. Their structures were determined based on some pieces of spectroscopic and chemical evidence. Compound 1 exhibited cytotoxic activity against five human cancer cell lines, with IC50 values ranging from 5.4 to 8.6 μg/ml.


Targeting HSP90 Gene Expression with 17-DMAG Nanoparticles in Breast Cancer Cells.
Dysregulation of HSP90 gene expression is known to take place in breast cancer. Here we used D,L-lactic-co-glycolic acid-polyethylene glycol-17-dimethylaminoethylamino-17-demethoxy geldanamycin (PLGA-PEG-17DMAG) complexes and free 17-DMAG to inhibit the expression of HSP90 gene in the T47D breast cancer cell line. The purpose was to determine whether nanoencapsulating 17DMAG improves the anti-cancer effects as compared to free 17DMAG. The T47D breast cancer cell line was grown in RPMI 1640 supplemented with 10% FBS. Encapsulation of 17DMAG was conducted through a double emulsion method and properties of copolymers were characterized by Fourier transform infrared spectroscopy and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity was by MTT assay. After treatment of T47D cells with a given amount of drug, RNA was extracted and cDNA was synthesized. In order to assess HSP90 gene expression, real-time PCR was performed. Taking into account drug load, IC50 was significant decreased in nanocapsulated 17DMAG in comparison with free 17DMAG. This finding was associated with decrease of HSP90 gene expression. PLGA-PEG-17DMAG complexes can be more effective than free 17DMAG in down-regulating of HSP90 expression, at the saesm time exerting more potent cytotoxic effects. Therefore, PLGA-PEG could be a superior carrier for this type of hydrophobic agent.


Inverse and forward dynamics: models of multi-body systems.
Connected multi-body systems exhibit notoriously complex behaviour when driven by external and internal forces and torques. The problem of reconstructing the internal forces and/or torques from the movements and known external forces is called the 'inverse dynamics problem', whereas calculating motion from known internal forces and/or torques and resulting reaction forces is called the 'forward dynamics problem'. When stepping forward to cross the street, people use muscle forces that generate angular accelerations of their body segments and, by virtue of reaction forces from the street, a forward acceleration of the centre of mass of their body. Inverse dynamics calculations applied to a set of motion data from such an event can teach us how temporal patterns of joint torques were responsible for the observed motion. In forward dynamics calculations we may attempt to create motion from such temporal patterns, which is extremely difficult, because of the complex mechanical linkage along the chains forming the multi-body system. To understand, predict and sometimes control multi-body systems, we may want to have mathematical expressions for them. The Newton-Euler, Lagrangian and Featherstone approaches have their advantages and disadvantages. The simulation of collisions and the inclusion of muscle forces or other internal forces are discussed. Also, the possibility to perform a mixed inverse and forward dynamics calculation are dealt with. The use and limitations of these approaches form the conclusion.


Obturator Dislocation of the Hip with Associated Femoral Head Impaction and Medial Wall Fracture of the Acetabulum.
The combination of traumatic obturator dislocations and a femoral head impaction is rare and the treatment challenging. This report describes the successful management of this rare injury in a young patient. A 22-year-old truck driver involved in a ski accident sustained an obturator dislocation of the right hip associated with a femoral head impaction in the weight-bearing zone and a medial wall fracture of the acetabulum. After an initial closed reduction within 6 hours after the accident, for the definitive treatment, the hip joint was exposed through a Kocher-Langenbeck approach with trochanter flip osteotomy and surgical hip dislocation. A closing wedge intertrochanteric osteotomy was performed aiming to turn the head impaction out of the weight-bearing zone and the large head defect filled with the bone block removed from the osteotomy. The medial wall fragment was fixed, and the graft and osteotomies were stabilized with screws and a blade plate. The patient was mobilized with partial weight-bearing for 3 months then he progressively started full weight-bearing and normal daily activities. 5 years after the injury, the patient was completely asymptomatic, and radiographs demonstrated union of all osteotomies, osseous integration and remodeling of the bone graft as well as correct congruity of the hip joint. The intertrochanteric osteotomy aims to turn the impacted zone out of the weight-bearing area. Bone grafting of the defect helps to restore congruence and containment of the hip and additionally reinforces the femoral neck. To manage all the lesions present, a trochanteric flip approach with surgical hip dislocation is mandatory.


[APPLICATION OF SPLIT-THICKNESS SCALP GRAFT AND TEMPOROPARIETAL FASCIA FLAP IN LOW HAIRLINE AURICLE RECONSTRUCTION IN MICROTIA PATIENTS].
To investigate the application and effectiveness of split-thickness scalp graft and temporoparietal fascia flap in the low hairline auricle reconstruction in microtia patients. Between July 2010 and April 2015, 23 patients with low hairline microtia (23 ears) underwent low hairline auricle reconstruction. There were 16 males and 7 females with the mean age of 12 years (range, 6-34 years). The left ear was involved in 10 cases, and the right ear in 13 cases. There were 18 cases of lobule-type, 4 cases of concha-type, and 1 case of small concha-type. Referring to Nagata's two-stage auricular reconstruction method, the first stage operation included fabrication and grafting of autogenous costal cartilage framework; after 6 months, second stage operation of depilation and formation of cranioauricular sulcus was performed. The split-thickness scalp was taken from the part of the reconstructive ear above hairline. The hair follicles and subcutaneous tissue layers in hair area were cut off during operation. The area of depilation and auriculocephalic sulcus were covered with temporoparietal fascia flap. Then split-thickness skin was implanted on the surface of temporoparieta fascia flap. All operations were successfully completed. Healing of incision by first intention was obtained, without related complication. The patients were followed up 6-20 months (mean, 12 months). The reconstructed ear had satisfactory appearance and, had no hair growth. The application of split-thickness scalp graft and temporoparietal fascia flap in low hairline auricle reconstruction in microtia patients can achieve satisfactory results.


Statin treatment and 3' polyadenylation of eNOS mRNA.
Statins have been shown to increase endothelial nitric oxide synthase expression via enhanced mRNA stability. Because the poly(A) tail is an important determinant of transcript stability, we sought to characterize the effect of statins on eNOS mRNA 3' polyadenylation. Endothelial cells treated with statins had a time- and dose-dependent increase in eNOS transcripts with long poly(A) tails (75 to 160 adenosines). This effect was dependent on 3-hydroxy-3-methylglutaryl (HMG)-coenxyme A (CoA) reductase inhibition and was observed with both lipophilic (simvastatin) and hydrophilic (rosuvastatin) statins. In mRNA stability assays, polyadenylated eNOS transcripts from statin-treated cells were 2- to 3-fold more stable than transcripts from untreated cells. The effect of statins on eNOS polyadenylation was related to cytoskeleton organization; there was increased eNOS mRNA polyadenylation after Rho inhibition and cytochalasin D treatment. Further, we found increased phosphorylation of RNA polymerase II in statin-treated cells, suggesting that statin-induced polyadenylation involved modulation of RNA polymerase II activity. Our data provide insight into a mechanism by which statins enhance eNOS mRNA stability and increase eNOS protein: statins increase eNOS mRNA polyadenylation through Rho-mediated changes in the actin cytoskeleton.


Importance of prumycin produced by Bacillus amyloliquefaciens SD-32 in biocontrol against cucumber powdery mildew disease.
Powdery mildew disease of cucurbits is caused mainly by Podosphaera fusca, which is one of the most important limiting factors in cucurbit production worldwide. Previously we reported that Bacillus amyloliquefaciens biocontrol strain SD-32 produces C17 bacillomycin D and [Ile 2002]surfactin, and that these metabolites play important roles in SD-32's biocontrol over cucumber gray mold disease. Our further investigation demonstrated that the culture broth and its supernatant suppressed cucumber powdery mildew disease in greenhouse experiments. However, the active principle(s) remained unknown. The active compound was isolated from the culture supernatant after anti-powdery mildew disease activity-guided purification and identified as prumycin. Prumycin significantly suppressed the disease, whereas bacillomycin D and [Ile 2002]surfactin did not. Prumycin did not induce the expression of plant defense genes (PR1a and VSP1), suggesting that it does not act via plant defense response. Light microscopic observations of prumycin-treated cucumber cotyledon suggested that prumycin inhibits the conidial germination of P. fusca. This study demonstrates that prumycin is a major factor in SD-32's suppression of cucumber powdery mildew disease. Our findings shed light for the first time on prumycin's role in biocontrol by Bacillus against this disease. © 2017 Society of Chemical Industry.


Augmentation of hematopoiesis by fibroblast-mediated interleukin-6 gene therapy in mice with chemotherapy.
Murine fibroblast NIH3T3 cells engineered to secrete interleukin-6 (NIH3T3-IL-6) were implanted intraperitoneally into mice and observed for their hematopoietic effects with or without 5-fluorouracil (5-FU) administration. In normal mice, the platelet and neutrophil counts in peripheral blood increased significantly after implantation of NIH3T3-IL-6 cells, but the total white blood cell numbers showed no obvious elevation. The granulocyte-macrophage colony-forming unit (CFU-GM) and megakaryocyte colony-forming unit (CFU-MK) numbers formed by stem cells in bone marrow and spleen were also found to be significantly increased after implantation of NIH3T3-IL-6 cells when compared with those in mice after implantation of NIH3T3 cells transduced with neomycin gene (NIH3T3-Neo). To observe the protective effects of NIH3T3-IL-6 cells on hematopoietic depression in chemotherapy-treated mice, the mice were preinjected with 5-FU at a dosage of 150 mg/kg before implantation of NIH3T3-IL-6 cells. The platelet and neutrophil counts showed accelerated recovery after implantation of NIH3T3-IL-6 cells. The numbers of CFU-GM and CFU-MK in bone marrow and spleen were also found to be markedly increased in hematopoietic-depressed mice when compared with those in mice implanted with NIH3T3-Neo cells. These data suggest that fibroblast-mediated IL-6 gene therapy, which can augment hematopoiesis in mice with or without chemotherapy, will be of great help in the recovery from hematopoietic depression after chemotherapy.


