Clinical outcomes of radiofrequency catheter ablation of ventricular tachycardia in patients with hypertrophic cardiomyopathy.
Monomorphic ventricular tachycardia (VT) is rare in patients with hypertrophic cardiomyopathy (HCM), management of which is challenging. Limited data exists on the utility of catheter ablation for the treatment of VT in this population. We aimed to assess clinical outcomes of catheter ablation for VT in HCM patients. A systematic search, without language restriction, using PubMed, EMBASE, SCOPUS, Google Scholar, and ClinicalTrials.gov was performed. The meta-analysis was performed using a meta-package for R version 4.0/RStudio version 1.2 and Freeman Tukey double arcsine method to establish the variance of raw proportions. Outcomes measured included (1) acute procedure success (defined as noninducible for clinical VT), (2) freedom from VT at follow-up, (3) mortality. This systematic review of six studies (three from the United States and three from Japan) incorporated a total of 68 drug-refractory HCM patients who underwent VT radiofrequency catheter ablation (mean age 57.6 ± 13.3 years, mean LVEF 45.8 ± 15.4%, 85% men, maximum septal wall thickness 17.4 ± 4.6 mm, and 32.3% with an apical aneurysm). Acute procedural success was achieved in 84.5% patients (95% confidence interval [CI]: 70.6%-95.2%) with 27.9% patients had recurrent VT requiring multiple ablations (median 1, IQR 1-3). During the follow-up period (18.3 ± 11.7 months), the pooled incidence of freedom from recurrent VT after index procedure was 70.2% (95% CI: 51.9%-86.2%), while after the last ablation was 82.8% (95% CI: 57%-99.2%). There were two deaths during follow-up, one from heart failure and one from SCD 0.8% (95% CI: 0%-5.8%). The results of our pooled analysis demonstrated that catheter ablation for VT in HCM patients was associated with high acute procedural success, and reduced VT recurrence-findings comparable to previously published reports in other disease substrates.


In-situ preparation of poly(propylene fumarate)--hydroxyapatite composite.
In-situ precipitation of hydroxyapatite (HAp) in the presence of poly(propylene fumarate) (PPF) is investigated. Amorphous calcium phosphate (ACP) precipitates in the presence of the polymer and remains in the amorphous form for a relatively long time, e.g. even after 24 h of coexistence with the mother solution. Our observations suggest that PPF interacts with the surface of the ACP particles and prevents them from transformation to crystalline hydroxyapatite. The PPF polymer seems to be more efficient in hindering the ACP to HAp transformation at higher pH conditions. From spectroscopic observations we hypothesize that the C=O bond of the PPF molecules interact with the calcium ion of the ACP particles. In case of low molecular weight PPF this interaction may lead to the incorporation of the polymer within the growing ACP particles.


Identification and characterization of oligomeric proanthocyanidins with significant anti-cancer activity in adzuki beans (Vigna angularis).
The aim of the present study was to characterize and evaluate the anti-cancer activity of proanthocyanidin-enriched fractions from adzuki beans. For this purpose, we concentrated proanthocyanidins from adzuki beans (Vigna angularis) into five fractions using Amberlite XAD-1180N, Toyopearl HW40F, and Sepacore C-18 reverse-phase flash column chromatography. Proanthocyanidin-enriched fractions were characterized as (epi)catechin hexamer, heptamer, and octamer, epigallocatechin-(epi)catechin pentamer, and epigallocatechin-(epi)catechin hexamer using electrospray ionization time-of-flight mass spectrometry and thiolytic degradation. These fractions showed significant anti-cancer activity against the human PC-3 prostate cancer cell line. They also significantly suppressed the expression of the fatty acid-binding protein 5 gene, which plays critical roles in cell growth and metastasis in prostate cancer.


Trends in utilization: has extremity MR imaging replaced diagnostic arthroscopy?
To examine the relative change in utilization of magnetic resonance (MR) imaging of the extremities versus diagnostic and therapeutic arthroscopy. Using the 1993, 1996, and 1999 nationwide Medicare Part B databases, utilization rates (per 100000) were determined for upper and lower extremity MR imaging, diagnostic arthroscopy and therapeutic arthroscopy using CPT-4 codes. Utilization of extremity MR imaging was compared with that of diagnostic and therapeutic arthroscopy in 10 geographic regions of the United States and tracked over time. Combined lower and upper extremity MR imaging utilization per 100000 increased from 393 to 1056 in 1999 (+168.7%). Utilization of diagnostic arthroscopy of the extremities decreased from 18 in 1993 to 8 in 1999 (-55.6%); therapeutic arthroscopy rates increased from 461 in 1993 to 636 in 1999 (+40.0%). Specifically, from 1993 to 1999, utilization of lower extremity MR imaging increased from 270 to 661 (+144.8%). Utilization of diagnostic arthroscopy of the knee over the same time period decreased from 11 to 5 (-54.5%); therapeutic arthroscopy increased from 394 to 501 (+27.2%). Similarly, utilization rates for upper extremity MR imaging increased from 123 to 395 (+221.1%). Utilization of diagnostic arthroscopy of the shoulder over the same time period decreased from 7 to 2 (-71.4%); therapeutic arthroscopy increased from 44 to 104 (+136.4%). No specific geographic trends were ascertained. The utilization of MR imaging of the extremities has markedly increased from 1993 to 1999. During the same time period the utilization of diagnostic arthroscopy has decreased and that of therapeutic arthroscopy has increased. These findings support the hypothesis that there is increased reliance of clinical practitioners on the diagnostic information provided by MR imaging in preoperative clinical decision-making.


The History of Incidentally Discovered Penetrating Aortic Ulcers of the Abdominal Aorta.
The management of incidentally discovered penetrating ulcers of the abdominal aorta (PUAA) is not well described. A search of computed tomography (CT) angiography imaging reports for the words "penetrating ulcer" was performed from October 2010 to August 2011. Patients with a PUAA were identified, and their clinical course was followed through December 2014 (n = 53). No specific intervention for the ulcers was sought unless additional aortic pathology necessitated intervention. Prospective and retrospective review of imaging was performed by dedicated vascular radiologists. Aortic diameters and ulcer dimensions were measured for patients with repeat imaging. Mann-Whitney U, Fisher's exact, and Pearson correlation coefficient tests were performed for statistical analysis. The calculated incidence of PUAA for patients undergoing CT imaging was 0.48%. Age at diagnosis was 71.6 ± 10.5 years in a population that included 35 (66.0%) males. Repeat imaging was performed for 29 (54.7%) patients. Median clinical and imaging follow-up was 36 (1-127) months and 34 (1-89) months. A history of hypertension (92.5%), hyperlipidemia (77.4%), and tobacco use (81.8%) was common. Twenty-seven (50.9%) had concomitant aneurysms not necessarily associated with PUAA. No aortic aneurysm or PUAA rupture occurred, but the population was sick with 19 patients (35.8%) deceased at the end of the study. Median aortic diameter growth rate through the PUAA was 0.5 (0-11.4) mm/year. No difference in mortality or aortic pathology was detected in patients with aortic growth rates >1 mm/year compared with <1 mm/year (P = 0.21 and P = 0.71, respectively). Patients with PUAA in general are elderly with multiple comorbidities. A large percentage of patients have concurrent, separate, aortic pathology, most frequently aortic aneurysms. Small changes in the appearance of the PUAA were frequent but did not equate with abdominal aortic catastrophe. Long-term mortality for this population was high, but the ulcer growth during follow-up did not suggest PUAA treatment would improve survival.


