Opioid dependence disorder and comorbid chronic pain: comparison of groups based on patient-attributed direction of the causal relationship between the two conditions.
Chronic pain is highly prevalent in treatment-seeking opioid-dependent patients; therefore, this comorbid presentation is an important clinical consideration for both addiction and pain specialists. The objectives of the present study were to examine whether the direction of causal attribution of opioid dependence disorder and chronic pain resulted in two distinct clinical populations, and, if so, to compare treatment received during the 5-year follow-up period. Participants comprised opioid-dependent patients with chronic pain who reported a perceived causal relationship, in either direction, between the development of these two conditions (n = 252). A range of health- and addiction-related instruments were used at study inception. Treatment characteristics were obtained for the follow-up period from national health registers. Those reporting that pain caused opioid dependence disorder (n = 174; 69%) were characterised by poorer pain-related health, more illicit cannabinoid use (p = 0.031), more frequent illicit use of opioid analgesics (p = 0.025) and they were in receipt of higher doses of prescribed opioid analgesics. Those reporting that opioid dependence disorder caused pain (n = 78; 31%) were characterised by poorer overall physical health (p = 0.002), more severe psychiatric symptoms and more overall drug use (p = 0.001). Two distinct clinical populations were identified, determined by how participants perceive the causal relationship between opioid dependence disorder and chronic pain. These two populations have differing clinical profiles and treatment requirements: those reporting that pain caused opioid dependence disorder were characterised by poorer pain-related health and more illicit use of drugs with analgesic properties; and those reporting that opioid dependence disorder caused pain were characterised by more overall use of substances, multiple substance use and more intravenous substance use and poorer general health. Identifying the causal direction, where such a relationship exists, could help addiction and pain services to develop more effective, individualised treatment strategies.


Treatment of acetaminophen-induced hepatitis and fulminant hepatic failure with extracorporeal sorbent-based devices.
When a patient with acetaminophen overdose arrives in the emergency room more than 14 hours after ingestion, the value of N-acetylcysteine is unproven and patient mortality is at least 10%. Anecdotal case reports have indicated benefit of extracorporeal detoxification of these late-arriving patients with acetaminophen overdose. We identified 10 patients with serious acetaminophen overdose, 8 that arrived in the emergency room 16 to 44 hours after acetaminophen overdose with plasma levels predicting severe hepatic toxicity, and 2 that arrived in the emergency room 8 to 12 hours after overdose but with exceedingly high levels. All patients developed severe hepatitis (mean peak alanine aminotransferase, 4,052; mean peak protime, 25 seconds). At 16 to 68 hours after overdose, the patients were treated for 4 to 6 hours with the Liver Dialysis System (Hemocleanse Inc, W. Lafayette, IN), a single-access hemodiabsorption system indicated for treatment of serious drug overdose and for treatment of hepatic encephalopathy. Acetaminophen levels fell an average of 73% during treatment. Treatment was repeated 24 or 48 hours later if acetaminophen was still measurable in plasma. All 10 patients recovered intrinsic liver function and general health, with liver enzymes starting to normalize 24 hours after treatment, and were discharged 3 to 7 days after overdose. No patient required liver transplant. Because market introduction of Liver Dialysis, there have been 40 more patients with acetaminophen-induced hepatotoxicity treated with Liver Dialysis. All have recovered liver function without long-term sequelae. Though most of these patients with already established hepatic toxicity from acetaminophen would recover without extracorporeal blood therapy, treatment with the Liver Dialysis System should assure recovery from acute hepatic failure, and may shorten the clinical course of the illness.


Evaluation of Cardiopulmonary Resuscitation Conditions in Turkey: Current Status of Code Blue.
Globally, previously determined teams activated by 'code blue' calls target rapid and organised responses to medical emergency situations. This study aimed to evaluate the cardiopulmonary resuscitation (CPR) conditions in Turkey. A web-based survey was sent to anaesthesiologists in Turkey via email. The survey included 36 questions about demographic features and 'code blue' practices and procedures. A total of 180 participants were included. The mean working duration was 16.1±7.5 years. Of the anaesthesiologists who participated, 35% worked in university, 26.1% in education and research, 1.7% in city hospitals, 18.9% in state hospitals and 18.3% in private hospitals; 68.3% had CPR certification. There were code blue systems in 97.6% of the organisations. For code blue calls, 71.9% were activated by calling '2222'. There were 41.5% organisations with code blue teams of 3-4 people, whereas 26.7% had 2-member teams. Among call responders, 68.5% were anaesthesia technicians/paramedics, 60.7% were anaesthesiologists and 42.7% were anaesthesia assistants. In organisations, 66.3% regularly conducted code blue training. In total, 63.3% of the participants stated that the time to reach the location was nearly 2-4 minutes. During CPR, the use of capnography was 18.3%. Of the participants, 73.8% chose endotracheal intubation as priority airway device during CPR. Today, code blue practice is an important quality criterion for hospitals. This study shows the current status of 'code blue' according to the results of respondent data completing the survey. To prevent in-hospital cardiac arrest, a chain of preventive measures should be established, including personnel training, monitoring of patients, recognition of patient deterioration, the presence of a call for help system and effective intervention.


The role of epigenetics in the biology of multiple myeloma.
Several recent studies have highlighted the biological complexity of multiple myeloma (MM) that arises as a result of several disrupted cancer pathways. Apart from the central role of genetic abnormalities, epigenetic aberrations have also been shown to be important players in the development of MM, and a lot of research during the past decades has focused on the ways DNA methylation, histone modifications and noncoding RNAs contribute to the pathobiology of MM. This has led to, apart from better understanding of the disease biology, the development of epigenetic drugs, such as histone deacetylase inhibitors that are already used in clinical trials in MM with promising results. This review will present the role of epigenetic abnormalities in MM and how these can affect specific pathways, and focus on the potential of novel 'epidrugs' as future treatment modalities for MM.


[Controversies in surgical treatment of advanced ovarian cancer].
Cytoreductive surgery has traditionally been regarded as a cornerstone in the primary treatment of advanced ovarian cancer. Both five year survival and median survival are better for patients with small residual masses. Despite many similar reports showing the prognostic significance of postoperative residual tumour, the survival benefits of cytoreductive surgery still remain scientifically unproven and controversial. There have been no prospective controlled clinical trials. The question remains as to whether the observed survival benefits for patients subjected to primary cytoreductive surgery are an effect of surgery skills or tumour biology. The proponents of tumour biology claim that cytoreductive surgery is a selective procedure and that patients with better prognosis are selected. Therefore a randomized study between primary cytoreduction and neoadjuvant chemotherapy in patients that cannot be optimally cytoreduced seems warranted, though one problem with such a study is how to select eligible patients. During chemotherapy and after relapse several types of operations are used in ovarian cancer: secondary cytoreductive surgery, interval cytoreductive surgery, second-look surgery and palliative secondary surgery. So far interval cytoreductive surgery during chemotherapy is the only type of operation which in a prospective randomized study showed significant improvement in long-term survival. This paper discusses indirect evidence in the literature in support of or in contradiction to the primary debulking hypotheses and also indications and impact of surgical procedures during chemotherapy.


Investigation of Filter Cake Evolution in Carbonate Formation Using Polymer-Based Drilling Fluid.
Drilling fluid and filtrates invasion often alter the near-wellbore flow properties during overbalanced drilling. The utilization of polymeric gels to prevent drilling fluid loss reduces the risk of formation damage caused by this alteration. In this study, the internal and external filter cake evolution by polyacrylamide (PAM) cross-linked with polyethylenimine (PEI) was investigated. The analysis conducted in this study showed that the cross-linked polymer activates and forms a mature gel inside the formation's pores. Gel also formed a dense uniform structure on the rock's surface, preventing further fluid loss. A high sealing pressure of up to 1000 psi was achieved, allowing drilling to continue without the need for additional casing string to prevent lost circulation. Moreover, the PAM/PEI formula showed less invasion of filtrate and evolution of a thin shallow internal filter cake that penetrated less than half of the filter disk thickness. In comparison to the full invasion and particle depositions that occurred with the water-based mud (WBM), the PAM/PEI formula is expected to reduce the impact of lost circulation materials (LCMs) on formation damage.


Sexual epigenetics: gender-specific methylation of a gene in the sex determining region of Populus balsamifera.
Methylation has frequently been implicated in gender determination in plants. The recent discovery of the sex determining region (SDR) of balsam poplar, Populus balsamifera, pinpointed 13 genes with differentiated X and Y copies. We tested these genes for differential methylation using whole methylome sequencing of xylem tissue of multiple individuals grown under field conditions in two common gardens. The only SDR gene to show a marked pattern of gender-specific methylation is PbRR9, a member of the two component response regulator (type-A) gene family, involved in cytokinin signalling. It is an ortholog of Arabidopsis genes ARR16 and ARR17. The strongest patterns of differential methylation (mostly male-biased) are found in the putative promoter and the first intron. The 4th intron is strongly methylated in both sexes and the 5th intron is unmethylated in both sexes. Using a statistical learning algorithm we find that it is possible accurately to assign trees to gender using genome-wide methylation patterns alone. The strongest predictor is the region coincident with PbRR9, showing that this gene stands out against all genes in the genome in having the strongest sex-specific methylation pattern. We propose the hypothesis that PbRR9 has a direct, epigenetically mediated, role in poplar sex determination.