Profiling of exome mutations associated with progression of HBV-related hepatocellular carcinoma.
Recent advances in sequencing technology have allowed us to profile genome-wide mutations of various cancer types, revealing huge heterogeneity of cancer genome variations. However, its heterogeneous landscape of somatic mutations according to liver cancer progression is not fully understood. Here, we profiled the mutations and gene expressions of early and advanced hepatocellular carcinoma (HCC) related with Hepatitis B-viral infection. Integrative analysis was performed with whole-exome sequencing and gene expression profiles of the 12 cases of early and advanced HCCs and paired non-tumoral adjacent liver tissues. A total of 293 tumor-specific somatic variants and 202 non-tumoral variants were identified. The tumor-specific variants were found to be enriched at chromosome 1q particularly in the advanced HCC, compared to the non-tumoral variants. Functional enrichment analysis revealed frequent mutations at the genes encoding cytoskeleton organization, cell adhesion, and cell cycle-related genes. In addition, to elucidate actionable somatic mutations, we performed an integrative analysis of gene mutations and gene expression profiles together. This revealed the 48 mutated genes which were differentially mutated with concomitant gene expression enrichment. Of these, CTNNB1 was found to have a pivotal role in the differential progression of the HCC subgroup. In conclusion, our integrative analysis of whole-exome sequencing and transcriptome profiles could provide actionable mutations which might play pivotal roles in the heterogeneous progression of HCC.


Pippin: A random forest-based method for identifying presynaptic and postsynaptic neurotoxins.
Presynaptic and postsynaptic neurotoxins are two types of neurotoxins from venomous animals and functionally important molecules in the neurosciences; however, their experimental characterization is difficult, time-consuming, and costly. Therefore, bioinformatics tools that can identify presynaptic and postsynaptic neurotoxins would be very useful for understanding their functions and mechanisms. In this study, we propose Pippin, a novel machine learning-based method that allows users to rapidly and accurately identify these two types of neurotoxins. Pippin was developed using the random forest (RF) algorithm and evaluated based on an up-to-date dataset. A variety of sequence and motif features were combined, and a two-step feature-selection algorithm was employed to characterize the optimal feature subset for presynaptic and postsynaptic neurotoxin prediction. Extensive benchmark tests illustrate that Pippin significantly improved predictive performance as compared with six other commonly used machine-learning algorithms, including the naïve Bayes classifier, Multinomial Naïve Bayes classifier (MNBC), AdaBoost, Bagging, K-nearest neighbors, and XGBoost. Additionally, we developed an online webserver for Pippin to facilitate public use. To the best of our knowledge, this is the first webserver for presynaptic and postsynaptic neurotoxin prediction.


Theoretical Exploration of Barrel-Shaped Drops on Cactus Spines.
To survive an arid environment, desert cacti are capable of harvesting water from fog by transporting condensed water drops using their spines. Cactus spines have a conical shape. In this work, on the basis of the difference of liquid pressure, a new theoretical model has been developed for a barrel-shaped liquid drop on a conical wire. This model is further simplified to interpret the effects of contact angles, conical angle, surface microgrooves, and gravity on the drop movement along a cactus spine.


[Development of a charter for older people in clinical trials: PREDICT].
Recent national guidelines on dementia and stroke demonstrate an unmistakable age gap: although both conditions are very prevalent in older people, the evidence supporting these guidelines is mainly drawn from research performed in younger patients. These examples are illustrative of a wider problem. When it comes to drug trials the underrepresentation of elderly people in clinical studies can have devastating effects. Under- and overtreatment as well as 'off label' prescription are common in this age group and they are overrepresented when it comes to negative treatment outcomes and adverse effects. Awareness of the pervasiveness of these problems is growing and there are several initiatives to improve medication safety in elderly patients. However, most of these focus on medication that is already certified, leaving the principle cause of the problem, namely the exclusion of the elderly from clinical trials, untouched. This issue is now being tackled by a European research consortium called PREDICT (Increasing the PaRticipation of the ElDerly In Clinical Trials). Using a multi-method approach this project assesses the participation of older people in recent and ongoing trials, surveys their views on facilitators and barriers to participation, as well as those of health professionals and ethicists and aims to use these findings to draft a charter for the rights of elderly people in clinical trials.


Temporal artery biopsy and corticosteroid treatment.
Eighty-four of 132 patients with clinically genuine cranial arteritis had histological evidence of inflammation at temporal artery biopsy. The highest incidence of a positive result (82%) was in patients biopsied before corticosteroid therapy. The figure fell to 60% if corticosteroids had been given for less than a week before biopsy and 10% thereafter.


[Prediction of human orthostatic tolerance by changes in arterial and venous hemodynamics in the microgravity environment].
The authors intentionally present exclusively the results of their recent studies of arterial and venous hemodynamics as predictors of human orthostatic tolerance (OT) during space flight and on return to Earth. There is a sufficient demonstration of the in-flight OT predictability by arterial hemodynamic reactions to LBNP and venous hemodynamic changes in response to the lower extremities occlusion. Three levels of cerebral blood flow deficits in the course of the lower body negative pressure test (LBNP) performed in microgravity were first defined. The authors offer quantitative arguments for the dependence of cerebral flow deficit on the degree of LBNP tolerance degradation. Patterns of arterial hemodynamics during LBNP were used successfully to diagnose the actual orthostatic tolerance and also to follow its trend as flight extended, which attests to the predictability of OT change in an individual cosmonaut on space flight. Occlusion plethysmography of legs revealed three levels of response of the most informative venous parameters (capacity, distensibility and rate of filling) correlating with severity of OT degradation.


A critical review of antiquity, authorship and contents of Haramekhala: A medieval work on humanities.
Ayurvedic science of life is one of the great contributions of India to the systems of health science. Apart from classical medical works, much information related to this Indian system is found elsewhere in other branches of science, such as Philosophy, Joutishya, Natya, Kavya, etc. Still much Ayurvedic information is clubbed in other compilations meant for general purpose. However, it is unfortunate that not all such works came into lime light; and still remain in the dark for many reasons. Haramekhala written by Mahuka is one such work, which contains Ayurvedic information along with various other themes, such as cosmetics. The author Mahuka lived in Dharanivaraha rajya of central India during Chapa Dynasty in 9(th)-10(th) century A.D. Haramekhala also known as Prayogamala comprises of five Paricchedas written in Prakrita language, later added by translations in Sanskrit called Chaya and foot notes in Sanskrit called Tika. The detail about this book is described in this article.


Effects of contraction duration on low-frequency fatigue in voluntary and electrically induced exercise of quadriceps muscle in humans.
The aims of this study were to investigate if low-frequency fatigue (LFF) dependent on the duration of repeated muscle contractions and to compare LFF in voluntary and electrically induced exercise. Male subjects performed three 9-min periods of repeated isometric knee extensions at 40% maximal voluntary contraction with contraction plus relaxation periods of 30 plus 60 s, 15 plus 30 s and 5 plus 10 s in protocols 1, 2 and 3, respectively. The same exercise protocols were repeated using feedback-controlled electrical stimulation at 40% maximal tetanic torque. Before and 15 min after each exercise period, knee extension torque at 1, 7, 10, 15, 20, 50 and 100 Hz was assessed. During voluntary exercise, electromyogram root mean square (EMGrms) of the vastus lateralis muscle was evaluated. The 20-Hz torque:100-Hz torque (20:100 Hz torque) ratio was reduced more after electrically induced than after voluntary exercise (P < 0.05). During electrically induced exercise, the decrease in 20:100 Hz torque ratio was gradually (P < 0.05) reduced as the individual contractions shortened. During voluntary exercise, the decrease in 20:100 Hz torque ratio and the increase in EMGrms were greater in protocol 1 (P < 0.01) than in protocols 2 and 3, which did not differ from each other. In conclusion, our results showed that LFF is dependent on the duration of individual muscle contractions during repetitive isometric exercise and that the electrically induced exercise produced a more pronounced LFF compared to voluntary exercise of submaximal intensity. It is suggested that compensatory recruitment of faster-contracting motor units is an additional factor affecting the severity of LFF during voluntary exercise.


Evaluation of CD30/CD4/CD8 in triple-negative invasive ductal carcinoma of breast in association with clinicopathological prognostic factors.
Triple-negative breast cancer (TNBC) lacks the benefits of receptor-targeted therapeutic strategies. The limitations in treatment options along with poor patients' outcome heighten the need for novel approaches. Due to recent concentration on the role of biomarkers in prognosis, treatment, and survival of various cancer subtypes, this study involves an investigation of CD4, CD8, and CD30 markers detected by immunohistochemistry in TNBCs and their association with clinicopathological and prognostic factors. Tissue samples of 85 hormone receptor- and human epidermal growth factor receptor-2-negative ductal breast carcinomas extracted from the archive of pathology department. Regarding CD4/CD8 ratio, the infiltrated T-lymphocytes were investigated. The tumoral tissue regions were also identified to be immunohistochemically assessed for the CD30 expression levels. With an elevated CD4/CD8 ratio, a significant increase in lymph node involvement was observed (P < 0.05); in contrast, increased expression levels of CD8 were related to significant reduction of lymph node involvement. CD30 overexpression was found to be significantly associated with shortened overall survival (OS) and highly involvement of lymph nodes. Following the progression in stage and grade of tumor, CD4/CD8 ratio and CD30 expression levels are increased and are accompanied by adverse prognosis and poor OS, while CD8-enhanced expression carries a favorable prognostic impact as it improves OS status. Therefore, all these findings could be of interest in the field of target therapy.


Enantioselective Synthesis and in Vivo Evaluation of Regioisomeric Analogues of the Antimalarial Arterolane.
We describe the first systematic study of antimalarial 1,2,4-trioxolanes bearing a substitution pattern regioisomeric to that of arterolane. Conformational analysis suggested that trans-3″-substituted trioxolanes would exhibit Fe(II) reactivity and antiparasitic activity similar to that achieved with canonical cis-4″ substitution. The chiral 3″ analogues were prepared as single stereoisomers and evaluated alongside their 4″ congeners against cultured malaria parasites and in a murine malaria model. As predicted, the trans-3″ analogues exhibited in vitro antiplasmodial activity remarkably similar to that of their cis-4″ comparators. In contrast, efficacy in the Plasmodium berghei mouse model differed dramatically for some of the congeneric pairs. The best of the novel 3″ analogues (e.g., 12i) outperformed arterolane itself, producing cures in mice after a single oral exposure. Overall, this study suggests new avenues for modulating Fe(II) reactivity and the pharmacokinetic and pharmacodynamic properties of 1,2,4-trioxolane antimalarials.