Faecal incontinence in children with spina bifida: the best conservative treatment.
Incontinence is one of the major stigmata affecting the quality of life of the myelodysplastic patient. The appropriate management of the neuropathic bladder has led most patients to survive with good conditions. Major advances have also been made in the treatment of faecal incontinence for enabling patients to achieve their full potential, to become integrated in society and to be as independent as possible. We present the results of the Retrograde Colonic Enema (RCE) in 33 patients suffering neurogenic faecal incontinence. We believe that the RCE is one of the best conservative methods of treatment for relieving faecal incontinence originating from spina bifida and other neurological problems with intestinal dysfunction.


Acute neonatal nonketotic hyperglycinemia: normal propionate and methylmalonate metabolism.
Propionyl-CoA carboxylase and combined methylmalonyl-CoA (MMA-CoA) racemase and -mutase activities were studied in liver and fibroblasts of two patients with the acute neonatal form of nonketotic hyperglycemia. In all experiments, these enzyme activities studied in tissues of the patients were within the range of healthy control subjects, whereas no propionyl-CoA carboxylase activity was measurable in the fibroblasts of a patient with propionic acidemia. Subcellular fractionation of liver and fibroblasts indicated that the normal amounts of MMA-CoA found after incubation of whole tissue homogenate were formed by propionyl-CoA carboxylase, a mitochondrial enzyme, and not be acetyl-CoA carboxylase, which theoretically could also be involved in the carboxylation of propionyl-CoA. From the above data as well as from clinical and biochemical observations in three patients, it was concluded that there exists a true nonketotic hyperglycinemia which is not related etiologically to the different disorders of the ketotic hyperglycinemia syndrome. True nonketotic hyperglycinemia is not associated with ketoacidosis even after loading with propionate- and MMA precursors. It must be distinguished by exclusion from mild forms of the ketotic hyperglycinemia syndrome which may present clinically as hyperglycinemia without ketosis.


Exosome biogenesis, secretion and function of exosomal miRNAs in skeletal muscle myogenesis.
Exosomes are membrane-bound extracellular vesicles that are produced in the endosomal compartment of most mammalian cell types and then released. Exosomes are effective carriers for the intercellular material transfer of material that can influence a series of physiological and pathological processes in recipient cells. Among loaded cargoes, non-coding RNAs (ncRNAs) vary for the exosome-producing cell and its homeostatic state, and characterization of the biogenesis and secretion of exosomal ncRNAs and the functions of these ncRNAs in skeletal muscle myogenesis remain preliminary. In this review, we will describe what is currently known of exosome biogenesis, release and uptake of exosomal ncRNAs, as well as the varied functions of exosomal miRNAs in skeletal muscle myogenesis.


Antibiotic-free combinational hyaluronic acid blend nanofibers for wound healing enhancement.
An innovative approach in the functionalization of nanofibers (NFs) for wound healing relies on non-antibiotic combinational therapy to subdue microbial invasion while reducing antimicrobial resistance and enhancing healing. Despite great potentials, wound healing efficacy of NFs embedding antimicrobial metal nanoparticles (NPs)/essential oils has been scarcely documented. We developed combinational NFs using an electrospinnable hyaluronic acid/polyvinyl alcohol/polyethylene oxide blend embedding a new ZnO NPs/cinnamon essential oil (CEO) antimicrobial combination. Fourier transform infrared, X-ray diffraction and transmission electron microscopy confirmed the presence of HA and distribution of ZnO NPs and CEO within NFs. Results for mean diameter, thermal stability, hydrophilicity, tensile strength, in vitro biodegradability, and cytocompatibility of crosslinked combinational NFs were intermediate between those of their singly loaded counterparts. All NFs inhibited the growth of Staphylococcus aureus (S. aureus). Compared with singly loaded NFs, combinational NFs showed the greatest healing efficacy of full thickness S. aureus inoculated incision wounds in rats in terms of bacterial inhibition following a single application, healing speed, and quality of skin structure recovery as verified by morphological, microbiological, and histopathological studies. Results highlighted the potentials of metal NPs/essential oil functionalization of nanofibrous wound dressings as an emerging antibiotic-free combinational approach for more effective and safer wound healing.


Vexed mutations promote degeneration of dopaminergic neurons through excessive activation of the innate immune response.
The hallmark of Parkinson's disease (PD) is the loss of dopaminergic (DA) neurons in the brain. However, little is known about why DA neurons are selectively vulnerable to PD. We previously completed a screen identifying genes associated with the progressive degeneration of DA neurons. Here we describe the role of a previously uncharacterized gene, CG42339, in the loss of DA neurons using Drosophila Melanogaster. CG42339 mutants display a progressive loss of DA neurons and locomotor dysfunction, along with an accumulation of advanced glycation end products (AGEs) in the brain. Based on this phenotype, we refer to CG42339 as vexed. We demonstrate that vexed is specifically required within cortex glia to maintain neuronal viability. Loss of vexed function results in excessive activation of the innate immune response in the brain, leading to loss of DA neurons. We show that activation of the innate immune response leads to increased nitric oxide signaling and accumulation of AGEs, which ultimately result in neurodegeneration. These results provide further insight into the relationship between the role of the immune response in the central nervous system and how this impacts neuronal viability.


Paraneoplastic hypereosinophilia in a patient with peripheral T cell lymphoma, not otherwise specified.
Under normal physiological conditions, the bone marrow (BM) will have between 1% and 6% eosinophils, translating into a peripheral count of 0.05 - 0.5 ×109/L eosinophils in the blood smear. This process is coordinated by transcription factors with specific roles in differentiation and activation. Secondary eosinophilia may be a paraneoplastic syndrome, related to the presence of a subsequent malignancy, as presented in this case report. Such paraneoplastic manifestations should be addressed properly in order for the patient to receive the best treatment of choice. Even if eosinophilia was associated with B-cell malignancies before, this is a report associating this symptom to a peripheral T-cell lymphoma, not other specified, thus emphasizing the importance of a complex approach for the management of the oncological patient.