Quantitative assay for totipotent reconstituting hematopoietic stem cells by a competitive repopulation strategy.
Although hematopoiesis is known to originate in a population of very primitive cells with both lymphopoietic and myelopoietic potential, a procedure for enumerating such cells has to date not been available. We now describe a quantitative assay for long-term repopulating stem cells with the potential for reconstituting all hematopoietic lineages. This assay has two key features. The first is the use of competitive repopulation conditions that ensure not only the detection of a very primitive class of hematopoietic stem cells but also the survival of lethally irradiated mice transplanted with very low numbers of such cells. The second is the use of a limiting-dilution experimental design to allow stem cell quantitation. The assay involves transplanting limiting numbers of male "test" cells into lethally irradiated syngeneic female recipients together with 1-2 x 10(5) syngeneic female marrow cells whose long-term repopulating ability has been compromised by two previous cycles of marrow transplantation. The proportion of assay recipients whose regenerated hematopoietic tissues are determined to contain greater than or equal to 5% cells of test cell origin (male) greater than or equal to 5 weeks later is then used to calculate the frequency of competitive repopulating units (CRU) in the original male test cell suspension (based on Poisson statistics). Investigation of this assay system has shown that all three potential sources of stem cells (test cells, compromised cells, and the host) can under appropriate circumstances contribute to long-term hematopoietic regeneration, thus establishing both the competitive pressure of hematopoietic stem cells in the cotransplanted compromised population and in the host, and the need to use genetic markers to track the specific contribution of the injected test cells. Analysis of the frequency of CRU in test marrow suspensions that varied widely in their CRU content gave similar values when endpoints of either 5 or 10 weeks posttransplantation were used and when either recipient marrow or thymus was used to identify progeny populations. In addition, repopulation of marrow and thymus was found to be associated in most mice injected with limiting numbers of test cells. These findings are consistent with the conclusion that the assay is highly selective for a very primitive, totipotent, reconstituting hematopoietic stem cell and should therefore be particularly useful in future gene therapy-oriented research as well as for more basic studies of hematopoietic stem cell regulation and differentiation.


Effect of quinidine on cation exchange in cultured cells.
The effects of quinidine on membrane ion exchange were examined using monolayer cultures of mammalian cells. Quinidine, in concentrations from 10(-6) to 10(-3) M, produced a prompt inhibition of the passive Na influx, dose-dependent along a sigmoid log dose-response curve. This effect was at a maximum for each concentration of the drug within 30 seconds of application. Passive Na influx (pmol/cm2/sec) decreased from 18.8 to 17.6 (P less than .05) and 10.5 (P less than .001) in the presence of 10(-6) and 10(-3) M quinidine, respectively. In the continued presence of quinidine, there was no further time-dependent effect on the Na influx, nor was there any tendency for the influx to recover. Washing the cells free of quinidine, however, resulted in a return of Na influx to control levels within 1 to 3 minutes. After 1 to 2 minute of quinidine treatment, coupled active Na efflux/K influx rapidly declined, reaching minimum values for each concentration between 2 to 4 minutes of drug treatment. Beyond that time, active Na/K fluxes again increased, but to values which remained significantly less than control, for up to 4 hours. Ten minutes of exposure to quinidine were required before any demonstrable effect on the passive K efflux could be recorded. In the presence of quinidine, there was reduced membrane turnover of both Na and K, but such that after a brief initial period (10 minutes or less) both ions were in flux equilibrium, explaining the absence of change in [Nai] and [Ki] in the presence of quinidine. Calculations of Ec1 indicated that, when present for 4 hours, quinidine did not change the Em in these cells although significant (P less than .001) reductions in apparent PNa and Pk values were recorded. The effect on PNa was much greater than that on Pk. The quinidine-induced flux changes occurred in a definite temporal sequence suggesting that they could all be explained on the basis of one direct initial action. This initial direct action, namely the prompt reduction in Na influx, by modifying Na pump activity, could lead to a decreased K efflux, secondary to the depressed Na-coupled active K influx via the Na pump.


Quenching and Enhancement Effects of ATP Extractants, Cleansers, and Sanitizers on the Detection of the ATP Bioluminescence Signal †.
Techniques for measuring ATP bioluminescence are being used widely as rapid methods for the assessment of the cleanliness of food-processing plants. Sanitizer or cleanser residues could present a potential problem in the use of these ATP bioluminescence techniques due to the degradation of the firefly luciferin-luciferase substrate-enzyme system by these cleaning chemicals. The objectives of this study were the evaluation of the quenching and enhancement effects on the detection of the ATP bioluminescence signal using various ATP extractants, commercial cleansers, and sanitizers, and the determination of the antimicrobial properties of different concentrations of cleansers and sanitizers on Escherichia coli OI57:H7, Listeria monocytogenes , Staphylococcus aureus , and Pseudomonasfragi . Extractants evaluated were benzalkonium chloride, Triton X-100,benzethonium chloride, cetylpyridinium chloride, and trichloroacetic acid. Cleansers evaluated were an alkaline foam and an acid foam. Also evaluated were a quaternary ammonium sanitizer, a d-limolene sanitizer, commercial sodium hypochlorite, and household bleach (sodium hypochlorite). The extractant cetylpyridinium chloride (0.0125%) did not have a statistically significant effect on the detection of the ATP bioluminescence signal at a 95% confidence level. A transition from enhancement to quenching as a concentration-dependent phenomenon was observed for the alkaline foam, acid foam, commercial sodiumhypochlorite,d-limolene,and household bleach. An enhancement effect that did not appear to be concentration-dependent was observed for the quaternary ammonium sanitizer. Antimicrobial disc assays demonstrated that in some cases the cleanser or sanitizer concentration was not effective against the bacteria, but enhanced or quenched the detection of the bioluminescence signal, leading to false-positive or false-negative results respectively.


An evaluation of a periodontal plastic surgical procedure for the reconstruction of interdental papillae in maxillary anterior region: A clinical study.
In today's world, people are very much aware about their looks and personality. They are getting more concerned about the esthetics and thus are not ready to compromise the appearance of black holes, especially in the anterior region of the mouth. Various techniques like orthodontic correction, prosthetic veneers and various periodontal surgical methods have been used to cover these unaesthetic open embrasures. In the present study, a variant technique given by Beagle in 1992 was used to cover these open gingival embrasures. The technique uses a gingival flap from the labial aspect to close the open gingival embrasures thus solving the problem of black holes. This clinical study was aimed to reconstruct the lost or blunted interdental papillae with gingival tissue for esthetic purpose and for maintaining oral health with the objective to determine the extent to which the procedure can revert the maxillary esthetics. The patients selected were those who were having a complaint of at least one black hole in the maxillary anterior region with grade '0' or '1' type of contour of interdental tissues. A total of 39 open embrasures were surgically closed using this technique. Various indices were taken pre-surgically and then again post surgically. Plaque index and gingival index showed an initial increase in the scores at the end of 1 week. Later, there was a gradual fall till the end of the study. Bleeding index significantly increased at the end of 12 weeks (P<0.001) but reduced to insignificant levels at the end of 24 weeks (P<0.09). The sulcus depth increased by about 1.19 mm. There was improvement in the contour of interdental tissues in 51% of cases and in 38.46% the interdental papillae completely obliterated the open embrasures. The surgical technique used here for reconstruction of interdental papilla was fairly successful. However, use of bone grafts or soft tissue grafts would have improved the results further.


Adaptive Mutations in RNA Polymerase and the Transcriptional Terminator Rho Have Similar Effects on Escherichia coli Gene Expression.
Modifications to transcriptional regulators play a major role in adaptation. Here, we compared the effects of multiple beneficial mutations within and between Escherichia coli rpoB, the gene encoding the RNA polymerase β subunit, and rho, which encodes a transcriptional terminator. These two genes have harbored adaptive mutations in numerous E. coli evolution experiments but particularly in our previous large-scale thermal stress experiment, where the two genes characterized alternative adaptive pathways. To compare the effects of beneficial mutations, we engineered four advantageous mutations into each of the two genes and measured their effects on fitness, growth, gene expression and transcriptional termination at 42.2 °C. Among the eight mutations, two rho mutations had no detectable effect on relative fitness, suggesting they were beneficial only in the context of epistatic interactions. The remaining six mutations had an average relative fitness benefit of ∼20%. The rpoB mutations affected the expression of ∼1,700 genes; rho mutations affected the expression of fewer genes but most (83%) were a subset of those altered by rpoB mutants. Across the eight mutants, relative fitness correlated with the degree to which a mutation restored gene expression back to the unstressed, 37.0 °C state. The beneficial mutations in the two genes did not have identical effects on fitness, growth or gene expression, but they caused parallel phenotypic effects on gene expression and genome-wide transcriptional termination.


Spatiotemporal distribution, source analysis and ecological risk assessment of polychlorinated biphenyls (PCBs) in the Bohai Bay, China.
As a class of persistent organic pollutants (POPs), the spatial and temporal distribution of polychlorinated biphenyls (PCBs) in seawater is important for environmental assessment. Surface water samples were collected from 35 stations during summer and 36 stations during autumn of 2020 in the Bohai Bay. The concentration, composition, distribution and sources of PCBs were analyzed to assess the ecological impact of PCBs. The average concentration of ∑18PCBs was 124.6 ng/L (range of 28.1-445.5 ng/L) in summer and 122.8 ng/L (range of 21.0-581.4 ng/L) in autumn. PCBs in surface seawater of the Bohai Bay showed high near-shore and low far-shore characteristics, indicating the serious influence of land-based sources such as port activities and river inputs. Proportion analysis showed that Tetra-PCBs and Penta-PCBs were the major constituents in most stations. It was assessed as moderate and high risk (MRQ > 0.1) by mixture risk quotient (MRQ) and concentration addition (CA) model in surface seawater of the Bohai Bay. Principal component analysis (PCA) was used to explain the sources of PCBs in the Bohai Bay. PCBs in the Bohai Bay may come from commercial PCBs and their incineration products, municipal landfills, wood and coal combustion, and industrial activities, etc.


Application of an interpretable classification model on Early Folding Residues during protein folding.
Machine learning strategies are prominent tools for data analysis. Especially in life sciences, they have become increasingly important to handle the growing datasets collected by the scientific community. Meanwhile, algorithms improve in performance, but also gain complexity, and tend to neglect interpretability and comprehensiveness of the resulting models. Generalized Matrix Learning Vector Quantization (GMLVQ) is a supervised, prototype-based machine learning method and provides comprehensive visualization capabilities not present in other classifiers which allow for a fine-grained interpretation of the data. In contrast to commonly used machine learning strategies, GMLVQ is well-suited for imbalanced classification problems which are frequent in life sciences. We present a Weka plug-in implementing GMLVQ. The feasibility of GMLVQ is demonstrated on a dataset of Early Folding Residues (EFR) that have been shown to initiate and guide the protein folding process. Using 27 features, an area under the receiver operating characteristic of 76.6% was achieved which is comparable to other state-of-the-art classifiers. The obtained model is accessible at https://biosciences.hs-mittweida.de/efpred/. The application on EFR prediction demonstrates how an easy interpretation of classification models can promote the comprehension of biological mechanisms. The results shed light on the special features of EFR which were reported as most influential for the classification: EFR are embedded in ordered secondary structure elements and they participate in networks of hydrophobic residues. Visualization capabilities of GMLVQ are presented as we demonstrate how to interpret the results.