A live-attenuated and an inactivated chimeric porcine circovirus (PCV)1-2 vaccine are both effective at inducing a humoral immune response and reducing PCV2 viremia and intrauterine infection in female swine of breeding age.
The objective of this pilot study was to determine the efficacy of inactivated (1 or 2 dose) and live-attenuated chimeric porcine circovirus (PCV)1-2 vaccines in sows using the PCV2-spiked semen model. Thirty-five sows were randomly divided into 6 groups: negative and positive controls, 1 dose inactivated PCV1-2 vaccine challenged (1-VAC-PCV2), 2 dose inactivated PCV1-2 vaccine challenged (2-VAC-PCV2), 1 dose live-attenuated PCV1-2 vaccine unchallenged (1-LIVE-VAC), and 1 dose live-attenuated PCV1-2 vaccine challenged (1-LIVE-VAC-PCV2). The inactivated PCV1-2 vaccine induced higher levels of PCV2-specific antibodies in dams. All vaccination strategies provided good protection against PCV2 viremia in dams, whereas the majority of the unvaccinated sows were viremic. Four of the 35 dams became pregnant: a negative control, a positive control, a 2-VAC-PCV2 sow, and a 1-LIVE-VAC-PCV2 sow. The PCV2 DNA was detected in 100%, 67%, and 29% of the fetuses obtained from the positive control, inactivated vaccinated, or live-attenuated vaccinated dams, respectively. The PCV2 antigen in hearts was only detectable in the positive control litter (23% of the fetuses). The PCV1-2 DNA was detected in 29% of the fetuses in the litter from the 1-LIVE-VAC-PCV2 dam. Under the conditions of this pilot study, both vaccines protected against PCV2 viremia in breeding age animals; however, vertical transmission was not prevented.


A case of disseminated superficial porokeratosis associated with giant porokeratosis in pregnancy.
A 23-year-old pregnant lady presented with dark raised lesions over face, axillae, and upper limbs of 15-day duration. She was 35 weeks pregnant at the time of onset of the lesions. Dermatological examination revealed hyperpigmented plaques on the face and papules with raised borders in the axillae and proximal arms. Skin biopsy from both the lesions revealed a diagnosis of porokeratosis. She was treated with emollients alone and the lesions regressed four weeks following delivery. This case is being reported for the rare occurrence of the combination of disseminated superficial porokeratosis with giant porokeratosis in pregnancy.


Effects of a New Form of Resistance-Type High-Intensity Interval Training on Cardiac Structure, Hemodynamics, and Physiological and Performance Adaptations in Well-Trained Kayak Sprint Athletes.
This study examined the effects of a resistance-type high-intensity interval training (RHIIT) matched with the lowest velocity that elicited V . O2peak (100% v V . O2peak) in well-trained kayak sprint athletes. Responses in cardiac structure and function, cardiorespiratory fitness, anaerobic power, exercise performance, muscular strength, and hormonal adaptations were examined. Male kayakers (n = 24, age: 27 ± 4 years) were randomly assigned to one of three 8-wk conditions (N = 8): (RHIIT) resistance training using one-armed cable row at 100% v V . O2peak; paddling-based HIIT (PHIIT) six sets of paddling at 100% v V . O2peak; or controls (CON) who performed six sessions including 1-h on-water paddling/sessions at 70-80% maximum HR per week. Significant increases (p < 0.05) in V . O2peak, v V . O2peak, maximal cardiac output, resting stroke volume, left ventricular end-systolic dimension, 500-m paddling performance were seen pre- to post-training in all groups. Change in V . O2peak in response to PHIIT was significantly greater (p = 0.03) compared to CON. Also, 500-m paddling performance changes in response to PHIIT and RHIIT were greater (p = 0.02, 0.05, respectively) than that of CON. Compared with pre-training, PHIIT and RHIIT resulted in significant increases in peak and average power output, maximal stroke volume, end-diastolic volume, ejection fraction, total testosterone, testosterone/cortisol ratio, and 1,000-m paddling performance. Also, the change in 1,000-m paddling performance in response to PHIIT was significantly greater (p = 0.02) compared to that of CON. Moreover, maximum strength was significantly enhanced in response to RHIIT pre- to post-training (p < 0.05). Overall, RHIIT and PHIIT similarly improve cardiac structure and hemodynamics, physiological adaptations, and performance of well-trained kayak sprint athletes. Also, RHIIT enhances cardiorespiratory fitness and muscular strength simultaneously.


Stable prostacyclin analogue preventing microcirculatory derangement in experimental cerebral ischemia in cats.
We evaluated the effect of a stable synthetic prostacyclin analogue, TRK-100, on the microcirculatory derangement occurring in feline pial vessels with endothelial damage after middle cerebral artery occlusion. Fifteen adult cats were divided into an untreated group (Group 1, n = 8) and a treated group (Group 2, n = 7). Thirty minutes after 10 minutes of ultraviolet irradiation, which selectively damaged endothelium in the pial vessels, the middle cerebral artery was occluded in both groups and maintained for 30 minutes. In Group 2, 50 ng/kg/min TRK-100 was continuously infused intravenously following ultraviolet irradiation. In both the pial arteries and veins, platelet aggregate adhesion to the endothelium with subsequent thrombus formation was significantly (p less than 0.01 and p less than 0.05, respectively) inhibited during middle cerebral artery occlusion in Group 2 compared with Group 1. Similarly, blood flow stasis in the pial veins was effectively prevented in Group 2 during occlusion. Furthermore, the pial artery diameter returned to the control level during the late period of occlusion, whereas in Group 1 the pial artery remained constricted. Our data suggest that TRK-100 can prevent microcirculatory derangement in the acute stage of ischemic stroke.


A case of prune-belly syndrome: prenatal diagnostic problems.
The authors discuss a case of "Prune-belly syndrome" which could be diagnosed prenatally thanks to echography; they stress the importance of echographic controls since the first gestational weeks to better recognize pathological findings, and describe their attempts to drain the megavesica. However these attempts could not reverse the ominous prognosis.


Cognitive contributions to theory of mind ability in children with a traumatic head injury.
The objective of the current study is to examine the contribution of intellectual abilities, executive functions (EF), and facial emotion recognition to difficulties in Theory of Mind (ToM) abilities in children with a traumatic head injury. Israeli children with a traumatic head injury were compared with their non-injured counterparts. Each group included 18 children (12 males) ages 7-13. Measurements included reading the mind in the eyes, facial emotion recognition, reasoning the other's characteristics based on motive and outcome, Raven's Coloured Progressive Matrices, similarities and digit span (Wechsler Intelligence Scale for Children - Revised 95 subscales), verbal fluency, and the Behaviour Rating Inventory of Executive Functions. Non-injured children performed significantly better on ToM, abstract reasoning, and EF measures compared with children with a traumatic head injury. However, differences in ToM abilities between the groups were no longer significant after controlling for abstract reasoning, working memory, verbal fluency, or facial emotion recognition. Impaired ToM recognition and reasoning abilities after a head injury may result from other cognitive impairments. In children with mild and moderate head injury, poorer performance on ToM tasks may reflect poorer abstract reasoning, a general tendency to concretize stimuli, working memory and verbal fluency deficits, and difficulties in facial emotion recognition, rather than deficits in the ability to understand the other's thoughts and emotions. ToM impairments may be secondary to a range of cognitive deficits in determining social outcomes in this population.


Catalytic Mechanism and Product Specificity of Protein Arginine Methyltransferase PRMT7: A Study from QM/MM Molecular Dynamics and Free Energy Simulations.
QM/MM molecular dynamics and potential of mean force (PMF) free-energy simulations are performed for wild-type PRMT7 and E172Q, E181Q, and Q329A mutants in this work, and the catalytic mechanism, product specificity, and the role of key residues for the PRMT7 activity are investigated. The main strategies of PRMT7 in reducing the activation barrier for methyl transfer that are found in this study include (1) formation of reactive (near attack) conformations for the substrate Arg, (2) strengthening the active-site interactions at the transition state, and (3) generation of more effective nucleophiles by changing charge distributions on the target Arg through active-site interactions. More importantly, it is shown that it is a combination of these different factors that determines the PRMT7 methylation activity and substrate/product specificity. By taking these factors into consideration, it is possible to provide explanations for the observed effects of some mutations. For E172Q, E181Q, and Q329A, the simulation results suggest that E172Q has the least activity among the three mutants. The free energy barrier increases by 7 and 3 kcal/mol, respectively, as a result of the E181 → Q and Q329 → A mutations. The results showed that PRMT7 has a preference of adding a methyl group to the ω-guanidino nitrogen Nη2 atom of the substrate Arg and that the second methylation reactions cannot occur, which are consistent with previous investigations.


Testing fine motor coordination via telehealth: Effects of video characteristics on reliability and validity.
Background There is limited research about the effects of video quality on the accuracy of assessments of physical function. Methods A repeated measures study design was used to assess reliability and validity of the finger-nose test (FNT) and the finger-tapping test (FTT) carried out with 50 veterans who had impairment in gross and/or fine motor coordination. Videos were scored by expert raters under eight differing conditions, including in-person, high definition video with slow motion review and standard speed videos with varying bit rates and frame rates. Results FTT inter-rater reliability was excellent with slow motion video (ICC 0.98-0.99) and good (ICC 0.59) under the normal speed conditions. Inter-rater reliability for FNT 'attempts' was excellent (ICC 0.97-0.99) for all viewing conditions; for FNT 'misses' it was good to excellent (ICC 0.89) with slow motion review but substantially worse (ICC 0.44) on the normal speed videos. FTT criterion validity (i.e. compared to slow motion review) was excellent (β = 0.94) for the in-person rater and good ( β = 0.77) on normal speed videos. Criterion validity for FNT 'attempts' was excellent under all conditions ( r ≥ 0.97) and for FNT 'misses' it was good to excellent under all conditions ( β = 0.61-0.81). Conclusions In general, the inter-rater reliability and validity of the FNT and FTT assessed via video technology is similar to standard clinical practices, but is enhanced with slow motion review and/or higher bit rate.