Long-term functional outcome of suprasellar germinomas: usefulness and limitations of radiotherapy.
We investigated the long-term functional outcome of patients with suprasellar germinoma after radiotherapy to determine the usefulness and limitations of radiotherapy for these tumors. From among 54 cases of intracranial germ cell tumor at Kitasato University Hospital, 12 patients with suprasellar germinoma who were treated with radiotherapy but not chemotherapy retrospectively investigated for mental, hormonal and visual functions. The follow-up period ranged from 63 to 262 months (mean, 161.1 months). The mortality rate was zero and there was no recurrence of tumors. However, three patients treated with local irradiation alone showed metastasis to the ventricles or spinal cord. With regard to mental function, 50% of the patients showed remarkably low mental function after radiotherapy. With regard to pituitary hormonal function, deficiency of ADH, GH, ACTH, and TSH was documented in 75%, 41.7%, 16.7% and 8.3% of the patients, respectively, before radiotherapy. Prolactin was elevated in 50% of the patients. After radiotherapy, 91.7% needed hormone replacement. With regard to visual function, most patients showed an improvement or no change after radiotherapy. In conclusion, radiotherapy for suprasellar germinomas gave long-time survival. However, such radiotherapy may cause mental and pituitary hormonal dysfunction. Our results show that while radiotherapy is useful for treating suprasellar germinomas, its dose have some limitations.


Shoulder muscles recruitment during a power backward giant swing on high bar: a wavelet-EMG-analysis.
This study aimed at determining the upper limb muscles coordination during a power backward giant swing (PBGS) and the recruitment pattern of motor units (MU) of co-activated muscles. The wavelet transformation (WT) was applied to the surface electromyographic (EMG) signal of eight shoulder muscles. Total gymnast's body energy and wavelet synergies extracted from the WT-EMG by using a non-negative matrix factorization were analyzed as a function of the body position angle of the gymnast. A cross-correlation analysis of the EMG patterns allowed determining two main groups of co-activated muscles. Two wavelet synergies representing the main spectral features (82% of the variance accounted for) discriminated the recruitment of MU. Although no task-group of MU was found among the muscles, it appeared that a higher proportion of fast MU was recruited within the muscles of the first group during the upper part of the PBGS. The last increase of total body energy before bar release was induced by the recruitment of the muscles of the second group but did not necessitate the recruitment of a higher proportion of fast MU. Such muscle coordination agreed with previous simulations of elements on high bar as well as the findings related to the recruitment of MU.


Distinct amygdala-autonomic arousal profiles in response to fear signals in healthy males and females.
The amygdala has a key role in regulating arousal and vigilance, and responds to both visual and vocal signals of fear, including facial expressions of fear. In this study, we used functional MRI to examine sex differences in the magnitude, extent, lateralization and time course of amygdala responses to facial signals of fear, in a relatively large sample of males and females. Skin conductance was recorded simultaneously with functional imaging to examine concomitant changes in emotional arousal, and to provide an independent index of response attenuation. Scanning and skin conductance recording was undertaken during perception of facial fear stimuli. Sex differences were apparent in the laterality and time course of fear perception. In males, the right amygdala and autonomic arousal attenuated over the late half of the experiment. By contrast, females showed persistent bilateral amygdala responses, with a tendency towards greater left amygdala engagement during the late phase. Females also showed a greater general extent of amygdala response. We suggest that distinct evolutionary pressures might contribute to a lower threshold for vigilance to signals of danger in females, reflected in a profile of sustained amygdala-arousal interaction.


A Regression Framework for Effect Size Assessments in Longitudinal Modeling of Group Differences.
The use of growth modeling analysis (GMA)--particularly multilevel analysis and latent growth modeling--to test the significance of intervention effects has increased exponentially in prevention science, clinical psychology, and psychiatry over the past 15 years. Model-based effect sizes for differences in means between two independent groups in GMA can be expressed in the same metric (Cohen's d) commonly used in classical analysis and meta-analysis. This article first reviews conceptual issues regarding calculation of d for findings from GMA and then introduces an integrative framework for effect size assessments that subsumes GMA. The new approach uses the structure of the linear regression model, from which effect sizes for findings from diverse cross-sectional and longitudinal analyses can be calculated with familiar statistics, such as the regression coefficient, the standard deviation of the dependent measure, and study duration.


Reactivity to alcohol cues in alcoholics and non-alcoholics: implications for a stimulus control analysis of drinking.
The present study is an attempt to identify responses to alcohol-related stimuli which might differentiate alcoholics from non-alcoholics. The assumption was that alcoholics would be more reactive to alcohol cues because of prior conditioning history with respect to alcohol and drinking. Eight alcoholics in treatment were compared with ten non-alcoholic controls and two recovering alcoholics, using swallowing and salivation as the principal dependent measures. (The concordance of swallowing and salivation was validated using dental rolls with an independent group of ten alcoholics.) Five-minute "sniff-trials" were provided in which subjects smelled either cedar chips or their favorite alcoholic beverage, in a labelled container. Swallowing (salivation) and craving (desire to drink alcohol) were significantly elevated in alcohol-sniffing trials for alcoholics in treatment compared with non-alcoholics; cardiac rate and galvanic skin response duration were also elevated in alcoholics in treatment, though not significantly. Recovering alcoholics resembled alcoholics in treatment more closely than they resembled non-alcoholics. The data were examined in the context of conditioned withdrawal resembled non-alcoholics. The data were examined in the context of conditioned withdrawal and homeostatic protective mechanisms. Implications for the stimulus control analysis of drinking were discussed.


Translational control of long-term synaptic plasticity and memory storage by eIF2alpha.
Both long-lasting changes in synaptic function and long-term memory require gene expression. However, the molecular mechanisms by which gene expression is turned on are not fully understood. In this review, we highlight the role of the eukaryotic initiation factor 2 alpha (eIF2alpha) signalling pathway in long-term synaptic plasticity and memory.


Endoscopic esophageal varix ligation: technique and preliminary results in children.
A technique for treating esophageal variceal hemorrhage in children using endoscopically placed rubber ligatures was evaluated in six children. The method offers a major advantage over chemical obliteration of varices by sclerosants in the absence of systemic, local, or distant organ reactions and, perhaps, in the avoidance of esophageal motor dysfunction.


