Chemistry inside molecular containers in the gas phase.
Inner-phase chemical reactions of guest molecules encapsulated in a macromolecular cavity give fundamental insight into the relative stabilization of transition states by the surrounding walls of the host, thereby modelling the situation of substrates in enzymatic binding pockets. Although in solution several examples of inner-phase reactions are known, the use of cucurbiturils as macrocyclic hosts and bicyclic azoalkanes as guests has now enabled a systematic mass spectrometric investigation of inner-phase reactions in the gas phase, where typically the supply of thermal energy results in dissociation of the supramolecular host-guest assembly. The results reveal a sensitive interplay in which attractive and repulsive van der Waals interactions between the differently sized hosts and guests need to be balanced with a constrictive binding to allow thermally activated chemical reactions to compete with dissociation. The results are important for the understanding of supramolecular reactivity and have implications for catalysis.


The DNA-binding protein E12 co-operates with XMyoD in the activation of muscle-specific gene expression in Xenopus embryos.
Two alternatively spliced products of the human E2A gene, E12 and E47, encode helix-loop-helix DNA-binding proteins. Here we describe the isolation of two Xenopus cDNAs; one, XE12, is structurally similar to human E12 and the other contains a sequence similar to E47. Transcripts of both cDNAs are present at all the stages of Xenopus development tested and in all regions of the embryo. The DNA binding properties of in vitro translated XE12 are indistinguishable from those of human E12. We have shown previously that an embryonic muscle DNA-binding activity, EMF1, that binds to a promoter sequence required for the expression of the cardiac actin gene, contains the Xenopus myogenic factor XMyoD. Here we show that it also contains protein that interacts with an anti-E12 antiserum, suggesting that XE12 and XMyoD proteins, or very similar ones, are present in EMF1. We have addressed the functional role of XE12 in muscle gene transcription in Xenopus embryos by injecting in vitro synthesized RNA into the two cell embryo. Overexpression of XE12 and XMyoD augments by greater than 10-fold the ectopic activation of the endogenous cardiac actin gene that can be produced by XMyoD alone. Our DNA binding results strongly suggest that this effect is mediated through a direct interaction of the XE12-XMyoD complex with specific sites in the cardiac actin promoter. We suggest that XE12 is functionally important in muscle gene activation in embryonic development.


MOG-IgG1 and co-existence of neuronal autoantibodies.
The presence of co-existent neuronal antibodies (neuronal-IgG) in patients with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG1) is not yet well understood. The aim of this study was to investigate the co-existence of a broad range of neuronal-IgG in MOG-IgG1+ patients. MOG-IgG1+ patients were tested for 17 neuronal-IgGs in cerebrospinal fluid (CSF) and serum including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, GABAA-R-IgG, GAD65-IgG, mGLUR1-IgG, DPPX-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1,2,Tr, and ANNA1,2,3. Clinical and radiological features of MOG-IgG1+ with NMDA-R-IgG in CSF were compared to a control cohort of MOG-IgG1+ patients without NMDA-R-IgG. A total of 376 MOG-IgG1+ patients underwent testing for neuronal-IgGs. Serum testing for neuronal-IgGs (113 adults, 142 children) identified one child with NMDA-R-IgG (0.7%), one child with CASPR2-IgG (0.7%), one adult with LGI1-IgG (0.9%) and one adult with GABAA-R-IgG (0.9%). CSF testing for neuronal-IgGs (97 adults, 169 children) identified seven children (4%) and seven adults (7%) with NMDA-R-IgG, and one adult with GABAA-R-IgG (1%). The MOG-IgG1+/NMDA-R-IgG+ patients had a median age of 17 (range: 2-39) years. Features associated with MOG-IgG1+/NMDA-R-IgG+ included encephalopathy (p = 0.001), seizures (p = 0.045), and leptomeningeal enhancement (p = 0.045). NMDA-R-IgG was the most frequently detected neuronal-IgG to co-exist with MOG-IgG1. MOG-IgG1+/NMDA-R-IgG+ patients most often presented with encephalopathy and seizures. Testing for MOG-IgG1 and NMDA-R-IgG may be warranted in patients with encephalopathy and inflammatory demyelinating syndromes.


Health, Religiosity and Hatred: A Study of the Impacts of COVID-19 on World Jewry.
This exploratory study examines the likely causes of the alarming global rise of antisemitism during the COVID-19 pandemic. Beginning with an appraisal of today's world Jewry, this exploratory study highlights the main social, health, and religious impacts COVID-19 has had on Jews worldwide and goes on to highlight how various Jewish communities managed and adjusted to COVID-19 public health restrictions. From this contextual backdrop, an assessment of how and why antisemitism has surged during the pandemic is presented, along with a review of what efforts are being taken to curtail this rise in hatred toward Jews. A central aim of this study is to underline the point that until meaningful, broad, and international steps are taken to curb online hate, the historic antisemitic tropes and myths suggesting Jews are the cause of disease will undoubtedly evolve and surge (especially across social media) during future pandemics and times of global crisis and unrest.


Neuroblastoma: imaging evaluation by sequential Tc-99m MDP, I-131 MIBG, and Ga-67 citrate studies.
Fourteen children with histopathologically confirmed neuroblastoma underwent sequential correlative imaging studies using I-131 MIBG, Tc-99m MDP, and Ga-67 citrate during various stages of the disease. Of the patients 86% showed I-131 MIBG accumulation in the primary tumoral site, whereas 71% showed Tc-99m MDP and 79% Ga-67 citrate uptake. In 86% at least one of the two latter radiopharmaceuticals concentrated in the primary tumor. The use of all three radiopharmaceuticals raised the detection rate to 93%. Of the osseous or extraosseous metastases 100% were detected by Tc-99m MDP studies. The I-131 MIBG studies were positive in 71% of the osseous metastases and in 70% of the extraosseous metastases. No Ga-67 citrate uptake was demonstrated in osseous metastases, although one extraosseous lung metastasis concentrated this radiopharmaceutical. Tc-99m MDP bone imaging was the best method for diagnosing metastatic spread of the disease and for monitoring the results of treatment. Primary tumor uptake was best indicated by I-131 MIBG. Both Ga-67 citrate and I-131 MIBG were superior to Tc-99m MDP with regard to accurately demonstrating the extent of primary tumors. Only Tc-99m MDP indicated the relationship of these tumors to the kidneys and neighboring osseous structures, providing early screening of kidney compression. Ga-67 citrate study was mainly indicated in tumors with catecholamine depletion, which failed to concentrate the other two radiopharmaceuticals. I-131 MIBG proved especially useful in detecting neuroblastoma with negative Tc-99m MDP and Ga-67 citrate studies and also proved to be helpful with those cases in which I-131 MIBG was planned for therapy. The following strategy is suggested for evaluating neuroblastoma.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of psyllium vs. placebo on constipation, weight, glycemia, and lipids: A randomized trial in patients with type 2 diabetes and chronic constipation.
To compare the effects of baked psyllium supplementation versus those who received a placebo on constipation symptoms, body weight, glycemic and lipids control in patients with type 2 diabetes (T2D) and chronic constipation. In a single-blinded, randomized controlled trial, 51 patients with T2D and chronic constipation with body mass index (BMI) 20-47 kg/m2 received either 10 g of psyllium pre-mixed in cookies twice per day or placebo cookies for 12 weeks. Constipation symptoms, body mass index (BMI), fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and lipid profile were determined at the beginning and end of 4, 8, and 12-week period. Constipation was evaluated with a stool diary (ROME III). The psyllium group showed improvement in constipation symptoms, body weight, glucose and lipid values compared with the baseline and the placebo group. Body weight and FPG decreased from baseline in the psyllium group (P < 0.001 and P = 0.056, respectively). The differences (95% CI) of absolute change of body weight (-2.0 (-3.0, -1.0) kg; P < 0.001), FPG (-13.6 (-24.3, -2.9) mg/dl; P = .040), and HbA1c (-1.7 (-2.9, -0.5)); P = 0.002) between the groups were statistically significant. Cholesterol (-21.5 (-25.6, -14.4); P < 0.001), triglycerides (-20.0 (-32.3, -7.7); P = 0.021) and constipation symptoms (1.5 (0.4, 2.3); P < 0.001) decreased in the psyllium group. The compliance was good and no adverse effects were observed. In patients with T2D and chronic constipation, psyllium supplementation decreased constipation symptoms, body weight, glycemic, cholesterol, and increased HDLC levels.


Field management of neonatal diarrhea.
This article deals with the management and health factors involved in raising healthy calves. Practical considerations are given for veterinarians to implement a disease control program. Various management techniques concerning the feeding, housing, and ventilation of the neonate are also discussed.


The development and decline of forward masking.
Three experiments investigated the forward masking of brief sinusoids by bursts of noise for masker durations of between 5 and 320 ms and for masker-signal delays between 5 and 40 ms. Experiment 1 showed that, for a 2-kHz signal and a 5-ms delay, long-duration maskers produced much more masking than brief maskers of the same spectrum level. As masker-signal delay was increased, thresholds dropped more rapidly for long than for brief maskers, so that at a delay of 40 ms the difference between thresholds produced by long and by brief maskers was reduced. Experiment 2 showed that, for a 2-kHz signal, the transition from simultaneous masking to forward masking was accompanied by a large drop of about 23 dB in threshold. For a 250-Hz signal this large drop did not occur until masker-signal delay was increased from 10 to 20 ms. For shorter masker-signal delays, brief 250-Hz maskers produced thresholds higher than those produced by longer maskers. The results of Experiment 2 are consistent with the idea that ringing on the basilar membrane causes the responses to masker and signal to overlap for delay times up to 10 ms. Experiment 3 compared the recovery functions for 3 markers of different durations, where the masker levels were adjusted so that each produced equal masking of a 2-kHz signal at a delay of 5 ms. Brief intense maskers produced slower recovery than longer weaker ones, indicating that the recovery from a given amount of forward masking depends on how that masking developed. The implications of this finding for attempts to explain forward masking in terms of short-term adaptation are discussed.


Clinical manifestation and neurosurgical intervention of encephalocraniocutaneous lipomatosis--a case report and review of the literature.
Currently, there are only a few reported cases of symptomatic or asymptomatic subpial (intramedullary) spinal lipoma, and therefore no guidelines are available to indicate surgery. These lesions are infrequently associated with spina bifida. Herein, we provide our experience in the neurosurgical intervention of compressive myeloradiculopathy for encephalocraniocutaneous lipomatosis (ECCL). The patient initially presented with bilateral upper hand paralysis, then regained muscle power after surgery and during 1 year of follow-up. We discuss the neurosurgical indications and intervention, imaging studies, other associated symptoms, and the pathogenesis of ECCL in an infant.