Detection of Triacetone Triperoxide by High Kinetic Energy Ion Mobility Spectrometry.
High Kinetic Energy Ion Mobility Spectrometry (HiKE-IMS) is a versatile technique for the detection of gaseous target molecules that is particularly useful in complex chemical environments, while the instrumental effort is low. Operating HiKE-IMS at reduced pressures from 10 to 60 mbar results in fewer ion-neutral collisions than at ambient pressure, reducing chemical cross-sensitivities and eliminating the need for a preceding separation dimension, e.g., by gas chromatography. In addition, HiKE-IMS allows operation over a wide range of reduced electric field strengths E/N up to 120 Td, allowing separation of ions by low-field ion mobility and exploiting the field dependence of ion mobility, potentially allowing separation of ion species at high E/N despite similar low-field ion mobilities. Given these advantages, HiKE-IMS can be a useful tool for trace gas analysis such as triacetone triperoxide (TATP) detection. In this study, we employed HiKE-IMS to detect TATP. We explore the ionization of TATP and the field-dependent ion mobilities, providing a database of the ion mobilities depending on E/N. Confirming the literature results, ionization of TATP by proton transfer with H3O+ in HiKE-IMS generates fragments, but using NH4+ as the primary reactant ion leads to the TATP·NH4+ adduct. This adduct fragments at high E/N, which could provide additional information for reliable detection of TATP. Thus, operating HiKE-IMS at variable E/N in the drift region generates a unique fingerprint of TATP made of all ion species related to TATP and their ion mobilities depending on E/N, potentially reducing the rate of false positives.


Interobserver concordance of Ki67 labeling index in breast cancer: Japan Breast Cancer Research Group Ki67 ring study.
The standardized assessment of Ki67 labeling index (LI) is of clinical importance to identify patients with primary breast cancer who could benefit from chemotherapy. In this study, we evaluated the interobserver concordance of Ki67 LI assessment. Six surgical pathologists participated and all the slides were prepared from archival breast cancer tissues fixed in 10% buffered formalin for 24 h and stained with MIB-1. Three independent studies were conducted. In the first study, 30 stained slides were assessed using two different methods: the scoring system, with a positive rate scored from 1 (0-9%) to 10 (90-100%) by visual estimate; and the counting method, with approximately 1000 cells counted in hot spots. In the second study, 20 tumors with Ki67 LI 5-25% were assessed, and in the third study, 15 printed photographs of stained slides were assessed to avoid variations by selecting different fields. In study 1, the counting system (intraclass correlation coefficient [ICC], 0.66 [95% confidence interval 0.52-0.78]) demonstrated a better correlation than the scoring system (ICC, 0.57 [0.42-0.72]). In study 2, the assessment for Ki67 LI of 5-25% demonstrated a correlation (ICC, 0.68 [0.50-0.81]) similar to that of study 1 (unrestricted range of Ki67 LI). In study 3, the assessment of Ki67 LI by counting yielded a good concordance (ICC, 0.94 [0.88-0.97]). In conclusion, there was better concordance with the counting system, and concordance was high when the assessed field was predetermined, indicating that the selection of the evaluation area is critical for obtaining reproducible Ki67 LI in breast cancer.


SWIFTCORE: a tool for the context-specific reconstruction of genome-scale metabolic networks.
High-throughput omics technologies have enabled the comprehensive reconstructions of genome-scale metabolic networks for many organisms. However, only a subset of reactions is active in each cell which differs from tissue to tissue or from patient to patient. Reconstructing a subnetwork of the generic metabolic network from a provided set of context-specific active reactions is a demanding computational task. We propose SWIFTCC and SWIFTCORE as effective methods for flux consistency checking and the context-specific reconstruction of genome-scale metabolic networks which consistently outperform the previous approaches. We have derived an approximate greedy algorithm which efficiently scales to increasingly large metabolic networks. SWIFTCORE is freely available for non-commercial use in the GitHub repository at https://mtefagh.github.io/swiftcore/.


Effect of age on horizontal eye movement latency.
Reaction time to initiate an eye movement to a target which suddenly appeared 2.8 degrees from fixation was measured for older and younger adults. Healthy men and women were tested in a series of trials; on one-half of these trials prior knowledge of the target's location was given (simple reaction time), whereas on the remaining trials the target could appear to left or right of fixation with equal probability (choice reaction time). For both simple and choice trials, the mean reaction times for younger adults were significantly faster than for older adults. Simple reaction time trials were no faster than choice trials for either age group. In addition to mean reaction times, the distribution of the response times were examined for each age group. The shapes of the two distributions were symmetric; however, the SD of the older adults' scores was greater than that of the younger adults.


Using chemopreventive agents to enhance the efficacy of cancer therapy.
Emerging evidence suggests that cancer preventative agents might be combined with chemotherapy or radiotherapy for the more effective treatment of cancer. Recent studies suggest that genistein and other dietary compounds that prevent cancer may enhance the efficacy of cancer therapeutics by modifying the activity of key cell proliferation and survival pathways, such as those controlled by Akt, nuclear factor-kappaB, and cyclooxygenase-2. In this article, we summarize the findings of recent investigations of chemopreventive agents in combination with cancer treatment regimens.


Feasibility and Efficacy of Delivering Cognitive Behavioral Therapy Through an Online Psychotherapy Tool for Depression: Protocol for a Randomized Controlled Trial.
Major depressive disorder (MDD) is a prevalent and debilitating mental health disorder. Among different therapeutic approaches (eg, medication and psychotherapy), psychotherapy in the form of cognitive behavioral therapy (CBT) is considered the gold standard treatment for MDD. However, although efficacious, CBT is not readily accessible to many patients in need because of hurdles such as stigma, long wait times, high cost, the large time commitment for health care providers, and cultural or geographic barriers. Electronically delivered cognitive behavioral therapy (e-CBT) can effectively address many of these accessibility barriers. This study aims to investigate the efficacy and feasibility of implementing an e-CBT program compared with in-person treatment for MDD. It is hypothesized that the e-CBT program will offer results comparable with those of the in-person treatment program, regarding symptom reduction and quality of life improvement. This nonrandomized controlled trial intervention will provide e-CBT for MDD through the Online Psychotherapy Tool, a secure, cloud-based, digital mental health platform. Participants (aged 18-65 years) will be offered 12 weekly sessions of an e-CBT program tailored to MDD to address their depressive symptoms. Participants (n=55) will complete predesigned modules and homework assignments while receiving personalized feedback and interacting with a therapist through the platform. Using clinically validated symptomology questionnaires, the efficacy of the e-CBT program will be compared with that of a group (n=55) receiving in-person CBT. Questionnaires will be completed at baseline, at week 6 and week 12, and at a 6-month follow-up. Focus groups will be conducted to investigate personal, cultural, and social factors impacting the accessibility and feasibility of implementing a web-based psychotherapy tool from a patient and care provider perspective. Inclusion criteria include diagnosis of MDD, competence to consent to participate, ability to speak and read English, and consistent and reliable access to the internet. Exclusion criteria include active psychosis, acute mania, severe alcohol or substance use disorder, and active suicidal or homicidal ideation. Ethics approval was obtained in January 2019, and recruitment of participants began in June 2019. Recruitment has been conducted via social media, web-based communities, and physician referrals. To date, 52 participants have been recruited to the e-CBT group, and 48 patients have been recruited to the in-person CBT group. Data collection is expected to be completed by March 2021, and analyses are expected to be completed by June 2021, as linear regression (for continuous outcomes) and binomial regression analysis (for categorical outcomes) are still being conducted. The results of this study can provide valuable information for the development of more accessible and scalable mental health interventions with increased care capacity for MDD, without sacrificing the quality of care. ClinicalTrials.gov NCT04478058; http://clinicaltrials.gov/ct2/show/NCT04478058. DERR1-10.2196/27489.


[Perspectives on gender sensitive health reporting].
Based on the different health status of women and men the advantages of gender-sensitive compared to gender-differentiated health reporting are pointed out. The main focus is on considerations how gender-sensitive perspectives can be implemented within health monitoring at federal level. Possible guidelines are suggested.


Appearance of the oocyte activation of mouse round spermatids cultured in vitro.
This study was undertaken to determine the expression time of fertilization and oocytes activation abilities of spermatids in the mouse. When elongating or elongated spermatids isolated from fresh testes of adult males (B6D2F1) were injected into mature mouse oocytes, both spermatids could activate the mature oocytes and occur fertilization. On the one hand, the round spermatids could not activate mature oocytes, when microinjected into oocytes. In some experiments, recovered round spermatids were cultured under co-culture systems using Sertoli cells as a feeder cell. Under the co-culture system, developed elongating spermatids could stimulate and fertilized mature oocytes. These results indicate that the start of oocyte activation appearance is between the stage of round spermatid and elongating spermatids and the activation ability increases with the advance of spermiogensis. On the other hand, round spermatids isolated from males of ICR strain mouse already have the oocyte activation ability and the fertilizing ability. The result obtained suggests that the expression time of the oocyte activating ability is difficult between the mouse strain.


Overview of clinical forensic services in various countries of the European Union.
Examination of a person who has been a victim of a physical or sexual assault may be very important for upcoming legal proceedings. In the context of a clinical forensic examination, physical findings are recorded and biological trace material is gathered and secured. Ideally, all forensic findings are documented in a detailed report combined with photographic documentation, which employs a forensic scale to depict the size of the injuries. However, the integrity of such forensic findings depends particularly on two factors. First, the examination needs to be conducted professionally to ensure that the findings are properly admissible as court evidence. Second, the examination should take place as soon as possible because the opportunity to successfully secure biological samples declines rapidly with time. Access to low-threshold clinical forensic examinations is not evenly provided in all member states of the European Union (EU); in some states, they are not available at all. As part of the JUSTeU! (Juridical standards for clinical forensic examinations of victims of violence in Europe) project, the Ludwig Boltzmann Institute for Clinical Forensic Imaging in Graz, Austria created (in cooperation with its international partner consortium) a questionnaire: the purpose was to collect information about support for victims of physical and/or sexual assault in obtaining a low-threshold clinical forensic examination in various countries of the EU. Our paper provides a summary of the responses and an overview of the current situation concerning provided clinical forensic services.