Wnt signalling in mouse gastrulation and anterior development: new players in the pathway and signal output.
Embryonic development and adult homeostasis are dependent upon the coordinated action of signal transduction pathways such as the Wnt signalling pathway which is used iteratively during these processes. In the early post-implantation mouse embryo, Wnt/β-catenin signalling activity plays a critical role in the formation of the primitive streak, progression of gastrulation and tissue patterning in the anterior-posterior axis. The net output of the signalling pathway is influenced by the delivery and post-translational modification of the ligands, the counteracting activities of the activating components and the negative modulators, and the molecular interaction of β-catenin, TCF and other factors regulating the transcription of downstream target genes.


End-of-Life Issues in UK Medical Schools.
A descriptive study to determine the current status of end-of-life (EOL) issues in UK medical schools. A brief questionnaire was mailed to the 31 medical schools in the United Kingdom in the spring of 2013. Data analysis consisted of frequency distributions. All schools offered some exposure to the topic of dying, death and bereavement, and palliative care, although the orientation had increased somewhat from an earlier study in 2000. The palliative medicine specialist and the nurse specialist in palliative care are the most consistent members of the team. Most schools have hospice participation, with time spent with a hospice patient increasing over the period. Data suggest that UK medical schools have addressed EOL issues. These findings should have significance for medical schools considering changes in their EOL offerings.


Trigeminal pain under vagus nerve stimulation.
Three epilepsy patients treated by cyclic continuous vagus nerve stimulation (VNS) experienced trigeminal pain during the periods of stimulation, which was reported as toothache in the left lower jaw, ipsilateral to the side of stimulation. The symptom occurred with a latency of days to weeks following an increase in stimulation current intensity (SCI). Trigeminal pain was reversible with decrease in SCI, or subsided due to habituation. These findings show that clinically relevant effects of VNS on nociception may occur. Because of the late onset and variable form of this side effect, trigeminal pain may not be regarded as VNS-related which may result in unnecessary diagnostic and therapeutic procedures.


[The registry for severe allergic reactions in German-speaking countries. Recent data and perspectives].
The anaphylaxis registry collects data from patients with severe allergic reactions via an online questionnaire. Currently 85 centers from Germany, Austria, and Switzerland are involved. The data are entered by allergists. They cover demographical data, data of the elicitors, concomitant diseases, circumstances of the allergic reactions, and information about the treatment of affected patients. Until to date the data show that the elicitor profile of severe allergic reactions depends on the age of patients. In childhood, food allergens are the most frequent elicitors, whereas in adults insect stings are most frequently the cause of anaphylaxis. The analysis of concomitant diseases suggests that allergic diseases like allergic asthma, allergic rhinitis or atopic dermatitis occur frequently in children with anaphylaxis, whereas in adults cardiovascular diseases predominate. The data about the medical treatment of affected patients show that antihistamines and corticosteroids are often used in German-speaking countries for the treatment of severe allergic reactions, whereas adrenaline, the drug of choice, is only rarely used (< 20%). The registry is an important clinical epidemiological tool which allows to generate research but also disease management-related questions.


How can psychosomatic physicians contribute to behavioral medicine?
In Japan, there is a unique clinical department, "Psychosomatic Medicine", while there is not a department of behavioral science or behavioral medicine in medical schools. Although only eight medical schools have the department, psychosomatic physicians in the department have been involved with behavioral medicine. In the present manuscript, the author would like to introduce the contribution to behavioral medicine made by psychosomatic physicians in three aspects, education, clinical settings, and research, and propose some strategy for psychosomatic physicians to get more involved with behavioral medicine.


Urchin-like band-matched Fe2O3@In2S3 hybrid as an efficient photocatalyst for CO2 reduction.
Herein, an urchin-like Fe2O3@In2S3 hybrid composite is designed and synthesized using a facile process. The composite efficiently harvests light in both the ultraviolet and visible regions, and the unique hierarchical structure provides several advantages for photocatalytic applications: (i) a suitable band-matching structure and broadband-light absorbing capacity enable the reduction of CO2 into hydrocarbon, (ii) the extensive network of interfacial contact between nano-sized Fe2O3 and In2S3 significantly increases the separation of charge carriers and enhances the utilization of photogenerated electron-hole pairs, and (iii) an abundance of surface oxygen vacancies provide numerous active sites for CO2 molecule adsorption. The optimized Fe2O3@In2S3 composite generated CO from the photocatalytic reduction of CO2 at a rate of 42.83 μmol·g-1·h-1, and no signs of deactivation were observed during continued testing for 32 h under 300 W Xe lamp irradiation.


Total Shoulder Arthroplasty in the Athlete and Active Individual.
Shoulder arthroplasty is becoming more commonly performed in the United States. As it increases, the population also becomes younger, and their demands are different from the older population. Earlier studies have suggested that although young patients have functional outcomes similar to older patients, their satisfaction scores were not as high. Recent literature has demonstrated that young or active individuals with a total shoulder arthroplasty (TSA) have good return rates to sports. Hemiarthroplasty and reverse shoulder arthroplasty, when compared with TSA, have lower but also reasonable return rates to sports.


PAM50 Provides Prognostic Information When Applied to the Lymph Node Metastases of Advanced Breast Cancer Patients.
Purpose: Transcriptional pathway activity and the molecular subtypes of breast cancer metastases have been shown to significantly influence patient postrelapse survival. Here, we further determine the relevance of clinically employed gene signatures in the advanced breast cancer (ABC) setting.Experimental Design: Sufficient RNA for expression profiling was obtained from distant metastatic or inoperable loco-regional relapse tissue by fine-needle aspiration from 109 patients of the Swedish TEX clinical trial. Gene signatures (GGI, 70 gene, recurrence score, cell-cycle score, risk of recurrence score, and PAM50) were applied to all metastases, and their relationship to long- (5-year) and short-term (1.5-year) postrelapse survival at all and locoregional lymph nodes (n = 40) versus other metastatic sites (n = 69) combined was assessed using Kaplan-Meier and/or multivariate Cox regression analyses.Results: The majority of metastases were classified into intermediate or high-risk groups by all signatures, and a significant association was found between metastatic signature subgroups and primary tumor estrogen receptor status and histologic grade (P < 0.05). When considering all sites of metastasis, only PAM50 was statistically significant in Kaplan-Meier analysis (Log-rank P = 0.008 and 0.008 for long- and short-term postrelapse breast cancer-specific survival, respectively). This significance remained in both uni- and multivariate models when restricting analyses to lymph node metastases only, and a similar trend was observed in other metastatic sites combined, but did not reach formal significance.Conclusions: Our findings are the first to demonstrate that the PAM50 signature can provide prognostic information from the lymph node metastases of ABC patients. Clin Cancer Res; 23(23); 7225-31. ©2017 AACR.