[Study of protein binding in ketoprofen using liquid chromatography frontal analysis in comparison with capillary electrophoresis frontal analysis].
A method of high performance liquid chromatography-frontal analysis (HPLC-FA) was developed to study the binding of ketoprofen to human serum albumin (HSA) and it was compared with high performance capillary electrophoresis-frontal analysis (HPCE-FA). The separation was performed using Pinkerton GFF II-S5-80 internal-surface reversed-phase silica column (150 mm x 4.6 mm i.d., 5 microm) at pH 7.4 in a 67 mmol/L isotonic sodium phosphate buffer at 37 degrees C. Other conditions included a flow rate of 0.2 mL/min, UV detection at a wave-length of 254 nm and an injection volume of 950 microL. A trapezoidal peak of the unbound ketoprofen appeared after HSA elution in the chromatogram. The plateau height of the peak was employed to determine the concentration of unbound ketoprofen in the HSA equilibrated sample solution. The HPLC-FA method provides the advantage of high sensitivity and however the disadvantages of large sample size and long analytical time when compared with HPCE-FA. HPLC-FA is applicable to the binding parameter estimation of ketoprofen to both primary and secondary sites, which are 0.37 x 10(6) L/mol and 1.4 for K1 (the association constant) and n (the number for the binding sites per molecule HSA), respectively, and 0.005 x 10(6) L/mol and 7.2 for K2 and n2, respectively. In contrast, HPCE-FA measures parameters for only the secondary binding sites; K2 of 0.018 x 10(6) L/mol and n2 of 2.54 can be estimated. It is found that ketoprofen binds mainly at the primary sites at a lower mole ratio of ketoprofen versus HSA, and the binding at the secondary sites occurs at a higher ratio.


Single-Center Prospective Trial Investigating the Feasibility of Serial FDG-PET Guided Adaptive Radiation Therapy for Head and Neck Cancer.
We investigated in a single-center prospective trial (NCT03376386) the use of serial fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) to determine the boost dose and to guide boost segmentation in head and neck cancer. Patients were eligible when treated with curative radiation therapy with or without systemic treatment for T2-4 squamous cell carcinoma of the hypopharynx, larynx, or oropharynx (20 patients in total). FDG-PET/CT scans were made at baseline and for redelineation and replanning at the end of weeks 2 and 4 of radiation therapy. The metabolically active part of the primary tumor received a 4 Gy boost on top of the 70 Gy baseline dose per partial metabolic response. The study would be considered feasible when ≥80% of adaptations were successful and no Common Terminology Criteria for Adverse Events grade ≥4 acute toxicity occurred. One patient received 70 Gy after complete metabolic response in week 2, and 12 patients received 78 Gy because of partial metabolic response at weeks 2 and 4. Seven patients received 74 Gy, either because of complete metabolic response at week 4 (n = 3) or a missed FDG-PET/CT (n = 4). The patients missed their FDG-PET/CT scans because they did not fast (n = 2) or at patients' request (n = 2). In addition to the 4 missed FDG-PET/CT scans, 2 adaptive plans could not be finished successfully owing to logistical problems. In total, 85% of adaptations were completed correctly. No patient experienced grade ≥4 toxicity, and 40% had grade 3 dysphagia (tube feeding) during treatment. This decreased at 12 weeks posttreatment to 20%. This prospective trial demonstrates the feasibility of serial FDG-PET/CT scans for dose escalation and patient selection.


Fate of microinjected sperm components in the mouse oocyte and embryo.
Intact mouse sperm or mouse sperm tails alone, labelled with MitoTracker Green FM fluorochrome, were injected into mouse oocytes and the cells cultured in vitro for up to 5 days. The dye stained midpiece mitochondria, the sperm tail coarse fibres and the sperm perforatorium. Intact sperm (or tails injected with separated heads) induced normal embryonic development. The mitochondria could be identified in embryos up to the 4-cell stage, remaining associated with the sperm tail. They largely disappeared by the 8-cell stage, when only a minority of embryos (6/43) could be found with small patches of mitochondria. Axonemal elements could be identified coiled up in single external blastomeres as late as day 5 blastocysts. By contrast, mitochondria as well as tail components could be identified up to 5 days after injection of sperm tails alone into non-activated oocytes and also in embryos that arrested development before the 8-cell stage. We conclude that disappearance of the labelled sperm mitochondria in normally cleaving embryos is not due to fading or inactivation of the fluorochrome marker, but is rather an event specifically tied to cell cycle activities around the second cell division.


Radiofrequency Interference in the Clinical Laboratory.
Radiofrequency interference (RFI) is a known medical device safety issue, but there are no documented cases of interference resulting in erroneous laboratory results. We investigated unexpected failure of a hematology analyzer resulting in erroneous WBC counts. Hardware failure was initially suspected, but temporal association with increased power output from a nearby antenna prompted investigation for RFI. Power output from an antenna located approximately 4 feet from the analyzer was increased to ensure sufficient signal for emergency communications in the building. Interference from the antenna resulted in aberrant side scatter and abnormal WBC counts. Powering down the antenna returned the instrument to normal working conditions. We have shown RFI as the root cause of erroneous WBC counts in a hematology analyzer. We propose that RFI should be on the list of potential interfering mechanisms when clinical laboratory instruments generate inconsistent or unreliable results.


"Boarding-Up": Radiation Damage and Radionuclide Leaching Kinetics in Linker-Capped Metal-Organic Frameworks.
For the first time, we report the ability to control radionuclide species release kinetics in metal-organic frameworks (MOFs) as a function of postsynthetic capping linker installation, which is essential for understanding MOF potential as viable radionuclide wasteform materials or versatile platforms for sensing, leaching, and radionuclide sequestration. The radiation damage of prepared frameworks under γ radiation has also been studied. We envision that the presented studies are the first steps toward utilization of the reported scaffolds for more efficient nuclear waste administration.


Nucleotide sequence of the genetic loci encoding subunits of Bradyrhizobium japonicum uptake hydrogenase.
An indispensable part of the hydrogen-recycling system in Bradyrhizobium japonicum is the uptake hydrogenase, which is composed of 34.5- and 65.9-kDa subunits. The gene encoding the large subunit is located on a 5.9-kilobase fragment of the H2-uptake-complementing cosmid pHU52 [Zuber, M., Harker, A.R., Sultana, M.A. & Evans, H.J. (1986) Proc. Natl. Acad. Sci. USA 83, 7668-7672]. We have now determined that the structural genes for both subunits are present on this fragment. Two open reading frames are present that correspond in size and deduced amino acid sequence to the hydrogenase subunits, except that the small-subunit coding region contains a leader peptide of 46 amino acids. The two genes are separated by a 32-nucleotide intergenic region and likely constitute an operon. Comparison of the deduced amino acid sequences of the B. japonicum genes with those from Desulfovibrio gigas, Desulfovibrio baculatus, and Rhodobacter capsulatus indicates significant sequence identity.


Mechanisms of tilt-induced vasovagal syncope in healthy volunteers and postural tachycardia syndrome patients without past history of syncope.
Upright tilt table testing has been used to test for vasovagal syncope (VVS) but can result in "false positives" in which tilt-induced fainting (tilt+) occurs in the absence of real-world fainting. Tilt+ occurs in healthy volunteers and in patients with postural tachycardia syndrome (POTS) and show enhanced susceptibility to orthostatic hypotension. We hypothesized that the mechanisms for hypotensive susceptibility differs between tilt+ healthy volunteers (Control-Faint (N = 12)), tilt+ POTS patients (POTS-Faint (N = 12)) and a non-fainter control group of (Control-noFaint) (N = 10). Subjects were studied supine and during 70° upright tilt while blood pressure (BP), cardiac output (CO), and systemic vascular resistance (SVR), were measured continuously. Impedance plethysmography estimated regional blood volumes, flows, and vascular resistance. Heart rate was increased while central blood volume was decreased in both Faint groups. CO increased in Control-Faint because of reduced splanchnic vascular resistance; splanchnic pooling was similar to Control-noFaint. Splanchnic blood flow in POTS-Faint decreased and resistance increased similar to Control-noFaint but splanchnic blood volume was markedly increased. Decreased SVR and splanchnic arterial vasoconstriction is the mechanism for faint in Control-Faint. Decreased CO caused by enhanced splanchnic pooling is the mechanism for faint in POTS-Faint. We propose that intrahepatic resistance is increased in POTS-Faint resulting in pooling and that both intrahepatic resistance and splanchnic arterial vasoconstriction are reduced in Control-Faint resulting in increased splanchnic blood flow and reduced splanchnic resistance.


Analysis of preoperative serum levels of MMP1, -2, and -9 in patients with site-specific head and neck squamous cell cancer.
Head and neck squamous cell cancer (HNSCC) includes tumors of various anatomical sites sharing common etiological factors. Serum levels of MMP1, MMP2, and MMP9 were analyzed in patients with oropharyngeal, laryngeal, and hypopharyngeal carcinomas in an effort to elucidate the pathobiology and in order to find useful biomarkers of site-specific HNSCC. The study group comprised of 46 patients with HNSCC (21 with oropharyngeal, 21 with laryngeal and 4 with hypopharyngeal cancer). Serum levels of MMP1, -2, and -9 were determined by the MAGPIX multiplex method. P16 protein was detected by immunohistochemistry. Serum levels of matrix metalloproteinases (MMPs) were correlated with clinicopathological features of carcinomas and were compared with respect to tumor site. Significant correlations were confirmed between p16 positivity and oropharyngeal cancer, MMP1 and p16 positivity, and recurrence and smoking. Statistically significant differences in serum levels of MMPs between cancer of different locations were not found. MMP1 expression is significantly affected by smoking habit and by p16 and might mediate etiopathogenetical process in cancerogenesis of HNSCC. Our pilot study did not establish any utility of MMP1, -2, or -9 in clinical practice as diagnostic/prognostic markers.


Experimental observation of effects of seeds on polymer crystallization.
The effects of two seeds on the melt crystallization of isotactic polypropylene were experimentally investigated. The seed, which has the flat surface full of a nonuniform size distribution, has provided a right surface pattern to activate effectively the heterogeneous nucleation. In contrast, the seed, which has the curved surface full of a uniform size distribution, has failed to induce the heterogeneous nucleation. The results from the present work have also shown that the seed with strong nucleating ability leads to the formation of large crystals but the seed without nucleating ability does not influence much the crystal size.