Electrochemical Nonadiabatic Electron Transfer via Tunneling to Solution Species through Thin Insulating Films.
Described here is a semiquantitative theoretical treatment of the kinetics of outer sphere electrochemical reactions. The framework presented here, which is based on simple physical arguments, predicts heterogeneous rate constants consistent with previous experimental observations (k0 > 10 cm/s). This theory is applied to the analysis of voltammetry experiments involving ultramicroelectrodes modified with thin, insulating oxide films where electronic tunneling between the electrode and redox species in solution (metal-insulator-solution tunneling) is expected to play a prominent role. It is shown that analysis of the voltammetric response of an outer sphere redox couple can be used to track changes in the structure of the adsorbed insulating layer.


In vivo investigation of brain and systemic ketobemidone metabolism.
Ketobemidone metabolites have previously been identified in urine and plasma; here we show, for the first time, that norketobemidone and ketobemidone N-oxide are present in in vivo microdialysate from rat brain (striatum) after reverse microdialysis, suggesting striatal metabolism of ketobemidone. Ketobemidone metabolites were also identified in in vivo microdialysate samples from brain and blood, as well as in urine from rats, after subcutaneous administration of ketobemidone. Three Phase I metabolites (norketobemidone, ketobemidone N-oxide and hydroxymethoxyketobemidone) and three Phase II metabolites (glucuronic acid conjugates of ketobemidone, norketobemidone and hydroxymethoxyketobemidone) were identified in the microdialysates after subcutaneous administration. Coupled capillary liquid chromatography tandem mass spectrometry (LC-MS/MS) and SPE (boronate)-MS/MS were utilized for the analysis of the biological samples. The Phase I metabolites were identified by comparing the retention times and tandem mass spectra of the microdialysates with synthetic standards. The Phase II metabolites were identified by determination of exact masses and by comparing the tandem mass spectra of the microdialysates with those of synthetic standards for the aglycones. Hydroxyketobemidone, a catechol-type Phase I metabolite, was selectively isolated by solid-phase boronate-complexation but identified in urine alone. This work demonstrated that the in vivo microdialysis technique in combination with LC-MS/MS can be used to study the local metabolism of a drug in the brain.


Short-range multispectral imaging is an inexpensive, fast, and accurate approach to estimate biodiversity in a temperate calcareous grassland.
Image sensing technologies are rapidly increasing the cost-effectiveness of biodiversity monitoring efforts. Species differences in the reflectance of electromagnetic radiation can be used as a surrogate estimate plant biodiversity using multispectral image data. However, these efforts are often hampered by logistical difficulties in broad-scale implementation. Here, we investigate the utility of multispectral imaging technology from commercially available unmanned aerial vehicles (UAVs, or drones) in estimating biodiversity metrics at a fine spatial resolution (0.1-0.5 cm pixel resolution) in a temperate calcareous grassland in Oxfordshire, UK. We calculate a suite of moments (coefficient of variation, standard deviation, skewness, and kurtosis) for the distribution of radiance from multispectral images at five wavelength bands (Blue 450 ± 16 nm; Green 560 ± 16 nm; Red 650 ± 16 nm; Red Edge 730 ± 16 nm; Near Infrared 840 ± 16 nm) and test their effectiveness at estimating ground-truthed biodiversity metrics from in situ botanical surveys for 37-1 × 1 m quadrats. We find positive associations between the average coefficient of variation in spectral radiance and both the Shannon-Weiner and Simpson's biodiversity indices. Furthermore, the average coefficient of variation in spectral radiance is consistent and highly repeatable across sampling days and recording heights. Positive associations with biodiversity indices hold irrespective of the image recording height (2-8 m), but we report reductions in estimates of spectral diversity with increases to UAV recording height. UAV imaging reduced sampling time by a factor of 16 relative to in situ botanical surveys. We demonstrate the utility of multispectral radiance moments as an indicator of biodiversity in this temperate calcareous grassland at a fine spatial resolution using a widely available UAV monitoring system with a coarse spectral resolution. The use of UAV technology with multispectral sensors has far-reaching potential to provide cost-effective and high-resolution monitoring of biodiversity.


Polarized near-infrared intersubband absorptions in CdSe colloidal quantum wells.
Colloidal quantum wells are two-dimensional materials grown with atomically-precise thickness that dictates their electronic structure. Although intersubband absorption in epitaxial quantum wells is well-known, analogous observations in non-epitaxial two-dimensional materials are sparse. Here we show that CdSe nanoplatelet quantum wells have narrow (30-200 meV), polarized intersubband absorption features when photoexcited or under applied bias, which can be tuned by thickness across the near-infrared (NIR) spectral window (900-1600 nm) inclusive of important telecommunications wavelengths. By examination of the optical absorption and polarization-resolved measurements, the NIR absorptions are assigned to electron intersubband transitions. Under photoexcitation, the intersubband features display hot carrier and Auger recombination effects similar to excitonic absorptions. Sequenced two-color photoexcitation permits the sub-picosecond modulation of the carrier temperature in such colloidal quantum wells. This work suggests that colloidal quantum wells may be promising building blocks for NIR technologies.


Continuing evaluation of coronary care.
Continuing evaluation of coronary care is necessary to determine its present effectiveness and to establish direction in the effort to decrease mortality after myocardial infarction. Data have been collected on 157 consecutive patients diagnosed as having myocardial infarction who were admitted to the coronary-care unit at St. Joseph's Hospital and Medical Center, Phoenix, Ariz. The hospital is a teaching hospital with a 560-bed capacity. Data sheets were completed on each patient at the time of transfer from the coronary-care unit. The accumulated data were processed by a computer at the end of a 13-month period. The overall mortality for the group was 16.5 per cent. The factors which were found to have a significant effect on mortality were: (1) location of infarction, (2) presence of heart failure, (3) occurrence of cardiogenic shock, (4) age, and (5) the presence of intraventricular conduction defect. In 19 of the 26 deaths after myocardial infarction, the terminal event was associated with congestive heart failure, pulmonary edema, or cardiogenic shock. Three patients died of resistant arrhythmia, four of ventricular rupture. These figures indicate that arrhythmia is not a primary cause of death after myocardial infarction and that attention must also be directed to the early diagnosis and treatment of left ventricular failure if coronary care survival rates are to improve.


Preparation and preservation of viable Akkermansia muciniphila cells for therapeutic interventions.
The anaerobic gut bacterium Akkermansia muciniphila is a well-characterised member of the mucosal microbiota and has shown to be a gut symbiont in human. A. muciniphila has been negatively associated with obesity and its associated metabolic disorders in various human cohorts while treatment with A. muciniphila cells reversed highfat diet-induced obesity and its associated metabolic disorders in mouse models. Therefore, administration of A. muciniphila has been suggested as a possible new therapeutic treatment for these omnipresent diseases. Here we describe a potentially scalable workflow for the preparation and preservation of high numbers of viable cells of A. muciniphila obtained from 1 l laboratory scale growth under strict anaerobic conditions for therapeutic interventions. This resulted in viable A. muciniphila cells with high yields and very high stability, with up to 97.9±4.5% survival for a time period of 1 year at -80 °C in glycerol-amended medium. Moreover, various quality assessment and control procedures were developed to ensure the use of viable cells of A. muciniphila. Several microscopic, culturing, and molecular approaches were applied to monitor the presence, abundance and recovery of A. muciniphila before, during, and after its administration to high-fat treated mice. We show that viable A. muciniphila cells can be recovered from caecal and colon content (up to 1×1010 cells/g), testifying for the efficiency of the described workflow.


HIV-1 infection and the developing nervous system: lineage-specific regulation of viral gene expression and replication in distinct neuronal precursors.
Neurologic abnormalities are common in HIV-1 infected patients and often represent the dominant clinical manifestation of pediatric AIDS. Although the neurological dysfunction has been directly related to CNS invasion by HIV-1, the pathogenesis of neurologic disorders remains unclear. Microglia and macrophages are major HIV-1 targets in the brain, whereas HIV-1 infected neurons or glial cells have been rarely reported. This suggests that indirect mechanisms may account for the severe neuronal damage observed in these patients. Nevertheless, immature, mitotically active neuronal and glial cells, which are present during fetal development, are susceptible to HIV-1 infection and replication in vitro, suggesting that HIV-1 infection during organ development may present unique features. To better characterize virus-host cells interactions in the developing CNS, we have examined the susceptibility of embryologically and biochemically distinct neuronal cell lines to HIV-1 infection. Here we show that mitotically active, immature neurons of distinct lineages, have different susceptibilities to HIV-1 infection and replication and different abilities to support viral gene expression. Mutational analysis of HIV-1 LTR reveals that a region of the viral promoter between nucleotide -255 to -166 is responsible for most quantitative and qualitative differences in viral transactivation among different neuroblasts. This suggests that specific regions of the viral promoter and cellular factors, either lineage- or differentiation-dependent, which bind to those regions, may contribute to control the levels of virus replication and possibly restrict the viral tropism in the developing brain. This may contribute to the establishment of a virus reservoir in the immature CNS and participate by either direct or indirect mechanisms to the severity of the AIDS-related pediatric neurological dysfunction.


