Acute Kidney Injury Due to Inferior Vena Cava Stenosis After Liver Transplantation: A Case Report About the Importance of Hepatic Vein Doppler Ultrasound and Clinical Assessment.
Acute kidney injury (AKI) is a frequent complication after liver transplantation. In some patients, prompt intervention targeted at a specific etiology is of paramount importance. A 25 years old man with advanced liver cirrhosis caused by sclerosing cholangitis and autoimmune hepatitis underwent orthotopic liver transplantation. One month after surgery, severe AKI developed in conjunction with recurrent ascites and lower extremity edema. Notable clinical findings included a persistently low urinary sodium excretion, a bland urinary sediment, and an abnormally monophasic hepatic vein waveform on Doppler ultrasound. Inferior vena cava stenosis. Angioplasty with stent installation. Rapid improvement of renal function after stent installation. The following case illustrates the importance of integrating clinical cues, ultrasound features, and laboratory findings. The combination of AKI associated with lower extremity edema, abnormal monophasic hepatic vein flow on Doppler ultrasound, and a low urinary sodium excretion after liver transplantation should evoke the possibility of inferior vena cava stenosis as the etiologic factor.


Anxio-depressive symptoms in Moroccan women with gynecological cancer: Relief factors.
Psychosocial determinants can affect the mental health of women who have been diagnosed with gynecological cancer. The aim of this study was to examine how social support and self-esteem are associated with anxiety and depression symptoms in women with gynecological cancer, and who are treated by radical surgery. A cross-sectional study was performed, within the oncology department of Ibn Rochd University Hospital, Casablanca, on 100 Moroccan women. They all had undergone radical surgery for gynecological cancer, hysterectomy and/or oophorectomy. Our results showed that patients with gynecological cancer treated by radical surgery exhibited high prevalence rates of anxiety (66%) and depression symptoms (59%). Associations showed that age, having children, medical coverage system, area of residence, working status and socioeconomic status were significantly related to the prevalence of anxiety and depression symptoms (P<0.05). The general social support, family support and significant other support besides high self-esteem reduce significantly the risk of getting anxiety and depression symptoms (P-values<0.05). Among patients with gynecological cancer treated by radical surgery, high prevalence of anxiety and depression symptoms was found. Social support and high self-esteem could help improve mental health issues related to this type of cancer.


Dynamic Changes in Lumbar Spine Kinematics During Gait May Explain Improvement in Back Pain and Disability in Patients With Hip-Spine Syndrome.
Prospective cohort. Determine if total hip arthroplasty (THA) changes lumbar spine kinematics during gait in a manner that explains the improvements in back pain seen in patients with hip-spine syndrome. For patients with hip-spine syndrome, improvements in both hip and back pain have been demonstrated after THA; however, the exact mechanism of improvement in back pain remains unknown, as no corresponding changes in lumbar spine static radiographic parameters have been identified. Thirteen patients with severe, unilateral hip osteoarthritis scheduled to undergo THA with concomitant back pain and disability were tested at baseline and 6 months after THA. Harris Hip Score (HHS) and Oswestry Disability Index questionnaires were completed; the static orientation of the spine and pelvis were measured on standing radiographs, and lumbar spine kinematics were measured during treadmill walking using a validated measurement system that matched subject-specific bone models created from CT scans to dynamic biplane radiographs. After THA, both the Oswestry Disability Index (36.3-11.3, P <0.001) and Harris Hip Score (55.7-77.9, P <0.001) improved; however, there were no changes in static intervertebral or pelvis orientation. During gait after THA, the overall lumbar spine (L1 to L5) was less lordotic from heel strike to contralateral toe off ( P <0.001), the L4 and L5 vertebra were less anteriorly tilted by 3.9° ( P =0.038) from midstance to contralateral heel strike and by 3.9° ( P =0.001) during stance, respectively. The decreased anterior tilt of the 2 lowest lumbar vertebrae and the corresponding loss of lumbar lordosis may reduce facet loading during the stance phase of gait after THA. This change in lumbar spine kinematics during gait is a potential mechanism to explain the observed improvements in back pain and disability after THA. 4.


Pneumonia: challenges in the definition, diagnosis, and management of disease.
Defining health care-associated pneumonia, which includes both hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), is problematic and controversial. Aspiration pneumonia is often included as a subtype of HAP but may be related to community-acquired aspiration events. Scoring systems exist and new surveillance guidelines have been implemented to make early recognition of pneumonia more precise and objective. Management and prevention should follow recommendations, including early empirical therapy, targeted therapy, and limited duration of treatment. Patients with trauma present a challenge to the diagnosis and management of pneumonia, because of increased risk for aspiration and underlying chest and pulmonary injury.


Poor Response to Standard Chemotherapy in Early T-precursor (ETP)-ALL: A Subtype of T-ALL Associated with Unfavourable Outcome: A Brief Report.
Early T-precursor (ETP)-ALL, a type of T-ALL, is a new pathobiologic entity with distinct immunophenotype (CD1a(-), CD8(-), CD5(weak/absent) with stem-cell/myeloid markers) and genetic expression, poor response to standard intensive chemotherapy and very high risk of relapse. The genetic mutations typically associated with the pathogenesis of acute myeloid leukemia are seen with increased prevalence in ETP-ALL. No Indian data exists regarding this rare entity. Recently we have seen six cases of ETP-ALL and hereby reporting their clinical characteristics and treatment outcome. All patients were given induction chemotherapy according to standard protocols. Only one out of six patients could achieve remission after induction therapy. Rest five patients died because of their leukemia. This reflects the aggressive biology of this disease and its poor response to standard chemotherapy regimens generally used in T-ALL. The limited experience with ETP-ALL reflects whether rarity of this condition or failure to recognize this is not clear at this time. More studies are required to understand the basic biology of this disease and new therapeutic strategies need to be devised.


[Electron probe x-ray microanalysis of human aorta with isthmus stenosis].
Aortas with isthmus stenosis (coarctation) can be regarded as a model for those changes of the vessel wall, that depend on blood pressure, as one can compare the proximal region (high pressure) with the distal one (low pressure). The Na, Mg, P, S, Cl, K, and Ca content of the vessel walls of 5 patients (age: 2 months to 34 years) were determined by electron probe microanalysis. We have used cryostat sections and measured the element concentrations from the lumen to the outer media. In this paper we discuss especially the measurements of Ca and P, as the mineral being deposited in the vessel wall, e.g. in arteriosclerosis, contains Ca and P. Up to 18 years Ca and P enrichments are found only in a subintimal band parallel to the lumen. The proximal region of the aorta of a 34 years old patient, however, demonstrated Ca and P enrichments in the whole media with a high peak in the subintimal band. The enrichments are proximally always higher than distally. Only in the distal region of the 2 months old infant no Ca or P enrichments were found, but they appeared proximally. Thus high blood pressure causes an enrichment of Ca and P in a subintimal band very rapidly and promotes the mineralization of the vessel wall. The quantitative electron probe microanalysis demonstrated these pathological alterations.


Matsuda-Heck arylation of itaconates: a versatile approach to heterocycles from a renewable resource.
Itaconic acid esters and hemiesters undergo Pd-catalyzed coupling reactions with arene diazonium salts in high to excellent yields. The coupling products of ortho-nitro arene diazonium salts can be converted in one or two steps to benzazepine-2-ones.


Pyrazine Based Type-I Sensitizing Assemblies for Photoreduction of Cu(II) in 'One-Pot Three-Component' CuAAC Reaction Under Aerial Conditions.
Photosensitizing assemblies of pyrazine derivative PDA have been developed which exhibit a high photostability, 'lighted' excited state, balanced redox potential, high transportation potential and activate oxygen via type-I pathway only. These PDA assemblies in combination with Cu(II) ions catalyze the CuAAC reaction via in situ reduction of Cu(II) ions without any reducing or stabilizing agent. The present protocol has wide substrate scope with recyclability of the catalytic system up to six catalytic cycles and is applicable to gram-scale synthesis.


Interaction between travel restriction policies and the spread of COVID-19.
To investigate the interaction between travel restriction policies and the spread of COVID-19, we collected data on human mobility trends, population density, Gross Domestic Product (GDP) per capita, daily new confirmed cases (or deaths), and the total confirmed cases (or deaths), as well as governmental travel restriction policies from 33 countries. The data collection period was from April 2020 to February 2022, resulting in 24,090 data points. We then developed a structural causal model to describe the causal relationship between these variables. Using the Dowhy method to solve the developed model, we found several significant results that passed the refutation test. Specifically, travel restriction policies played an important role in slowing the spread of COVID-19 until May 2021. International travel controls and school closures had an impact on reducing the spread of the pandemic beyond the impact of travel restrictions. Additionally, May 2021 marked a turning point in the spread of COVID-19 as it became more infectious, but the mortality rate gradually decreased. The impact of travel restriction policies on human mobility and the pandemic diminished over time. Overall, the cancellation of public events and restrictions on public gatherings were more effective than other travel restriction policies. Our findings provide insights into the effects of travel restriction policies and travel behavioral changes on the spread of COVID-19, while controlling for informational and other confounding variables. This experience can be applied in the future to respond to emergent infectious diseases.


Maxillofacial growth and speech outcome after one-stage or two-stage palatoplasty in unilateral cleft lip and palate. A systematic review.
The number of surgical procedures to repair a cleft palate may play a role in the outcome for maxillofacial growth and speech. The aim of this systematic review was to investigate the relationship between the number of surgical procedures performed to repair the cleft palate and maxillofacial growth, speech and fistula formation in non-syndromic patients with unilateral cleft lip and palate. An electronic search was performed in PubMed/old MEDLINE, the Cochrane Library, EMBASE, Scopus and CINAHL databases for publications between 1960 and December 2015. Publications before 1950-journals of plastic and maxillofacial surgery-were hand searched. Additional hand searches were performed on studies mentioned in the reference lists of relevant articles. Search terms included unilateral, cleft lip and/or palate and palatoplasty. Two reviewers assessed eligibility for inclusion, extracted data, applied quality indicators and graded level of evidence. Twenty-six studies met the inclusion criteria. All were retrospective and non-randomized comparisons of one- and two-stage palatoplasty. The methodological quality of most of the studies was graded moderate to low. The outcomes concerned the comparison of one- and two-stage palatoplasty with respect to growth of the mandible, maxilla and cranial base, and speech and fistula formation. Due to the lack of high-quality studies there is no conclusive evidence of a relationship between one- or two-stage palatoplasty and facial growth, speech and fistula formation in patients with unilateral cleft lip and palate.