Purification and some properties of alkaline pullulanase from a strain of bacillus no. 202-1, an alkalophilic microorganism.
Pullulanase (pullulan 6-glucanohydrolase EC 188.8.131.52) was purified about 290-fold from the culture fluid of Bacillus No. 202-1 by DEAE-cellulose adsorption, acetone fractionation, (NH4) 2SO4 precipitation and DEAE--cellulose column chromatography followed by Sephadex G-200 molecular sieve chromatography. The enzyme gave a single band of protein by disc polyacrylamide gel electrophoresis. The molecular weight was estimated as 92 000 by sodium dodecyl sulfate gel electrophoresis. The isolectric point was lower than pH 2.5. The optimum pH for enzyme action was about 8.5-9.0. The action of the enzyme on amylopectin and glycogen resulted in increase in the iodine coloration of 85% and 70%, respectively. The enzyme completely hydrolyzed 1,6-alpha-glucosidic linkages in amylopectin, glycogen and pullulan.


Nitrogen budgets of agricultural fields of the Changjiang River basin from 1980 to 1990.
To assess the fate of the large amounts of nitrogen (N) brought into the agricultural environment by human activities in the Changjiang River basin, we used [China's county level agricultural database of 1980 and 1990. National Resources and Environmental Data Center, China] and published conversion data to set up a complete N budget for the Changjiang River basin. Sources considered include imported N such as atmospheric deposition, inorganic fertilizer, biological fixation and manure. Dominant losses considered include crop harvests, denitrification of soil nitrate and NH3 volatilization, and the budget was estimated from the difference between all inputs and all outputs. Therefore, the geographic distribution of excess N, considered as lost, by N storage in farmland and N transported to water bodies in Changjiang River basin was analyzed. In the Changjiang River basin, the anthropogenic reactive N has far exceeded the terrestrial bio-fixed N in nature, and human activities have significantly altered the N cycle in this region. The total inputs of N in 1980 and 1990 were 8.0 and 12.9 Tg N, respectively. The total N outputs are 4.41 Tg N in 1980 and 6.85 Tg N in 1990. Thus, the excess N that was stored in farmland was 1.51 Tg N at 1980 and 2.67 Tg N at 1990, respectively, and losses through transportation to water bodies in 1980 was 2.08 and 3.38 Tg N in 1990, respectively. Our research shows that from 1980 to 1990, cultivated land increased 5.9%, grain production increased 30% and N fertilizer-use increased 106%, but the N fertilizer-use efficiency decreased 36%, and the variations in the distribution of N fertilizer-use efficiency, N budgets and N transport to water bodies tended to coincide with each other geographically.


Accuracy of prenatal detection of facial clefts and relation between facial clefts, additional malformations and chromosomal abnormalities: a large referral-center cohort.
Facial clefts belong to the most common congenital malformations and their prenatal diagnosis is a constant challenge. The aim of this study was to determine the accuracy of prenatal ultrasound in correctly classifying facial clefts. Furthermore, we aimed to specify the distribution of the type of clefts and underlying genetic conditions. All fetuses seen with suspected facial cleft in the Department of Obstetrics, Charité - Universitätsmedizin Berlin during a period of 23 years (1999-2022) were included in this retrospective study. Clefts were classified according to the classification of Nyberg. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed. 292 patients were included in the study. The most common type of clefts were unilateral cleft lip and palate (CL-P) (53.6%) and bilateral CL-P (30.6%), followed by CL (8.1%), CP (5.1%) and median CL-P (2.6%). The overall pre- and postnatal concordance rate corresponding to a correct prenatal diagnosis was high, 88.9%, ranging from 73.7% (CL) to 93.7% (unilateral CL-P). Most of the median clefts (95.2%) and CP (93.3%) were associated with other sonographic abnormalities, as well as 52.2% of bilateral CL-P. Chromosomal abnormalities, mostly trisomy 13 and trisomy 18, were observed in in the median CL-P (47.6%), bilateral CL-P (31.1%) and CP (26.7%) groups, in contrast to the CL (9.1%) and unilateral CL-P (12.9%) groups. It was exceptional to have a chromosomal abnormality without additional malformations (4.8%). The mortality rate including one late miscarriage, 5 IUFD's, 74 TOPs and 6 palliative cares at birth was 29.8%, particularly high for median clefts (90.5%). Prenatal ultrasound exhibited a high accuracy to assess the type of facial clefts with an average rate of 88.9% (73.7%-93.7%) and a concordance rate of up to 93.7%, depending on the type of cleft. The search for additional malformations as well as clarifying underlying genetic conditions is essential. This allows for a targeted counseling of the parents and to best prepare for postnatal care, including surgery by the maxillofacial team.


On the Computational Power of Spiking Neural P Systems with Self-Organization.
Neural-like computing models are versatile computing mechanisms in the field of artificial intelligence. Spiking neural P systems (SN P systems for short) are one of the recently developed spiking neural network models inspired by the way neurons communicate. The communications among neurons are essentially achieved by spikes, i. e. short electrical pulses. In terms of motivation, SN P systems fall into the third generation of neural network models. In this study, a novel variant of SN P systems, namely SN P systems with self-organization, is introduced, and the computational power of the system is investigated and evaluated. It is proved that SN P systems with self-organization are capable of computing and accept the family of sets of Turing computable natural numbers. Moreover, with 87 neurons the system can compute any Turing computable recursive function, thus achieves Turing universality. These results demonstrate promising initiatives to solve an open problem arisen by Gh Păun.


Correlation between low-level expression of the tumor suppressor gene TAp73 and the chemoresistance of human glioma stem cells.
Glioma stem cells (GSCs) are regarded as the root of glioma growth and recurrence. Chemoresistance is one of the characteristics of GSCs that increases the difficulties in eradicating the cells by anticancer drugs. The objective of this study is to investigate the correlation between expression of the tumor suppressor gene TAp73 and the chemoresistance of human GSCs. MTT and tumor sphere formation assays were used to analyze the chemoresistance phenotype of GSCs derived from primary human glioma specimens under cisplatin exposure. Reverse transcription real-time PCR was applied for assaying mRNA levels of TAp73. Protein levels of TAp73, p21, Bax, and cleared caspase 3 were assayed by western blot. Cell apoptosis was analyzed by flow cytometry after the annexin V fluorescence staining. GSCs exhibited increased chemoresistance compared to differentiated glioma cells (DGCs) derived from the same tumor specimen. The expression of TAp73 was lower in GSCs and was not sensitive to cisplatin treatment as compared to DGCs. Overexpression of TAp73 by transfection increased the apoptosis of GSCs in the presence of cisplatin and reduced the chemoresistance of GSC. TAp73 knockdown by siRNA in DGCs reduced cisplatin-induced apoptosis and increased the resistance to cisplatin. These findings indicate that TAp73 silencing is hallmark of GSC to maintain their chemoresistance phenotype. Thus, targeting TAp73 may provide a novel strategy to eradicating GSCs.


The effects of the COVID-19 pandemic on drug and poison-related deaths in Gold Coast, Australia.
COVID-19 is postulated to impact drug- and poison-related deaths. America has reported an increased in drug-related deaths, whereas Australia has reported a decline. Regional studies are scant and may not mirror national data. Characterising drug and poison-related deaths during COVID-19 at a regional level would inform local interventions and policies on the current and future pandemics. A 4-year retrospective study from January 1, 2018, to December 31, 2019 (pre-COVID-19 pandemic) and from January 1, 2020, to December 31, 2021 (COVID-19 pandemic) of all drug and poison-related deaths admitted to the Gold Coast University Hospital under Coronial investigation. Drug and poison-related deaths increased in both the proportion and absolute numbers before and during the COVID-19 pandemic. There was no statistical difference in age, sex, location of death, manner of death and classification of drugs and poison implicated. Although there is an increase in drug and poison-related deaths, the overall demographic and pattern have not changed. Further studies to account for the variation may enable implementation of targeted public health interventions to address the burden of related deaths in regional settings in the context of future pandemics.


Hyperglycemia and blood glucose deterioration are risk factors for severe COVID-19 with diabetes: A two-center cohort study.
We aimed to assess whether blood glucose control can be used as predictors for the severity of 2019 coronavirus disease (COVID-19) and to improve the management of diabetic patients with COVID-19. A two-center cohort with a total of 241 confirmed cases of COVID-19 with definite outcomes was studied. After the diagnosis of COVID-19, the clinical data and laboratory results were collected, the fasting blood glucose levels were followed up at initial, middle stage of admission and discharge, the severity of the COVID-19 was assessed at any time from admission to discharge. Hyperglycemia patients with COVID-19 were divided into three groups: good blood glucose control, fair blood glucose control, and blood glucose deterioration. The relationship of blood glucose levels, blood glucose control status, and severe COVID-19 were analyzed by univariate and multivariable regression analysis. In our cohort, 21.16% were severe cases and 78.84% were nonsevere cases. Admission hyperglycemia (adjusted odds ratio [aOR], 1.938; 95% confidence interval [95% CI], 1.387-2.707), mid-term hyperglycemia (aOR, 1.758; 95% CI, 1.325-2.332), and blood glucose deterioration (aOR, 22.783; 95% CI, 2.661-195.071) were identified as the risk factors of severe COVID-19. Receiver operating characteristic (ROC) curve analysis, reaching an area under ROC curve of 0.806, and a sensitivity and specificity of 80.40% and 68.40%, respectively, revealed that hyperglycemia on admission and blood glucose deterioration of diabetic patients are potential predictive factors for severe COVID-19. Our results indicated that admission hyperglycemia and blood glucose deterioration were positively correlated with the risk factor for severe COVID-19, and deterioration of blood glucose may be more likely to the occurrence of severe illness in COVID-19.


Mechanisms of interleukin-2-mediated signaling and role of calcium in T cell mitogenesis.
In T lymphocytes stimulated by concanavalin A (Con A), interleukin 2 (IL-2) acts on the late G1 stage of the cell cycle. Ca2+ uptake by T cells was not enhanced with the stimulation of Con A (initiation) or IL-2 (late G1 stage), but Ca2+ requirement was observed at the two stages. These results indicate that the enhancement of Ca2+ uptake is not necessary, but intracellular Ca2+ may act as an important messenger in T cell mitogenesis.


Is ERCP a reasonable diagnostic method for excluding pancreatic and hepatobiliary disease in patients with a Billroth II resection?
ERCP was performed in 57 patients who had undergone Billroth II resection. Cannulation of the papilla of Vater was successfully accomplished in 31 cases (55%). The success rate of ERCP was clearly dependent on the type of Billroth II resection presenting.