Relationship between speed and EEG activity during imagined and executed hand movements.
The relationship between primary motor cortex and movement kinematics has been shown in nonhuman primate studies of hand reaching or drawing tasks. Studies have demonstrated that the neural activities accompanying or immediately preceding the movement encode the direction, speed and other information. Here we investigated the relationship between the kinematics of imagined and actual hand movement, i.e. the clenching speed, and the EEG activity in ten human subjects. Study participants were asked to perform and imagine clenching of the left hand and right hand at various speeds. The EEG activity in the alpha (8-12 Hz) and beta (18-28 Hz) frequency bands were found to be linearly correlated with the speed of imagery clenching. Similar parametric modulation was also found during the execution of hand movements. A single equation relating the EEG activity to the speed and the hand (left versus right) was developed. This equation, which contained a linear independent combination of the two parameters, described the time-varying neural activity during the tasks. Based on the model, a regression approach was developed to decode the two parameters from the multiple-channel EEG signals. We demonstrated the continuous decoding of dynamic hand and speed information of the imagined clenching. In particular, the time-varying clenching speed was reconstructed in a bell-shaped profile. Our findings suggest an application to providing continuous and complex control of noninvasive brain-computer interface for movement-impaired paralytics.


Clinical rescue evaluation in laparoscopic surgery for hepatic metastases by colorectal cancer.
Laparoscopy is an increasingly important tool in the staging and treatment for potentially resectable liver metastases. The clinical risk score (CRS) is useful in selecting patients for diagnostic laparoscopy before planning resection of colorectal metastases. This study evaluates the effect of staging laparoscopy (SL) combined with CRS. From January 2004 to December 2007, CRS evaluation and SL were performed in 65 consecutive patients with colorectal metastases, before planned open-exploration and resection. Patients were assigned to a CRS, which is based on 5 factors related to the primary tumor and the hepatic disease. This study was aimed at recognizing occult unresectable metastases, by combining laparoscopy and CRS. Only 62 patients had a complete SL examination (3 were excluded for dense adhesions). A group of 24 patients was identified as unresectable, and 38 patients as resectable. In the latter group, 3 patients directly had laparoscopic treatment. In all, 38 patients underwent laparotomy (35 resectable, and 3 patients with dense adhesions that could not have a complete laparoscopic treatment).Resection was carried out in 30 of 38 (78.9%) cases, and the remaining 21% gave false-negative results. In all, there were 32 of 65 (49.2%) unresectable patients, and 75% of them were recognized by SL. Laparoscopy identified the majority of patients with occult unresectable disease, improved resectability, and it should be a routine in patients being considered for potentially curative hepatic resection. The CRS, earlier shown to predict survival after hepatic resection, identifies high-risk patients, who are most likely to benefit from laparoscopy, and may improve resource utilization.


Selective and Fast Analysis of Chlorinated Paraffins in the Presence of Chlorinated Mono-, Di-, and Tri-Olefins with the R-Based Automated Spectra Evaluation Routine (RASER).
Chlorinated paraffins (CPs) are complex mixtures consisting of various C homologues (nC ≈ 10-30) and Cl homologues (nCl ≈ 2-20). Technical CP mixtures are produced on a large scale (>106 t/y) and are widely used such as plasticizers in plastic and coolants in metalwork. Since 2017, short-chain CPs (C10-C13) are classified as persistent organic pollutants (POPs) by the Stockholm Convention but longer-chain CPs are not regulated. Analysis of technical CP mixtures is challenging because they consist of hundreds of homologues and millions of constitutional isomers and stereoisomers. Furthermore, such mixtures can also contain byproducts and transformation products such as chlorinated olefins (COs). We applied a liquid-chromatography method coupled to an atmospheric pressure chemical ionization technique with a high-resolution mass detector (LC-APCI-Orbitrap-MS) to study CP and CO homologues in two plastic materials. Respective mass spectra can contain up to 23,000 signals from 1320 different C-Cl homologue classes. The R-based automated spectra evaluation routine (RASER) was developed to efficiently search for characteristic ions in these complex mass spectra. With it, the time needed to evaluate such spectra was reduced from weeks to hours, compared to manual data evaluation. Unique sets of homologue distributions could be obtained from the two plastic materials. CPs were found together with their transformation products, the chlorinated mono-olefins (COs), di-olefins (CdiOs), and tri-olefins (CtriOs) in both plastic materials. Based on these examples, it can be shown that RASER is an efficient and selective tool for evaluating high-resolution mass spectra of CP mixtures containing hundreds of homologues.


Space and time efficient virtual quadtress.
The quadtree has recently become a major data structure in image processing. This correspondence investigates ways in which quadtrees may be efficiently stored as a forest of quadtrees and as a new structure we call a compact quadtree. These new structures are called virtual quadtrees because the basic operations we expect to perform in moving about within a quadtree can also be performed on the new representations. Space and time efficiency are investigated and it is shown these new structures often given an improvement in both.


Wnt signaling influences the development of murine epidermal Langerhans cells.
Langerhans cells (LCs) are distinct dendritic cells (DCs) that populate stratified squamous epithelia. Despite extensive studies, our understanding of LC development is incomplete. Transforming growth factor β1 (TGFβ1) is required for LC development, but other epidermis-derived influences may also be important. Recently, EpCAM (CD326) has been identified as a cell surface protein discriminating LCs from Langerin(+) dermal DCs and other DCs in the skin. EpCAM is a known transcriptional target of the Wnt signaling pathway. We hypothesized that intraepidermal Wnt signaling might influence LC development. Addition of Wnt3A into cultures of bone-marrow-derived cells in combination with TGFβ1, GM-CSF, and M-CSF resulted in increased (33%; P<0.05) accumulation of EpCAM(+) DCs. In contrast, addition of the Wnt antagonist dickkopf-related protein 1 (Dkk1) decreased the number of EpCAM(+) DCs (21%; P<0.05). We used K14-KRM1; K5-rtTA; tetO-Dkk1 triple-transgenic and K5-rtTA; tetO-Dkk1 double-transgenic mice to test the in vivo relevance of our in vitro findings. Feeding doxycycline to nursing mothers induced expression of Dkk1 in the skin of transgenic pups, causing an obvious hair phenotype. Expression of Dkk1 reduced LC proliferation (40%; P<0.01) on P7, decreased LC densities (26%; P<0.05) on P14, and decreased EpCAM expression intensities on LCs as well (33%). In aggregate, these data suggest that Wnt signaling in skin influences LC development.


Cytotoxic Effects of Mangosteen Pericarp Extracts on Oral Cancer and Cervical Cancer Cells.
Despite immense advancements in treatment modalities, cancer remains a dreadful disease until the present. The major influencing factors behind the increased mortality rate of cancer are increased drug resistance and severe adverse effects caused by conventional cancer therapies. To overcome these limitations, the current medical field is focusing more on natural phyto-derived molecules to mitigate cancer. Mangosteen is a phytotherapeutic with potent anti-inflammatory and antioxidant properties. In the present study, we investigated the anticancer potential of the crude ethanolic extract of mangosteen against two dreadful forms of cancers, namely, oral cancer and cervical cancer, in vitro. The pericarp of Garcinia mangostana or mangosteen was removed, air-dried, ground to fine powder, and macerated with ethanol. The extract obtained was then filtered and extracted with water for 48 h. The aqueous fraction thus obtained was then concentrated with a rotary evaporator at 40°C and dried with a freeze dryer. The anticancer efficacy of these extracts was investigated in human tongue squamous cell carcinoma (H357) cells and cervical cancer cells (HeLa) using the MTT assay, TUNEL assay, western blotting, and flow cytometry techniques. The crude mangosteen pericarp extract (MPE) significantly inhibited the growth of H357 and HeLa cells in a dose-dependent manner. Moreover, mangosteen induced early apoptosis in these cells after 48 h of incubation. Mangosteen also upregulated the expression of pro-apoptotic proteins, including caspases and Bax, and downregulated the expression of anti-apoptotic protein Bcl-2. The MPE exerted significant cytotoxicity against the H357 and HeLa cells in a dose-dependent manner and promoted their apoptosis. Hence, this natural phytoextract can be considered a potent anticancer agent for treating oral cancer and cervical cancer.


A custom MR-compatible dataglove for fMRI of the human motor cortex at 7T.
We present a custom-built MR-compatible data glove to capture hand motion during concurrent fMRI experiments at 7 Tesla. Thermal and phantom tests showed our data glove can be used safely and without degradation of image quality. Subject-specific Blood Oxygen Level Dependent (BOLD) signal models, for use in fMRI analysis, were constructed based on recorded kinematic measurements. Experiments revealed the relative fMRI BOLD signal contribution of flexing, extending, and sustained isotonic extension. The ability to evaluate subject performance in real-time and create subject-specific BOLD signal models enables a wide range of experimental paradigms with improved data quality.Clinical Relevance- Using an MR compatible dataglove, subject specific Blood Oxygen Signal Level Dependent (BOLD) signal models can be constructed to study how the brain implements fine motor control.


A Hybrid Kinematic-Acoustic System for Automated Activity Detection of Construction Equipment.
Automatically recognizing and tracking construction equipment activities is the first step towards performance monitoring of a job site. Recognizing equipment activities helps construction managers to detect the equipment downtime/idle time in a real-time framework, estimate the productivity rate of each equipment based on its progress, and efficiently evaluate the cycle time of each activity. Thus, it leads to project cost reduction and time schedule improvement. Previous studies on this topic have been based on single sources of data (e.g., kinematic, audio, video signals) for automated activity-detection purposes. However, relying on only one source of data is not appropriate, as the selected data source may not be applicable under certain conditions and fails to provide accurate results. To tackle this issue, the authors propose a hybrid system for recognizing multiple activities of construction equipment. The system integrates two major sources of data-audio and kinematic-through implementing a robust data fusion procedure. The presented system includes recording audio and kinematic signals, preprocessing data, extracting several features, as well as dimension reduction, feature fusion, equipment activity classification using Support Vector Machines (SVM), and smoothing labels. The proposed system was implemented in several case studies (i.e., ten different types and equipment models operating at various construction job sites) and the results indicate that a hybrid system is capable of providing up to 20% more accurate results, compared to cases using individual sources of data.