α-Subunit Tyrosine Phosphorylation Is Required for Activation of the Large Conductance Ca2+-Activated Potassium Channel in the Rabbit Sphincter of Oddi.
Large conductance Ca2+-activated potassium (BKCa) channels are regulated by intracellular free Ca2+ concentrations ([Ca2+]i) and channel protein phosphorylation. In hypercholesterolemia (HC), motility impairment of the sphincter of Oddi (SO) is associated with abnormal [Ca2+]i accumulation in smooth muscle cells of the rabbit SO (RSOSMCs), which is closely related to BKCa channel activity. However, the underlying mechanisms regulating channel activity remain unclear. In this study, an HC rabbit model was generated and used to investigate BKCa channel activity of RSOSMCs via SO muscle tone measurement in vitro and manometry in vivo, electrophysiological recording, intracellular calcium measurement, and Western blot analyses. BKCa channel activity was decreased, which correlated with [Ca2+]i overload and reduced tyrosine phosphorylation of the BKCa α-subunit in the HC group. The abnormal [Ca2+]i accumulation and decreased BKCa channel activity were partially restored by Na3VO4 pretreatment but worsened by genistein in RSOSMCs in the HC group. This study suggests that α-subunit tyrosine phosphorylation is required for [Ca2+]i to activate BKCa channels, and there is a negative feedback between the BKCa channel and the L-type voltage-dependent Ca2+ channel that regulates [Ca2+]i. This study provides direct evidence that tyrosine phosphorylation of BKCa α-subunits is required for [Ca2+]i to activate BKCa channels in RSOSMCs, which may be the underlying physiological and pathologic mechanism regulating the activity of BKCa channels in SO cells.


Clinical and biological prediction of axillary and internal mammary lymph node metastases in breast cancer.
We assessed the relationships among histological axillary (AX) or internal mammary (IM) metastases and clinical and biological variables, and then attempted to evaluate their predictive values for AX and IM metastases in 128 patients with invasive breast cancer. As the results, these clinical and biological variables were significantly correlated with AX and IM metastases. However, a metastatic index calculated from clinical and biological variables was not much better in prediction of the AX metastases than axillary nodal status, whereas it was useful to predict the IM metastases. Thus, the predictive ability was still limited. Since accurate prediction of AX and IM metastases is critical to therapeutic choice, however, further study would be required.


Relationships between fuselloviruses infecting the extremely thermophilic archaeon Sulfolobus: SSV1 and SSV2.
The fusellovirus SSV2 from an Icelandic Sulfolobus strain was isolated, characterized and its complete genomic sequence determined. SSV2 is very similar in morphology, replication, genome size and number of open reading frames (ORFs) to the type virus of the family, SSV1 from Japan, except in its high level of uninduced virus production. The nucleotide sequences are, however, only 55% identical to each other, much less than related bacteriophage, related animal viruses and the rudiviruses of Sulfolobus, SIRV1 and SIRV2. Nevertheless the genome architecture is very similar between the two viruses, indicating that despite this genomic dissimilarity the virus genomes are mostly homologous. Unlike SSV1, the sequence of SSV2 indicates integration into a glycyl tRNA gene and is completely missing a DNA packaging gene. There is a unique, perfectly tandemly directly repeated sequence of 62 nucleotides in SSV2 that has no similarity to known sequences or structures. By comparison to the SSV2 genome, an integrated partial fusellovirus genome was found in the Sulfolobus solfataricus P2 genome further confirming the dynamism of the Sulfolobus genome. Clustering of cysteine codon containing ORFs both in SSV1 and SSV2 indicates that these Fuselloviridae arose from a genome fusion event.


Does expressive writing or an instructional intervention reduce the impacts of test anxiety in a college classroom?
Test anxiety is a major concern in education because it causes uncomfortable feelings in test-anxious students and may reduce the validity of exam scores as a measure of learning. As such, brief and cost-effective interventions are necessary to minimize the negative impact of test anxiety on students' academic performance. In the present experiment, we examine two such interventions: expressive writing (Experiment 1) and an instructional intervention (Experiment 2), with the latter developed from a similar intervention for stereotype threat. Across four authentic exams in a psychology class, students alternated between completing the intervention and a control task immediately before completing the exams. Neither intervention was effective at reducing test anxiety or improving exam performance. The present results suggest that these interventions may not be successful in addressing the impacts of test anxiety in all classroom settings.


An aptamer-based biosensor for mammalian initiation factor eukaryotic initiation factor 4A.
Aptamers are short single-stranded DNA or RNA sequences that are selected in vitro based on their high affinity to a target molecule. Here we demonstrate that an RNA aptamer selected against eukaryotic initiation factor 4A (eIF4A) serves as an efficient biosensor. The aptamer, when immobilized to resin, purifies eIF4A from crude cell extracts by affinity pull-down, and 32P-labeled aptamer can detect some 300 ng of eIF4A by dot-blot analysis. Moreover, by use of an aptamer-immobilized sensor chip, we developed a surface plasmon resonance assay to detect eIF4A at the nanogram level within whole cell lysates after optimizing sample preparation, thereby showing a real-time sensor for eIF4A in cell extract solution.


Bridging chromatin structure and function over a range of experimental spatial and temporal scales by molecular modeling.
Chromatin structure, dynamics, and function are being intensely investigated by a variety of methods, including microscopy, X-ray diffraction, nuclear magnetic resonance, biochemical crosslinking, chromosome conformation capture, and computation. A range of experimental techniques combined with modeling is clearly valuable to help interpret experimental data and, importantly, generate configurations and mechanisms related to the 3D organization and function of the genome. Contact maps, in particular, as obtained by a variety of chromosome conformation capture methods, are of increasing interest due to their implications on genome structure and regulation on many levels. In this perspective, using seven examples from our group's studies, we illustrate how molecular modeling can help interpret such experimental data. Specifically, we show how computed contact maps related to experimental systems can be used to explain structures of nucleosomes, chromatin higher-order folding, domain segregation mechanisms, gene organization, and the effect on chromatin structure of external and internal fiber parameters, such as nucleosome positioning, presence of nucleosome free regions, histone posttranslational modifications, and linker histone binding. We argue that such computations on multiple spatial and temporal scales will be increasingly important for the integration of genomic, epigenomic, and biophysical data on chromatin structure and related cellular processes.


hCG day progesterone level has no impact on the frozen thawed embryo transfer cycle outcome.
To assess the association between hCG day progesterone levels and subsequent frozen-thawed embryo transfer (FET) cycle outcome in infertile women with and without polycystic ovary syndrome (PCOS). Data of 178 women who underwent FET at a university-based infertility clinic between January 2016 and December 2019 were reviewed. The study group consisted of women who had progesterone elevation (PE) during fresh controlled ovarian stimulation (COS) cycle. A sub-group analysis was also performed in PCOS and non-PCOS patients. There were no differences in clinical pregnancy (47.7 % vs. 50.7 %, p = 0.729), miscarriage (15.9 % vs. 22.4 %, p = 0.359), and live birth rates (27.3 % vs. 23.9 %, p = 0.652) following FET between women with and without PE in the fresh cycle. The results remained non-significant regarding the clinical pregnancy (46.7 % vs. 53.4 %, p = 0.549), miscarriage (13.3 % vs. 27.6 %, p = 0.133), and live birth rates (26.7 % vs. 19.0 %, p = 0.408) in participants with PCOS (n = 88). hCG day progesterone level in the fresh COS cycle does not have a significant impact on the subsequent FET cycle neither in PCOS nor in non-PCOS women.


A mid-central N450 component of the ERP distinguishes trial-by-trial effects of target familiarity and context strength.
N400-like components in the ERP are commonly understood as being inversely related to the degree at which contextual factors have prepared the brain for the processing of meaningful stimuli. Here we show independent and systematic effects of familiarity and context on mid-central N450 in a simple visual priming task. Participants selected a target digit defined by color while ignoring a distractor digit. Pairs of two subsequent displays (prime, probe) were considered. Probe target familiarity could be high (prime-probe target repetition), low (novel probe target), or very low (probe target=prime distractor). Context strength depended on history of the probe distractor and could be high (prime-probe distractor repetition), low (novel probe distractor), or very low (probe distractor=prime target). The seven priming conditions showed exactly the predicted order of N450 amplitude, with largest N450 for strong context/low target familiarity and smallest N450 for weak context/high target familiarity. Results significantly broaden the view of N400, as a universal marker of stimulus familiarity and context strength also in basic, non-linguistic settings.


Legal and policy considerations in using clinical practice guidelines.
The increased use of clinical practice guidelines has implications for both public policy and for litigation. Physicians are concerned that the introduction of practice guidelines will reduce their clinical decision-making authority and that the failure to follow clinical practice guidelines will lead to medical liability. Although practice guidelines are an increasing part of medical practice, there has been only limited litigation to determine the extent to which guidelines will be used to set the applicable standard of care. This article discusses the potential legal and public policy issues raised by the introduction and use of clinical practice guidelines. From a legal perspective, the primary issue is whether guidelines will be used to set the "standard of care" or will be one piece of evidence that a jury would use to determine the outcome of medical liability litigation. Based on an assessment of the applicable legal and policy considerations, the article concludes that courts should admit guidelines into evidence, but that they should not be used as the sole determinant of the standard of care. Instead, guidelines should be treated as one piece of evidence to be weighed by the jury. This approach will facilitate physician acceptance of guidelines by not imposing liability for the failure to follow guidelines without additional evidence to determine the standard of care.


Fabrication of porphyrin-based magnetic covalent organic framework for effective extraction and enrichment of sulfonamides.
The dehydration reaction of tetraamino porphyrin and 4,4'-biphenyldicarboxaldehyde was performed for the synthesis of a novel covalent organic framework (COF), which was decorated on magnetic Fe3O4 to obtain core-shell structured Fe3O4@COFs nanospheres for the first time, for effective extraction and enrichment of sulfonamides (SAs). The morphology and structure of the synthesized nanospheres were characterized through various methods. The extraction conditions for six SAs including sulfadiazine, sulfamerazine, sulfamethazine, sulfamonomethoxine, sulfamethoxazole, sulfadimethoxine were systematically optimized. Fe3O4@COFs nanospheres were evaluated for magnetic solid-phase extraction. By coupling with high-performance liquid chromatography, a facile and sensitive method was established for the quantitation analysis of six SAs. The method showed good linearity ranging from 1 to 500 ng mL-1 with R2 > 0.99, high sensitivity with LODs in the range of 0.2-1 ng mL-1, and high precision with RSDs≤6.3%. This method was further applied into determination of SAs in environmental water and food samples, with recoveries in the range of 65.3%-107.3% and RSDs≤6.7%. These successful applications suggest that the core-shell structured Fe3O4@COFs nanospheres could be used as a potential adsorbent for efficient extraction and analysis of trace SAs.