Prognostic risk model development and prospective validation among patients with cervical cancer stage IB2 to IIB submitted to neoadjuvant chemotherapy.
This study was designed to develop a risk model for disease recurrence among cervical cancer patients who underwent neoadjuvant chemotherapy and radical surgery. Data for 853 patients were obtained from a retrospective study and used to train the model, and then data for 447 patients from a prospective cohort study were employed to validate the model. The Cox regression model was used for calculating the coefficients of the risk factors. According to risk scores, patients were classified into high-, intermediate-, and low-risk groups. There were 49 (49/144, 34%) recurrences observed in the high-risk group (with a risk score ≥ 2.65), compared with 3 (3/142, 2%) recurrences in the low-risk group (with a risk score < 0.90). Disease-free survival (DFS) was significantly different (log-rank p < 0.001) among the three risk groups; the risk model also revealed a significant increase in the accuracy of predicting 5-year DFS with the area under the ROC curve (AUC = 0.754 for risk model vs 0.679 for FIGO stage system); the risk model was also validated with data from the prospective study (log-rank p < 0.001, AUC = 0.766). Both high-risk and intermediate-risk patients can be more effectively identified by this risk model.


Genomovar diversity amongst Burkholderia cepacia complex isolates from an Australian adult cystic fibrosis unit.
In this study, a combination of recA-based PCR assays and 16S rDNA restriction fragment length polymorphism (RFLP) analysis was used to determine the genomovar diversity of clinical Burkholderia cepacia complex isolates. Twenty-eight isolates were prospectively collected from patients attending a large Australian adult cystic fibrosis (CF) unit, 22 isolates were referred from other Australian CF units and a further eight isolates originated from patients without CF. The 28 prospectively collected isolates were distributed amongst the following genomovars: Burkholderia cepacia genomovar I (28.6%), Burkholderia multivorans (21.4%), Burkholderia cepacia genomovar III (39.3%), Burkholderia vietnamiensis(3.6%) and Burkholderia ambifaria (7.1%). The results of this study highlight the usefulness of 16S rDNA RFLP typing for the identification of other Burkholderia spp. and non-fermenting gram-negative bacteria.


A molecular marker associated with mild hemoglobin H disease.
The clinical spectrum of HbH disease varies from a benign disorder to a severe anemia which is blood-transfusion dependent. Heterogeneity at the clinical level is now being understood in terms of the underlying molecular defects. In this study a mild phenotype found in a group of patients with HbH disease is associated with two types of alpha-thalassemia. These are: alpha+-thalassemia (-alpha 3.7/) and alpha 0-thalassemia (--SEA/). In contrast, a second group with more severe HbH disease has a non-deletional alpha-thalassemia defect instead of alpha+-thalassemia (genotype alpha alpha T/--SEA). In the majority of cases, the basis for non-deletional alpha-thalassemia is Hb Constant Spring.


Formation and characteristics of curcumin-loaded binary gels formed from large yellow croaker (Pseudosciaena crocea) roe protein isolate and gellan gum.
The aim of this study was to investigate the effect of gellan gum (GG) on the cold gelation of large yellow croaker roe protein isolate (pcRPI). The water-holding ability and storage modulus of the pcRPI-GG binary gels increased with the GG concentration, where the storage modulus of the pcRPI-0.2% GG gel was approximately 30.7 times that of the pure pcRPI gel. Compare to the other binary gels, pcRPI-0.2% GG gels exhibited a lower lacunarity and higher junction density, with a denser, more aggregated microstructure. Consequently, curcumin was embedded in pcRPI-0.2% GG gels, and simulated gastrointestinal digestion test results showed that GG addition effectively protected and slowed curcumin release in the gastrointestinal environment. These findings may contribute to elucidating the interaction of pcRPI with GG and demonstrate the potential of binary gels for the embedding and delivery of active substances.


Histology of Barrett's esophagus and dysplasia.
This article explores issues related to the diagnosis of Barrett's esophagus (BE) in endoscopic biopsies and dysplasia in Barrett's epithelium. The definitions of BE, including long- and short-segment BE, are reviewed, with an emphasis on the significance of intestinal metaplasia (IM). IM of the gastroesophageal junction and cardia is reviewed and problems in its distinction from short-segment BE are discussed. In addition, the article reviews the classification of dysplasia in Barrett's mucosa, with reference to problematic areas, such as sampling error and interobserver variability. Biomarkers and their role in the diagnosis of dysplasia and stratification of risk are summarized.


Three-year clinical outcomes with the ABSORB bioresorbable vascular scaffold in real life: Insights from the France ABSORB registry.
The aim of this study was to determine the 3-year outcomes of patients treated with Absorb bioresorbable vascular scaffold (BVS) implantation. Randomized trials and observational registries performed in patients undergoing percutaneous coronary intervention have demonstrated higher 1-year and midterm rates of device thrombosis and adverse events with BVS compared to contemporary drug eluting stent. Data on long-term follow-up of patients treated with BVS are scarce. All patients treated with BVS were included in a large nationwide prospective multicenter registry (FRANCE ABSORB). The primary endpoint was a composite of cardiovascular death, myocardial infarction, and target lesion revascularization at 3 years. Secondary endpoints were 3-year scaffold thrombosis and target vessel revascularization (TVR). Between September 2014 and April 2016, 2070 patients were included (mean age 55 ± 11 years; 80% men). The indication was acute coronary syndrome (ACS) in 49% of patients. At 3 years, the primary endpoint occurred in 184 patients (8.9%) and 3-year mortality in 43 patients (2.1%). Scaffold thrombosis and TVR rates through 3 years were, respectively, 3 and 7.6%. In a multivariable analysis, independent predictors of primary endpoint occurrence were diabetes, oral anticoagulation, active smoking, absence of initial angiographic success and the association of a total BVS length ≥30 mm with the use of 2.5 mm diameter BVS. Although 3-year mortality was low in this ACS population, device-related events were significant beyond 1 year. Total BVS length and 2.5 mm BVS were associated with higher rates of MACE at long-term follow-up.


Pravastatin induces NO synthesis by enhancing microsomal arginine uptake in healthy and preeclamptic placentas.
Pravastatin, a known inducer of endothelial nitric-oxide synthase (eNOS) was demonstrated in human placenta, however the exact mechanism of it's action is not fully understood. Since placental NO (nitric oxide) synthesis is of primary importance in the regulation of placental blood flow, we aimed to clarify the effects of pravastatin on healthy (n = 6) and preeclamptic (n = 6) placentas (Caucasian participants). The eNOS activity of human placental microsomes was determined by the conversion rate of C14 L-arginine into C14 L-citrulline with or without pravastatin and Geldanamycin. Phosphorylation of eNOS (Ser1177) was investigated by Western blot. Microsomal arginine uptake was measured by a rapid filtration method. Pravastatin significantly increased total eNOS activity in healthy (28%, p<0.05) and preeclamptic placentas (32%, p<0.05) using 1 mM Ca2+ promoting the dissociation of a eNOS from it's inhibitor caveolin. Pravastatin and Geldanamycin (Hsp90 inhibitor) cotreatment increased microsomal eNOS activity. Pravastatin treatment had no significant effects on Ser1177 phosphorylation of eNOS in either healthy or preeclamptic placentas. Pravastatin induced arginine uptake of placental microsomes in both healthy (38%, p < 0.05) and preeclamptic pregnancies (34%, p < 0.05). This study provides a novel mechanism of pravastatin action on placental NO metabolism. Pravastatin induces the placental microsomal arginine uptake leading to the rapid activation of eNOS independently of Ser1177 phosphorylation. These new findings may contribute to better understanding of preeclampsia and may also have a clinical relevance.


Quantum mechanical/molecular mechanical studies on spectral tuning mechanisms of visual pigments and other photoactive proteins.
The protein environments surrounding the retinal tune electronic absorption maximum from 350 to 630 nm. Hybrid quantum mechanical/molecular mechanical (QM/MM) methods can be used in calculating excitation energies of retinal in its native protein environments and in studying the molecular basis of spectral tuning. We hereby review recent QM/MM results on the phototransduction of bovine rhodopsin, bacteriorhodopsin, sensory rhodopsin II, nonretinal photoactive yellow protein and their mutants.


Utilization of the venturi effect to introduce micro-particles for epidermal vaccination.
Skin represents a potent immunological induction site, with a dense network of special antigen-presenting cells (APCs) in the epidermal layer. DNA vaccination targeting APCs offers a promising new therapeutic intervention for a wide range of diseases. A unique biomedical device, the venturi powdered injection system (venturi), is proposed for the epidermal delivery of DNA vaccines. The novelty of this hand-held venturi device is in using the venturi effect to entrain DNA-coated micro-particles into an established quasi-steady transonic helium flow and accelerate them to an appropriate momentum for penetrating the skin or mucosal tissue to achieve an immunological effect. In this paper, computational fluid dynamics (CFD) has been employed to scrutinize an experimental venturi device. Key features of gas dynamics and gas-particle interactions have been presented. A parallel extension was added to improve the uniformity of gas and particle flow for a better particle penetration distribution. The overall capability of the venturi biolistic configuration for delivering micro-particles has been explored and discussed. Statistical analysis has shown that the modelled micro-particles have achieved a mean velocity of 654m/s for intracellular DNA vaccine delivery applications.


Longitudinal Reciprocal Relationships Between Quality of Life and Coping Strategies Among Women with Breast Cancer.
Research on quality of life (QoL) among women with breast cancer has often examined the impact of coping strategies on QoL. However, the transactional model of stress and coping would argue that QoL can impact coping. This reciprocal relationship between QoL and coping has been inadequately studied. This study examined reciprocal relationships over 18 months between QoL and coping (positive and negative coping) among women with breast cancer. Three-wave cross-lagged structural equation modelling (SEM) analysis was used over three timepoints post-diagnosis (T1-T3; N = 637, 577, 553, respectively). SEM results revealed a significant reciprocal relationship between negative coping and QoL, indicating that negative coping predicted subsequent QoL, which in turn predicted later negative coping. Although QoL at cancer diagnosis predicted subsequent positive coping, we did not find a reciprocal relation between QoL and positive coping. Findings expand our knowledge of the relation between QoL and coping by suggesting the reciprocal relationship between negative coping and QoL among women with breast cancer.