Transcriptome analysis in cotton boll weevil (Anthonomus grandis) and RNA interference in insect pests.
Cotton plants are subjected to the attack of several insect pests. In Brazil, the cotton boll weevil, Anthonomus grandis, is the most important cotton pest. The use of insecticidal proteins and gene silencing by interference RNA (RNAi) as techniques for insect control are promising strategies, which has been applied in the last few years. For this insect, there are not much available molecular information on databases. Using 454-pyrosequencing methodology, the transcriptome of all developmental stages of the insect pest, A. grandis, was analyzed. The A. grandis transcriptome analysis resulted in more than 500.000 reads and a data set of high quality 20,841 contigs. After sequence assembly and annotation, around 10,600 contigs had at least one BLAST hit against NCBI non-redundant protein database and 65.7% was similar to Tribolium castaneum sequences. A comparison of A. grandis, Drosophila melanogaster and Bombyx mori protein families' data showed higher similarity to dipteran than to lepidopteran sequences. Several contigs of genes encoding proteins involved in RNAi mechanism were found. PAZ Domains sequences extracted from the transcriptome showed high similarity and conservation for the most important functional and structural motifs when compared to PAZ Domains from 5 species. Two SID-like contigs were phylogenetically analyzed and grouped with T. castaneum SID-like proteins. No RdRP gene was found. A contig matching chitin synthase 1 was mined from the transcriptome. dsRNA microinjection of a chitin synthase gene to A. grandis female adults resulted in normal oviposition of unviable eggs and malformed alive larvae that were unable to develop in artificial diet. This is the first study that characterizes the transcriptome of the coleopteran, A. grandis. A new and representative transcriptome database for this insect pest is now available. All data support the state of the art of RNAi mechanism in insects.


Structure and properties of oil bodies in diatoms.
Diatoms accumulate triacylglycerols in spherical organelles called oil bodies when exposed to nutrient deprivation conditions. Oil body biology in diatoms has attracted significant attention due to the complexity of the intracellular organelles and the unique combination of genes generated by the evolutionary history of secondary endosymbiosis. The demand for biofuel production has further increased the interest in and importance of a better understanding of oil body biology in diatoms, because it could provide targets for genetic engineering to further enhance their promising lipid accumulation. This review describes recent progress in studies of the structure and properties of diatom oil bodies. Firstly, the general features of diatom oil bodies are described, in particular, their number, size and morphology, as well as the quantity and quality of lipids they contain. Subsequently, the diatom oil body-associated proteins, which were recently discovered through oil body proteomics, are introduced. Then, the metabolic pathways responsible for the biogenesis and degradation of diatom oil bodies are summarized. During biogenesis and degradation, oil bodies interact with other organelles, including chloroplasts, the endoplasmic reticulum and mitochondria, suggesting their dynamic nature in response to environmental changes. Finally, the functions of oil bodies in diatoms are discussed.This article is part of the themed issue 'The peculiar carbon metabolism in diatoms'.


Possibilities and perspectives of pharmacotherapy for endothelial protection.
Endothelial dysfunction appears to be an early event in most forms of cardiovascular disease. The dysfunction may involve a decreased formation, inactivation, or action of nitric oxide or prostacyclin as well as an increased formation of contracting factors, eg, prostaglandin H2 and endothelin-1. Cardiovascular drugs can improve endothelial function either indirectly through their effects on cardiovascular risk factors, such as hypertension, hyperlipidemia, and diabetes or directly through endothelial actions. Direct and indirect endothelial protective effects of cardiovascular drugs may significantly contribute to normal organ perfusion and a reduced incidence of myocardial infarction, stroke, and renal failure in patients. Endothelium-dependent vascular regulation in health and in various cardiovascular diseases as well as the effects of currently available cardiovascular drugs are reviewed.


Role play, a teaching strategy for psychiatry - students' comparative perspective versus traditional teaching.
To compare the effectiveness of conventional teaching methodology against the role play method from the standpoint of medical students. The questionnaire-based study was conducted at Majmah University, Saudi Arabia, during the 2018-19 academic year, and comprised final year medical students. The study was conducted in two settings during the psychiatry module; first while discussing suicide and second while discussing violence. In both the settings, the students were divided in two randomised groups of cases and controls. The controls were taught with conventional methodology, while the cases were taught primarily using role play. Data was collected using a questionnaire pertaining to students' level of satisfaction regarding different aspects of the learning process. Data was analysed using SPSS 21. In the first setting, there were 53 students; 29(54.7%) controls and 24(45.3%) cases. In the second setting there were 54 students; 27(50%) cases and as many controls. In both settings, students in the control group rated conventional teaching significantly more interactive compared to the role play method (p<0.05). Clarification of doubt was more in the control group in the first setting (p<0.05). Although change in curricula is the need of the time, students' feedback is essential.


Mechanisms of angioregression of the corpus luteum.
The corpus luteum is a transient ovarian endocrine gland that produces the progesterone necessary for the establishment and maintenance of pregnancy. The formation and function of this gland involves angiogenesis, establishing the tissue with a robust blood flow and vast microvasculature required to support production of progesterone. Every steroidogenic cell within the corpus luteum is in direct contact with a capillary, and disruption of angiogenesis impairs luteal development and function. At the end of a reproductive cycle, the corpus luteum ceases progesterone production and undergoes rapid structural regression into a nonfunctional corpus albicans in a process initiated and exacerbated by the luteolysin prostaglandin F2α (PGF2α). Structural regression is accompanied by complete regression of the luteal microvasculature in which endothelial cells die and are sloughed off into capillaries and lymphatic vessels. During luteal regression, changes in nitric oxide transiently increase blood flow, followed by a reduction in blood flow and progesterone secretion. Early luteal regression is marked by an increased production of cytokines and chemokines and influx of immune cells. Microvascular endothelial cells are sensitive to released factors during luteolysis, including thrombospondin, endothelin, and cytokines like tumor necrosis factor alpha (TNF) and transforming growth factor β 1 (TGFB1). Although PGF2α is known to be a vasoconstrictor, endothelial cells do not express receptors for PGF2α, therefore it is believed that the angioregression occurring during luteolysis is mediated by factors downstream of PGF2α signaling. Yet, the exact mechanisms responsible for angioregression in the corpus luteum remain unknown. This review describes the current knowledge on angioregression of the corpus luteum and the roles of vasoactive factors released during luteolysis on luteal vasculature and endothelial cells of the microvasculature.


Early postnatal handling and environmental enrichment improve the behavioral responses of 17-month-old 3xTg-AD and non-transgenic mice in the Forced Swim Test in a gender-dependent manner.
Forced Swimming Test (FST) models behavioural despair in animals by loss of motivation to respond or the refusal to escape. The present study was aimed at characterizing genetic (genotype and gender) and environmental factors (age/stage of disease and rearing conditions: C, standard; H, early postnatal handling; EE, environmental enrichment consisting in physical exercise as well as social and object enrichment) that may modulate the poor behavioural and cognitive flexibility response we have recently described in 12-month-old male 3xTg-AD mice in the FST. The comprehensive analysis of the ethogram shown in the FST considered the intervals of the test (0-2 and 2-6min), all the elicited behavioural responses (immobility, swimming and climbing) and their features (total duration and frequency of episodes). The long persistence of behaviours found in 17-month-old (late-stages of disease) 3xTg-AD mice was comparable to that recently described in males at 12 months of age (beginning of advanced stages) but also suggested increased age-dependent frailty in both genotypes. The poor behavioral flexibility of 3xTg-AD mice to elicit the behavioural despair shown by the NTg mice, was also found in the female gender. Finally, the present work demonstrates that early-life interventions were able to improve the time and frequency of episodes of immobility, being more evident in the female gender of both old NTg and 3xTg-AD mice. Ontogenic modulation by early-postnatal handling resulted in a more effective long-term improvement of the elicited behaviours in the FST than that achieved by environmental enrichment. The results talk in favor of the beneficence of early-life interventions on ageing in both healthy and disease conditions.


Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of the mother.
This report describes an infant with multiple congenital anomalies born to a 20-year-old mother with juvenile rheumatoid arthritis who had been taking weekly low-dose methotrexate (MTX) during the first trimester of pregnancy. The abnormalities found were consistent with those associated with maternal ingestion of MTX at dosage levels used to induce abortions, i.e., the group of abnormalities referred to as the "aminopterin syndrome." Although weekly low-dose MTX has been associated with spontaneous abortions, this is, to our knowledge, the first case report describing multiple congenital abnormalities consistent with MTX embryopathy secondary to weekly low-dose MTX treatment.


Evaluation of oxidative status in iron deficiency anemia through total antioxidant capacity measured using an automated method.
Oxidative stress, an increase in oxidants and/or a decrease in antioxidant capacity, is one of the potential biochemical mechanisms involved in the pathogenesis of iron deficiency anemia. The objective of this study was to evaluate the oxidative status and to determine whether there is any relationship between oxidative status and the severity of anemia in patients with iron deficiency anemia using an automated method. Twenty-six subjects with iron deficiency anemia and 20 healthy controls were enrolled in the present study. Serum total antioxidant capacity, serum total peroxide level and oxidative stress index were determined in all study subjects. Serum total antioxidant capacity was significantly lower in patients with iron deficiency anemia than controls (p<0.05), while serum total peroxide level and oxidative stress index were significantly higher (both p<0.05). There was a significant correlation between hemoglobin level and serum total peroxide level, oxidative stress index and total antioxidant capacity (r=-0.504, p<0.05; r=-0.503, p<0.05; r=0.417, p<0.05, respectively). Increased oxidative stress may play a role in the pathogenesis of iron deficiency anemia. Supplementation of antioxidant vitamins in conjunction with iron replacement therapy may offer better responses and provide early resolution of symptoms related to iron deficiency anemia. The automated assay is a reliable and easily applied method for measurement of serum total antioxidant capacity in iron deficiency anemia.


Active disturbance rejection control based robust output feedback autopilot design for airbreathing hypersonic vehicles.
Since motion control plant (y(n)=f(⋅)+d) was repeatedly used to exemplify how active disturbance rejection control (ADRC) works when it was proposed, the integral chain system subject to matched disturbances is always regarded as a canonical form and even misconstrued as the only form that ADRC is applicable to. In this paper, a systematic approach is first presented to apply ADRC to a generic nonlinear uncertain system with mismatched disturbances and a robust output feedback autopilot for an airbreathing hypersonic vehicle (AHV) is devised based on that. The key idea is to employ the feedback linearization (FL) and equivalent input disturbance (EID) technique to decouple nonlinear uncertain system into several subsystems in canonical form, thus it would be much easy to directly design classical/improved linear/nonlinear ADRC controller for each subsystem. It is noticed that all disturbances are taken into account when implementing FL rather than just omitting that in previous research, which greatly enhances controllers' robustness against external disturbances. For autopilot design, ADRC strategy enables precise tracking for velocity and altitude reference command in the presence of severe parametric perturbations and atmospheric disturbances only using measurable output information. Bounded-input-bounded-output (BIBO) stable is analyzed for closed-loop system. To illustrate the feasibility and superiority of this novel design, a series of comparative simulations with some prominent and representative methods are carried out on a benchmark longitudinal AHV model.