Dexamethasone for the prevention of postpericardiotomy syndrome: A DExamethasone for Cardiac Surgery substudy.
The postpericardiotomy syndrome (PPS) is a common complication following cardiac surgery. The pathophysiology remains unclear, although evidence exists that surgical trauma and the use of cardiopulmonary bypass provoke an immune response leading to PPS. We hypothesized that an intraoperative dose of dexamethasone decreases the risk of PPS, by reducing this inflammatory response. We performed a subanalysis of the DECS study, which is a multicenter, double-blind, placebo-controlled, randomized trial of 4,494 patients undergoing cardiac surgery with use of cardiopulmonary bypass. The aim of the DECS study was to investigate whether a single intraoperative dose of 1 mg/kg dexamethasone reduced the incidence of a composite of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization. In this substudy, we retrospectively analyzed the occurrence of PPS in 822 patients who were included in the DECS trial and underwent valvular surgery. Postpericardiotomy syndrome was diagnosed if 2 of 5 listed symptoms were present: unexplained fever, pleuritic chest pain, pericardial or pleural rub, new or worsening pericardial or pleural effusion. All medical charts, x-rays, and echocardiograms were reviewed. Secondary end point was the occurrence of complicated PPS, defined as PPS with need for evacuation of pleural effusion, pericardiocentesis, and tamponade requiring intervention or hospital readmission for PPS. This is a blinded, single-center, post hoc analysis. Postpericardiotomy syndrome occurred in 119 patients (14.5%). The incidence of PPS after dexamethasone compared with placebo was 13.5% vs 15.5% (relative risk 0.88, 95% CI 0.63-1.22). For complicated PPS, the incidence was 3.8% versus 3.2% (relative risk 1.17, 95% CI 0.57-2.41, P = .66), respectively. In patients undergoing valvular cardiac surgery, high-dose dexamethasone treatment had no protective effect on the occurrence of PPS or complicated PPS.


Gender differences with short-term vs 12 months dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: 2-years follow-up results of the REDUCE trial.
Gender differences in the thrombotic and bleeding risk have been suggested to condition the benefits of antithrombotic therapies in Acute Coronary Syndrome (ACS) patients, and mainly among those undergoing percutaneous coronary interventions with drug eluting stents (DES). The impact of gender on the optimal duration of dual antiplatelet therapy (DAPT) in ACS patients is still unexplored and was, therefore, the aim of the present sub-study. REDUCE was a prospective, multicenter, randomized investigator-initiated study designed to enroll 1500 ACS patients after treatment with the COMBO Dual Stent Therapy, based on a noninferiority design. Patients were randomized in a 1:1 fashion to either 3 or 12 months of DAPT. Primary study endpoint was a composite of all-cause mortality, myocardial infarction, definite/probable stent thrombosis (ST), stroke, target-vessel revascularization (TVR) and bleedings (BARC II, III, V) at 12 months. Secondary endpoints were cardiovascular mortality and the individual components of the primary endpoint within 24 months. From June 2014 to May 2016 300 women and 1196 men were included in the study. Among them, 43.7% of females and 51.9% of males were assigned to the 3 months DAPT treatment. Baseline characteristics were well matched between the two arms, with the exception of a lower rate of TIMI flow < 3 (p = 0.04), lower systolic blood pressure (p = 0.05) and use of spironolactone (p = 0.006) among women and a more advanced age (p = 0.05) among men receiving a short-term DAPT. At a mean follow-up of 525 (± 198) days, no difference in the primary endpoint was observed according to DAPT duration in both females [6.9% vs 5.9%, HR (95% CI) = 1.19 (0.48-2.9), p = 0.71] and males [8.2% vs 9%, HR (95% CI) = 0.92 (0.63-1.35), p = 0.67; p INT = 0.20]. Results were confirmed after correction for baseline differences [females: adjusted HR (95% CI) = 1.12 (0.45-2.78), p = 0.81; males: adjusted HR (95% CI) = 0.90 (0.61-1.32), p = 0.60]. Comparable rates of survival, thrombotic (MI, stent thrombosis, TVR, stroke) and bleeding events were observed with the two DAPT strategies, with no impact of gender. The present study shows that among ACS patients randomized in the REDUCE trial, a 3 months DAPT strategy offers comparable results as compared to a standard 12 months DAPT at 2-years follow-up in both male and female gender.


Evaluation of disease outbreak in terms of physico-chemical characteristics and heavy metal load of water in a fish farm with machine learning techniques.
Diseases are quite common in fish farms because of changes in physico-chemical characteristics in the aquatic environment, and operational concerns, i.e., overstocking and feeding issues. In the present study, potential factors (water physico-chemical characteristics and heavy metal load) on the disease-causing state of the pathogenic bacteria Lactococcus garvieae and Vagococcus sp. were examined with machine learning techniques in a trout farm. Recording of physico-chemical characteristics of the water, fish sampling and bacteria identification were carried out at bimonthly intervals. A dataset was generated from the physico-chemical characteristics of the water and the occurrence of bacteria in the trout samples. The eXtreme Gradient Boosting (XGBoost) algorithm was used to determine the most important independent variables within the generated dataset. The most important seven features affecting bacteria occurrence were determined. The model creation process continued with these seven features. Three well-known machine learning techniques (Support Vector Machine, Logistic Regression and Naïve Bayes) were used to model the dataset. Consequently, all the three models have produced comparable results, and Support Vector Machine (93.3% accuracy) had the highest accuracy. Monitoring changes in the aquaculture environment and detecting situations causing significant losses through machine learning techniques have a great potential to support sustainable production.


Usefulness of BFB/EMG in facial palsy rehabilitation.
To analyze and to compare the recovery and the development of synkinesis in patients with idiopathic facial palsy (Bell's palsy) following treatment with two methods of rehabilitation, kinesitherapy (KT) and biofeedback/EMG (BFB/EMG). Retrospective cases--series review. Seventy-four patients with Bell' palsy were clinically evaluated within 1 month from onset of palsy and at 12 months after palsy (House scale and synkinesis evaluation). Electromyography (EMG) and Electroneurography (ENG) were performed about 4 weeks after palsy to better evaluate functional abnormalities due to facial nerve lesion. The patients followed two different protocols for rehabilitation: the first 32 patients were treated with therapeutic exercises performed by therapists (KT group), the latter 42 patients were treated using BFB/EMG methods (BFB group) with inhibition of synkinetic movement as the primary goal. KT and BFB patients were evaluated for clinical and neurophysiological characteristics before rehabilitative treatment. BFB patients showed better clinical recovery and minor synkinesis than KT patients. BFB/EMG seems to be more useful than KT in Bell's palsy treatment. This could be due to the fact that BFB/EMG gives more accurate information than KT on muscle activation with better modulation in voluntary recruitment of motor unit.


Molecular dynamics simulation study of DNA conformation changes caused by the dinuclear platinum(II) complexes with the bisphosphonate group.
Bisphosphonate (BP) has been widely used as a bone-targeting group, and the BP-modified platinum(II) complexes have shown potential to as anticancer drugs against bone-related diseases, such as osteosarcoma. DNA conformation changes induced by the BP-modified dinuclear platinum(II) complexes have been investigated using molecular dynamics simulations. The results indicated that the BP-modified dinuclear platinum(II) complexes coordinated to DNA results in DNA structural distortions, including twisting, unwinding and bending. Furthermore, the rigidity of the bridging linkers in the BP-modified platinum(II) complex may induce more significant DNA structural distortions with same spans. The results provide the detail information of DNA conformational changes induced by the BP-modified platinum(II) complexes with different flexibility of bridging linkers, and are helpful for exploring novel platinum-based antitumor drugs.


The nature of the decrease in blood-cerebrospinal fluid barrier exchange during postnatal brain development in the rat.
1. The blood-cerebrospinal fluid (CSF) exchange of a wide range of passively transported lipid insoluble compounds (0.43-5.4 nm molecular radius) has been investigated in rats at different stages of postnatal development (2 days old to adult). A novel 'litter-based' model for investigating blood-CSF barrier exchange in immature animals is described. 2. At each age investigated there was a clear inverse correlation between molecular radius and blood-CSF barrier exchange, in addition to an overall decrease in blood-CSF barrier exchange with increasing age. 3. The decrease in blood-CSF barrier exchange with age was not consistent with a reduction in pore diameters, nor does it appear to be due to an increase in the CSF sink effect with age. It seems likely to be due to a relative decrease in the number of a population of large diameter pores.


Total Knee Arthroplasty in Patients Who had a Prior Anterior Cruciate Ligament Reconstruction: Balancing Remains the Issue.
Following anterior cruciate ligament (ACL) injury, 20% of patients will develop osteoarthritis. Despite this, there remains a paucity of data describing outcomes of total knee arthroplasty (TKA) after prior ACL reconstruction. We aimed to describe survivorships, complications, radiographic results, and clinical outcomes of TKA after ACL reconstruction in one of the largest series to date. We identified 160 patients (165 knees) who underwent primary TKA following prior ACL reconstruction between 1990 and 2016 using our total joint registry. The mean age at TKA was 56 years (range, 29-81), 42% were women, and their mean body mass index was 32. Ninety percent of knees were posterior-stabilized designs. Survivorship was assessed using the Kaplan-Meier method. The mean follow-up was 8 years. The 10-year survivorships free of any revision and any reoperation were 92 and 88%, respectively. Seven patients were revised for instability (6 global and 1 flexion), 4 for infection, and 2 for other reasons. There were 5 additional reoperations: 3 manipulations under anesthesia, 1 wound debridement, and 1 arthroscopic synovectomy for patellar clunk. Nonoperative complications occurred in 16 patients, 4 of which were flexion instability. Radiographically, all nonrevised knees were well-fixed. Knee Society Function Scores significantly improved from preoperative to 5 years postoperative (P < .0001). Survivorship of TKA in post-ACL reconstruction knees was lower than expected with instability being the most common reason for revision. In addition, the most common nonrevision complications were flexion instability and stiffness requiring manipulations under anesthesia, indicating that achieving soft tissue balance in these knees may be difficult.