Transplantation of photobiomodulation-preconditioned diabetic stem cells accelerates ischemic wound healing in diabetic rats.
Diabetic foot ulcer is the most costly and complex challenge for patients with diabetes. We hereby assessed the effectiveness of different preconditioned adipose-derived mesenchymal stem cells (AD-MSCs) and photobiomodulation protocols on treating an infected ischemic wound in type 1 diabetic rats. There were five groups of rats: (1) control, (2) control AD-MSCs [diabetic AD-MSCs were transplanted (grafted) into the wound bed], (3) AD-MSC + photobiomodulation in vivo (diabetic AD-MSCs were grafted into the wound, followed by in vivo PBM treatment), (4) AD-MSCs + photobiomodulation in vitro, and (5) AD-MSCs + photobiomodulation in vitro + in vivo. Diabetic AD-MSCs preconditioned with photobiomodulation had significantly risen cell function compared to diabetic AD-MSC. Groups 3 and 5 had significantly decreased microbial flora correlated to groups 1 and 2 (all, p = 0.000). Groups 2, 3, 4, and 5 had significantly improved wound closure rate (0.4, 0.4, 0.4, and 0.8, respectively) compared to group 1 (0.2). Groups 2-5 had significantly increased wound strength compared to group 1 (all p = 0.000). In most cases, group 5 had significantly better results than groups 2, 3, and 4. Preconditioning diabetic AD-MSCs with photobiomodulation in vitro plus photobiomodulation in vivo significantly hastened healing in the diabetic rat model of an ischemic infected delayed healing wound.


Comparative transcriptomic analysis of porcine epidemic diarrhea virus epidemic and classical strains in IPEC-J2 cells.
In recent years, porcine epidemic diarrhea (PED) has become widespread and caused huge economic losses for the global pig industry. There is growing evidence that frequent outbreaks of diarrhea are caused by the variants of porcine epidemic diarrhea virus (PEDV) with high pathogenicity. Herein, an epidemic strain of PEDV HLJ strain was isolated and characterized from Heilongjiang Province of China, and the whole genomic expression profile of intestinal porcine epithelial cells (IPEC-J2) infected with HLJ strain was investigated in comparison with classical CV777 strain. A total of 26,851 genes were identified, of these, 25,880 were known genes and 971 were novel genes. There were 258 differentially expressed genes (DEGs) identified between PEDV HLJ-infected and uninfected cells at 24 h post infection (hpi), and 201 DEGs between PEDV HLJ and CV777 infection. A comparative analysis revealed that 258 DEGs were enriched in 468 gene ontology (GO) terms and mapped to 179 KEGG pathways, and 201 DEGs in 1120 GO terms and mapped to 115 KEGG pathways for HLJ-infected cells in contrast to the uninfected and CV777-infected cells, respectively. Specifically, PEDV HLJ strain could activate anti-viral innate immune response and inflammation more intensively than CV777, in which mRNA levels of interferon (IFN-β), chemokines (CCL5 and CXCL10) and pro-inflammatory cytokines (IL-8 and TNF-α) were induced earlier and more strongly. Subsequently, 20 DEGs and 5 proteins were selected and validated by real-time fluorescence quantitative PCR (RT-qPCR) and western blot, and the results were consistent with the transcriptomic analysis. Overall, this study may be helpful for understanding the pathogenesis mechanism of PEDV variants, and contribute to the effective prevention and control of PEDV infection.


Ultrastructure of nematocytes and one-celled tentacles of the freshwater coelenterate, Calpasoma dactyloptera.
Calpasoma dactyloptera, a tentacled form of minute, freshwater coelenterate, has been investigated by light and electron microscopy and time-lapse cinematography. Each tentacle consists of a protrusion from a single ectodermal epithelial cell termed a tentaculocyte. Thus, unlike most coelenterate tentacles, neither mesoglea nor endoderm is present in the tentacle. Large numbers of nematocytes are present, however. When the nematocytes are poised, they sit within tentaculocyte vesicles which represent invaginations of the plasma membrane. A cnidocil protrudes into the external medium. The bottom of each nematocyte is elongated as a stalk which extends to the tentacle base, coursing through tubular membrane lined channels within the tentaculocyte. A network of fibers and microtubules, originating in the cnidocil, extends to the base of the nematocyte stalk.


[Structural-functional units of epidermis].
The available data suggest that epidermis is organized in discrete structural and functional units (SFUs) reproduced both in vivo and in vitro. SFUs are formed in a culture of epidermal keratinocytes by self-organization of the forming cellular elements. SFUs are capable of self-sustaining and form a niche for the stem cells. At the same time, due to the maintained asymmetric kinetics of the stem cell proliferation, SFUs serve as a barrier for their uncontrolled replication.


Sociodemographic disparities in oral health-related quality of life of schoolchildren in rural and urban areas.
To assess the association between residence place, socioeconomic conditions and oral health-related quality of life (OHRQoL) among schoolchildren from southern Brazil. Participants were 9-14-year-old schoolchildren from rural and urban municipal schools from Rosário do Sul, Brazil. The Child Perceptions Questionnaire (CPQ11-14) was used to assess OHRQoL. A structured questionnaire collected data on sociodemographic condition (family income), residence place (urban or rural), use of dental services, and behavioral variables. Clinical oral examination recorded the presence of missing teeth and the gingival bleeding index. Multilevel Poisson regression analysis with a hierarchical approach assessed the association between predictors and CPQ11-14 scores. Rate ratios (RR) and 95% confidence intervals (CI) were estimated. A total of 373 schoolchildren were included (rural area=122; urban area=251), with a mean CPQ11-14 score of 11.83, ranging from 0 to 42. Low-income schoolchildren living in rural areas had 15% higher CPQ11-14 scores than high-income schoolchildren living in urban areas. In urban areas, family income predicted OHRQoL, with low-income schoolchildren having 9% higher CPQ11-14 scores than high-income children. In rural areas, schoolchildren with low household income had 19% higher CPQ11-14 scores than high-income children. Schoolchildren from low-income families had a poorer OHRQoL irrespective of their area of residence (rural or urban). The association between family income and OHRQoL was more pronounced among children living in rural areas.


Factors Associated With Ovarian Preservation in Children and Adolescents With Primary Tumors of Ovary.
To determine management of pediatric ovarian masses and identify the factors associated with ovarian preservation. From January, 2002 to January, 2019 the case records of 72 patients (median age 14 y), who underwent surgery for ovarian tumors were retrospectively reviewed. Tumors were most common in the age group 14-17 yrs (58.3%) and most (91.7%) were benign. The most common presenting symptom was abdominal pain (80.5%) followed by vomiting, elevated body temperature, nausea and palpable abdominal mass. 25 (34.7%) patients had an ovarian torsion. Six out of 72 (8.3%) patients had malignant tumors. Of the patients with malignant tumors, 75% had abnormal alpha-fetoprotein and 50% had abnormal b-human chorionic gonadotropin levels (P<0.001). Ovarian-preserving surgery was successfully performed in 74.3% of the benign lesions and two patients (25%) with malignant tumors (P=0.004). Factors associated with ovarian-preserving surgery are benign tumor, normal tumor markers levels, and smaller size of tumor.


Developmental toxicity and induction of vitellogenin in embryo-larval stages of zebrafish (Danio rerio) exposed to methyl Paraben.
MethylParaben (MP), a methyl ester of p-hydroxybenzoic acid, is used as an anti-microbial preservative in foods, drugs and cosmetics for decades. It enters the aquatic environment, and can have toxic effects on aquatic organisms. Little is known on the developmental toxicity of MP exposure to zebrafish during early life stages. In this study, the developmental effects of MP were evaluated in embryo-larval zebrafish (at concentrations ranging from 100μM, 200μM, 400µM, 800μM and 1000μM for 96h post fertilization (hpf). The survival, hatching, heart beat rate and developmental abnormalities were observed in the embryos exposed to MP. MP exposure resulted in decreased heart rate and hatching rate. Defects including pericardial edema blood cell accumulation and bent spine were observed in all the treated concentration, except at 100μM. With increasing concentrations, the frequency of these defects increased. The 96 hpf LC50 of MP was calculated to be 428μM (0.065mg/L). Furthermore, RT-PCR result showed that in larval zebrafish exposed to 100μM (0.015mg/L) of MP till 96 hpf, expression of vitellogenin I (Vtg -I) was significantly upregulated compared to the control group. This data suggest that even though lower concentrations of MP do not cause phenotypic malformations, it leads to dysregulated expression of estrogenic biomarker gene Vtg-I.


Bacterial counts in carious dentine under restorations: 2-year in vivo effects.
Little is known about the long-term effects of fluoride-releasing materials on carious dentine in vivo. The aim was to investigate the 2-year influence of a resin-modified glass ionomer cement (RM-GIC) and amalgam on the bacteriological counts of carious dentine that remained under class I restorations. To enable a split-mouth design, 33 molar pairs in 33 patients (mean age 15.1 years, SD 1.4) were selected, based on clinically and radiographically diagnosed occlusal dentine caries. The enamel of the carious molars was removed, and the carious dentine was sampled under aseptic conditions just beneath the dentinoenamel junction. The molars were alternately restored with RM-GIC or amalgam without further removal of carious dentine. The samples were processed for microbiological determination of total viable counts (TVC), mutans streptococci (MS), and lactobacilli (LB). The molar pairs of 25 patients were reevaluated after 2 years using the same clinical techniques and were permanently restored after complete caries removal. Both materials showed a substantial decrease in numbers of TVC and LB of the carious dentine after the 2-year period. Compared to amalgam, the decrease in the numbers of LB was significantly more pronounced for RM-GIC. No microorganisms were detected in only 11 molars (6 RM-GIC and 5 amalgam) after the 2-year period. Based on this study, we suggest that complete removal of carious dentine is still the best conservative treatment, irrespective of the restorative material used.


Local injection of thrombin-related peptide (TP508) in PPF/PLGA microparticles-enhanced bone formation during distraction osteogenesis.
We have previously demonstrated that injections of the thrombin-related peptide, TP508, into the lengthening gap have significantly enhanced bone consolidation in a rabbit model of distraction osteogenesis. This study was to further test the effect of a single TP508 injection in slow release preparation on bone formation during distraction osteogenesis. Rabbits had left tibiae lengthened unilateral lengthener at rate of 1.4 mm/day for 6 days. TP508 was injected into as the following: Group 1, TP508 in saline; Group 2, in PPF/PLGA [poly(propylene fumarate)/poly(D,L-lactic-co-glycolic acid)] microparticles; and Group 3, dextran gel only. All the animals were killed 2 weeks after lengthening. On radiographies, more bone was formed in the two TP508-treated groups at first and secnd week postlengthening than that of the control Group 3. Microcomputed tomography (microCT) at 2 weeks indicated that the most advanced bone formation and remodeling was seen in Group 2. The mean volumetric BMD of the regenerates was significantly higher in the TP508 treated groups compared to the control group (p < 0.05). Histological evaluations supported the radiographic and the microCT results. In conclusion, we have demonstrated that a single injection of small amount of TP508 (300 microg) at the end of lengthening phases has significantly enhanced bone consolidation process in a rabbit model of distraction osteogenesis. The delivery of TP508 in PPF/PLGA microparticles appears to lead to a better quality bone formation over the saline delivery, further examinations are needed to confirm if PPF/PLGA microparticles may be desirable drug delivery form in augmenting bone formation.