Serial reconstruction of the characteristic granule of the Langerhans cell.
Three-dimensional models of individual granules in the same Langerhans cell were made after analyzing serial sections of human epidermis in the electron microscope. These models revealed that the granule is made up of a flattened or curved orthogonal net of particles which is bounded externally by a limiting membrane and which may be disc-shaped, cup-shaped, or combinations of both shapes. This variety of shapes accounts for the many configurations of the granule seen in individual electron micrographs. Usually, the granule has a vesicular portion at, or near one margin. This demonstration of the three-dimensional structure of the granule establishes the inaccuracy of previously used descriptive terms, the granule should be called simply the "Langerhans cell granule."


Measuring the Refractive Index of Bovine Corneal Stromal Cells Using Quantitative Phase Imaging.
The cornea is the primary refractive lens in the eye and transmits >90% of incident visible light. It has been suggested that the development of postoperative corneal haze could be due to an increase in light scattering from activated corneal stromal cells. Quiescent keratocytes are thought to produce crystallins that match the refractive index of their cytoplasm to the surrounding extracellular material, reducing the amount of light scattering. To test this, we measured the refractive index (RI) of bovine corneal stromal cells, using quantitative phase imaging of live cells in vitro, together with confocal microscopy. The RI of quiescent keratocytes (RI = 1.381 ± 0.004) matched the surrounding matrix, thus supporting the hypothesis that keratocyte cytoplasm does not scatter light in the normal cornea. We also observed that the RI drops after keratocyte activation (RI = 1.365 ± 0.003), leading to a mismatch with the surrounding intercellular matrix. Theoretical scattering models showed that this mismatch would reduce light transmission in the cornea. We conclude that corneal transparency depends on the matching of refractive indices between quiescent keratocytes and the surrounding tissue, and that after surgery or wounding, the resulting RI mismatch between the activated cells and their surrounds significantly contributes to light scattering.


Micelle-Directing Synthesis of Ag-Doped WO3 and MoO3 Composites for Photocatalytic Water Oxidation and Organic-Dye Adsorption.
In this paper, an Ag-doped WO3 (and MoO3 ) composite has been prepared by following a simple micelle-directed method and high-temperature sintering route. The as-prepared samples were characterized by X-ray diffraction, inductively coupled plasma, transmission electron microscopy, X-ray photoelectron spectroscopy, UV/Vis diffuse reflectance spectroscopy, Brunauer-Emmett-Teller, photoluminescence spectroscopy, and electrochemical impedance spectroscopy techniques. The photocatalytic experiments reveal that their oxygen-production rates are up to 95.43 μmol (75.45 μmol) for Ag-doped WO3 (MoO3 ), which is 9.5 (7.3) times higher than that of pure WO3 : 9.012 μmol (MoO3 : 9.00 μmol) under visible-light illumination (λ≥420 nm), respectively. The improvement of their photocatalytic activity is attributed to the enhancement of their visible-light absorption and the separation efficiency of photogenerated carriers by Ag doping. Moreover, Ag-doped WO3 (MoO3 ) also shows excellent adsorption of rhodamine B (RhB) and methylene blue (MB) in aqueous solution, with maximum adsorption capacities towards RhB and MB of 822 and 820 mg g-1 for Ag-doped WO3 , and 642 and 805 mg g-1 for Ag-doped MoO3 , respectively.


Lessons Learned from Enhancing Sentinel Surveillance for Cholera in Post-Earthquake Nepal in 2016.
A major earthquake in 2015 that struck Nepal created a favorable environment for the rapid spread of infectious diseases. In anticipation of a cholera outbreak in 2016, UNICEF, Johns Hopkins University, and the Group for Technical Assistance, Nepal, collaborated to assist the government of Nepal to strengthen early warning surveillance, laboratory-based diagnosis, and field investigation. This article outlines the challenges and lessons learned in cholera prevention and control based on the authors' experiences in 2016. Priorities for the future plan should include sustaining the enhanced surveillance system for acute gastroenteritis and cholera, rolling out a rapid diagnostic test, and ensuring rapid and systematic epidemiological investigation and environmental testing.


Existing and Future Educational Needs in Graduate and Postgraduate Education.
This review was designed to make recommendations on future educational needs, principles of curricular development, and how the International Society for Sexual Medicine (ISSM) should address the need to enhance and promote human sexuality education around the world. To explore the ways in which graduate and postgraduate medical education in human sexuality has evolved and is currently delivered. We reviewed existing literature concerning sexuality education, curriculum development, learning strategies, educational formats, evaluation of programs, evaluation of students, and faculty development. We reviewed literature relating to four main areas: (i) the current status of the international regulation of training in sexual medicine; (ii) the current delivery of education and training in sexual medicine; (iii) resident and postgraduate education in sexual medicine surgery; and (iv) education and training for allied health professionals. The main findings in these four areas are as follows. Sexual medicine has grown considerably as a specialty during the past 20 years, with many drivers being identified. However, the regulatory aspects of training, assessment, and certification are currently in the early stages of development and are in many ways lagging behind the scientific and clinical knowledge in the field. However, there are examples of the development of curricula with accompanying assessments that have attempted to set standards of education and training that might underlie the delivery of high-quality care to patients in sexual medicine. The development of competence assessment has been applied to surgical training in sexual medicine, and there is increasing interest in simulation as a means of enhancing technical skills training. Although the focus of curriculum development has largely been the medical profession, there is early interest in the development of standards for training and education of allied health professionals. Organizations of professionals in sexual health, such as the ISSM, have an opportunity, and indeed a responsibility, to provide and disseminate learning opportunities, curricula, and standards of training for doctors and allied health professionals in sexual medicine. Eardley I, Reisman Y, Goldstein S, et al. Existing and Future Educational Needs in Graduate and Postgraduate Education. J Sex Med 2017;14:475-485.


Parent's reports predict their child's developmental problems.
To document parental reports about their child's delayed development, 180 consecutive parents/guardians of children, ages ranging from 16 to 70 months, were surveyed. Parents reported a mean of 8.28 (SD 4.55) problems. Symptoms most reported were not talking well (79.5%), poor speech (59.8%), immaturity (58.0%), understands poorly (55.4%), bowel/bladder problems (50.9%), seldom plays with others (47.3%), attention (46.4%), eating (43.8%), clumsy-gross motor (40.2%), and clumsy-fine motor (40.2%). There was an association between delayed development and symptoms about eating, bowel-bladder, clumsy fine-motor, not talking well, understands poorly, immature, and seldom plays with others (p<0.05). The presence of language symptoms increased the odds of delayed development by 2.25. Relevant symptoms differed by developmental domains and different groups of items predicted specific delays. Parent reports indicated quantifiable difficulties requiring detailed assessments.


Acute ascites accompanying hepatitis A infection in a child.
A seven-year-old child developed ascites when recovering from hepatitis A infection. Accumulation of intraperitoneal fluid was confirmed by ultrasonic study. The clinical course was otherwise uneventful and the ascites disappeared after a few days with no treatment, and did not recur for five years. Ascites may exceptionally accompany hepatitis A infection. Its appearance, however, does not indicate an unfavorable outcome.


25 Years of FUN!
Dr. Julio J. Ramirez, the founding president of the Faculty for Undergraduate Neuroscience (FUN), shared the comments below on November 13, 2016 at the 25th Anniversary of FUN's founding, when Drs. Sally Frutiger, Stephen George, Julio Ramirez, and Dennison Smith were recognized with the Founders Award for their efforts in launching FUN in 1991.


Chemotherapy for mustard-resistant ovarian adenocarcinoma: a randomized trial for CCNU and methyl-CCNU.
In view of the need for drugs which have antitumor activity in alkylating agent-resistant ovarian cancer or which might be more potent than standard agents, a randomized trial of two nitrosoureas, CCNU and methyl-CCNU, has been conducted. Of 31 evaluable patients who received at least one dose of CCNU (100 mg/m2 orally every 6 weeks), there were only two patients who experienced even transient improvement; 18 of these patients had two or more doses over a trial period of greater than or equal to 12 weeks. Of 26 evaluable patients who received at least one dose of methyl-CCNU (150 mg/m2 orally every 6 weeks), there was one patient who experienced transient improvement; this group included 14 patients receiving at least two doses and whose trial lasted greater than or equal 12 weeks. All patients had been previously treated with mustard-type alkylating agents. None of the responses were clinically useful. Thus, women with ovarian adenocarcinoma who have a history of prior chemotherapy are not likely to benefit from treatment with these nitrosoureas.


Prognostic significance of the delayed plantar reflex following spinal cord injury.
The delayed plantar reflex (DPR) is a pathologic flexor variant which requires unusually strong stimulation of the sole of the foot and is characterized by a prolonged interval between the stimulus and the response, slow and protracted plantarflexion of the great toe and/or other toes and slow return to the neutral position. The purpose of this study was to evaluate prospectively the functional outcome of spinal cord injury (SCI) patients based on the presence or absence of a DPR immediately following injury. Thirty-six subjects were evaluated within one week of injury. A complete neurological evaluation following American Spinal Injury Association (ASIA) standards was performed and the presence or absence of a DPR was noted on admission. Ambulation status and ASIA Impairment Scales were recorded at discharge from the rehabilitation unit and the data were analyzed by the Chi-square method with Yates' correction for continuity. The data demonstrated a high correlation of the DPR with motor complete injuries (p < 0.01) and a poor prognosis for recovery of ambulation (p < 0.01). Clinicians should recognize this abnormal reflex, which may be used in conjunction with a complete neurological examination, to help prognosticate future function in the acute SCI patient.


Crystal structure of a calponin homology domain.
The three-dimensional structure of the calponin homology domain present in many actin binding cytoskeletal and signal-transducing proteins has been determined at 2.0 A resolution.