Functional interference of Sp1 and NF-kappaB through the same DNA binding site.
Gene activation by NF-kappaB/Rel transcription factors is modulated by synergistic or antagonistic interactions with other promoter-bound transcription factors. For example, Sp1 sites are often found in NF-kappaB-regulated genes, and Sp1 can activate certain promoters in synergism with NF-kappaB through nonoverlapping binding sites. Here we report that Sp1 acts directly through a subset of NF-kappaB binding sites. The DNA binding affinity of Sp1 to these NF-kappaB sites, as determined by their relative dissociation constants and their relative efficiencies as competitor DNAs or as binding site probes, is in the order of that for a consensus GC box Sp1 site. In contrast, NF-kappaB does not bind to a GC box Sp1 site. Sp1 can activate transcription through immunoglobulin kappa-chain enhancer or P-selectin promoter NF-kappaB sites. p50 homodimers replace Sp1 from the P-selectin promoter by binding site competition and thereby either inhibit basal Sp1-driven expression or, in concert with Bcl-3, stimulate expression. The interaction of Sp1 with NF-kappaB sites thus provides a means to keep an elevated basal expression of NF-kappaB-dependent genes in the absence of activated nuclear NF-kappaB/Rel.


Functionalization-Free Microfluidic Electronic Tongue Based on a Single Response.
Electronic tongues (e-tongues) are promising analytical devices for a variety of applications to address the challenges of quality control in water monitoring and industries of foods, beverages, and pharmaceuticals. A crucial drawback in the current e-tongues is the need to recalibrate the device when one or more sensing units (usually with modified surface) are replaced. Another downside is the necessity to perform subsequent surface modifications and analyses to each of the diverse sensing units, undermining the simplicity and velocity of the method. These features have prevented widespread commercial use of the e-tongues. In this paper, we introduce a microfluidic e-tongue that overcomes all such limitations. The key principle of global selectivity of the e-tongue was achieved by recording only a single response, namely, the equivalent admittance spectrum of an association of resistors in parallel. Such resistors consisted of five nonfunctionalized stainless steel microwires (sensing units), which were short-circuited and coated with gold, platinum, nickel, iron, and aluminum oxide films. The microwires were inserted in a chip composed of a single piece of polydimethylsiloxane (PDMS). Using impedance spectroscopy, the e-tongue was successfully applied in classification of basic tastes at a concentration below the threshold for the human tongue. In addition, our chip allowed the distinction of various chemicals used in oil industry. Finally, our cleanroom-free prototyping allows the mass production of chips with easily replaceable and reproducible sensing units. Hence, one can now envisage the widespread dissemination of e-tongues with fast and reproducible data.


Behavioural and epigenetic effects of paternal exposure to cannabinoids during adolescence on offspring vulnerability to stress.
Chronic cannabinoid exposure during adolescence in male rats induces chronic cognitive and emotional impairments. However, the impact of this form of exposure on offspring vulnerability to stress is unknown. The aim of this study was to evaluate the behavioural and epigenetic effects of stress in the offspring of male rats whose fathers were exposed to cannabinoids during adolescence. Male adolescent offspring of Win55,212-2 (1.2 mg/kg) treated rats were exposed during one week to variable stressors and subjected to behavioural tests of anxiety and episodic-like memory, followed by an assessment of global DNA methylation and expression of DNA methyltransferases enzymes DNMT1 and DNMT3a mRNA in the prefrontal cortex. Stress exposure induced a significant anxiogenic-like effect but did not affect the episodic-like memory in the offspring of Win55,212-2 exposed fathers in comparison to the offspring of non-exposed fathers. These behavioural changes were subsequent to a significant increase in global DNA methylation and DNMT1 and DNMTa3 transcription in the prefrontal cortex. These data suggest that the deleterious effect of chronic exposure to cannabinoids during adolescence are not limited to the exposed individuals but may increase the vulnerability to stress-induced anxiety in the offspring and alter their epigenetic programming.


A heparin-binding protein involved in inhibition of smooth-muscle cell proliferation.
A heparin-binding protein was isolated from bovine uteri and purified to homogeneity. This protein appears as a double band of approx. 78 kDa in SDS/polyacrylamide-gel electrophoresis and has an isoelectric point of 5.2. The binding of heparin to this protein is saturable. No other glycosaminoglycan from mammalian tissue, such as hyaluronic acid, chondroitin sulphate, dermatan sulphate or keratan sulphate, binds to the 78 kDa protein. Dextran sulphate binds in a non-saturable fashion. Certain heparan sulphate polysaccharide structures are required for binding to the 78 kDa protein. Some proteoheparan sulphates, such as endothelial cell-surface proteoheparan sulphate, show only weak interaction with the 78 kDa protein in contrast with a basement-membrane proteoheparan sulphate from HR-9 cells. Antibodies against the 78 kDa protein inhibit binding of proteoheparan [35S]sulphate from basement membranes to smooth-muscle cells. Conventional antibodies, Fab fragments and some monoclonal antibodies, inhibit smooth-muscle cell proliferation in a similar range as that observed for heparin. The protein was detected in a variety of tissues and cells but not in blood cells. A possible role of this protein as a receptor for heparin or heparan sulphate and its function in the control of the arterial wall structure are discussed.


PROPHET, a national computing resource for life science research.
PROPHET is a national computing resource tailored to meet the data management and analysis needs of life scientists working in a wide variety of disciplines, ranging from pharmacology to molecular biology. The PROPHET system offers a fully integrated graphics-oriented environment designed to aid research scientists in the manipulation and analysis of scientific spreadsheets of data, graphs, molecular structures, biological simulation models, and protein and nucleic acid sequences, and it includes access to a range of molecular structure and sequence databases. This paper briefly describes the PROPHET system, some of its current capabilities, and plans for a new fully distributed version of the system now under development.


Complete nucleotide sequence of a French bean storage protein gene: Phaseolin.
The complete nucleotide sequences of the gene and the mRNA coding for a specific phaseolin type French bean major storage protein have been determined. Comparison of these sequences reveals a phaseolin gene structure consisting of 80 base pairs (bp) of 5' untranslated DNA, 1,263 bp of protein-encoding DNA which is interrupted by five intervening sequences (IVS1, 72 bp; IVS2, 88 bp; IVS3, 124 bp; IVS4, 128 bp; and IVS5, 103 bp), and 135 bp of 3' untranslated DNA. Sequences characteristic of eukaryotic promoters "CCAAT" and "TATA" are present in the 5' flanking DNA, and the eukaryotic poly(A) addition signal A-A-T-A-A-A occurs 16 bp before the first nucleotide of poly(A). The derived amino acid sequence yields an amino acid composition and a molecular weight compatible with those found for the beta-type phaseolin protein. Two regions that probably serve as carbohydrate-peptide linkage recognition sites have been identified. A region of highly hydrophobic amino acids at the NH(2) terminus of the protein suggests the presence of a signal peptide in the newly synthesized phaseolin protein.


Improvement of lower urinary tract symptoms and sexual activity after open simple prostatectomy: prospective analysis of 50 cases.
To evaluate the improvement of Lower Urinary Tract Symptoms (LUTS) and Erectile Function (EF) evaluated before and after Open Simple Prostatectomy, focusing on which patients this procedure allows better outcomes in term of sexual activity. 50 men with large size benign prostatic hyperplasia (BHP) greater than 80 gr were prospectively evaluated before and 6 months after Open Simple Prostatectomy (Freyer procedure) between October 2012 to September 2013. Patients had a pre-operative transrectal ultrasound (TRUS) for volume evaluation and filled pre and post operative questionnaires for International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) score. Mean patients age was 71 years (D.S. 3,5), mean prostate volume results 103 ml (D.S. 23,7); regarding LUTS and EF, mean improvement of IPSS score was 15,3 (D.S. 4) and mean increase of IIEF-5 score was 3,4 (D.S.3). This study highlights a correlation between patients' age and increase of IIEF-5 score; no correlation with prostate size was found. According to the EAU Guidelines 2014, large size BPH (over 80-100 mL) with LUTS refractory to medical management continue to have open prostatectomy as the treatment of choice. In our experience we found not only an reduction of LUTS after the procedure but also an improvement of erectile function; this improvement was related with patient's age.


Super-resolution imaging properties of cascaded microsphere lenses.
In this paper, the imaging properties of a cascaded microsphere lens are studied. The cascaded microsphere lens consists of two lenses. A hexagonally close-packed 960-nm-diameter array of polystyrene microspheres is used as the first lens. The second lens is a single silica microsphere with a diameter of about 5 μm. A Blu-ray disc is observed by both the cascaded microsphere lens and the single silica microsphere. Studies reveal that the magnification of the cascaded microsphere lens is about 1.4 times greater than that of the single silica microsphere, while the field of view of the cascaded microsphere lens, which is close to the diameter of the polystyrene microsphere, is decreased. The focal position of the cascaded lens microsphere must be close to the sample in order to observe it.


CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction.
Despite its established inter-individual variability, sildenafil has been the subject of only a few pharmacogenetic investigations, with limited data regarding the genetic modulators of its pharmacokinetics. We conducted a pharmacogenetic sub-study of patients randomized to sildenafil (n=85) in the RELAX trial, which investigated the impact of high-dose sildenafil in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). In the overall population, the CYP3A4 inferred phenotype appeared associated with the dose-adjusted peak concentrations of sildenafil at week 12 and week 24 (adjusted P=0.045 for repeated measures analysis), although this P-value did not meet our corrected significance threshold of 0.0167. In the more homogeneous Caucasian subgroup, this association was significant (adjusted P=0.0165 for repeated measures). Hence, CYP3A4 inferred phenotype is associated with peak sildenafil dose-adjusted concentrations in patients with HFpEF receiving high doses of sildenafil. The clinical impact of this association requires further investigation.