Influence on ictal seizure semiology of rapid withdrawal of carbamazepine and valproate in monotherapy.
To quantify changes in ictal seizure semiology during rapid withdrawal of carbamazepine (CBZ) and valproate (VPA) from a monoregimen in presurgical evaluation. Therapeutic intensive seizure analysis (TISA) with video-EEG monitoring was used in 33 patients with pharmacoresistant partial epilepsy undergoing complete withdrawal of CBZ (20 patients) or VPA (13 patients) from a monoregimen. Monitoring phases included a 3-day baseline phase, a 3-day rapid antiepileptic drug (AED) withdrawal phase, and another 3-day AED-free phase with AEDs in subtherapeutic levels. Seizure variables as complete processes and their various elements (ictal signs) were analyzed, including duration (seconds), intensity (on a scale of 0 to 3), frequency (number per 3 days), and total duration of seizures and ictal signs in 3 days (seconds). The localization of seizure patterns on ictal EEG recording (EEG seizure onset) and the first appearing clinical ictal phenomena (initial ictal signs) were recorded. A total of 188 seizures in the CBZ group and 57 seizures in the VPA group were investigated. Compared with the baseline phase, the CBZ group showed increases in duration, frequency of seizures, various ictal signs, and secondarily generalized tonic and clonic signs during the following two phases. Significantly increased values of the VPA group were observed in seizure duration and frequency of hypermotoric phenomena during the AED-free phase. More patients in the CBZ group had secondarily generalized clonic signs during the AED-free phase. EEG seizure onset and initial ictal signs showed no obvious changes between study phases. Withdrawal of CBZ is followed more quickly by an increase of seizure frequency and severity than is the case for VPA withdrawal. Both CBZ and VPA withdrawal influences seizure propagation rather than the seizure-onset characteristics, which speaks in favor of its use in presurgical evaluation.


Correction to: Role of MicroRNAs in Anxiety and Anxiety-Related Disorders.
The chapter 'Role of MicroRNAs in Anxiety and Anxiety-Related Disorders' has now been made available open access under a CC BY 4.0 license.


Computed axial tomography versus NMR for the diagnosis of neurocysticercosis.
A case of generalised neurocysticercosis in a 45-year-old woman is presented with CT and NMR findings. The great additional value of NMR for the diagnosis of this disease is stressed.


Oncolytic viruses as treatment for adult and pediatric high-grade gliomas: On the way to clinical success.
High-grade gliomas (HGGs) are the most common and aggressive primary brain tumors in both adult and pediatric populations. Despite the multimodal treatment modality currently available for HGG, the prognosis is dismal, with a low overall survival rate at two years after diagnosis. In the last decade, oncolytic virotherapy has emerged as a promising and feasible therapeutic tool in management of these tumors due to its oncolytic and immunostimulatory properties. Various oncolytic viruses, such as herpes simplex virus, adenovirus, poliovirus, reovirus, parvovirus and others, have been evaluated in the early stages of the clinical setting with regard to improving the outcome of patients with HGG. In this review, we summarize completed and ongoing clinical trials of oncolytic virotherapy for adult and pediatric malignant gliomas in terms of safety and efficacy, followed by a brief discussion about the current status and future directions of this therapy in the brain tumor field.


Comparative in vitro evaluation of remaining dentine thickness following instrumentation with hand and rotary endodontic files during pulpectomy in primary molars: a systematic review.
The aim was to compare the remaining dentine thickness (RDT) following instrumentation with hand and rotary endodontic files during pulpectomy in primary molars. Research question was 'Is there any difference between the remaining dentine thickness following instrumentation with hand and rotary endodontic files during pulpectomy in primary molars?'. Electronic Databases like MEDLINE PubMed, Cochrane Library, EBSCOhost, Google scholar and grey literature were searched between January 1, 2006 and August 31, 2022 for in vitro and ex vivo studies that compared hand and rotary endodontic instrumentation to evaluate the RDT in primary molars. Articles published in English or which could be translated into English were searched. Two reviewers independently selected studies, extracted data, assessed risk of bias using the Revised, validated version of MINORS criteria. Twelve studies were included in qualitative analysis. All included studies showed low risk of bias. Six studies showed more RDT with rotary instrumentation compared to manual instrumentation. Whereas, five studies showed variable results for RDT with manual and rotary instrumentation at different levels of root canals. One study showed no significant difference between manual and rotary instrumentation. In view of methodological heterogeneity of the findings, a meta-analysis was not conducted. High quality of evidence based on low risk of bias was found in all the included studies. Statistically, rotary instrumentation showed more RDT than manual instrumentation according to majority of studies. Despite the shortcomings of this systematic review, it is possible to infer that the use of rotary instrumentation provides more RDT and thus there is considerable conservation of tooth structure.


Celiac disease with mild to moderate histologic changes is a common cause of chronic diarrhea in Indian children.
In developed countries, small bowel histology in coeliac disease is a spectrum, ranging from normal with increased intraepithelial lymphocytes to the classic flat mucosa. In developing countries, mild to moderate enteropathies in children with chronic diarrhea and growth failure are assumed to be caused by tropical sprue, persistent infections, or malnutrition with bacterial overgrowth. We report the prevalence and histology of coeliac disease in children with chronic diarrhea at a tertiary referral hospital in North India. Two hundred fifty-nine children with symptoms indicating coeliac disease attended the All India Institute of Medical Sciences. Histology was graded after a modified Marsh classification. Serum immunoglobulin A anti-endomysial antibodies (AEA) were assayed using indirect immunofluorescence. Subjects with abnormal histology and positive AEA were put on a gluten free diet (GFD). Coeliac disease was diagnosed on small intestinal biopsy changes and a clinical response to a GFD. Severe enteropathies were present in 63 (24%) subjects, and 58 (92%) responded to a GFD. Sixty-six (25%) had moderate histologic changes, 61 responding to a GFD. AEA was positive in 56 of 63 patients with severe and 65 of 66 with moderate enteropathies. Fifty-seven children had mild enteropathies, and 19 of 20 with positive AEA responded clinically to a GFD. Coeliac disease is more common than previously believed. It presents a variable histology, and diagnoses may be missed or delayed if based only on severe enteropathies. Serology is a useful adjunct to diagnosis, and diagnostic criteria need to be developed appropriately for coeliac disease in developing countries despite limited facilities.


Syndrome of hyporeninemic hypoaldosteronism. Study of two cases and review of the literature.
Two patients with chronic mild to moderate renal failure presenting with unexplained hyperkalemia were studied, and found to have hyporeninemic hypoaldosteronism. Hyperkalemia, generally uncommon in nonoliguric stable renal failure, resulted from the combination of apparent insensitivity of the diseased kidney to aldosterone and variable degrees of impairment in the reninaldosterone axis. The clinical picture, the methods of establishing the diagnosis, the therapeutic alternatives and the possible pathogenetic mechanisms involved are described.


Prostaglandin EP receptors and their roles in mucosal protection and ulcer healing in the gastrointestinal tract.
Endogenous prostaglandins (PGs) play an important role in modulating the mucosal integrity and various functions of the alimentary tract, and E type PGs are most effective in these actions. PGE2 protects against acid reflux esophagitis and affords gastric cytoprotection against ethanol and indomethacin. These effects are mimicked by EP1 agonists and attenuated by an EP1 antagonist. Adaptive cytoprotection induced by mild irritants is also attenuated by the EP1 antagonist as well as indomethacin. PGs contribute to capsaicin-induced gastric cytoprotection, yet this effect is mitigated by indomethacin and sensory deafferentation but not the EP1 antagonist. Similarly, PGE2 does not exhibit gastric cytoprotection in EP1-receptor knockout mice, while capsaicin-induced protection is observed in animals lacking either EP1 receptors but disappears in IP-receptor knockout mice. In the duodenum, acid perfusion produces damage in animals lacking EP3 receptors. The protective effect of PGE2 on indomethacin-induced small intestinal damage is mimicked by both EP3 and EP4 agonists. PGE2 also shows a healing-promoting effect on gastric ulcers as well as intestinal lesions via the activation of EP4 receptors. The underlying mechanisms of these actions of PGE2 in the stomach, duodenum, or small intestine are related to inhibition of stomach contraction (EP1), stimulation of duodenal HCO3- secretion (EP3/EP4), or suppression of bacterial invasion due to inhibition of intestinal contraction (EP4) and stimulation of mucus secretion (EP3/EP4) respectively, although the mechanisms related to the esophageal protection remain unknown. Furthermore, the healing-promoting effect is associated with the stimulation of angiogenesis via an increase in VEGF expression (EP4).


Penetration of amoxicillin into cerebrospinal fluid.
The penetration of amoxicillin into cerebrospinal fluid (CFS) in the presence of meningeal inflammation was evaluated in patients with tuberculous meningitis. Serum and CSF concentrations of amoxicillin were measured at 2 h in nine patients who received a 1-g oral dose and at 1.5 and 4 h in ten patients who received a 2-g intravenous injection of sodium amoxicillin. After the oral dose, CSF concentrations ranged from 0.1 to 1.5 mug/ml. After the intravenous injection, CSF concentrations ranged from 2.9 to 40.0 mug/ml at 1.5 h and from 2.6 to 27.0 mug/ml at 4 h. These data on penetration suggest that parenterally administered sodium amoxicillin may be of value in the therapy of acute bacterial meningitis.


Human T-cell leukaemia virus type I and neurological disease.
Tropical spastic paraparesis is thought to be caused either directly by human T-cell leukaemia virus type I (HTLV-1), or by the immune response to the virus. Recent work has identified differences between tropical spastic paraparesis patients and healthy carriers of HTLV-I, both in the virus and in the host's T-cell response to the virus. These differences may provide clues to the pathogenesis of tropical spastic paraparesis.


How task-sharing in abortion care became the norm in Sweden: A case study of historic and current determinants and events.
We performed a country case study using thematic analysis of interviews and existing grey and published literature to identify facilitators and barriers to the implementation of midwife-provided abortion care in Sweden. Identified facilitating factors were: (1) the historical role and high status of Swedish midwives; (2) Swedish research and development of medical abortion that enabled an enlarged clinical role for midwives; (3) collaborations between individual clinicians and researchers within the professional associations, and the autonomy of clinical units to implement changes in clinical practice; (4) a historic precedent of changes in abortion policy occurring without prior official or legal sanction; (5) a context of liberal abortion laws, secularity, gender equality, public support for abortion, trust in public institutions; and (6) an increasing global interest in task-shifting to increase access and reduce costs. Identified barriers/risks were: (1) the lack of systems for monitoring and evaluation; and (2) a loss of physician competence in abortion care.