Properties of the peripheral opiate receptors in the cat nictitating membrane.
The noradrenaline overflow and the contractile response elicited by nerve stimulation of the muscle were inhibited by 1 micron morphine in the cat nictitating membrane. This concentration of morphine did not modify the response of the muscle to exogenous noradrenaline. The inhibitory effect of morphine was increased by low Na+ (50 mM), whereas the capacity of naloxone as antagonist to morphine was higher with 150 mM than with 50 mM Na+. These results suggest that the peripheral opiate receptors which interact with noradrenergic neurotransmission could show a sodium allosteric transformation similar to that described for the brain opiate receptor. The effect of morphine was enhanced by manganese ion in the presence of normal Na+. The responses of the cat nictitating membrane to nerve stimulation were not altered in the presence of the protein modifying reagent DTNB [5,5'-dithiobis-(2-nitrobenzoic acid)] but the effect of morphine on the adrenergic neurotransmission was diminished by DTNB with 150 mM Na+. It is postulated that the affinity of the ligands for presynaptic receptors which regulate adrenergic neurotransmission might be modified during the physiological changes in ion concentration which accompany nerve depolarization.


Rapid diagnosis of tuberculous peritonitis by T cell-based assays on peripheral blood and peritoneal fluid mononuclear cells.
The utility of a newly-developed Mycobacterium tuberculosis-specific enzyme-linked immunosorbent spot (ELISPOT) assay for diagnosis of tuberculous peritonitis (TBP) has not been fully assessed. All patients with suspected TBP in a tertiary care hospital in an intermediate TB burden country were prospectively enrolled over a 30-month period. ELISPOT assays were performed on peripheral mononuclear cells (PBMC) and mononuclear cells from peritoneal fluid (PF-MC). Sixty-four patients with suspected TBP were enrolled. Of these, 30 (47%) were classified as having TBP (27 confirmed and 3 probable cases), and 25 (39%) were classified as not having active tuberculosis. The remaining 9 (14%) with possible TBP were excluded from the final analysis. Five (8%) of the total 64 patients gave indeterminate PBMC ELISPOT results and 7 (18%) of 39 patients who underwent PF-MC ELISPOT assay revealed indeterminate PF-MC ELISPOT results. The sensitivity and specificity, respectively, of the tested methods for diagnosing TBP were as follows: PBMC ELISPOT (≥ 6 spots), 86% and 67%; PF-MC ELISPOT (≥ 14 spots), 92% and 86%; PF-MC ELISPOT/PBMC ELISPOT ratio (≥ 2), 75% and 93%; and PF ADA levels (≥ 38 IU/L), 95% and 100%. The areas under the receiver operating characteristics curves were as follows: PF-MC ELISPOT, 0.96; PF ADA, 0.96; PBMC ELISPOT, 0.88; and PF-MC ELISPOT/PBMC ELISPOT ratio, 0.87, respectively. Although the ELISPOT assay does not outperform PF ADA, the ELISPOT assay using PBMC and PF-MC is a useful adjunct for diagnosing TBP, especially for a rule-in test when PF/MC/PBMC ELISPOT ratio (≥ 2) is used. However, the relatively high proportion of indeterminate results limits test utility, so further studies are needed to develop an optimized assay prototype.


Cellular senescence in pathologic retinal angiogenesis.
Pathologic angiogenesis causes blindness in many eye diseases. Crespo-Garcia, Tsuruda, and Dejda et al. employed bioinformatics to characterize cell senescence as a primary factor in the common pathogenesis of retinopathies. They validated their findings using human and mouse retina with proliferative retinopathy. Clearance of senescent cells suppressed neovessel growth.


Long-term follow-up of survivors of prehospital sudden cardiac death treated with coronary bypass surgery.
Although coronary artery bypass surgery is beneficial to patients with severe coronary artery disease, its role in preventing the recurrence of prehospital cardiac arrest in patients is not clear. In this article, we report on the long-term follow-up of 49 survivors of prehospital coronary arrest who had coronary artery bypass surgery. Prior to their prehospital cardiac arrest, 14% of the patients had a history of unstable angina. Coronary angiograms obtained after prehospital cardiac arrest showed that 71% of the patients had three-vessel coronary artery disease and 6% had single-vessel disease. The mean left ventricular ejection fraction was 45%. There were four postoperative deaths; three were caused by pump failure, and one was caused by refractory ventricular arrhythmias. After a maximum follow-up period of 102 months (mean of 55.4 months), there were seven cardiac deaths; five of the patients died of recurrent ventricular fibrillation, and two patients' deaths were related to refractory heart failure. Actuarial analyses of the 49 patients showed that the probability of survival at 6 months, 1 year, 2 years, 3 years, and 5 years was 92%, 92%, 89%, 82%, and 72%, respectively. After surgery, 35 of the 45 patients who were discharged from the hospital were asymptomatic, and 23 of the 32 patients who were employed when their prehospital cardiac arrest occurred returned to their employment. We concluded that coronary artery bypass surgery is beneficial to certain survivors of prehospital sudden death. After surgery, most patients are asymptomatic and capable of returning to their employment and the recurrence of prehospital sudden death is low.


Design and powering of cystic fibrosis clinical trials using pulmonary exacerbation as an efficacy endpoint.
Reduction in pulmonary exacerbations is an important efficacy endpoint for CF clinical studies. Powering exacerbation endpoints requires estimation of the future exacerbation incidence in CF study populations, but rates differ across the population. We have estimated exacerbation rates for Epidemiologic Study of CF subpopulations stratified by age, FEV(1)% predicted, sex, weight-for-age percentile, respiratory signs and symptoms, and history of exacerbation and bacterial culture. Sample sizes required to attain 80% power to detect exacerbation reductions of 20% to 80% in 1:1 randomized studies of 3 to 12 month duration were determined. Exacerbation treatments with "any" antibiotic (new oral quinolone, new inhaled antibiotic, or intravenous (IV) antibiotic) and with IV antibiotics were studied. At all ages, decreased FEV(1), female sex, exacerbation history, and Pseudomonas aeruginosa culture history were associated with increased treatment for exacerbation. These data should assist investigators in the design of future CF exacerbation studies.


Medical management of late intrauterine death using a combination of mifepristone and misoprostol.
To assess the efficacy and safety of mifepristone in combination with misoprostol in the management of late fetal death. Observational study. Aberdeen Maternity Hospital, Aberdeen. A consecutive series of 96 women with intrauterine death after 24 weeks of gestation were studied. Each woman received a single dose of 200 mg mifepristone orally, following which a 24-48 hour interval was recommended before administration of misoprostol. For gestations of 24-34 weeks, 200 microg of intravaginal misoprostol was administered, followed by four oral doses of 200 microg at three hourly intervals. Gestations over 34 weeks were given a similar regimen but a reduced dose of 100 microg misoprostol. The average induction to delivery interval was 8.5 hours. Ninety-five women (98.9%) were delivered within 72 hours of administration of first dose of misoprostol, with 66.7%, 87.5%, 92.7% and 95.8% women delivering within 12, 24, 36 and 48 hours, respectively. No significant correlation was found between mean induction to delivery interval and maternal age, parity, Bishop's score, birthweight and mifepristone/ misoprostol interval. The induction to delivery interval was shorter with increasing gestation (P = 0.04). Mild side effects were noted in eight (8.3%) women. Three (3.1%) women had treatment for presumed or proven pelvic sepsis. No cases of uterine tachysystole, haemorrhage or coagulopathy were recorded. The combination of mifepristone and misoprostol for induction of labour following late fetal death is an effective and safe regimen. The induction to delivery interval with this regimen appears shorter than studies using mifepristone or misoprostol.


The Experience of Gender Incongruity in the Christian Church: A Qualitative Study.
This study was designed to understand the interaction between Christian faith and gender incongruence. An anonymous online survey was advertised to the Australian Christian community. Individuals with first-hand experience of transgender issues were eligible to participate. There were 122 eligible responses. This paper describes the experience of the 30 participants experiencing gender incongruence. Persons in the church experiencing gender incongruence desired to hold onto faith. As a result, they experienced a tension between the desire to remain in the church, and the desire to live congruously with their gender, which could lead to expulsion. Strategies to reconcile these two factors varied.


Children as organ donors: legal rights and ethical issues.
As the number of children in need of organ transplants increases as a result of medical advances, so does the demand for organs that can be used in transplantation. In the face of compelling medical need, prospective donors as well as prospective recipients are subject to strong pressures. Social workers can play a large role in protecting the rights and interests of both groups of young clients.


Metabolism and nutritional frontiers in pediatric surgical patients.
The successful treatment of pediatric surgical disease requires an understanding of the acute metabolic stress response. Poor clinical outcome can result when the metabolic demands of acute injury exceed the ability of endogenous host mechanisms to compensate. Appropriate exogenous supplementation may provide the metabolic and nutritional support crucial to recovery. As knowledge in this area grows, more effective treatment strategies are evolving. The potential for further advances, especially in the infant critical care population, offers the hope for substantial progress in the near future.


Adaptive fuzzy dynamic surface sliding mode control of large-scale power systems with prescribe output tracking performance.
This paper focuses on an adaptive fuzzy based dynamic surface sliding mode control (ADSSMC) strategy for multi-machine power systems with SVC. The main characteristics of the proposed ADSSMC strategy are: (1) System robustness and the convergency speed of all surface error are enhanced by combining dynamic surface control with sliding mode, leading to the structural complexity of the controller in backstepping control scheme is eliminated; (2) By introducing an error performance conversion function, the errors of desired trajectory and system output are always within a predetermined range; (3) In the adaptive regulation laws, the number of estimated parameters of the control system is significantly reduced due to the utilization of the estimations of weight vector norm instead of the weight vectors itself. The stability analysis proves that the proposed ADSSMC control strategy can guarantee the boundaries of all signals in the closed-loop control system. Experimental results verify the effectiveness of the proposed ADSSMC scheme.


Genome Sequences of 26 White Sucker Hepatitis B Virus Isolates from White Sucker, Catostomus commersonii, Inhabiting Transboundary Waters from Alberta, Canada, to the Great Lakes, USA.
We report 26 genome sequences of the white sucker hepatitis B virus (WSHBV) from the white sucker, Catostomus commersonii The genome length ranged from 3,541 to 3,543 bp, and nucleotide identity was 96.7% or greater across genomes. This work suggests a geographical range of this virus that minimally extends from the Athabasca River, Alberta, Canada, to the Great Lakes, USA.


Total internal reflection with fluorescence correlation spectroscopy: Applications to substrate-supported planar membranes.
In this paper, the conceptual basis and experimental design of total internal reflection with fluorescence correlation spectroscopy (TIR-FCS) is described. The few applications to date of TIR-FCS to supported membranes are discussed, in addition to a variety of applications not directly involving supported membranes. Methods related, but not technically equivalent, to TIR-FCS are also summarized. Future directions for TIR-FCS are outlined.