Nonpharmacologic Interventions for Reducing Blood Pressure in Adults With Prehypertension to Established Hypertension.
Background Nonpharmacologic interventions that modify lifestyle can lower blood pressure (BP) and have been assessed in numerous randomized controlled trials and pairwise meta-analyses. It is still unclear which intervention would be most efficacious. Methods and Results Bayesian network meta-analyses were performed to estimate the comparative effectiveness of different interventions for lowering BP. From 60 166 potentially relevant articles, 120 eligible articles (14 923 participants) with a median follow-up of 12 weeks, assessing 22 nonpharmacologic interventions, were included. According to the surface under the cumulative ranking probabilities and Grading of Recommendations Assessment, Development and Evaluation (GRADE) quality of evidence, for adults with prehypertension to established hypertension, high-quality evidence indicated that the Dietary Approach to Stop Hypertension (DASH) was superior to usual care and all other nonpharmacologic interventions in lowering systolic BP (weighted mean difference, 6.97 mm Hg; 95% credible interval, 4.50-9.47) and diastolic BP (weighted mean difference, 3.54 mm Hg; 95% credible interval, 1.80-5.28). Compared with usual care, moderate- to high-quality evidence indicated that aerobic exercise, isometric training, low-sodium and high-potassium salt, comprehensive lifestyle modification, breathing-control, and meditation could lower systolic BP and diastolic BP. For patients with hypertension, moderate- to high-quality evidence suggested that the interventions listed (except comprehensive lifestyle modification) were associated with greater systolic BP and diastolic BP reduction than usual care; salt restriction was also effective in lowering both systolic BP and diastolic BP. Among overweight and obese participants, low-calorie diet and low-calorie diet plus exercise could lower more BP than exercise. Conclusions DASH might be the most effective intervention in lowering BP for adults with prehypertension to established hypertension. Aerobic exercise, isometric training, low-sodium and high-potassium salt, comprehensive lifestyle modification, salt restriction, breathing-control, meditation and low-calorie diet also have obvious effects on BP reduction.


Reduction of fatty liver in rats by nicotinamide via the regeneration of the methionine cycle and the inhibition of aldehyde oxidase.
Nonalcoholic fatty liver disease, which has been rapidly increasing in the world in recent years, is roughly classified into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis. This study was based on our previous reports that stated that the combination treatment of N1-methylnicotinamide (MNA) and hydralazine (HYD) improves fatty liver in NAFL model rats. This finding was attributed to the MNA metabolism inhibition by HYD, which is a strong inhibitor of aldehyde oxidase (AO); this results in an increase in hepatic MNA and improved fatty liver. We hypothesized that orally administered nicotinamide (NAM), which is the precursor of MNA and is a form of niacin, would be efficiently metabolized by nicotinamide N-methyltransferase in the presence of exogenous S-adenosylmethionine (SAM) in NAFL rats. To address this issue, NAFL model rats were orally administered with NAM, SAM, and/or HYD. As a result, liver triglyceride (TG) and lipid droplet levels were barely altered by the administration of NAM, SAM, NAM+SAM, or NAM+HYD. By contrast, the triple combination of NAM+SAM+HYD significantly reduced hepatic TG and lipid droplet levels and significantly increased hepatic MNA levels. These findings indicated that the combination of exogenous SAM with AO inhibitors, such as HYD, has beneficial effects for improving fatty liver with NAM.


Prolonged hospitalization because of inappropriate delay of warfarin therapy in deep venous thrombosis.
Current anticoagulation practices of physicians in an academic medical center were examined by retrospective review of records of 26 patients admitted for uncomplicated deep venous thrombosis (DVT) between 1978 and 1982. Patients received intravenous heparin for an average of 11.5 +/- 2.8 days. Warfarin therapy was started on day 8.3 +/- 3.1 and therapeutic oral anticoagulation was achieved by day 14.5 +/- 4.5. Total hospital stay averaged 16.8 +/- 5.1 days. No patient received concurrent initiation of heparin and warfarin therapy and only two patients received warfarin before day 5. These findings are in contrast to anticoagulation practices in Great Britain and Scandinavia where concurrent initiation of heparin and warfarin has been common practice for many years. Such a regimen is safe and usually requires fewer days of hospitalization for DVT. We conclude that failure to start warfarin therapy on the first hospital day resulted in a costly and unnecessarily prolonged hospital stay.


Immunochemical approaches for detection of aflatoxin B1 in herbal medicines.
Aflatoxin B1 (AFB1) is a toxic low-molecular-weight secondary metabolite of Aspergillus flavus and A. parasiticus. AFB1 was classified as a Group I carcinogen by the World Health Organisation for Research on Cancer in 1993. AFB1 is an unavoidable natural contaminant of some herbal medicine, able to cause serious health issues for humans consuming the related medicine. Therefore, this study aimed to develop an efficient fluorescence polarisation immunoassay (FPIA) and a rapid, low-cost, and easy-to-use membrane-based flow-through immunoassay (MBA) for determination of AFB1 in herbal medicine Origanum vulgare L., Rubus idaeus L., Urtica dioica L. and Sorbus aucuparia L. A cut-off level of the developed MBA was 0.8 ppb. Validation of the developed test was performed with blank and spiked samples. Using three naturally contaminated or three artificially spiked samples. The FPIA showed a linear working range of 8.6 to 64 ppb, and a half maximal inhibitory concentration (IC50 ) of 24 ppb. The results were in good correlation with the enzymelinked immunosorbent assay (ELISA) results (the IC50 0.1 ppb). Both the sample preparation and analysis are simple, cost-effective and easy to perform on-site in non-laboratory environments. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used as a confirmatory technique.


Control of simulator sickness in an AH-64 aviator.
An active 33-year-old Army AH-64 aviator with simulator sickness refractory to routine preventive measures was successfully managed with transdermal scopolamine. Although adaptation is the ultimate means for control of simulator sickness, the use of anti-motion sickness medication, specifically transdermal scopolamine, may be a useful adjuvant in selected aviators.


Life Cycle Assessment of sewage sludge mono-digestion and co-digestion with the organic fraction of municipal solid waste at a wastewater treatment plant.
Wastewater treatment plants (WWTPs) aim to increase energy independence by intensifying biogas production. The study involved Life Cycle Assessment (LCA) comparing sewage sludge (SS) anaerobic co-digestion (AcD) with the organic fraction of municipal solid waste (OFMSW) at WWTP against SS anaerobic mono-digestion (AD). The LCA was based on the authors' research showing that methane production related to wet mass in AcD was higher than in AD by 86.4, 225.8, and 354.3 % for SS:OFMSW mixing ratios of 75:25, 50:50, and 25:75, respectively. The LCA was conducted for 1 kWh of biogas energy produced at a WWTP and included two subsystems: energy production (AD/AcD and CHP) and associated digestate management (drying, incineration with energy reuse, residual landfilling). CML-IA baseline 2013 and Recipe 2016 Midpoint (H) LCIA methodologies indicated the environmental impacts on abiotic depletion - fossil fuels (fossil resource scarcity), global warming, human toxicity (non-carcinogenic), freshwater, and marine aquatic ecotoxicity. AD of SS in all categories was characterized by the highest impact. The impact decreased with an increase in the OFMSW rate. Both methodologies showed a significant impact of AD and AcD on global warming, which indicated the need for the determination of the carbon footprint (CF) of 1kWh biogas energy production (gCO2 kWh-1) at WWTP, using IPCC 2021 GWP100 (incl. CO2 uptake). The CF was the highest for biogas energy production in SS AD (1509 gCO2 kWh-1) and it decreased with the increase of OFMSW content in AcD (872-481 gCO2 kWh-1). This was also observed for the management of associated digestate. CF changed from 1508 gCO2 kWh-1 for SS AD to 396 gCO2 kWh-1 for SS: OFMSW mixing ratio of 25: 75 in AcD. The environmental burdens associated with biogas energy production and digestate management were equally significant. Finally, the formula for economic and ecological comparison of SS AD and AcD with OFMSW was proposed.


Pembrolizumab-induced severe rejection and graft intolerance syndrome resulting in renal allograft nephrectomy.
Pembrolizumab is a selective anti-programmed cell death protein-1 (PD-1) humanized monoclonal antibody that inhibits PD-1 activity by binding to the PD-1 receptor that is found on activated T-cells. The goal of the treatment is to allow the immune system to target and destroy cancer cells by preventing cancer cells from binding to PD-1 receptors, leading to decreased tumor growth. The activation of T-cells by pembrolizumab not only leads to the destruction of malignant cells but also attacks the donor alloantigens that are present in a renal transplant, resulting in graft rejection. We present a case of a 46-year-old African American female with history of renal transplant who was treated with pembrolizumab for stage IV B endometrial adenocarcinoma and experienced renal transplant rejection and severe graft intolerance syndrome.Management and outcome: Due to ongoing graft intolerance, a transplant nephrectomy was performed. Allograft pathology was consistent with non-viable kidney with tubulitis, interstitial fibrosis and necrosis consistent with transplant rejection without any evidence of malignancy. As emphasized in our case, there is a very high risk of graft rejection in patients who need to be placed on immunomodulators such as pembrolizumab, so the risk versus benefit needs to be assessed and discussed. Our case is unique because pembrolizumab not only caused graft rejection but also severe graft intolerance syndrome which led to transplant nephrectomy. Further guidelines are needed in renal transplant patients requiring PD-1 inhibitors to establish the ideal treatment plan of immunosuppression management and anti-cancer treatments.


Techniques for early diagnosis of oral squamous cell carcinoma: Systematic review.
The diagnosis of early oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) is of paramount clinical importance given the mortality rate of late stage disease. The aim of this study is to review the literature to assess the current situation and progress in this area. A search in Cochrane and PubMed (January 2006 to December 2013) has been used with the key words "squamous cell carcinoma", "early diagnosis" "oral cavity", "Potentially Malignant Disorders" y "premalignant lesions". The inclusion criteria were the use of techniques for early diagnosis of OSCC and OPMD, 7 years aged articles and publications written in English, French or Spanish. The exclusion criteria were case reports and studies in other languages. Out of the 89 studies obtained initially from the search 60 articles were selected to be included in the systematic review: 1 metaanalysis, 17 systematic reviews, 35 prospective studies, 5 retrospective studies, 1 consensus and 1 semi-structured interviews. The best diagnostic technique is that which we have sufficient experience and training. Definitely tissue biopsy and histopathological examination should remain the gold standard for oral cancer diagnose. In this systematic review it has not been found sufficient scientific evidence on the majority of proposed techniques for early diagnosis of OSCC, therefore more extensive and exhaustive studies are needed.