ADAM19 and TUBB1 Correlate with Tumor Infiltrating Immune Cells and Predicts Prognosis in Osteosarcoma.
Osteosarcoma is the most common type of primary malignant bone tumor. This study aimed to explore potential key prognostic genes and their roles in osteosarcoma. Three microarray datasets for osteosarcoma were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened by the Limma package. Functional enrichment analysis was performed based on DAVID, GeneMANIA, and Metascape databases. Prognostic value of DEGs was elevated by survival analysis. CIBERSORT was used to assess the infiltrating abundance of 22 immune cells, followed by the Pearson correlation analysis between immune cells and prognosis-related genes. Gene set enrichment analysis and drug-gene interactions prediction were performed for prognosis-related genes. A total of 8 common up-regulated DEGs and 13 common down-regulated DEGs were screened in the GSE36001 and GSE56001 datasets. Enrichment analysis showed these DEGs were implicated in platelet activation, SMAD protein phosphorylation, lymphocyte/leukocyte/T cells activation, and cell migration. Survival analysis indicated that elevated expression of ADAM19 and TUBB1 were associated with a favorable prognosis. CIBERSORT algorithm revealed the higher infiltrating level of CD8 T cells, macrophages M0, and M2 in osteosarcoma. ADAM19 expression positively correlated with naïve B cells and negatively correlated with activated dendritic cells infiltrating abundance. TUBB1 expression positively correlated with gamma delta T cells while negatively correlated with helper follicular T cells infiltrating abundance. A total of 56 drugs were found to target TUBB1. ADAM19 and TUBB1 could be prognostic biomarkers in osteosarcoma. Both their expression correlates with tumor infiltrating immune cells. TUBB1 was a multi-drug target that might be a therapeutic target in osteosarcoma.


Heart rate variability in severe right or left heart failure: the role of pulmonary hypertension and resistances.
The decrease in heart rate variability (HRV) might be related to the hemodynamic status in heart failure. However, HRV in patients with severe isolated right heart failure has not been extensively studied. This study compared HRV in patients with congestive heart failure (CHF) and in patients with isolated right heart failure. Time and frequency domain analysis of HRV on 24-h ECG recording was assessed in 15 healthy subjects and in two groups of patients with severe heart failure awaiting heart or heart/lung transplantation. These were 15 patients with CHF due to idiopathic dilated cardiomyopathy (IDC) and 10 patients with isolated right heart failure due to primary pulmonary hypertension (PPH). Measurement of HRV were significantly decreased in both groups of patients compared with the control group. Patients with IDC had higher pulmonary capillary wedge pressure than patients with PPH (P=0.04) but lower pulmonary artery pressure and lower pulmonary vascular resistance (PVR) (P<0.0001). However, all the measurements of HRV were significantly lower in patients with IDC than in patients with PPH (range 22-77%, P<0.05 to P<0.01). None of the HRV measurements correlated with filling pressure measurements. The increase in pulmonary vascular resistance in heart failure is not the main causal factor behind a decrease in HRV.


Creatine salts provide neuroprotection even after partial impairment of the creatine transporter.
Creatine, a compound that is critical for energy metabolism of nervous cells, crosses the blood-brain barrier (BBB) and the neuronal plasma membrane with difficulty, and only using its specific transporter. In the hereditary condition where the creatine transporter is defective (creatine transporter deficiency) there is no creatine in the brain, and administration of creatine is useless lacking the transporter. The disease is severe and incurable. Creatine-derived molecules that could cross BBB and plasma membrane independently of the transporter might be useful to cure this condition. Moreover, such molecules could be useful also in stroke and other brain ischemic conditions. In this paper, we investigated three creatine salts, creatine ascorbate, creatine gluconate and creatine glucose. Of these, creatine glucose was ineffective after transporter block with guanidine acetic acid (GPA) administration. Creatine ascorbate was not superior to creatine in increasing tissue creatine and phosphocreatine content after transporter impairment, however even after such impairment it delayed synaptic failure during anoxia. Finally, creatine gluconate was superior to creatine in increasing tissue content of creatine after transporter block and slowed down PS disappearance during anoxia, an effect that creatine did not have. These findings suggest that coupling creatine to molecules having a specific transporter may be a useful strategy in creatine transporter deficiency. In particular, creatine ascorbate has effects comparable to those of creatine in normal conditions, while being superior to it under conditions of missing or impaired creatine transporter.


Effect of different types of elemental sulfur on bioleaching of heavy metals from contaminated sediments.
The application of two different types of elemental sulfur (S0) was studied to evaluate the efficiency on bioleaching of heavy metals from contaminated sediments. Bioleaching tests were performed in suspension and in the solid-bed with a heavy metal contaminated sediment using commercial sulfur powder (technical sulfur) or a microbially produced sulfur waste (biological sulfur) as substrate for the indigenous sulfur-oxidizing bacteria and thus as acid source. Generally, using biological sulfur during suspension leaching yielded in considerably better results than technical sulfur. The equilibrium in acidification, sulfur oxidation and metal solubilization was reached already after 10-14 d of leaching depending upon the amount of sulfur added. The metal removal after 28 d of leaching was higher when biological sulfur was used. The biological sulfur added was oxidized with high rate, and no residual S0 was detectable in the sediment samples after leaching. The observed effects are attributable to the hydrophilic properties of the biologically produced sulfur particles resulting in an increased bioavailability for the Acidithiobacilli. In column experiments only poor effects on the kinetics of the leaching parameters were observed replacing technical sulfur by biological sulfur, and the overall metal removal was almost the same for both types of S0. Therefore, under the conditions of solid-bed leaching the rate of sulfur oxidation and metal solubilization is more strongly affected by transport phenomena than by microbial conversion processes attributed to different physicochemical properties of the sulfur sources. The results indicate that the application of biological sulfur provides a suitable means for improving the efficiency of suspension leaching treatments by shortening the leaching time. Solid-bed leaching treatments may benefit from the reuse of biological sulfur by reducing the costs for material and operating.


Assay of dopamine and its metabolites in human and rat retina.
Human and rat retina dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured after various delays in enucleation and freezing of the eyes. Human eyes were enucleated 45 min to 4 h after death, kept at 4 degrees C and frozen at -70 degrees C from 1.5 to 15 h after enucleation. In human retina, maximal DA concentration (4.85 ng/mg prot.) was obtained from eyes enucleated with a delay of 1 h and frozen with a delay of 2 h. After longer delays, DA concentrations decreased. Retinas of humans who died during the night had lower DA retina concentrations compared to those who died during daytime. Rats were decapitated and the eyes enucleated within 5 min or with a delay up to 8 h before freezing at -70 degrees C or kept at 4 degrees C for 5 min to 12 h before being frozen at -70 degrees C. Delays in enucleation of the rat eyes markedly decreased DA retinal concentrations with a minimal value reached as soon as 2 h after death. However, when the rat eyes were kept at 4 degrees C the minimal value was obtained after a longer period of time (about 7 h). Our results thus show that time of death and delays in enucleation and freezing significantly influence DA and its metabolite concentrations in retinas of rats and humans.


Goiter in pregnant teenagers.
Enlargement of the thyroid gland is common in adolescent girls, but there have been no previous reports of the frequency of goiter in pregnant teenagers. This study was undertaken to determine the prevalence of goiter in 309 consecutive pregnant adolescent patients, ages 11 to 19 years, who presented for prenatal care at the University of California (San Diego) Medical Center Teen OB Clinic. Eighteen patients (6%) were found to have a goiter. Subsequent diagnostic tests revealed that 28% of the patients had autoimmune thyroid disorders (chronic thyroiditis or Graves' disease), and the remainder had nontoxic goiters or subacute thyroiditis. Black patients had significantly more thyroid disease than Mexican-American (p less than 0.01) or white patients (p less than 0.005). The incidence of thyroid problems during pregnancy did not differ significantly from that of 600 nonpregnant teenagers who came to the general Adolescent Medicine Clinic for other health problems. Because abnormalities in thyroid function may have potentially adverse implications for mothers and their infants, we recommend careful evaluation of all pregnant teenagers with goiter to assess maternal thyroid function and to provide treatment if necessary.


The use of scintiangiography with technetium 99m in the diagnosis of traumatic pseudoaneurysm.
Pseudoaneurysm formation is a known complication of peripheral arterial access procedures. Although standard contrast angiography has been considered the diagnostic study of choice to identify pseudoaneurysms, isotope angiography has been described as an alternative method. In this study, we examined the role of 99mTc-tagged red blood cell scans in the diagnosis of traumatic pseudoaneurysm. Forty patients underwent scans; 25 scans were reported as abnormal and 15 as normal. There were no false-negative results; one scan had false-positive results (2.5%). The presence of pseudoaneurysm among the patients with abnormal scans was verified at operation in 23 of 25 patients. The one false-positive test was verified by ultrasound. All patients with normal scans were followed up for verification. Follow-up time ranged from 2 to 28 months. Radionuclide vascular flow study appears to give information similar to that of conventional angiography. With a series false-positive rate of 2.5%, the examination has a high specificity. The 99mTc-tagged red blood cell scan is a viable alternative to conventional angiography for the diagnosis of traumatic pseudoaneurysms and is associated with less radiation and morbidity.


The use of a 'phantom scalp' to assess the possible direct pickup of mobile phone handset emissions by electroencephalogram electrode leads.
A 'Phantom Scalp' was constructed from a conducting foam mat to form a layer under a 62-electrode electroencephalogram cap closely approximating the electrical properties of a human scalp. The mat was placed over a polystyrene manikin head to preserve a correct anatomical arrangement. Electrical signals were recorded with a Global System for Mobile (GSM) communications mobile phone handset in place against the side of the 'head'. Amplitude spectra were compared for three phone conditions: 'off', 'standby' and 'transmit'. At 217 Hz, significant differences were obtained between 'transmit' and the other two conditions, but no significant differences were noted for the physiologically important range 0.5-30 Hz. An anomalous difference was noted for one electrode in the range 30-45 Hz.


Linear mixed effects models.
Statistical models provide a framework in which to describe the biological process giving rise to the data of interest. The construction of this model requires balancing adequate representation of the process with simplicity. Experiments involving multiple (correlated) observations per subject do not satisfy the assumption of independence required for most methods described in previous chapters. In some experiments, the amount of random variation differs between experimental groups. In other experiments, there are multiple sources of variability, such as both between-subject variation and technical variation. As demonstrated in this chapter, linear mixed effects models provide a versatile and powerful framework in which to address research objectives efficiently and appropriately.