Isolation and fusion studies on protoplasts from pollen tetrads.
Different enzymes were tested for isolation of intact protoplasts from pollen tetrads. About 80% isolation was achieved from pollen tetrads of Cajanus cajan and Zea mays and about 60% from Luffa cylindrica and Lycopersicon esculentum after 4 h of treatment with 5% cellulase. When these mononucleate protoplasts were incubated in presence of 0.05 M CaCl2 in 0.3 M glucose at pH 10.5, 70-80% fusion was achieved. Fusion was rare in sodium nitrate solutions.


Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer.
Kallikrein-related peptidases (KLKs) are a family of serine proteases that have been shown to be dysregulated in several malignancies including ovarian cancer. The control of kallikrein genes and their physiological function in cancer is not well understood. We hypothesized that microRNAs (miRNAs) represent a novel mechanism for post-transcriptional control of KLK expression in cancer. We first analysed miRNA expression in ovarian cancer in silico. A total of 98 miRNAs were reported to have altered expression in ovarian cancer. Three of these miRNAs were predicted to target KLK10. We experimentally verified the predicted miR-KLK10 interaction using two independent techniques, a luciferase assay with a construct containing the KLK10 3' untranslated region (UTR), pMIR-KLK10, and measuring KLK10 protein levels after transfection with miRNA. When we co-transfected cells with pMIR-KLK10 and either let-7f, miR-224, or mR-516a, we saw decreased luciferase signal, suggesting that these miRNAs can target KLK10. We then examined the effect of these three miRNAs on KLK10 protein expression and cell growth. Transfection of all miRNAs, let-7f, miR-224, and miR-516a led to a decrease in protein expression and cellular growth. This effect was shown to be dose dependent. The KLK10 protein levels were partially restored by co-transfecting let-7f and its inhibitor. In addition, there was a slight decrease in KLK10 mRNA expression after transfection with let-7f. Our results confirm that KLKs can be targeted by more than one miRNA. Increased expression of certain miRNAs in ovarian cancer can lead to decreased KLK protein expression and subsequently have a negative effect on cell proliferation. This dose-dependent effect suggests that a 'tweaking' or 'fine-tuning' mechanism exists in which the expression of one KLK can be controlled by multiple miRNAs. These data together suggest that miRNA may be used as potential therapeutic options and further studies are required.


Differential distribution of endothelin receptor subtypes in placentae from normal and growth-restricted pregnancies.
The endothelins (ETs) are potent vasoconstrictor peptides that bind to two distinct receptors, ETA and ETB. This study compares the localization of ETA and ETB receptors in placentae complicated by intrauterine growth retardation (IUGR) and abnormal umbilical Doppler waveform, gestationally matched controls, fetuses that were small for gestational age (SGA), and normal term placentae. Quantitative autoradiography was performed using ETA and ETB subtype-selective ligands. Both ETA and ETB receptors were expressed in the human placenta. Gestational and fetal size effects on the receptor density within stem villi were found, but no effect of abnormal placental blood flow could be demonstrated. A distinct spatial distribution of receptor subtypes within the placenta was observed. Smooth muscle cells expressed both receptors with ETA expression predominant in the proximal regions of the villous tree and ETB abundant in the periphery and decidua. Both receptors were also expressed at lower density on paravascular stromal cells in stem villi. Although these data do not demonstrate aberrant localization of ET receptors in IUGR and SGA placentae, the spatially distinct distribution of ET receptors in the human placenta suggests that ETs play a role in modulation of placental blood flow.


Bone-like crack resistance in hierarchical metastable nanolaminate steels.
Fatigue failures create enormous risks for all engineered structures, as well as for human lives, motivating large safety factors in design and, thus, inefficient use of resources. Inspired by the excellent fracture toughness of bone, we explored the fatigue resistance in metastability-assisted multiphase steels. We show here that when steel microstructures are hierarchical and laminated, similar to the substructure of bone, superior crack resistance can be realized. Our results reveal that tuning the interface structure, distribution, and phase stability to simultaneously activate multiple micromechanisms that resist crack propagation is key for the observed leap in mechanical response. The exceptional properties enabled by this strategy provide guidance for all fatigue-resistant alloy design efforts.


Relationships between aerobic energy cost, performance and kinematic parameters in roller ski skating.
The aims of this study were to test the hypotheses that 1) the aerobic energy cost of roller ski skating (CS) is significantly related to level of performance and 2) a significant part of inter-individual differences of CS can be explained by kinematic parameters of skating locomotion. Oxygen uptake, kinematics of the knee and ankle joint, EMG of the vastus lateralis (VL) and gastrocnemius lateralis (GL) muscles, and roller ski velocity were recorded in 13 skiers who roller skied at 19.0 +/- 0.1 km x h(-1). CS was found to be 2.51 +/- 0.35 J x kg(-1) x m(-1) and significantly correlated with the skiers' level of performance (r = 0.61; p < 0.05). Significant relationships were found between CS and 1) knee angular amplitude (r = 0.75; p < 0.01) during the concentric phase, 2) VL average EMG during the concentric phase (r = 0.72; p < 0.01) and 3) VL and GL average EMG during the eccentric phase (p < 0.05). The results of this study showed that a significant part of performance could be explained by the aerobic energy cost of locomotion in skating. It can also be suggested that differences in upper/lower body utilization and/or in mechanical efficiency may explain the differences in CS.


Effect of ball size on player reaction and racket acceleration during the tennis volley.
The purpose of this study was to examine the effect of ball size on reaction time (from ball projection to initial racket movement), movement time (from ball projection to ball-racket impact), mean rectified acceleration and vibration frequency of the racket during the impact phase (100 ms duration after ball-racket impact) of the tennis volley. Twenty-nine beginning to intermediate level tennis players performed volleys under 18 experimental conditions including variations in lateral contact location (forehand and backhand), ball type (Penn oversize, Wilson oversize, regular size), and ball speed (fast, medium, slow). A ball machine was shielded so that the subjects could not predict the ball trajectory before it was released from the machine. Outcome measures were determined using a miniature uni-axial accelerometer and a Photogate timing device. ANOVA with repeated measures and Tukey's post hoc tests were used in statistical analyses (p < .025). The reaction times for the fast speed were significantly shorter than the corresponding times for the slow speed and the reaction times for the forehand volley were significantly shorter than that of the backhand volley. The significant interaction in movement time between ball speed and ball type indicates that the benefits of the larger ball (to slow the game down) increase as the ball speed increases. No significant effect of ball type or ball speed, or interactions were found on mean rectified acceleration and vibration frequency. These results suggest that oversized balls would not cause an increased load to the hitting arm while executing a tennis volley.


Furosemide stimulates renin expression in the kidneys of salt-supplemented rats.
This study was conducted to obtain information about a possible influence of salt transport by the thick ascending limb of Henle (TALH) and the macula densa on the expression of renin in the kidney. To this end, adult male rats were subcutaneously infused with furosemide (12 mg/24 h), an established inhibitor of TALH and macula densa salt transport, or with vehicle for 6 days. The animals had free access to chow, water and salt water (0.8% NaCl, 0.1% KCl) to maintain salt and water balance. Chronic furosemide treatment led to a 20-fold increase in urine flow rates and 50% increase in kidney weights, while urine osmolality decreased by 60% and body weight gain decreased by 40% in the furosemide-treated animals. Plasma renin activities increased from 2.9 +/- 0.5 ng angiotensin I h-1 ml-1 in controls to 10.6 +/- 2.2 ng angiotensin I h-1 ml-1 in furosemide-treated rats. In parallel, kidney areas immunoreactive for renin increased by 80% and the renal content of renin mRNA increased by 120% in the animals receiving furosemide. Under the assumption that the effects seen on renal renin expression were primarily due to the inhibition of TALH and macula densa function by furosemide, our findings suggest that salt transport across the TALH and macula densa exerts a negative control function not only on the secretion but also on the expression of renin in the kidney.


Metabolic Disorders and Mineral Density of the Bone Tissue in the Early Pathogenesis of Osteonecrosis: Study on Rabbits with Steroid-Induced Osteonecrosis.
The relationship between the appearance of bone metabolism disorders and the onset of steroid-induced osteonecrosis remains unclear. We studied the time course of calcium, phosphorus, osteocalcin, alkaline phosphatase, and mineral density of bone tissue in the subchondral bone of the femoral head of rabbits injected with steroids and attempted to precisely determine the time when disorders in bone metabolism started in animals with steroid-induced osteonecrosis. We detected bone metabolism disorders involved in the early pathogenesis of steroid-induced osteonecrosis, which were the cause, but not the result of this condition.


Geographical variation of carcinoma of the penis in Uganda.
A series of 458 cases of carcinoma of the penis occurring in Ugandan Africans is analysed. These were derived from the records of a country-wide biopsy service over the 5-year period 1964-68.Where circumcision is practised the incidence of this tumour is very low.However, the geographical variation also showed marked differences in the uncircumcised, regardless of tribal antecedents and sometimes over quite small distances.It is suggested, therefore, that in Uganda other aetiological factors apart from circumcision are operative and that these factors vary with geographical location rather than with tribal affiliation.


Screening behaviours, demographics, and stage at diagnosis in the publicly funded Ontario Breast Screening Program.
The Ontario Breast Screening Program (OBSP) offers free screening mammograms every 2 years, to women aged 50-74. Study objectives were to determine demographic characteristics associated with the adherence to OBSP and if women screened in the OBSP have a lower stage at diagnosis than non-screened eligible women. We used the Ontario cancer registry (OCR) to identify 48,927 women, aged 51-74 years, diagnosed with breast cancer between 2010 and 2017. These women were assigned as having undergone adherent screening (N = 26,108), non-adherent screening (N = 6546) or not-screened (N = 16,273) in the OBSP. We used multinomial logistic regression to investigate the demographic characteristics associated with screening behaviour, as well as the association between screening status and stage at diagnosis. Among women with breast cancer, those living in rural areas (versus the largest urban areas) had a lower odds of not being screened (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.68, 0.78). Women in low-income (versus high-income) communities were more likely not to be screened (OR 1.42, 95% CI 1.33, 1.51). When stratified, the association between income and screening status only held in urban areas. Non-screened women were more likely to be diagnosed with stage II (OR 1.91, 95% CI 1.82, 2.01), III (OR 2.96, 95% CI 2.76, 3.17), or IV (OR 8.96, 95% CI 7.94, 10.12) disease compared to stage I and were less likely to be diagnosed with ductal carcinoma in situ (DCIS) (OR 0.91, 95% CI 0.84-0.98). This study suggests that targeting OBSP recruitment efforts to lower income urban communities could increase screening rates. OBSP adherent women were more likely to be diagnosed with earlier stage disease, supporting the value of this initiative and those like it.