Vitamin D Deficiency and Autism Spectrum Disorder.
Vitamin D is a neurosteroid hormone crucially involved in neurodevelopment. Neural cell proliferation, neurotransmission, oxidative stress and immune function represent the main mechanisms mediated by vitamin D in the Central Nervous System. Therefore, its deficiency during pregnancy and early childhood may significantly impact on a developing brain, leading to possible adverse neuropsychological outcomes including Autism Spectrum Disorder (ASD). Significant vitamin D deficiency is described within children affected by ASD and in pregnant mothers whose offspring will later develop ASD, suggesting a possible role of the hormone as a contributing risk factor in the etiopathogenesis of ASD. We reviewed the actual literature on the potential contributing role of prenatal and early postnatal vitamin D deficiency in ASD etiopathogenesis, at both genetic and environmental levels, and the possible effect of vitamin D supplementation in autistic children. Conflicting but promising results emerged on the topic. Further Randomized Controlled Trials studies carried out during pregnancy and early infancy are necessary for better understanding the possible contribution of vitamin D deficiency in the etiopathogenesis of autism and the potential efficacy of the hormone supplementation in the improvement of ASD core symptoms.


Painful adult thoracic Scheuermann's disease. Diagnosis by discography and treatment by combined arthrodesis.
This is the case report of a 42-year-old woman with chronic thoracic pain, nonradicular and refractory to all nonoperative treatment. Radiographs showed the classic findings of Scheuermann's disease, but without abnormal kyphosis. Magnetic resonance imaging scans showed multilevel thoracic disc degeneration typical of long-term Scheuermann's disease. Thoracic discography revealed concordant pain at T6-7 and T7-8. Treatment consisted of an anterior fusion, T5-11, and posterior fusion of T3 through L1, with Cotrel-Dubousset instrumentation. At follow-up, she was pain free and able to work full time and had been able to return to golf, her favorite recreation. Discography of the thoracic spine, as of the lumbar spine, can reveal the true source of pain and thus lead to precise and effective treatment.


Palladium-Catalyzed Diversified Synthesis of Monofluorinated Alkenes from Allylic gem-Difluorides through Pd-OH Intermediate.
Significant advancements in synthesis of monofluoroalkenes via palladium-catalyzed reactions involving allylic gem-difluorides and diverse nucleophiles have been achieved. This method allows regioselective arylation, alkylation, allylation, alkenylation, and hydrogenation of allylic gem-difluorides, yielding high Z-selectivity and favorable product yields under mild conditions. Tolerating various functional groups, these transformations utilize a common Pd-OH intermediate. Additionally, employing triple Pd-catalyzed cross-coupling yields diverse trisubstituted alkenes efficiently.


Lipopolysaccharide induces physical proximity between CD14 and toll-like receptor 4 (TLR4) prior to nuclear translocation of NF-kappa B.
CD14, a GPI-linked protein, plays a pivotal role in LPS-mediated signaling by potentiating leukocyte adherence, activation, and cytokine production. Recent studies have identified the Toll-like receptor 4 (TLR4) as a membrane cofactor in LPS-mediated transmembrane signaling in cytokine induction, although the mechanism responsible for this cooperation is unknown. Using fluorescence resonance energy transfer (RET) techniques, we demonstrate that LPS triggers a physical association between CD14 and TLR4. Because LPS stimulation upregulates CD14 and TLR4 expression, it was necessary to control for the possibility that these newly expressed molecules were associated with one another independent of LPS stimulation. Although the calcium ionophore A23187 increased the expression of CD14 and TLR4, they did not exhibit energy transfer. However, following A23187 treatment, LPS promoted physical proximity between CD14 and TLR4. Therefore, we suggest that a close interaction between CD14 and TLR4 participates in LPS signaling, leading to nuclear translocation of NF-kappaB.


[Translated article] Wound closure after knee and hip replacement (TKA and THA): Survey results on the clinical practice in Spain.
In orthopaedic surgery, it is clear that an optimal standardised closure technique has not yet been developed. Locally, there are no objective data describing the standard surgical practice in wound closure. The aim of this study is to analyse the clinical practice of surgical wound closure in orthopaedic surgery by means of a survey of a representative local sample and thus obtain information on the context of closure in Spain. An ad hoc group of specialists in orthopaedic surgery and traumatology was formed. The group of experts, after analyzing the literature, developed a questionnaire of 32 closed multiple-choice questions divided into the following blocks: hemostasis, surgical wound closure (deep, superficial, and cutaneous), and dressings. A total of 471 surgeons responded to the survey completely and with sufficient information to perform the descriptive analysis. 79% believe that ATX can influence the decrease in surgical site infection rate. 96% believe that the type of deep closure at the level of the arthrotomy could influence outcomes and complications after hip and/or knee replacements. 85% believe that the type of shallow closure at the subcutaneous level may influence outcomes and complications after hip and/or knee replacement. 64% of surgeons use single-use incisional negative pressure therapy for the treatment of surgical wound complications (seroma, prolonged drainage, dehiscence). There is a high level of variability in wound closure in our setting and a low level of training on the subject. The authors recommend that the different scientific societies invest resources to improve training in this field and reduce the percentage of surgeons who are considered inadequately trained, as well as adapting closure techniques to those considered gold standard according to the evidence.


Parry Romberg Syndrome: A Unique Clinico-radiological Entity.
Parry Romberg syndrome (PRS) is an unusual neurological entity characterized by progressive hemifacial atrophy. We describe the case of a 17-year-old male who presented with recurrent seizures and facial asymmetry of 1 year duration. Computed tomography (CT) of the head showed right-sided hemifacial atrophy involving the subcutaneous fat, muscles, and bones alongwith subcortical white matter hypodensity, having parenchymal foci of calcification. The etiology of PRS is debated from being secondary to abnormalities in fat metabolism to autoimmune and inflammatory causes. The treatment is symptomatic and is targeted at relief of seizures and migraine. Steroids and other immunomodulators have proven successful in some cases. Surgical correction may be done once the disease stabilizes.


Patterns of body fat deposition in youth and their relation to left ventricular markers of adverse cardiovascular prognosis.
The patterns of body fat deposition in healthy youth and their relation to future development of cardiovascular disease remain incompletely understood. To further evaluate these patterns, we measured indirect indexes of central and general fat deposition in healthy adolescents (mean age 15.4+/-2.3 years) with family histories of hypertension. We examined the relation between these indexes and echocardiographic markers of adverse prognosis as well as the effect of gender and ethnicity. All 225 subjects (64% black and 48% female) had > or =1 biologic parent and 1 grandparent with hypertension. Skinfold thicknesses, waist-to-hip girth ratio, Quetelet index, Ponderal index, conicity, and Z score weight - Z score height were measured. Left ventricular (LV) mass, indexed LV mass, relative wall thickness (RWT), and midwall fractional shortening (MFS) were determined using echocardiography. In both black and white subjects, the adiposity indexes were significantly correlated with posterior wall thickness, total LV mass, and indexed LV mass (p <0.05 for all). Additionally, in black subjects, central adiposity was inversely related to MFS and directly related to RWT and septal thickness. General adiposity independently predicted indexed and nonindexed LV mass, whereas central adiposity predicted MFS and RWT. Compared with subjects with normal LV geometry, those with abnormal geometry were heavier and fatter based on every index of obesity (p <0.03 for all). Thus, indexes of fat deposition are significantly correlated with LV markers of adverse prognosis in healthy youth.


Use of 23Na nuclear magnetic resonance spectroscopy to determine the true intracellular concentration of free sodium in a halophilic eubacterium.
We present new data obtained by 23Na nuclear magnetic resonance spectroscopy, which can distinguish free intracellular sodium from cell-bound sodium, showing that the intracellular concentration of Na+ the halophilic eubacterium Vibrio costicola is only 5 to 20% of that in the extracellular medium. Previous methods could not distinguish free intracellular Na+ from that bound to cell structures, and it was believed that in halophilic eubacteria the total monovalent cation concentration inside matched that of the NaCl outside. Information obtained by the newer technology raises fundamental questions about the ways in which these organisms and others which live in hypersaline environments function and cope with osmotic stress.


Gut Microbiota in Cardiovascular Health and Disease.
Significant interest in recent years has focused on gut microbiota-host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. In addition to alterations in gut microbiota composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent studies revealed that gut microbiota can elicit a variety of effects on the host. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites, that can impact host physiology. Microbiota interact with the host through many pathways, including the trimethylamine/trimethylamine N-oxide pathway, short-chain fatty acids pathway, and primary and secondary bile acids pathways. In addition to these metabolism-dependent pathways, metabolism-independent processes are suggested to also potentially contribute to cardiovascular disease pathogenesis. For example, heart failure-associated splanchnic circulation congestion, bowel wall edema, and impaired intestinal barrier function are thought to result in bacterial translocation, the presence of bacterial products in the systemic circulation and heightened inflammatory state. These are thought to also contribute to further progression of heart failure and atherosclerosis. The purpose of the current review is to highlight the complex interplay between microbiota, their metabolites, and the development and progression of cardiovascular diseases. We will also discuss the roles of gut microbiota in normal physiology and the potential of modulating intestinal microbial inhabitants as novel therapeutic targets.


[Pedigree investigation of familial non-insulin dependent diabetes mellitus].
To discuss the inheritant mode of familial NIDDM. According to WHO criteria of DM, 100 NIDDM Probands with family history of DM were diagnosed and 100 persons were chosen at random for controls. The survey of DM was performed in both groups, including FBG, HbAlc, FINS. Some members had insulin release test. The prevalance rates of DM in familial DM group were 26 times of the control group (34.3% and 1.3%). The prevalance rate of DM among first-degree relation was 18 times higher than that in general population (28.3% and 1.5%). The rate of diabetes in the siblings and in the off-springs was 44.4% and 9.7% respectively. The pedigree analyses showed that 83.9% affected families had one diabetic parent, one half siblings had DM, and there was a successive transmission of DM through at least three generations in sixteen large families. Besides, the incidence of DM was much higher in females than in males (40% and 28%). Among affected parents, diabetlic mothers were much more than diabetic fathers (50.8% and 27.6% P < 0.01). Familial NIDDM had a familial aggregation. It was inherited in the manner of Mendelian autosomal dominant inheritance. The difference between the rate in DM mothers and fathers was probably due to unequal prevalance rate in females and males.