Cytokine profile in multiple myeloma.
Cytokines play a crucial role in the growth, survival and dissemination of malignant plasma cells in patients of multiple myeloma (MM). We estimated concentrations of five key cytokines: Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Tumor Necrosis Factor- alpha (TNF- α), B-cell activating factor (BAFF), and Receptor Activator of Nuclear Factor-κB ligand (RANKL) in newly diagnosed and relapsed/refractory MM (RRMM). The study groups include 68 newly diagnosed and 21 relapsed/refractory (RR) MM patients. 32 out of 68 newly diagnosed MM patients were evaluated for serum cytokine concentrations after their treatment. For survival analysis, the various parameters were studied in relation to both progression free survival (PFS) and overall survival (OS). The median serum levels of VEGF, IL-6, BAFF and RANKL were higher in RRMM compared with newly diagnosed patients. However, the difference was significant for BAFF levels (p = 0.04). The median serum levels of VEGF, IL-6, TNF-α, BAFF and RANKL were significantly higher in newly diagnosed and RRMM patients, compared to controls. We also observed lower plasma levels of VEGF (p=<0.0001) and BAFF (p=<0.0001) in BM compartment compared to the levels in serum from peripheral blood of newly diagnosed patients. Significant reduction in the median levels of IL-6, TNF-α, BAFF and RANKL was seen after 4-6 cycles of induction treatment in responders but not in non-responders. On survival analysis, RRMM patients had inferior median OS and PFS compared to that in newly diagnosed MM patients and found to be significantly associated with low haemoglobin representing the more aggressive disease biology in recurrent myeloma. The mean levels of IL-6 were significantly different in patients who died as compared to patients who were alive. The present study demonstrates that the serum levels of VEGF, IL-6, TNF, BAFF and RANKL are significantly elevated and decrease significantly after treatment. The concentrations of circulating cytokines will reflect those of the bone marrow and could be used for subsequent analyses.


Geographic Distribution of the Ciclovia and Recreovia Programs by Neighborhood SES in Bogotá: How Unequal is the Geographic Access Assessed Via Distance-based Measures?
Ciclovia, also known as Open Streets initiatives in other countries, are city streets that are closed to motorized traffic and opened during certain times to residents for engaging in physical activity (PA). These initiatives are viewed by policy makers and health and community advocates as being beneficial to social, environmental, and community health. This study explores the geographic distribution of Ciclovia and Recreovia and the differences in geographic access assessed via distance-based measures, based on the socioeconomic status (SES) of the area. Results from this study show that the median distance to the Ciclovia according to SES ranges from 2930 m for SES 1 (most disadvantaged) to 482 m for SES 6 (wealthiest). The median distance to the Recreovia sites ranges from 5173 m for SES 1 to 3869 m for SES 6. This study found revealing urban inequities in the distribution of Ciclovia, whereas there was less inequalities within the Recreovia sites. This study shows that urban interventions are needed to promote recreational activity and reduce health disparities in under resourced, low SES areas.


Transport of N-acetyl-D-mannosamine and N-acetyl-D-glucosamine in Escherichia coli K1: effect on capsular polysialic acid production.
N-Acetyl-D-mannosamine (ManNAc) and N-acetyl-D-glucosamine (GlcNAc) are the essential precursors of N-acetylneuraminic acid (NeuAc), the specific monomer of polysialic acid (PA), a bacterial pathogenic determinant. Escherichia coli K1 uses both amino sugars as carbon sources and uptake takes place through the mannose phosphotransferase system transporter, a phosphoenolpyruvate-dependent phosphotransferase system that shows a broad range of specificity. Glucose, mannose, fructose, and glucosamine strongly inhibited the transport of these amino-acetylated sugars and GlcNAc and ManNAc strongly affected ManNAc and GlcNAc uptake, respectively. The ManNAc and the GlcNAc phosphorylation that occurs during uptake affected NeuAc synthesis in vitro. These findings account for the low in vivo PA production observed when E. coli K1 uses ManNAc or GlcNAc as a carbon source for growth.


Predicting the occurrence of monooxygenases and their associated phylotypes in soil microcosms.
Cometabolic oxidation involves the oxidation of chemicals often by monooxygenases or dioxygenases and can be a removal process for environmental contaminants such as trichloroethene (TCE) or 1,4-dioxane. Information on the occurrence of these genes and their associated microorganisms in environmental samples has the potential to enhance our understanding of contaminant removal. The overall aims were to 1) ascertain which genes encoding for monooxygenases (from methanotrophs, ammonia oxidizing bacteria and toluene/phenol oxidizers) and other key enzymes are present in soil microcosms and 2) determine which phylotypes are associated with those genes. The approach involved a predictive tool called PICRUSt2 and 16S rRNA gene amplicon datasets from two previous soil microcosm studies. The following targets from the KEGG database were examined: pmo/amo, mmo, dmp/pox/tomA, tmo/tbu/tou, bssABC (and downstream genes), tod, xylM, xylA, gst, dhaA, catE, dbfA1, dbfA2 and phenol 2-monooxygenase. A large number of phylotypes were associated with pmo/amo, while mmo was linked to only five. Several phylotypes were associated with both pmo/amo and mmo. The most dominant microorganism predicted for mmoX was Mycobacterium (also predicted for pmo/amo). A large number of phylotypes were associated with all six genes from the dmp/pox/tomA KEGG group. The taxonomic associations predicted for the tmo/tbu/tou KEGG group were more limited. In both datasets, Geobacter was a key phylotype for benzylsuccinate synthase. The dioxygenase-mediated toluene degradation pathway encoded by todC1C2BA was largely absent, as were the genes (xylM, xylA) encoding for xylene monooxygenase. All other genes investigated were predicted to be present and were associated with a number of microorganisms. Overall, the analysis predicted the genes encoding for sMMO (mmo), T3MO/T3MO/ToMO (tmo/tbu/tou) and benzylsuccinate synthase (bssABC) are present for a limited number of phylotypes compared to those encoding for pMMO/AMO (pmo/amo) and phenol monooxygenase/T2MO (dmp/poxA/tomA). These findings suggest in soils contaminant removal via pMMO/AMO or phenol monooxygenase/T2MO may be common because of the occurrence of these enzymes with a large number of phylotypes.


Bone Tissue Responsiveness To Mechanical Loading-Possible Long-Term Implications of Swimming on Bone Health and Bone Development.
To revisit the bone tissue mechanotransduction mechanisms behind the bone tissue response to mechanical loading and, within this context, explore the possible negative influence of regular swimming practice on bone health, particularly during the growth and development period. Bone is a dynamic tissue, responsive to mechanical loading and unloading, being these adaptative responses more intense during the growth and development period. Cross-sectional studies usually report a lower bone mass in swimmers compared to athletes engaged in weigh-bearing sports. However, studies with animal models show contradictory findings about the effect of swimming on bone health, highlighting the need for longitudinal studies. Due to its microgravity characteristics, swimming seems to impair bone mass, but mostly at the lower limbs. It is unkown if there is a causal relationship between swimming and low BMD or if other confounding factors, such as a natural selection whithin the sport, are the cause.