Early weaning alters redox status in the hippocampus and hypothalamus of rat pups.
Exposure to environmental factors can program the metabolism, conferring resistance or increasing the risk to chronic disease development in childhood and adulthood. In this sense, lactation is an important period in this window of development. Herein, we investigated the effect of early weaning on neurochemical and behavioral changes in offspring at weaning and adulthood. Female and male pups were divided into four groups: (1) Control weaning (weaning on the PND21, pups were kept with the biological mother); (2) Early Weaning Bromocriptine group (EWB) (pharmacological weaning on PND16); (3) Early Weaning Cross-Fostering group (EWCF) (pups housed with a foster mother on PND16 up to PND21); (4) Early Weaning Without Care group (EWWC) (weaning on PND16, maternal separation). Weight control of pups was recorded from postnatal Day 16 to 59. On the 21st day, part of the pups was euthanized and the hippocampus and hypothalamus were removed for biochemical evaluation. The remaining pups were submitted to behavioral tests on the 60th postnatal day. Early weaning reduced the pups' body weight, in a sex-dependent way. At 60 days of age, male pups of EWCF and EWWC groups have lower body weight compared to control male, and female body weight was lower than male pups. In relation to biochemical changes in the brain, weaning altered the levels of oxidants, increased the enzymatic activity of superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as induced lipid peroxidation. Weaning was also able to alter long-term memory and induce anxious behavior in pups. Our results demonstrate that the different types of early weaning changed the parameters of redox status in the hippocampus and hypothalamus of pups (21 days old), suggesting a prooxidative profile, in addition, to alter learning/memory and inducing an anxious behavior in male offspring (60 days old).


A trimer model for water.
A statistical model for water is studied, where the molecules are represented by trimers in a triangular lattice. Each atom of a water molecule occupies a single site on the lattice, and the HOH bond angle is assumed to be 120 degrees. The molecules can interact via three different potentials: the excluded volume interaction, which prevents two molecules from occupying the same atom site, an attractive potential between any two nearest-neighbor atoms belonging to different molecules (the van der Waals interaction), and the hydrogen bond interaction, which occurs only for a particular orientation and displacement of a pair of molecules. The model is investigated by means of Monte Carlo simulations in the canonical and grand canonical ensembles. The Metropolis and the entropic sampling algorithms are used to obtain the thermodynamics of the system. We find that the entropic sampling prescription is the most efficient algorithm of them, providing information about the entropy and free energy of the system in a straightforward way. The curves for the polarization, number of hydrogen bonds, specific heat, and cumulant of energy were obtained as a function of the temperature and total concentration. In addition, the entropy of the noninteracting version of the model is compared to that of the angular trimers in a square lattice and triangles in a triangular lattice.


From outcome measurement to improving health outcomes after lower limb amputation-A narrative review exploring outcome measurement from a clinical practice perspective.
Outcome measurement is essential to understand the impact of clinical interventions and the performance of services. Despite national and professional body encouragement, and successful examples of system level outcome measurement within some health care settings, many barriers still exist preventing outcome measurement from becoming embedded in clinical practice. This paper presents a narrative review which aims to describe the state of the outcome measurement evidence base in prosthetic rehabilitation, as applied in clinical practice, with a view to identifying areas for future work aimed at making outcome measurement in prosthetic rehabilitation a meaningful reality. A literature search of four databases was undertaken, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis principals appropriate to narrative reviews, and using the search terms outcome, measur*, tool, scale, instrument, prosthe*, amput* and limb loss. A total of 1116 papers were identified. Following screening 35 papers, focusing on four main themes, were included in the review. Themes were: 1) What outcome domains should be measured? 2) How can these outcome domains be measured? 3) What are the barriers to outcome measurement? and 4) What can be learnt from examples of ROM in prosthetic rehabilitation? Findings suggest that successful outcome measurement is multifaceted. Understanding and embedding value at every step appears to be key to success. Addressing the questions of 'what' outcome domains to measure and 'how' to measure them, may help establish consensus. Routine outcome measurement practice at the clinical level should ensure data collection is valuable to clinical practice, makes use of information technology solutions and has organisational engagement.


1-Methylcyclopropene (1-MCP) retards the senescence of Pteridium aquilinum var. latiusculum by regulating the cellular energy status and membrane lipid metabolism.
1-MCP is an ethylene inhibitor which can delay the ripening and senescence of fruits and vegetables effectively. Pteridium aquilinum var. Latiusculum (PA) is one of the wild vegetables which is famous and nutrient in China. However, the mechanism of PA preservation treated with 1-MCP has not been reported. Consequently, the effects of postharvest 1-MCP treatment on the changes in quality, energy metabolism, and membrane lipid metabolism of PA were investigated in this study. The results indicated that 1-MCP treatment could effectively inhibit the decreases in firmness, titratable acid (TA) content and the increases in weight loss rate, malondialdehyde (MDA) content, membrane permeability, and membrane lipid metabolism-related enzymes in PA. The cellular energy charge (EC) and the levels of ATP, ATP/ADP, and ATP/AMP, the activities of energy metabolism-related enzymes, NAD+, and NADH were maintained, and the decreases in unsaturated fatty acids and the ratio of unsaturated-to-saturated fatty acids in the membrane of PA cells were effectively retarded by 1-MCP treatment. A positive correlation was observed between cellular ATP levels and the ratio of unsaturated-to-saturated fatty acids, while negative correlations were observed between the ratio of unsaturated-to-saturated fatty acids and both lipid peroxidation and membrane permeability. These results indicated that higher levels of energy status, unsaturated-to-saturated fatty acid ratios, and lipid metabolism in the membrane could preserve the membrane integrity of postharvest PA and effectively extend its shelf life.


Immunoevasive property of a polydnaviral product, CpBV-lectin, protects the parasitoid egg from hemocytic encapsulation of Plutella xylostella (Lepidoptera: Yponomeutidae).
Immunosuppression is the main pathological symptom of the diamondback moth, Plutella xylostella (Lepidoptera: Yponomeutidae), parasitized by an endoparasitoid wasp, Cotesia plutellae (vestalis, Hymenoptera: Braconidae). C. plutellae bracovirus (CpBV), which is a symbiotic virus of C. plutellae, has been known to be the main parasitic factor in the host-parasitoid interaction. CpBV-lectin, encoded in the viral genome and expressed in P. xylostella during early parasitization stage, was suspected to play a role in immunoevasion of defense response. Here we expressed CpBV-lectin in Sf9 cells using a recombinant baculovirus for subsequent functional assays. The recombinant CpBV-lectin exhibited hemagglutination against vertebrate erythrocytes. Its hemagglutinating activity increased with calcium, but inhibited by adding EDTA, indicating its C-type lectin property. CpBV-lectin showed specific carbohydrate-binding affinity against N-acetyl glucosamine and N-acetyl neuraminic acid. The role of this CpBV-lectin in immunosuppression was analyzed by exposing hemocytes of nonparasitized P. xylostella to rat erythrocytes or FITC-labeled bacteria pretreated with recombinant CpBV-lectin, which resulted in significant reduction in adhesion or phagocytosis, respectively. The immunosuppressive activity of CpBV-lectin was further analyzed under in vitro encapsulation response of hemocytes against parasitoid eggs collected at 1- or 24-h post-parasitization. Hemocytic encapsulation was observed against 1-h eggs but not against 24-h eggs. When the 1-h eggs were pretreated with the recombinant CpBV-lectin, encapsulation response was completely inhibited, where CpBV-lectin bound to the parasitoid eggs, but not to hemocytes. These results suggest that CpBV-lectin interferes with hemocyte recognition by masking hemocyte-binding sites on the parasitoid eggs.


Differential radiosensitivity among B cell subpopulations.
We have previously shown that low doses of ionizing radiation selectively impair a functionally defined B cell subpopulation. Normal mice, after exposure to 200 rad of ionizing radiation, have normal or near normal splenic plaque-forming cell responses to thymus-independent type 1 Ag, but reduced responses to thymus-independent type 2 Ag. Here, we confirm and extend the original findings by using hapten-specific serum RIA to demonstrate this differential radiosensitivity is systemic. We also examined splenocytes stained with a panel of lymphocyte surface Ag by FACS analysis to determine if these functional changes are accompanied by a physical alteration of the B cell pool of irradiated mice. Single-parameter FACS analyses demonstrate a diminution in both B cell number and the heterogeneity of membrane Ag expression within the surviving B cell pool after irradiation. In contrast, T cells are relatively radioresistant as the relative percentage of T cells in the irradiated splenocyte pool increases, whereas the heterogeneity of membrane Ag expression remains constant. Multiparameter FACS analyses indicate that B cells with the sIgM much greater than sIgD phenotype are more radiosensitive than B cells of the sIgM much less than sIgD phenotype. In addition, immunohistochemical analysis of splenic sections stained with anti-IgM or anti-IgD reveal the enhanced radiosensitivity of marginal zone B cells.


ColabFit exchange: Open-access datasets for data-driven interatomic potentials.
Data-driven interatomic potentials (IPs) trained on large collections of first principles calculations are rapidly becoming essential tools in the fields of computational materials science and chemistry for performing atomic-scale simulations. Despite this, apart from a few notable exceptions, there is a distinct lack of well-organized, public datasets in common formats available for use with IP development. This deficiency precludes the research community from implementing widespread benchmarking, which is essential for gaining insight into model performance and transferability, and also limits the development of more general, or even universal, IPs. To address this issue, we introduce the ColabFit Exchange, the first database providing open access to a large collection of systematically organized datasets from multiple domains that is especially designed for IP development. The ColabFit Exchange is publicly available at https://colabfit.org, providing a web-based interface for exploring, downloading, and contributing datasets. Composed of data collected from the literature or provided by community researchers, the ColabFit Exchange currently (September 2023) consists of 139 datasets spanning nearly 70 000 unique chemistries, and is intended to continuously grow. In addition to outlining the software framework used for constructing and accessing the ColabFit Exchange, we also provide analyses of the data, quantifying the diversity of the database and proposing metrics for assessing the relative diversity of multiple datasets. Finally, we demonstrate an end-to-end IP development pipeline, utilizing datasets from the ColabFit Exchange, fitting tools from the KLIFF software package, and validation tests provided by the OpenKIM framework.