The effect of temperature on the kinetic constants of human lactate dehydrogenase 1 and 5.
The kinetic constants of human lactate dehydrogenase 1 and 5 (L-lactate: NAD+ oxidoreductase, EC 126.96.36.199), assayed lactate-to-pyruvate increase with temperature. The reaction mechanism is ordered sequential as has been found with lactate dehydrogenase from other sources. The KM values for each substrate are larger for isoenzyme 5 than for 1. For lactate dehydrogenase 1 the KM(lactate) increases from 1.07 mM at 25 degrees C to 3.95 mM at 37 degrees C and for lactate dehydrogenase 5 it increases from 5.37 mM at 25 degrees C to 6.88 mM at 37 degrees C. The KM(NAD+) for lactate dehydrogenase 5 is 0.14 mM at 25 degrees C and 0.29 mM at 37 degrees C. The increase in the KM for each substrate with increasing temperature confirms that additional substrate is required for optimal reaction conditions at higher temperatures.


Evoked potentials recorded during routine EEG predict outcome after perinatal asphyxia.
To evaluate the added value of somatosensory (SEPs) and visual evoked potentials (VEPs) recorded simultaneously with routine EEG in early outcome prediction of newborns with hypoxic-ischemic encephalopathy under modern intensive care. We simultaneously recorded multichannel EEG, median nerve SEPs, and flash VEPs during the first few postnatal days in 50 term newborns with hypoxic-ischemic encephalopathy. EEG background was scored into five grades and the worst two grades were considered to indicate poor cerebral recovery. Evoked potentials were classified as absent or present. Clinical outcome was determined from the medical records at a median age of 21months. Unfavorable outcome included cerebral palsy, severe mental retardation, severe epilepsy, or death. The accuracy of outcome prediction was 98% with SEPs compared to 90% with EEG. EEG alone always predicted unfavorable outcome when it was inactive (n=9), and favorable outcome when it was normal or only mildly abnormal (n=17). However, newborns with moderate or severe EEG background abnormality could have either favorable or unfavorable outcome, which was correctly predicted by SEP in all but one newborn (accuracy in this subgroup 96%). Absent VEPs were always associated with an inactive EEG, and an unfavorable outcome. However, presence of VEPs did not guarantee a favorable outcome. SEPs accurately predict clinical outcomes in newborns with hypoxic-ischemic encephalopathy and improve the EEG-based prediction particularly in those newborns with severely or moderately abnormal EEG findings. SEPs should be added to routine EEG recordings for early bedside assessment of newborns with hypoxic-ischemic encephalopathy.


Towards a new definition of decompensated cirrhosis.
There is a universal agreement that the occurrence of clinical complications, such as ascites, hepatic encephalopathy, gastrointestinal bleeding, and jaundice mark the transition from the compensated to the decompensated stage of cirrhosis. Decompensation is associated with a substantial worsening of patient prognosis and is therefore considered the most important stratification variable for the risk of death. However, this classification is an oversimplification, as it does not discriminate between the prognostic subgroups that characterise the course of decompensation, which depends on the type and number of decompensating events. A deeper insight into the clinical course of decompensated cirrhosis is provided by observational studies characterising acute decompensation (AD), which occurs mostly in patients who have already experienced decompensating events. Decompensation presents as AD in a portion of patients while in many others it presents as a slow development of ascites or mild grade 1 or 2 hepatic encephalopathy, or jaundice, not requiring hospitalisation. Thus, we propose that decompensation of cirrhosis occurs through 2 distinct pathways: a non-acute and an acute (which includes acute-on-chronic liver failure) pathway. Moreover, while non-acute decompensation is the most frequent pathway of the first decompensation, AD mostly represents further decompensation.


Patent guide for miniaturists.
Inventors who are mystified by the concepts of "nonobviousness" and "enablement" may be surprised to find that the two concepts have a simple explanation in information theory. Viewing an invention as a low-probability, high-information event helps explain why an invention that appears inventive (nonobvious) to an inventor may appear obvious to a patent examiner, and suggests some strategies for overcoming the examiner's bias. Viewing enablement as a means of increasing the probability that a claimed invention can be practiced successfully helps in understanding how to support a broad claim effectively by virtual or "paper" patenting. The notion of entropy, or mean information content, as applied to inventions, may guide inventors in their search for new inventions.


Studies on the transverse tubule membrane Mg-ATPase. Lectin-induced alterations of kinetic behavior.
Transverse tubule (TT) membrane vesicles contain a very active Mg-ATPase (EC 188.8.131.52). Concanavalin A (ConA) and other lectins were found to activate the TT Mg-ATPase from chicken skeletal muscle up to 25-fold yielding specific activities greater than 800 mumol/h/mg. The sarcoplasmic reticulum Ca-ATPase and the sarcolemma Na,K-ATPase were unaffected by ConA. 125I-Labeled lectin binding to the TT membrane Mr 102,000 glycoprotein supports the contention that this protein is identical with or is intimately associated with the TT Mg-ATPase. The ATPase exhibited non-Michaelis-Menton kinetics with both apparent negative cooperativity (n = 0.723; S0.5, Mg-ATP = 14 microM) and substrate inhibition (Ki, Mg-ATP = 10.2 mM), both of which were eliminated in the presence of ConA. Under the same conditions, ConA also abolished the unusual temperature dependence and potent Triton X-100 inhibition. The similarities in ConA suppression of both Triton and substrate inhibition suggest that these ligands may be interacting through a non-catalytic site and that Triton is serving as a nucleotide-mimetic agent. The unique kinetic responses are consistent with a homotropic substrate modifier mechanism wherein the enzyme can be viewed as possessing a single catalytic and a single regulatory site on a single polypeptide chain. It is proposed that ConA interferes either with ligand interaction at a putative regulatory site or blocks communication between a regulatory site and the catalytic site. The possible nature of the regulatory site and its modulation by a ConA-like, endogenous, skeletal muscle lectin and their combined role in excitation-contraction coupling is discussed.


Performance and kinetic study of semi-dry thermophilic anaerobic digestion of organic fraction of municipal solid waste.
Anaerobic digestion (AD) of the organic fraction of municipal solid waste (OFMSW) is promoted as an energy source and waste disposal. In this study semi dry anaerobic digestion of organic solid wastes was conducted for 45 days in a lab-scale batch experiment for total solid concentration of 100g/L for investigating the start-up performances under thermophilic condition (50 °C). The performance of the reactor was evaluated by measuring the daily biogas production and calculating the degradation of total solids and the total volatile solids. The biogas yield at the end of the digestion was 52.9L/kg VS (volatile solid) for the total solid (TS) concentration of 100g/L. About 66.7% of the volatile solid degradation was obtained during the digestion. A first order model based on the availability of substrate as the limiting factor was used to perform the kinetic studies of batch anaerobic digestion system. The value of reaction rate constant, k, obtained was 0.0249 day(-1).


Soluble membrane antigens of brain tumors. I. Controlled testing for cell-mediated immune responses in a long surviving glioblastoma multiforme patient.
A patient with glioblastoma multiforme survived 18 years after diagnosis and underwent 20 operations for extracranial metastasis. An immunologic survey of the patient was made over a 1-year-period using in vitro tests of lymphocyte responsiveness and skin tests with control and tumor antigens isolated from autologous and allogenic brain cell membranes. Two tissue-associated soluble cell membrane antigens also present in normal white matter, and two tumor-associated antigens (TAA) produce cell-mediated immune responses in patients with brain tumors. One of these tumor-associated antigens predominates in meningioma cells. In addition some low molecular weight components appeared, which seemed to be unique for the glioblastoma cells from the long-surviving patient.


[Procurement strategy for a dose management system].
We present the different steps for procurement of a dose management system for a university hospital, starting from the Europe-wide request for proposals, the product presentations by the suppliers and the final decision. For a project of this size, it is advisable to involve external consultants, especially for preparation of the system specifications and the calculation of the total cost of ownership (TCO). Use cases were of special interest in assessing the functionality of the different systems. Following the product presentations some changes were made concerning the system specifications and minimum requirements. Qualified users like medical physics experts, radiologists and technicians as well as users from generic quality management should form the team for evaluation and final product decision.


Characterization of a hypoxia-response element in the Epo locus of the pufferfish, Takifugu rubripes.
Animals respond to hypoxia by increasing synthesis of the glycoprotein hormone erythropoietin (Epo) which in turn stimulates the production of red blood cells. The gene encoding Epo has been recently cloned in teleost fishes such as the pufferfish Takifugu rubripes (fugu) and zebrafish (Danio rerio). It has been shown that the transcription levels of Epo in teleost fishes increase in response to anemia or hypoxia in a manner similar to its human ortholog. However, the cis-regulatory element(s) mediating the hypoxia response of Epo gene in fishes has not been identified. In the present study, using the human hepatoma cell line (Hep3B), we have identified and characterized a hypoxia response element (HRE) in the fugu Epo locus. The sequence of the fugu HRE (ACGTGCTG) is identical to that of the HRE in the human EPO locus. However, unlike the HRE in the mammalian Epo locus, which is located in the 3' region of the gene, the fugu HRE is located in the 5' flanking region and on the opposite strand of DNA. This HRE is conserved in other teleosts such as Tetraodon and zebrafish in a similar location. A 365-bp fragment containing the fugu HRE was able to drive GFP expression in the liver of transgenic zebrafish. However, we could not ascertain if the expression of transgene is induced by hypoxia in vivo due to the low and variable levels of GFP expression in transgenic zebrafish. Our investigations also revealed that the Epo locus has experienced extensive rearrangements during vertebrate evolution.