Microvascular obstruction in non-infarct related coronary arteries is an independent predictor of major adverse cardiovascular events in patients with ST segment-elevation myocardial infarction.
Coronary microvascular obstruction (MVO) in infarct-related artery (IRA) territory has been associated with worse cardiovascular outcomes in patients presenting with ST-segment elevation myocardial infarction. However, the prognostic value of non-IRA MVO in this patient population remains unknown. One hundred ninety nine patients presenting to our institution with STEMI were enrolled. All patients underwent primary percutaneous coronary intervention per institutional STEMI protocol followed by a cardiac MRI within 1 week of presentation and the IRA and non-IRA MVO segments were determined. All cause death, recurrent myocardial infarction, hospitalization for heart failure, and ventricular tachycardia were counted as major adverse cardiovascular events (MACE). Patients with non-IRA MVO had lower composite MACE free survival at 6 months (HR 2.15, 95% CI, 1.06-4.35; p = 0.029) compared to those without non-IRA MVO. In a sub-analysis of patients with multi vessel disease (MVD), patients with non-IRA MVO also had lower composite MACE-free survival at 6 months as compared to those without non-IRA MVO (HR 2.47, 95% CI, 1.02-5.97; p = 0.037). Non-IRA MVO continued to be predictive of MACE in a cox proportional hazards model adjusting for additional prognostic factors using inverse probability weighting (p = 0.007). Non-IRA MVO was more prevalent in patients with LAD culprit vessel STEMI rather than those with RCA or Circumflex culprit vessels (p < 0.001). Patients presenting with STEMI and non-IRA MVO have significantly lower MACE free survival at 6 months as compared to those without non-IRA MVO.


Seven cases of parathyroid carcinoma and review of the literature.
Parathyroid cancer is a rare malignancy and an uncommon cause of hyperparathyroidism. In the present study, we present seven cases of parathyroid carcinoma. The female ratio was 5/7 (71.4%). Median age at diagnosis was 47 years, and median follow-up duration was 60 months (IQR 29-75). Mean calcium level at diagnosis was 12.7 mg/dL (range, 11.3-13.9), and mean parathormone level was 1115 ng/L (IQR 287-1470). Two patients (28.5%) had a palpable neck mass. Coexisting brown tumor was present in three patients (42.8%), and nephrolithiasis was found in one patient (14.2). Average tumor size was 29 mm (IQR 28-40). Capsular and vascular invasion were detected in six patients (85.7%), intrathyroidal spread was observed in two patients (28.5%), and soft tissue invasion was seen in three patients (42.8%). Parathyroid adenoma was present in one patient and parathyroid gland hyperplasia in another patient. Adjuvant radiotherapy was given to four patients (57.1%). There was no metastatic disease or death. At the last visit, two patients had increased parathormone levels and no additional focus could be detected in either. Patients with markedly elevated parathormone and calcium levels and a palpable larger mass on the neck should be evaluated for parathyroid cancer. En bloc resection is the mainstay treatment. Despite contradictory results, adjuvant radiotherapy to the neck may help to reduce the risk of local recurrence in patients with microscopic residual parathyroid carcinoma.


Pathogenesis-based new perspectives of management of ANCA-associated vasculitis.
While the pathogenesis of anti-neutrophil cytoplasmic autoantibody associated vasculitis (AAV) is still not fully elucidated, there is a mounting evidence that the process is initiated by inflammation and activation of innate immunity in the presence of predisposing factors, innate immunity abnormalities, aberrant responses of the adaptive immune system, and complement system activation. Biologics targeting inflammation-related molecules in the immune system have been explored to treat AVV, and these treatments have provided revolutionary advances. When focusing on the pathogenic mechanisms of AVV, this review presents the new findings regarding novel therapeutic approaches for the management of these conditions.


Polymorphism of the estrogen receptor β gene is related to infertility and infertility-associated endometriosis.
To determine the frequency of the estrogen receptor b gene (ERβ) +1730 G/A polymorphism in infertile women with and without endometriosis and controls. Case-control study that included 136 women with endometriosis, 69 women without endometriosis and 209 fertile women as controls. The ERβ gene + 1730 G/A polymorphism was identified by RFLP-PCR (Restriction Fragment Length Polymorphism - Polymerase Chain Reaction). Genotypes GG, GA and AA of the ERβ gene presented frequencies of 60.3%, 38.2% and 1.5%, respectively, in the women with endometriosis (p < 0.0022). Of the infertile women without endometriosis, 63.8% presented the normal homozygous genotype GG, 30.4% the GA heterozygous genotype, and 5.8% the homozygous mutated genotype AA (p < 0.0275). In the control group, 77.5% presented the normal homozygous genotype GG, 21.1% the heterozygous genotype GA, and 1.4% the homozygous mutated genotype AA. The data suggest that the estrogen receptor β gene (ERβ) +1730 G/A polymorphism can be associated with risk of infertility and endometriosis-associated infertility.


Genetic control and regulatory mechanisms of succinoglycan and curdlan biosynthesis in genus Agrobacterium.
Agrobacterium is a genus of gram-negative bacteria that can produce several typical exopolysaccharides with commercial uses in the food and pharmaceutical fields. In particular, succinoglycan and curdlan, due to their good quality in high yield, have been employed on an industrial scale comparatively early. Exopolysaccharide biosynthesis is a multiple-step process controlled by different functional genes, and various environmental factors cause changes in exopolysaccharide biosynthesis through regulatory mechanisms. In this mini-review, we focus on the genetic control and regulatory mechanisms of succinoglycan and curdlan produced by Agrobacterium. Some key functional genes and regulatory mechanisms for exopolysaccharide biosynthesis are described, possessing a high potential for application in metabolic engineering to modify exopolysaccharide production and physicochemical properties. This review may contribute to the understanding of exopolysaccharide biosynthesis and exopolysaccharide modification by metabolic engineering methods in Agrobacterium.