[Surveillance of plague in the State of Ceará: 1990-1999].
Serological surveillance activities regarding the foci of plague in Ceará State have detected a rising number of sentinel animals with antiplague antibodies in 1995, with a peak in 1997 demonstrating an increase in the plague bacteria activities throughout all the foci investigated. From a total of 110,725 serum samples collected from rodents (7,873) and domestic carnivores (102,852) analyzed by the Hemaglutination technique (HA) for antibodies against F1 antigen of Yersinia pestis 905 samples tested positive. In these samples there were 15 rodents (4 Rattus rattus and 11 Galea spp), 720 dogs and 170 cats. Of the 652 human suspected and contact cases investigated by HA, only two were positive. A third case had a positive hemoculture for Y. pestis. The isolate is highly pathogenic for laboratory animals and showed sensitivity to the antimicrobial drugs used for plague treatment.


Immunochemical and molecular differentiation of 43 000 molecular weight proteins associated with Torpedo neuroelectrocyte synapses.
Synaptic membranes, highly enriched in nicotinic receptor, contain three 43 000 molecular weight (Mr) peripheral proteins (distinctive in their peptide mapping profiles and earlier designated v1, v2, and v 3) as well as the receptor alpha 2 beta gamma delta integral membrane subunits. Of the three proteins, only v1 is copurified with the membrane-bound receptor, while v2 and v3 are prominent cytosolic proteins, which are retained at significant levels in receptor-rich membranes during multistep centrifugation and affinity partitioning purification procedures [Gysin, R., Wirth, M., & Flanagan, S. D. (1981) J. Biol. Chem. 256, 11373-11376]. Peptide mapping analysis of Torpedo v3 and rabbit skeletal actin indicates that the two proteins are closely related. The enzymatic activity, creatine phosphokinase (EC 126.96.36.199), copurifies with v2 during chromatofocusing fractionation of the cytosol. The Torpedo electroplax form of creatine phosphokinase has an electrophoretic mobility identical with that of the mammalian skeletal muscle form of the enzyme. Upon release of the membrane-bound forms of v1, creatine phosphokinase, and actin by the action of mild alkali, v1 remains in a high molecular weight form. Dissociation of v1 into lower molecular weight species requires urea or sodium dodecyl sulfate (NaDodSO4). Preparation of essentially pure v1 was achieved by eluting the v1 protein spots directly from naDodSO4-isoelectric focusing gels loaded with alkali extracts derived from membranes highly enriched in nicotinic receptor. Amino acid compositions of the purified fractions indicate that v1 and Torpedo creatine phosphokinase have distinct amino acid compositions from each other and from that of actin.(ABSTRACT TRUNCATED AT 250 WORDS)


Splenectomy in biliary atresia patients with recurrent jaundice following partial splenic embolization.
Splenectomy was performed for three patients with biliary atresia because of re-exacerbation of their jaundice following treatment by partial splenic embolization (PSE). The subjects' red blood cell count and hemoglobin, serum level of hepatic enzymes (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase, and lactic dehydrogenase), and total bilirubin (TB) were evaluated both before and after splenectomy in order to analyze the effects of splenectomy on these patients. The TB decreased significantly within 3 months after splenectomy in all three patients (13.0 +/- 1.6 mg/100 ml to 5.4 +/- 0.3 mg/100 ml, p < 0.05). The red blood cell count and hemoglobin increased gradually. There was a statistically significant correlation between the TB and the red blood cell count, and/or concentration of hemoglobin. The hepatic enzymes after splenectomy were not significantly different from those before splenectomy. The change in TB following splenectomy was essentially similar to that following PSE. These results suggested that the postoperative improvement in jaundice following splenectomy may not be due to improved hepatic function but merely a reflection of decreased red blood cell turnover. Splenectomy is a useful palliative procedure for jaundice in patients with biliary atresia for whom PSE is no longer effective.


Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review.
Hydroxychloroquine sulfate (HCQ, Plaquenil) is an analogue of chloroquine (CQ), an antimalarial agent, used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune disorders. Its use has been associated with severe retinal toxicity, requiring a discontinuation of therapy. Because it presents potential secondary effects including irreversible maculopathy, knowledge of incidence, risk factors, drug toxicity and protocol screening of the patients it represents important data for the ophthalmologists. Thus, it is imperative that rheumatologists, medical internists and ophthalmologists are aware of the toxicity from hydroxychloroquine they should also be careful to minimize its occurrence and effects.


Solid-supported cross-coupling catalysts derived from homogeneous nickel and palladium coordination complexes.
Solid-supported catalysts derived from homogeneous nickel(II) and palladium(II) non-symmetrical salen-type coordination complexes have been prepared and shown to be effective in the heterogeneous catalysis of carbon-carbon cross-coupling reactions. The nickel catalyst has been used in room-temperature Tamao-Kumada-Corriu reactions and the palladium catalyst in the Heck reaction at elevated temperatures. The complexes were prepared by improved methods and characterised by spectroscopic techniques. Comparisons between the solid-supported catalysts and their homogeneous analogues are reported. The single-crystal structure determination of the nickel and palladium complexes [M(salenac-OH)][M = Ni, Pd; salenac-OH = 9-(2',4'-dihydroxyphenyl)-5,8-diaza-4-methylnona-2,4,8-trienato](2-)] is reported.


Selective serotonin reuptake inhibitor (fluoxetine) decreases the effects of ghrelin on memory retention and food intake.
Ghrelin (Ghr) is an appetite stimulating hormone that is produced peripherally, by the stomach, and centrally as well. Previous investigations show that Ghr increases food intake and memory retention in rats, and that extra-hypothalamic structures, such as the hippocampus, participate in these effects. In the present work we analyzed the effect on food intake and memory retention induced by Ghr after serotonin (5-HT) availability modification at the serotoninergic synapses. Animals only treated with a selective serotonin reuptake inhibitor (SSRI), fluoxetine (FLU) 5 mg/kg or clomipramine (CLO) 2.5 and 5 mg/kg, showed a significant reduction in both food intake and memory retention. On the contrary, Ghr administration induces a significant increase in food intake and a dose-dependent increase in short and long term memory retention. When the animals were treated with FLU prior to Ghr injection, the food intake induced, as well as the expression of short and long term memory retention, was decreased. In conclusion, evidence presented in this paper suggests that the effects of Ghr on both feeding and memory retention in extra-hypothalamic structures such as the hippocampus, could depend on the availability of 5-HT.


Human T cell lymphotropic virus type 1-associated myelopathy in São Paulo, Brazil. Epidemiologic and clinical features of a university hospital cohort.
We report epidemiologic and clinical features of human T cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis in a Brazilian cohort of 86 patients from a university hospital. Cerebrospinal fluid (CSF) abnormalities and magnetic resonance imaging (MRI) findings were correlated with neurologic signs and symptoms. The patients' mean age at disease onset was 43.2 years and the female to male ratio 1.5:1. Risk factors for retroviral exposure included blood transfusions, sexual transmission and intravenous drug use. Neurologic manifestations consisted mostly of spastic paraparesis, of gradual and asymmetric onset, with increased deep-tendon reflexes. Disability was associated with disease duration. CSF findings included mild mononuclear pleocytosis and elevated protein levels. MRI showed hemispheric areas of high signal intensity in 32.7% and spinal cord atrophy in 5.6% of cases, particularly in patients with longer duration of disease. A high frequency of past blood transfusion (32.6%) suggests that blood-borne infection was an important means of HTLV infection before implementation of screening of blood donors in Brazil.


Tamoxifen induced-thrombocytopenia: it does occur.
Tamoxifen has been in the center of management of hormone-sensitive breast cancer. Furthermore, it represents the best example of chemo-prevention: It reduces the incidence of invasive breast cancer. However, it has some side effects, several of them are severe. Oncologists, hematologists, internal medicine specialists and gynecologists must know this agent in detail. Authors report a very rare side effect, thrombocytopenia, and discuss it briefly.


The silencing mediator of retinoid and thyroid hormone receptors (SMRT) regulates adipose tissue accumulation and adipocyte insulin sensitivity in vivo.
The silencing mediator of retinoid and thyroid hormone receptors (SMRT) serves as a corepressor for nuclear receptors and other factors. Recent evidence suggests that SMRT is an important regulator of metabolism, but its role in adipocyte function in vivo remains unclear. We generated heterozygous SMRT knock-out (SMRT(+/-)) mice to investigate the function of SMRT in the adipocyte and the regulation of adipocyte insulin sensitivity. We show that SMRT(+/-) mice are normal weight on a regular diet, but develop increased adiposity on a high-fat diet (HFD). The mechanisms underlying this phenotype are complex, but appear to be due to a combination of an increased number of smaller subcutaneous adipocytes as well as decreased leptin expression, resulting in greater caloric intake. In addition, adipogenesis of mouse embryonic fibroblasts (MEFs) derived from these mice was increased. However, adipocyte insulin sensitivity, measured by insulin-induced Akt phosphorylation and insulin-mediated suppression of lipolysis, was enhanced in SMRT(+/-) adipocytes. These finding suggest that SMRT regulates leptin expression and limits the ability of fat mass to expand with increased caloric intake, but that SMRT also negatively regulates adipocyte insulin sensitivity.


Midgut bacteria required for Bacillus thuringiensis insecticidal activity.
Bacillus thuringiensis is the most widely applied biological insecticide and is used to manage insects that affect forestry and agriculture and transmit human and animal pathogens. This ubiquitous spore-forming bacterium kills insect larvae largely through the action of insecticidal crystal proteins and is commonly deployed as a direct bacterial spray. Moreover, plants engineered with the cry genes encoding the B. thuringiensis crystal proteins are the most widely cultivated transgenic crops. For decades, the mechanism of insect killing has been assumed to be toxin-mediated lysis of the gut epithelial cells, which leads to starvation, or B. thuringiensis septicemia. Here, we report that B. thuringiensis does not kill larvae of the gypsy moth in the absence of indigenous midgut bacteria. Elimination of the gut microbial community by oral administration of antibiotics abolished B. thuringiensis insecticidal activity, and reestablishment of an Enterobacter sp. that normally resides in the midgut microbial community restored B. thuringiensis-mediated killing. Escherichia coli engineered to produce the B. thuringiensis insecticidal toxin killed gypsy moth larvae irrespective of the presence of other bacteria in the midgut. However, when the engineered E. coli was heat-killed and then fed to the larvae, the larvae did not die in the absence of the indigenous midgut bacteria. E. coli and the Enterobacter sp. achieved high populations in hemolymph, in contrast to B. thuringiensis, which appeared to die in hemolymph. Our results demonstrate that B. thuringiensis-induced mortality depends on enteric bacteria.