Identification of two preclinical canine models of atrial fibrillation to facilitate drug discovery.
Atrial fibrillation (AF) is the most common arrhythmia occurring in humans, and new treatment strategies are critically needed. The lack of reliable preclinical animal models of AF is a major limitation to drug development of novel antiarrhythmic compounds. The purpose of this study was to provide a comprehensive head-to-head assessment of 5 canine AF models. Five canine models were evaluated for the efficacy of AF induction and AF duration. We tested 2 acute models: short-term atrial tachypacing (AT) for 6 hours with analysis of AF at hourly increments, and carbachol injection into a cardiac fat pad followed by short-term AT. We also tested 3 chronic models: pacemaker implantation followed by either 4 weeks of AT and subsequent atrial burst pacing or intermittent long-term AT for up to 4-5 months to generate AF ≥4.5 hours, and finally ventricular tachypacing to induce heart failure followed by atrial burst pacing to induce AF. Careful evaluation showed that acute AT, AT for 4 weeks, and the heart failure model all were unsuccessful in generating reproducible AF episodes of sufficient duration to study antiarrhythmic drugs. In contrast, intermittent long-term AT generated AF lasting ≥4.5 hours in ∼30% of animals. The acute model using carbachol and short-term AT resulted in AF induction of ≥15 minutes in ≥75% of animals, thus enabling testing of antiarrhythmic drugs. Intermittent long-term AT and the combination of local carbachol injection with successive short-term AT may contribute to future drug development efforts for AF treatment.


Harnessing New and Existing Virtual Platforms to Meet the Demand for Increased Inpatient Palliative Care Services During the COVID-19 Pandemic: A 5 Key Themes Literature Review of the Characteristics and Barriers of These Evolving Technologies.
The COVID-19 pandemic has increased the demand for end-of-life services and bereavement support, and in many areas of the world, in-person palliative care is struggling to meet these needs. Local infection control measures result in limited visitation rights in hospital and patients are often dying alone. For many years, virtual platforms have been used as a validated alternative to in-person consults for outpatient and home-based palliative care; however, the feasibility and acceptability of a virtual inpatient equivalent is less studied. Virtual inpatient palliative care may offer a unique opportunity for patients to have meaningful interactions with their care team and family while isolated in hospital or in hospice. This narrative review examines strategies employed during the COVID-19 pandemic to implement virtual palliative care services in the inpatient setting. Five key themes were identified in the literature between January 2020-March 2021 in the LitCovid NCBI database: 1) overall acceptability of virtual inpatient palliative care during the pandemic, 2) important logistical considerations when developing a virtual inpatient palliative care platform, 3) commonly used technologies for delivering virtual services, 4) strategies for harnessing human resources to meet increased patient volume, and 5) challenges of virtual inpatient palliative care implementation. Upon review, telepalliative care can meet the increased demand for safe and accessible inpatient palliative care during a pandemic; however, in some circumstances in-person services should still be considered. The decision for which patients receive what format of care-in-person or virtual-should be decided on a case-by-case basis.


Effect of six months pranayama training on stress-induced salivary cortisol response among adolescents-Randomized controlled study.
A combination of yoga practices has been documented to reduce stress and stress-induced cortisol levels. The objective of the current study is to examine the effects of six months of a single pranayama practice (Bhramari [Bhr. P]) on reducing salivary cortisol response to the cold pressor test (CPT) among adolescents. Twenty-six healthy adolescents between the ages of 11 and 19 were randomly assigned to either yoga group (n-13) or control group (n-13). Yoga group participants were trained to do Bhr. P for 45 min, thrice a week for six months. All participants underwent CPT at baseline and at end of six months. Saliva samples were collected at baseline (t0), at 20 min (t1), 40 min (t2), and 60 min after the CPT (t3). Contradictory to our hypothesis, participants in the yoga group exhibited a higher salivary cortisol response to the CPT at t1 (p = 0.04) when compared to the control group. However, the t3 salivary cortisol levels showed a statistically significant reduction (p = 0.03) in yoga group when compared to the control group. A significant interaction with time (F (1, 88) = 316.5, p = .001, ηp2:0.91) and between the group × time (F (3, 88) = 2.83, p = 0.04, ηp2:0.8) was found after the intervention. An increase in the cortisol responsiveness observed in the study is an indication of the adaptive capability achieved through regular yoga training, evidenced by an initial rise in cortisol followed by a rapid fall below baseline after 60 min. Further research is required to conclusively determine the changes in cortisol levels over time in response to stress in long-term yoga practitioners.


Comparative transcriptomic analysis of seed coats with high and low lignin contents reveals lignin and flavonoid biosynthesis in Brassica napus.
Brassica napus L. (2n = 38, AACC) is one of the most important oil crops and sources of protein for animal feed worldwide. Lignin is a large molecule aromatic polymer and a major cell wall component. However, lignin in the seed coat reduces the availability and restricts the development of rapeseed cake. Therefore, it is critical to reduce the lignin content of the seed coat. Here, high-lignin (H-lignin) and low-lignin (L-lignin) content recombinant inbred lines (RILs) were selected from an RIL population for analysis. The cross-section results indicated that the seed coat of the H-lignin lines was thicker than that of the L-lignin lines, especially the palisade layer. The seed coats and embryos at 35, 40 and 46 days after flowering (DAF) were subjected to RNA sequencing (RNA-Seq), and the expression of the BnPAL and BnC4H gene families in the lignin pathway was significantly higher in the H-lignin seed coat than in the L-lignin seed coat. The Bn4CL gene family also showed this trend. In addition, among the genes related to plant hormone synthesis, BnaC02g01710D was upregulated and BnaA07g11700D and BnaC09g00190D were downregulated in H-lignin lines. Some transcription factors were upregulated, such as BnNAC080, BnNAC083, BnMYB9, BnMYB9-1, BnMYB60 and BnMYB60-1, while BnMYB91 was downregulated in H-lignin lines. Moreover, most genes of the flavonoid pathway, such as BnCHS and BnDFR, were strongly expressed in H-lignin seed coat. In Our study, some key genes such as hormone synthesis genes, transcription factors and miRNAs related to lignin and flavonoid biosynthesis were identified. A regulatory model of B. napus seed coat lignin was proposed. These results provide new insight into lignin and flavonoid biosynthesis in B. napus.


Cytogenetic effects of mutagens/carcinogens after activation in a microsomal system in vitro I. Induction of chromosome aberrations and sister chromatid exchanges by diethylnitrosamine (DEN) and dimethylnitrosamine (DMN) in CHO cells in the presence of rat-liver microsomes.
A rat-liver microsomal system in vitro has been used to activate two indirectly acting carcinogens, DMN and DEN. On activation, both compounds were extremely potent in inducing chromosomal aberrations as well as sister chromatid exchanges in Chinese hamster cells. The implications of these findings and the potential utility of this technique to detect mutagens/carcinogens are discussed.


Coronary Intervention Guided by Quantitative Flow Ratio vs Angiography in Patients With or Without Diabetes.
The clinical utility of the quantitative flow ratio (QFR), a novel angiography-based index for the functional assessment of coronary stenoses, has recently been demonstrated in patients undergoing percutaneous coronary intervention (PCI). This study aimed to ascertain whether the beneficial outcomes of QFR guidance for lesion selection during PCI is affected by diabetes status. This substudy from the FAVOR III China trial, in which diabetes was one of the prespecified factors for stratified randomization, compared clinical outcomes of QFR-guided vs angiography-guided PCI lesion selection according to the presence of diabetes. The primary endpoint was the 1-year risk of major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization). Among 3,825 patients enrolled, 1,295 (33.9%) had diabetes, 347 (26.8%) of whom were treated with insulin. Baseline characteristics were well balanced between treatment arms in both diabetic and nondiabetic patients. Compared with standard angiography-based lesion selection, the QFR-guided strategy consistently reduced the risk of 1-year MACE in both diabetic patients (6.2% vs 9.6%; HR: 0.64; 95% CI: 0.43-0.95) and nondiabetic patients (5.6% vs 8.3%; HR: 0.66; 95% CI: 0.49-0.89) (Pinteraction = 0.88). Among patients in whom PCI was deferred after QFR, the risk of 1-year MACE was similar in patients with and without diabetes (4.5% vs 6.2%; P = 0.51). A QFR-guided lesion selection strategy improves PCI outcomes compared with standard angiography guidance in patients both with and without diabetes. (The Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease [FAVOR III China Study]; NCT03656848).


[Immunogenicity of cancer-associated and cancer-specific antigens].
The immunogenicity and anti-tumor activity of tumor-specific and tumor-associated antigens (TSA and TAA) isolated from the Ehrlich ascites cancer (EAC) cell plasma membrane is assayed, and compared with the action of several crude antigenic preparations. Control animals die 26 days after the EAC cells inoculation. Crude antigenic preparations produce a delay of EAC development, but all the animals finally die. The purified TSA and TAA are active at very small amounts, and inhibit completely and permanently the tumor development. The procedure shows a new approach to cancer specific active immunotherapy.


Synthesis of calcium carbonate-quince bio-composite for programmed and on-demand drug release of paracetamol at target site: a green chemistry approach.
In this study, an inorganic-organic composite system was developed through biomineralization of calcium carbonate in the quince-seed mucilage-based hydrogel. Drug-polymer interactions were studied by FTIR, DSC, XRD and SEM analysis. The water absorption capacity was calculated by swelling index. Drug release was determined at various pH. Several in vitro kinetic models were applied to observe drug release behaviour. Studies of drug-polymer interactions and particle flow characteristics of the developed composite material have shown that there is good compatibility between drug and the excipients. The XRD and SEM results confirmed calcite polymorphs in the developed composite material. Thermograms showed that the developed composite material was heat stable. A restricted drug release was observed in an acidic medium (pH 1.2). A controlled drug release was depicted from the developed system at pH 6.8. The drug release mechanism of Super Case II was suggested. The developed system was considered to be an effective drug carrier for colon targeted oral delivery of non-steroidal anti-inflammatory drugs (NSAIDs) to avoid gastric irritation and risk of ulceration. An illustration of extraction of quince hydrogel and development of calcium carbonate-quince (CaCO3-Q) composite system; QSM = Quince seed mucilage. The online version contains supplementary material available at 10.1007/s00289-022-04400-1.