Bioavailability and bioconcentration potential of perfluoroalkyl-phosphinic and -phosphonic acids in zebrafish (Danio rerio): Comparison to perfluorocarboxylates and perfluorosulfonates.
Currently, information regarding bioavailability and bioconcentration potential of perfluoroalkyl phosphinic acids (PFPiAs) in aquatic organisms does not exist. The main objective of the present study was to assess uptake and elimination kinetics of PFPiAs in zebrafish (Danio rerio) following aqueous exposure. The results showed that PFPiA exposure can result in very high steady-state bioconentration factors (BCFss), compared to perfluorocarboxylates and perfluorosulfonates.C6/C10 PFPiA exhibited the highest BCFss, ranging between 10(7) and 10(10), orders of magnitude higher than those for long-chain perfluorocarboxylates. Strong positive relationships were observed between BCFss versus the membrane-water distribution coefficient (Dmw) and the protein-water partition coefficient (Kpw) of the studied perfluoroalkyl substances. However, BCFss exhibited a substantial drop for the very hydrophobic PFPiAs (C8/C10 and C6/C12 PFPiAs). The reduced BCFss of these long-chain PFPiAs (perfluoroalkyl chain length=18; Dmw=10(9)) is likely the result of reduced bioavailability due to interaction with solute molecules/organic matter present in the water phase and/or reduced gill membrane permeability. While PFPiAs can be metabolized to perfluoroalkyl phosphonic acids, the metabolic transformation rate seems insufficient to counteract the high degree of uptake across gill membranes. These findings help to better understand exposure pathways and bioaccumulation behavior of these important perfluorinated acids in aquatic systems.


Phosphorylation of protamines by protein kinase C: involvement of sites which are phosphorylated in vivo and are not affected by cAMP-dependent protein kinase.
Most fish protamines contain two phosphorylatable sites both of which incorporate phosphate in vivo. Here we show that in two protamines (salmine A1 and clupeine Y1) the site more distant from the N-terminus (residues 20-21) is unaffected by cAMP-dependent protein kinase while it represents the main target for protein kinase C. Such a phosphorylation is typically independent of Ca2+ and phospholipids: responsiveness to these effectors however is conferred by previous fragmentation of protamine with thermolysin. These results suggest that Ca2+, phospholipid-independent phosphorylation of protamine by protein kinase C might have physiological relevance and shed light on the structural basis for the specificity of such an unique process.


Necrostatin-1s Suppresses RIPK1-driven Necroptosis and Inflammation in Periventricular Leukomalacia Neonatal Mice.
Periventricular leukomalacia (PVL), a predominant form of brain injury in preterm survivors, is characterized by hypomyelination and microgliosis and is also the major cause of long-term neurobehavioral abnormalities in premature infants. Receptor-interacting protein kinase 1 (RIPK1) plays a pivotal role in mediating cell death and inflammatory signaling cascade. However, very little is known about the potential effect of RIPK1 in PVL and the underlying mechanism. Herein, we found that the expression level of RIPK1 was drastically increased in the brain of PVL neonatal mice models, and treatment of PVL neonatal mice with Necrostatin-1s (Nec-1s), an inhibitor of RIPK1, greatly ameliorated cerebral ischemic injury, exhibiting an increase of body weights, reduction of cerebral infarct size, neuronal loss, and occurrence of necrosis-like cells, and significantly improved the long-term abnormal neurobehaviors of PVL. In addition, Nec-1s significantly suppressed hypomyelination and promoted the differentiation of oligodendrocyte precursor cells (OPCs), as demonstrated by the increased expression levels of MBP and Olig2, the decreased expression level of GPR17, a significant increase in the number of CC-1-positive cells, and suppression of myelin ultrastructure impairment. Moreover, the mechanism of neuroprotective effects of Nec-1s against PVL is closely associated with its suppression of the RIPK1-mediated necrosis signaling molecules, RIPK1, PIPK3, and MLKL. More importantly, inhibition of RIPK1 could reduce microglial inflammatory injury by triggering the M1 to M2 microglial phenotype, appreciably decreasing the levels of M1 marker CD86 and increasing the levels of M2 markers Arg1 or CD206 in PVL mice. Taken together, inhibition of RIPK1 markedly ameliorates the brain injury and long-term neurobehavioral abnormalities of PVL mice through the reduction of neural cell necroptosis and reversing neuroinflammation.


Halogenated anesthetics vs intravenous hypnotics for short and long term sedation in the intensive care unit: A meta-analysis.
To comprehensively assess peer-reviewed studies using volatile (VA) or intravenous (i/v) anesthetics for sedation in intensive care units (ICUs), with the hypothesis that the type of sedation may have an impact on survival and other clinically relevant outcomes. Systematic review and meta-analysis of randomized and non-randomized trials. ICUs. Critically ill and postoperative patients. None. Studies comparing VA versus i/v anesthetics used in the ICU settings were independently systematically searched. Finally, 15 studies (1520 patients of predominantly surgical profile needed VA sedation for less than 96h) were included. VA had no impact on all-cause mortality (very low quality of evidence, Odds Ratio=0.82 [0.60-1.12], p=0.20). However, VA were associated with a reduction in duration of mechanical ventilation (p=0.03) and increase in ventilator-free days (p<0.001). VA also reduced postoperative levels of cardiac troponin (24h), time to extubation (p<0.001) and awakening (p=0.04). In this meta-analysis, volatile sedation vs propofol caused the increase in ventilator-free days, the reduction in the duration of mechanical ventilation, time to extubation and the troponin release in medical or surgical ICU patients, while in surgical ICU patients the time to awakening was shortened.


An asymmetric synthesis of (R) and (S)-1-alkoxy-2,3-propanediols including precursors to platelet activating factor.
The titanium-assisted nucleophilic opening of glycidol with primary aliphatic alcohols gives 1-alkoxy-2,3-propanediols. The titanium alkoxide used in the reaction should be the alkoxide of the alcohol used for the reaction. When optically active (S)-glycidol is used in the reaction, (S)-1-alkoxy-2,3-propanediols are obtained without loss of optical activity. When the reaction is carried out at 70-75 degrees C without solvent, the 1-alkoxy-2,3-propanediols are obtained in yields of 45-59%. The regioisomeric 2-alkoxy-1,3-propanediols are found to the extent of 4-6% in the reaction. The optical purity of glycidol can be measured from the high field (500 MHz) nuclear magnetic resonance spectrum of the Mosher ester.


Treatment principles of atopic dermatitis.
Atopic dermatitis (AD) is today the most common, chronic inflammatory skin disease among children in developed countries. Its cumulative prevalence varies from 20% in northern Europe and the USA to approximately 5% in Mediterranean countries. As a chronic disease it puts a special demand on treatment. There is no curative therapy, but competent guidance on treatment principles can control the disease in most, if not all children. This article summarizes the evidence-based knowledge that relates to the treatment of atopic eczema. It also gives advice and opinions on prophylactic measures as these are the focus of interest from most parents. This article should enable you to give advice and guidance to parents of children with AD, including what is necessary for diagnosis, what is of value and importance considering allergies and allergological investigations, allergen exposure, prophylactic measures, diets and indoor environment. Finally, you should be able to explain the diversity of treatment principles for parents.