Anaesthetic management of an emergency caesarean section in a complex immunologically compromised patient with pre-eclampsia and multifactorial thrombocytopaenia.
A 35-year-old gravida 3, para 0 woman required an emergency caesarean section for pre-eclampsia with severe features including a platelet count of 7 × 109.l-1. The patient's thrombocytopaenia was an acute on chronic presentation. In addition to pre-eclampsia, the patient had a complex background history which included autoimmune lymphoproliferative syndrome, the manifestations of which include autoimmune cytopaenias and recurrent infections. The patient also had common variable immune deficiency and acquired C1-esterase inhibitor deficiency which may cause life-threatening angioedema, including of the airway. In this report, we describe the potential anaesthetic challenges posed by this pre-eclamptic, immunologically compromised patient with severe thrombocytopaenia and the potential for difficult airway, and how these were addressed in a safe and timely manner. Specifically, we highlight the important considerations when performing a general anaesthetic in this unique combination of circumstances. Although the patient's conditions are rare, this case demonstrates that early multidisciplinary team input can help successfully guide the management of medically complex pregnant patients.


Mutation-driven epigenetic alterations as a defining hallmark of central cartilaginous tumours, giant cell tumour of bone and chondroblastoma.
Recently, specific driver mutations were identified in chondroblastoma, giant cell tumour of bone and central cartilaginous tumours (specifically enchondroma and central chondrosarcoma), sharing the ability to induce genome-wide epigenetic alterations. In chondroblastoma and giant cell tumour of bone, the neoplastic mononuclear stromal-like cells frequently harbour specific point mutations in the genes encoding for histone H3.3 (H3F3A and H3F3B). The identification of these driver mutations has led to development of novel diagnostic tools to distinguish between chondroblastoma, giant cell tumour of bone and other giant cell containing tumours. From a biological perspective, these mutations induce several global and local alterations of the histone modification marks. Similar observations are made for central cartilaginous tumours, which frequently harbour specific point mutations in the metabolic enzymes IDH1 or IDH2. Besides an altered methylation pattern on histones, IDH mutations also induce a global DNA hypermethylation phenotype. In all of these tumour types, the mutation-driven epigenetic alterations lead to a highly altered transcriptome, resulting for instance in alterations in differentiation. These genomic alterations have diagnostic impact. Further research is needed to identify the genes and signalling pathways that are affected by the epigenetic alterations, which will hopefully lead to a better understanding of the biological mechanism underlying tumourigenesis.


Four cDNA clones from the Shaker locus of Drosophila induce kinetically distinct A-type potassium currents in Xenopus oocytes.
The Shaker gene encodes the A-channel of larval and pupal muscle, or one or more of its subunits. Alternative splicing produces messages for several different proteins; two mRNA species have previously been shown to induce the expression of A-currents in Xenopus oocytes. Two additional mRNAs have now been tested and found to produce A-currents in oocytes. The four currents differ in kinetics of inactivation, indicating that the Shaker products may contribute to kinetic diversity in A-channels of the fly and that sequences in both the amino- and carboxy-terminal regions are important for inactivation.


Differences in the floral anthocyanin content of red petunias and Petunia exserta.
In order to resolve a conflict between previous papers regarding the floral anthocyanins of red flowers of Petunia exserta, a naturally occurring species, the HPLC profile of this species was compared with that of commercial red garden petunias. Both HPLC profiles extremely superficially resemble each other in terms of relative amounts and retention times of the major anthocyanins. However, co-elution on HPLC of the mixed sample resulted in clear separation of the components. Three major anthocyanins in red petunias were determined to be cyanidin 3-sophoroside, cyanidin 3-glucoside and peonidin 3-glucoside, which exhibited similar behaviors on HPLC to delphinidin 3-glucoside. delphinidin-3-rutinoside and petunidin 3-rutinoside, respectively, the major floral anthocyanins of P. exserta.


Chromosome mapping of the rod photoreceptor cGMP phosphodiesterase beta-subunit gene in mouse and human: tight linkage to the Huntington disease region (4p16.3).
The retinal degeneration mouse (gene symbol, rd) is an animal model for certain forms of human hereditary retinopathies. Recent findings of a nonsense mutation in the rd mouse PDE beta-subunit gene (Pdeb) prompted us to investigate the chromosome locations of the mouse and human genes. We have utilized backcross analysis in mice to verify and define more precisely the location of the Pdeb locus 6.1 +/- 2.3 cM distal of Mgsa on mouse chromosome 5. We have determined that the human gene (PDEB) maps to 4p16.3, very close to the Huntington disease (HD) region. Analysis of the comparative map for mice and humans shows that the mouse homologue of the HD gene will reside on chromosome 5. Linkage of the mouse Pdeb locus with other homologues in the human 4p16.3 region is maintained but gene order is not, suggesting at least three possible sites for the corresponding mouse HD gene.


The effect of chronic physical exercise on succinic dehydrogenase activity in the heart muscle of old rats.
Succinic dehydrogenase (SDH) activity, preferentially evidenced by cytochemical methods, has been measured by computer-assisted morphometry in the heart muscle of old sedentary and age-matched animals chronically undergone physical exercise (20 min, twice a day, 5 days a week). The area of the SDH-positive mitochondria (MA) and the overall area of the cytochemical precipitates due to SDH activity (PA) were semiautomatically measured and the ratios PA/MA as well as MA/overall myocardial tissue area analysed (MA/TA) were the parameters taken into account. No significant difference was found between the two groups investigated as regards PA/MA, whereas the MA/TA value is significantly increased in the animals undergone physical training. The present findings document that chronic physical exercise significantly increases the overall mitochondrial area involved in energy provision in the old myocardial tissue. Considering that myocardial function highly relies on mitochondrial metabolism, our results support a beneficial effect of chronic physical exercise on the old heart muscle.


VhaAC39-1 regulates gut homeostasis and affects the health span in Drosophila.
Gut homeostasis is a dynamically balanced state to maintain intestinal health. Vacuolar ATPases (V-ATPases) are multi-subunit proton pumps that were driven by ATP hydrolysis. Several subunits of V-ATPases may be involved in the maintenance of intestinal pH and gut homeostasis in Drosophila. However, the specific role of each subunit in this process remains to be elucidated. Here, we knocked down the Drosophila gene VhaAC39-1 encoding the V0d1 subunit of V-ATPases to assess its function in gut homeostasis. Knockdown of VhaAC39-1 resulted in the loss of midgut acidity, the increase of the number of gut microbiota and the impairment of intestinal epithelial integrity in flies. The knockdown of VhaAC39-1 led to the hyperproliferation of intestinal stem cells, increasing the number of enteroendocrine cells, and activated IMD signaling pathway and JAK-STAT signaling pathway, inducing intestinal immune response of Drosophila. In addition, knockdown of VhaAC39-1 caused the disturbance of many physiological indicators such as food intake, triglyceride level and fecundity of flies, which ultimately led to the shortening of the life span of Drosophila. These results shed light on the gut homeostasis mechanisms which would help to identify interventions to promote healthy aging.


The efficacy of polyphenols as an antioxidant agent: An updated review.
Global production of the two major poultry products, meat and eggs, has increased quickly. This, in turn, indicates both the relatively low cost and the customers' desire for these secure and high-quality products. Natural feed additives have become increasingly popular to preserve and enhance the health and productivity of poultry and livestock. We consume a lot of polyphenols, which are a kind of micronutrient. These are phytochemicals with positive effects on cardiovascular, cognitive, anti-inflammatory, detoxifying, anti-tumor, anti-pathogen, a catalyst for growth, and immunomodulating functions, among extra health advantages. Furthermore, high quantities of polyphenols have unknown and occasionally unfavorable impacts on the digestive tract health, nutrient assimilation, the activity of digestive enzymes, vitamin and mineral assimilation, the performance of the laying hens, and the quality of the eggs. This review clarifies the numerous sources, categories, biological functions, potential limitations on usage, and effects of polyphenols on poultry performance, egg composition, exterior and interior quality traits.


Relationship between reproductive allocation and relative abundance among 32 species of a Tibetan alpine meadow: effects of fertilization and grazing.
Understanding the relationship between species traits and species abundance is an important goal in ecology and biodiversity science. Although theoretical studies predict that traits related to performance (e.g. reproductive allocation) are most directly linked to species abundance within a community, empirical investigations have rarely been done. It also remains unclear how environmental factors such as grazing or fertilizer application affect the predicted relationship. We conducted a 3-year field experiment in a Tibetan alpine meadow to assess the relationship between plant reproductive allocation (RA) and species relative abundance (SRA) on control, grazed and fertilized plots. Overall, the studied plant community contained 32 common species. At the treatment level, (i) RA was negatively correlated with SRA on control plots and during the first year on fertilized plots. (ii) No negative RA-SRA correlations were observed on grazed plots and during the second and third year on fertilized plots. (iii) Seed size was positively correlated with SRA on control plots. At the plot level, the correlation between SRA and RA were not affected by treatment, year or species composition. Our study shows that the performance-related trait RA can negatively affect SRA within communities, which is possibly due to the tradeoffs between clonal growth (for space occupancy) and sexual reproduction. We propose that if different species occupy different positions along these tradeoffs it will contribute to biodiversity maintenance in local communities or even at lager scale.


Ultrasonographic Examination of the Equine Neonate: Thorax and Abdomen.
Diagnostic imaging can substantially augment physical examination findings in neonatal foals. Used in combination with radiography or as a stand-alone imaging modality, ultrasound evaluation of the thoracic and abdominal body cavities can be a high-yield diagnostic undertaking. Many of the conditions that afflict neonatal foals are highly amenable to sonographic interrogation, including pneumonia and other changes in the lungs associated with sepsis, systemic inflammatory response syndrome, multiple organ dysfunction, and prematurity; colic arising from medical and surgical causes; and urinary tract disorders. Sonographic imaging is not affected by intracavitary fluid accumulation and reveals abnormalities of soft tissue and bony origin.


Epidemiological Characteristics of Pancreatic Cancer in China From 1990 to 2019.
Pancreatic cancer is an aggressive cancer and is predicted to become the second leading cause of cancer-related deaths in China. To understand the epidemic trend of pancreatic cancer and formulate targeted preventive measures, it is important to analyze the incidence and mortality of pancreatic cancer. The incidence and mortality data of pancreatic cancer in China were obtained from Global Burden of Disease (GBD) data. We used joinpoint regression analysis to calculate the magnitude and direction of trends, and the age-period-cohort method to analyze the effects of chronological age, time period, and birth cohort. The age-standardized rates (ASRs) for both incidence and mortality of pancreatic cancer increased from 1990 to 2019, and were higher in males than females. The incidence and mortality rates have increased year by year in the age group above 25 years. The most common age group was 55-79 years, accounting for approximately 50% of all incident cases. In terms of incidence and mortality rates, the overall net drifts were above 0. The local drifts in all age groups were above 0 in both sexes and males, while the local drifts in the 15-39 age groups were below 0 in females. The longitudinal age curves increased with age, with higher incidence and mortality rates, mainly in older age groups. The period rate ratios increased by year. The cohort rate ratios showed an upward trend before 1970 and fluctuated after 1975. The burden of pancreatic cancer is still very high in China, and attention should be paid to the key population that is, males and older people. The results of our study can be used by policy makers to allocate resources efficiently to improve early diagnosis and treatment, improving the awareness of self-protection, and advocating a healthy lifestyle to prevent pancreatic cancer.