Eosinophil- and eosinophil granule-mediated pneumocyte injury.
The function of the eosinophil in eosinophilic pulmonary syndromes and asthma is uncertain. To determine if eosinophils might play a harmful role in these conditions, we cocultured purified human eosinophils, eosinophil major basic protein (MBP), and chromatographically eluted eosinophil granule fractions with human A549 and rat type II pneumocytes. Damage to these target cells was measured as cell lysis and nonlethal cell detachment. We found that unstimulated intact eosinophils affected minimal lysis or detachment of either pneumocyte target, but eosinophils stimulated with phorbol myristate acetate and other activators produced time- and dose-dependent nonlytic detachment of both targets. In contrast, supernatants from activated eosinophils did not produce significant injury, suggesting that close apposition of the effector and target cells was required. Catalase and superoxide dismutase did not inhibit the detaching activity of eosinophils, suggesting that hydrogen peroxide and superoxide anion were not activity of eosinophils, suggesting that hydrogen peroxide and superoxide anion were not responsible for mediating this form of injury. In contrast to our findings with intact eosinophils, we observed that the addition of purified eosinophil MBP to pneumocytes caused marked cytolysis with little detachment. When sequential fractions of eosinophil granules separated by Sephadex G-50 chromatography were added to A549 and rat type II pneumocyte targets, it was found that different fractions produced distinct forms of injury. Higher molecular weight fractions containing lysosomal enzymes and eosinophil peroxidase produced predominantly detachment, whereas fractions enriched in MBP produced lysis. These results indicate that intact eosinophils can produce nonlytic detachment of alveolar pneumocytes that is probably not dependent on the generation of toxic oxygen radicals but rather appears to be mediated by granule-associated products, possibly lysosomal enzymes. Furthermore, although intact eosinophils are not capable of lysing alveolar epithelial cells under the conditions of our assay, MBP has the potential to do so when the protein is released in high enough concentrations. The in vivo relevance of these findings in eosinophilic lung diseases may be that eosinophils, by producing both desquamation and death of alveolar epithelium cells, may increase the permeability of the alveolus to fluid and cells. Moreover, these forms of damage might also enhance the ingress of inhaled antigens across the pulmonary epithelial barrier, thus increasing immunologic sensitization.


Isolation and characterization of the genes encoding allophycocyanin subunits and two linker proteins from Synechocystis 6714.
Genes encoding the phycobilisome core subunits allophycocyanin alpha and beta and a small core linker protein in Synechocystis sp. strain PCC 6714 were cloned and sequenced. These genes form an operon, apcABC, with a single transcription start site and two possible termination sites, one following apcB and the other following apcC. The promoter region, like those of the apcABC operons of other cyanobacteria, does not resemble the consensus promoter sequences of Escherichia coli. However, the apcABC promoters identified in four strains of cyanobacteria have conserved sequences centered at -50 and -10 with respect to the start of transcription. The apcE gene, encoding the protein that links the phycobilisome core to the thylakoid membrane, was also cloned from Synechocystis 6714 and sequenced. It is unlinked to the apcABC operon. As in other Synechocystis strains, the LCM polypeptide encoded by the apcE gene contains three repeats of the basic phycobiliprotein linker domain. The apcE gene promoter sequence bears little resemblance to either the E. coli consensus or the apcABC promoter region, but it is similar to the corresponding regions of other cyanobacterial apcE genes. In these cases, there are conserved sequences centered at -40 and -10 with respect to the transcription start site. These conserved promoter elements from the apcABC and apcE genes were also identified in the corresponding 5'-flanking regions of eleven transcript starts for cpc genes encoding phycocyanin subunits in cyanobacteria and algal chloroplasts. These results suggest that a factor yet to be described participates in transcription of phycobiliprotein genes.


Effects of detraining on preconditioning exercise-induced neuroprotective potential after ischemic stroke in rats.
Preconditioning exercise prior to stroke exerts neuroprotection, which is an endogenous strategy that leads the brain cells to express several intrinsic factors and inhibits their apoptosis. However, it is unclear how long these benefits last after exercise cessation. The aim of this study was to investigate the effects of detraining on preconditioning exercise-induced neuroprotective potential after stroke. Rats were trained using a treadmill for aerobic exercise 5 days each week for 3 weeks, and their neuroprotective effects were examined until 3 weeks after exercise cessation. Stroke was induced by 60 min of left middle cerebral artery occlusion at 3 days, 1, 2, and 3 weeks after exercise cessation. Infarct volume, neurological deficits, sensorimotor function, expression levels of brain-derived neurotrophic factor (BDNF), hypoxia-induced factor-1α (HIF-1α), glial fibrillary acidic protein (GFAP), and P2X7 receptors, and apoptosis activity were examined using immunohistochemical and western blot analyses. Preconditioning exercise significantly reduced infarct volume and ameliorated sensorimotor function after stroke, and its beneficial effects were observed until 2 weeks after exercise cessation. The expression level of BDNF in the ischemic brain was significantly upregulated at 3 days after exercise cessation; however, the expression levels of HIF-1α, GFAP, and P2X7 receptor were significantly increased until 2 weeks after exercise cessation; thereby, significant anti-apoptotic effects were lost at 3 weeks of detraining. Our findings suggest that preconditioning exercise-induced neuroprotective potential may be lost shortly after exercise cessation. Neuroprotection through intrinsic protective factors, such as BDNF and HIF-1α, may provide different neuroprotective mechanisms in a time-dependent manner during detraining.


The Effect of Local Anesthetics and Contrast Agents on Radiofrequency Ablation Lesion Size.
Radiofrequency ablation (RFA) is a validated treatment option for the treatment of chronic pain in patients with lumbar spondylosis. Lesion size has been suggested to correlate with good clinical outcomes. This has created an abundance of scientific interest in the development of products with larger lesion characteristics. Needle characteristics, energy transfer, and heat rate are known to modify lesion size. Here, we demonstrate that common intraoperative solutions, such as lidocaine, iodine, and gadolinium-based products, can also affect lesion shape. To determine whether lidocaine and contrast agents modify lesion characteristics during the performance of monopolar RFA. Controlled, ex vivo study using clinically relevant conditions and pre-injections. Academic institution in a procedural setting. RFA lesion size was compared among six cohorts: 1) lidocaine 1%, 2) lidocaine 2%, 3) iohexol 180, 4) iohexol 240, 5) gadodiamide, and 6) control (no fluid control). Radiofrequency (RF) current was applied for 90 seconds at 80°C via 20-gauge 100-mm standard RFA needles with 10-mm active tips in orgranic chicken breasts without preservative at room temperature (21°C). Twelve lesions were performed for each medication cohort. The length, width, and depth of each lesion were measured. The statistical significance between each medication group and the control group was evaluated by t test. The mean lesion surface area of monopolar RFA without any pre-injection used was 80.8 mm2. The mean surface area of the monopolar RF lesion with a pre-injection of 0.2 mL of 2% lidocaine was 114 mm2, and the mean surface area of the monopolar RF lesion with a pre-injection of 0.2 mL of iohexol 240 was 130.6 mm2. The statistical analysis demonstrated that the control group had significantly smaller lesion sizes than did the groups in which lidocaine 2% and iohexol 240 were used (P<0.01). There were no statistically significant differences among the groups in which lidocaine 1%, iohexol 180, and gadodiamide were used. A notable difference was a 20% longer lesion with iohexol 240 compared with the control group and a 20% wider lesion with lidocaine 2% compared with the control group. In vivo anatomy within a human was not used in this study, nor were the chicken breasts heated to physiological temperature. Randomization of pieces of chicken breast did not occur, and thus intrinsic differences among the chicken breast pieces could play a confounding role. Lidocaine 2% and iohexol 240, when used as pre-injections in RFAs, were found to be associated with statistically significant increases in lesion surface area. However, RFAs with lidocaine 1%, iohexol 180, or gadodiamide were not found to produce a statistically significant difference in lesion size compared with monopolar RFA without the use of injectate.


The consequences of atheoretical, task-driven experimentation: theoretical comment on Paban, Chambon, Jaffard, and Alescio-Lautier (2005).
V. Paban, C. Chambon, M. Jaffard, and B. Alescio-Lautier (2005) concluded that their evidence "demonstrates the independence of aging and cholinergic lesion effects" and stated that "this was quite unexpected" (p. 943). This commentary suggests that the authors' negative findings were predictable, resulting from a focus on behavioral tests and functions unrelated to present evidence and theory concerning the cognitive functions of forebrain cholinergic systems. The article by V. Paban et al. serves as a useful illustration for the importance of theory- and hypothesis-driven assessment of behavioral functions, and for the unproductive consequences of experiments treating behavioral tests as assays used merely for the generation of behavioral correlates.


Chronic intraventricular infusion with NGF improves LTP in old cognitively-impaired rats.
Aged (21 months) cognitively-impaired male Sprague-Dawley rats received intraventricular infusion of nerve growth factor (NGF) or cytochrome C (Cit C) for 14 or 28 days using miniosmotic pumps and were evaluated either 1 week or 3 months after treatment. Groups of untreated young, aged-impaired and aged non-impaired rats were also evaluated. Under narcose recording and stimulating electrodes were stereotactically implanted in the dentate gyrus and the perforant path. The stimulation intensity was individually adjusted to obtain a half-maximal population spike (P) for test stimuli and a quarter-maximal for tetanization. The amplitude and latency of P and the slope (S) of the field EPSP were determined before and at 2, 5, 15, 30 and 60 min after tetanization at 400 Hz. Paired stimuli at 30 ms interval were also applied before and after tetanization. Aged, cognitively impaired rats showed an absent S potentiation and a delayed P potentiation, both in amplitude and latency, while non-impaired rats behaved like the young controls. Paired pulse inhibition showed no difference among groups before or after tetanization suggesting that the impaired potentiation is not due to an increased retroactive inhibition. NGF treatment ameliorates LTP deficits to levels equivalent to non-impaired rats, while Cit C controls showed no improvement. No differences appear among NGF treated groups, but evidence suggest that the animals evaluated 3 months after treatment developed a stronger potentiation.


Influence of third molar space on angulation and dental arch crowding.
The influence of the third molars on mandibular incisor crowding has been extensively studied but remains controversial. The purpose of this study was to ascertain whether, in Mongolian subjects, the lower third molar can affect anterior crowding and/or the inclination of teeth in the lower lateral segments. Panoramic radiographs, 45° oblique cephalograms, and dental casts were taken from Mongolian subjects (age range 18.3-24.1 years, mean 21.0 years) exhibiting impaction of all four third molars and an Angle Class I molar relationship. The Ganss ratio was calculated using panoramic radiographs, whereas the gonial angle and angulation of lower canines, premolars and molars were measured using 45° oblique cephalograms. Little's index of irregularity was calculated using dental casts. Significant relationships between the angulation of the third and second molars and between the first molars and second premolars were found. Conversely, there was no significant correlation between the angulation of third molars, first premolars and canines. The Ganss ratio calculations showed that the lower first and second molars and the second premolars inclined mesially if there was insufficient space for the lower third molars. However, there was no significant correlation between Little's index of irregularity and third molar angulation. Furthermore, although the third molar influences the lateral segments, no obvious relationship between the third molar and anterior crowding was observed. Therefore, the angulation of the third molar appears not to cause anterior crowding.