Poly ICL-CM dextran: an interferon inducer of reduced toxicity.
We have prepared soluble complexes of poly ICL-CM dextran that are as effective interferon IFN inducers, in mice and in rhesus monkeys, as poly ICLC. Toxicity testing was carried out in mice and, poly ICL-CM dextran is less toxic, in mice, than poly ICLC is.


The Epstein-Barr virus BFRF1 and BFLF2 proteins interact and coexpression alters their cellular localization.
The BFRF1 protein of Epstein-Barr virus (EBV) is a recently identified membrane protein that is the homolog of the alphaherpesvirus UL34 gene product. We report here that a yeast two-hybrid screen identified the BFLF2 gene product, a homolog of alphaherpesvirus UL31, as a protein that interacts with BFRF1. Expression of BFLF2 in mammalian cells revealed a protein of approximately 28 kDa that associated with BFRF1 in a noncovalently linked complex. When expressed alone, the BFRF1 protein was found in the cytoplasm and perinuclear region. BFLF2 was found diffusely in the nucleus in the absence of BFRF1, but coexpression of BFRF1 and BFLF2 resulted in colocalization of the two proteins at the nuclear rim. These data recapitulate the behavior of the alphaherpesvirus homologs of BFRF1 and BFLF2 and suggest that functional as well as structural and positional homology may be conserved.


Surveillance and Early Management of Deep Vein Thrombosis Decreases Rate of Pulmonary Embolism in High-Risk Trauma Patients.
Venous duplex ultrasound (VDU) is the modality of choice for surveillance of venous thromboembolism (VTE), but there is controversy about its appropriate implementation as a screening method. We hypothesize that VDU surveillance in trauma patients at high risk for VTE decreases the rate of pulmonary embolism (PE). One thousand two hundred and eighty-two trauma ICU admissions were screened with Greenfield's Risk Assessment Profile from August 2011 to September 2014. Four hundred and two patients were identified as high risk for VTE (Risk Assessment Profile ≥10). Those who received weekly VDU to evaluate for deep vein thrombosis (n = 259 [64%]) were compared with those who did not (n = 143 [36%]). Parametric data are reported as mean ± SD and nonparametric data are reported as median (interquartile range). Statistical significance was determined at an α level of 0.05. The overall study population was 47 ± 19 years old and 75% were male, 78% of injuries were blunt mechanism, Injury Severity Score was 28 ± 13, Risk Assessment Profile was 14 ± 4, and mortality was 14.3%. Deep vein thrombosis rate was 11.6% (n = 30) in the surveillance group vs 2.1% (n = 3) in the non-surveillance group (p < 0.001). Deep vein thromboses detected in the surveillance group were managed with systemic anticoagulation (43%) or with IVC filter placement (57%). In the surveillance group, the PE rate was 1.9% (n = 5) vs 7.0% (n = 10) in the non-surveillance group (p = 0.014). Trauma patients at high risk for VTE and who received VDU surveillance and early management of deep vein thrombosis have decreased rates of pulmonary embolism.


Emerging Perspectives on Resource Tracking and Animal Movement Ecology.
Resource tracking, where animals increase energy gain by moving to track phenological variation in resources across space, is emerging as a fundamental attribute of animal movement ecology. However, a theoretical framework to understand when and where resource tracking should occur, and how resource tracking should lead to emergent ecological patterns, is lacking. We present a framework that unites concepts from optimal foraging theory and landscape ecology, which can be used to generate and test predictions on how resource dynamics shape animal movement across taxa, systems, and scales. Consideration of the interplay between animal movement and resource dynamics not only advances ecological understanding but can also guide biodiversity conservation in an era of global change.


[Osteocartilaginous autograft after proximal resection of the scaphoid for radioscaphoid osteoarthritis].
Radioscaphoid osteoarthritis is usually a complication of scaphoid pseudarthrosis or chronic scapholunate disjunction. As an alternative to the classical surgical techniques used for this lesion, we propose a novel reconstruction method consisting In partial proximal resection of the scaphoid associated with interposition of a biological spacer composed of a osteocartilaginous rib graft. The purpose of this study was to present the technical aspects of this procedure and to report preliminary results in ten patients with radioscapular osteoarthritis treated between 1994 and 2001. We performed a retrospective analysis of the ten patients who underwent surgery from 1994 to 2001 for early-stage radioscaphoid osteoarthritis associated with scaphoid osteoarthritis in eight and chronic scapholunate disjunction in two. The procedure consisted in partial resection of the proximal portion of the scaphoid and insertion of an osteocartilaginous autograft harvested from a rib. Outcome was based on the clinical results (pain, motion, grip force, activity) and patient satisfaction. Bone healing was measured with plain x-rays and vitality of the osteocartilaginous graft with MRI. Mean follow-up was 4.6 years. Clinical outcome was considered excellent or good in eight patients, fair in one and poor in one (graft dislocation). All patients were satisfied or very satisfied except one (one failure). Radiological healing was achieved at three months in nine patients. Four patients underwent an MRI examination at thirteen months which demonstrated, in all patients: no sign of necrosis, healing of the graft-scaphoid interface, and no bony metaplasia in the cartilage. Compared with partial carpal arthrodesis and resection of the first row of the carpus, this palliative technique can be used to reconstruct the proximal portion of the carpal scaphoid in young patients with early-stage radioscaphoid osteoarthritis. As for arthroplasty or scaphoid implants, our goal was to achieve a satisfactory scaphoid height using a biological spacer after resection of the proximal 3/4 of the bone. The results of this technique are encouraging but must be examined with precaution due to the small number of patients and the short follow-up to date.


Amyotrophic lateral sclerosis and non-tau frontotemporal lobar degeneration.
Amyotrophic lateral sclerosis (ALS) is the major motor neuron disorder. The hallmark features are progressive, irreversible motor neuron loss leading to denervation atrophy of muscles and death, usually within 5 years of disease onset. The hallmark proteins of the pathognomonic inclusions are SOD-1, TDP-43, or FUS; rarely the disease is caused by mutation of the respective genes. Frontotemporal lobar degeneration (FTLD) is genetically, neuropathologically, and clinically heterogeneous and may present as a dementia with three major clinical syndromes dominated by behavioral, language, and motor disorders, respectively. The characteristic aggregate-forming protein in non-tau FTLD is either TDP-43 or FUS. It has been known for several years that frontotemporal dementia (or less severe forms of cognitive impairment) may coexist with ALS. Recent discoveries in genetics (e.g., C9orf72 mutation) and the subsequent neuropathologic characterization have revealed remarkable overlap between ALS and non-tau FTLD also at a molecular level, indicating common molecular pathways in pathogenesis. After a historic overview we demonstrate and compare the macroscopic and microscopic appearances and molecular characteristics with emphasis on genetic background, neuroanatomic distribution, and morphology of abnormal protein aggregates and their possible association with specific mutations. The clinicopathologic classifications and correlations are also discussed.


Migraine in patients with stroke and antiphospholipid antibodies.
The association between migraine and antibodies against antiphospholipids is controversial. We investigated the prevalence and the clinical feature of migraine in patients with ischemic stroke and antiphospholipid antibodies. Data were obtained from the medical records of 162 consecutive patients with ischemic stroke over a 2-year period. Ten patients with antiphospholipid antibodies were prospectively identified. A history of migraine was present in 6 of these patients and in only 5 of the 152 patients with negative results for antiphospholipid antibodies (chi-square = 47.68; P < .0001). In the former, migraine had been for a long time the only clinical problem before the occurrence of the ischemic stroke. These findings suggest that migraine is frequent and can be an early and a prominent symptom in the antiphospholipid antibodies syndrome. Further studies are needed to fully elucidate the association of migraine and antiphospholipid antibodies. A better knowledge of this association could allow an early identification of patients at high risk of stroke.


The Current Status of the Surgical Management of Complex Spinal Cord Lipomas: Still Navigating the Labyrinth?
This review summarises the classification, anatomy and embryogenesis of complex spinal cord lipomas and describes in some detail the technique of total lipoma resection and radical reconstruction of the affected neural placode. Its specific mission is to tackle two main issues surrounding the management of complex dysraphic lipomas: whether total resection confers better long-term benefits than partial resection and whether total resection does better than conservative treatment, i.e. no surgery, for asymptomatic lipomas. Accordingly, the 24-year progression-free survival data of the senior author and colleagues' series of over 300 cases of total resection are compared with historical data from multiple series (including our own) of partial resection, and total resection data specifically for asymptomatic lesions are compared with the two known series of non-surgical treatment of equivalent patients. These comparisons so far amply support the author's recommendation of total resection for most complex lipomas, with or without symptoms. The notable exception is the asymptomatic chaotic lipoma, whose peculiar anatomical relationship with the neural tissue defies even our aggressive surgical approach, and consequently projects worse results (admittedly of small number of cases) than for the other two lipoma subtypes of dorsal and transitional lesions. Prophylactic resection of asymptomatic chaotic lipomas is therefore not currently endorsed. We have also recently found that some dorsal lipomas with clear outline of the conus on preoperative imaging had a significantly better long-term prognosis of preserving neurourological functions without surgery. Whether this subset of lipomas should be managed conservatively until symptoms arise is now an open question awaiting a longer follow-up of a larger cohort of such patients.


Genetics of cell fusion: human chromosome 10 assignment of a gene (FUSE) that promotes polykaryocyte formation.
FUSE, a human gene which promotes polykaryocyte formation, has been identified and examined in cocultivation assays between rat XC cells and human-mouse hybrids retaining different combinations of human chromosomes. Polykaryocyte formation was never detected when parental cells of hybrids were cocultivated with XC cells. Somatic genetic synteny analysis employing different hybrid sets demonstrated that FUSE was coexpressed with the chromosome 10 markers glutamate oxaloacetate transaminase (GOTs) and an external membrane protein (EMP-130). Cytogenetic analysis confirmed this assignment to human chromosome 10. FUSE was expressed by hybrids made with both human leukocytes and fibroblasts from several individuals, indicating the gene is found in different tissues and may be ubiquitous. Only XC cells were involved in polykaryocyte formation as demonstrated by 33258 Hoechst staining and the absence of heteropolymers between rat and cell hybrid multimeric enzymes. Evidence suggests that the gene FUSE produces a nondiffusible and noninfectious product that is associated with the human-mouse hybrid surface.