Chronic relapsing experimental allergic encephalomyelitis: its value as an experimental model for multiple sclerosis.
Comparison of the pathohistology of chronic relapsing experimental allergic encephalomyelitis (CR-EAE) and multiple sclerosis (MS) reveals a close similarity. Thus, CR-EAE appears to be a valuable model for the study of pathogenetic factors leading to the formation of MS lesions, although the induction of the disease may be different (active sensitization with CNS antigens and adjuvant in CR-EAE versus unknown etiology in MS). CR-EAE furthermore mimicks the pathohistological patterns of other related human inflammatory demyelinating diseases (i.e., acute perivenous leukoencephalomyelitis and acute hemorrhagic leukoencephalomyelitis). The expression of an acute, predominantly inflammatory versus chronic inflammatory demyelinating disease in this model depends upon the time interval between sensitization and sampling of the animals. Recent evidence is discussed that a cooperation between cellular and humoral immune mechanisms, directed against multiple CNS antigens, is responsible for the formation of large demyelinated plaques in EAE and MS.


Preliminary experience with inhaled nitric oxide for acute pulmonary hypertension after heart transplantation.
Substantial interest has developed in the physiologic and therapeutic role of nitric oxide in the last few years. In patients with pulmonary hypertension it appears to be a useful selective pulmonary vasodilator; however, many issues of both staff and patient safety remained unanswered. This study examines further safety issues and also presents preliminary clinical experience in patients after orthotopic heart transplantation with pulmonary hypertension and right-sided ventricular failure. Atmospheric levels of nitric oxide and nitrogen dioxide are 100 times less than occupational health standards. When nitric oxide is used at 70 parts per million in the presence of a fraction of inspired oxygen greater than 0.60, nitrogen dioxide levels in the circuit exceed the published short-term exposure limit of the American Conference of Government Industrial Hygienist of 5 parts per million. Staff safety appears confirmed, but despite encouraging clinical results, further longer term safety and efficacy studies are indicated.


Detergent and methylene blue affect endothelium-dependent vasorelaxation and pressure/flow relations in rat blood perfused mesenteric arterial bed.
1. The autoperfused superior mesenteric arterial bed of the rat was used to study the opposition by carbachol of pressor responses to noradrenaline and the effects of methylene blue, the detergent CHAPS and indomethacin on pressure/flow relations. 2. Carbachol (1 ng-3 micrograms) reduced the pressor response to 1 microgram noradrenaline in a dose-dependent manner with an ED50 = 25.5 +/- 6.0 ng and a maximum inhibition of 51.8 +/- 1.9%. Perfusion of the mesenteric bed with 0.3% CHAPS in saline for 150s abolished the reduction by carbachol of the noradrenaline pressor response. The effect of carbachol was also abolished by infusion of 1% methylene blue into the mesenteric vascular bed. Indomethacin (5 mg kg-1) was without significant effect on the carbachol opposition of noradrenaline pressor responses. None of the 3 treatments had any effect on the response to 1 microgram noradrenaline. 3. Perfusion with CHAPS before determination of pressure/flow relations, or infusion of methylene blue during their determination, steepened the regression of pressure upon flow to the same extent; at all the flow rates used (0.4-3.54 ml min-1) pressure was greater as a result of the treatment than in control animals. Pretreatment with indomethacin had no effect on pressure/flow relations. 4. It is concluded that carbachol opposition to noradrenaline pressor responses in the blood perfused superior mesenteric arterial bed of the rat shows the characteristics of being mediated by endothelium-dependent relaxing factor (EDRF). Since vascular resistance increases more rapidly than in controls when the endothelium is functionally inhibited by treatment with CHAPS or perfusion with methylene blue, it appears that EDRF has a role in vivo in the modulation of myogenic vascular tone.


Adaptive threshold-stochastic resonance (AT-SR) in MHC clusters on the cell surface.
Highly conserved 2D receptor clusters (membrane rafts) of immunological signaling molecules with MHCI and MHCII antigens as their cores have been observed in the past on the surface of T- and B-cell lines of lymphoid origin, as well as on cells from patients with colon tumor and Crohn's disease. Conservativity is related to the ever presence of MHCI molecules. Although they are suspected to play a role in maintaining these clusters and facilitating transmembrane signaling, their exact role has been left largely enigmatic. Here we are suggesting stochastic resonance (SR), or "noise-assisted signal detection", as a general organizing principle for transmembrane signaling events evoked by processes like immune recognition and cytokine binding taking place in these clusters. In the conceptual framework of SR, in immune recognition as a prototype of transmembrane signaling, the sea of self-peptide-MHC complexes around a nonself-peptide presenting MHC is conceived as a source of quickly fluctuating unspecific signal ("athermal noise") serving the extra energy for amplifying the weak sub-threshold specific signal of the nonself-peptide presenting MHC. This same noise is also utilized for a readjustment of the threshold - and also the sensitivity and specificity - of detection by a closed loop feedback control of the TcR-CD8 (CD4) proximity on the detecting T-cell. The weak sub threshold specific signal of nonself-peptide presenting MHC is amplified by the superposing unspecific signals of the neighboring self peptide-MHC complexes towards the T-cell receptor as the detector. Because in a successful detection event both self- and nonself-peptides are detected simultaneously, the principle of coincidence (or lock-in) detection is also realized. The ever presence of MHC islands gets a natural explanation as a source of extra power - in a form of "athermal noise" - needed for coincidence detection and frequency encoding the evoked downstream signals. The effect is quite general, because the actual type of molecules surrounding a chief signaling molecule - like nonself-peptide holding MHC, interleukin-2 and -15 cytokine receptors (IL-2R/15R) - as the fluctuating interaction energy sources is immaterial. The model applies also for other types of signaling, such as those evoked by cytokine binding. The phenomenon of SR can also be interpreted as sampling of a low frequency, specific signal with a high frequency unspecific signal, the "noise". Recipes for identifying other forms of SR in membrane clusters with biophysical tools are recommended.


[Chemical Constituents from Infructescence of Platycarya strobilacea].
To study the chemical constituents of the chloroform and acetic ether fractions from infructescence of Platycarya strobilacea. The compounds were isolated and purified by various chromatographic methods. Spectral analysis were taken to identify the structures. Eleven compounds were isolated and identified as dotriacontane( 1), ursolic acid( 2),hexacosene( 3),β-sitosterol( 4),daucosterol( 5),2,5,8-trihydroxy-3-methoxy-1,4-naphthalenedione( 6),3,3'-dimethoxyellagic acid( 7),ellagic acid( 8),4'-hydroxyisoflavone-7-O-β-D-galactoside( 9),3,3'-dimethoxyellagic acid-4'-O-β-D-xylopyroside( 10), gallic acid( 11). Compounds 1,3 ~ 6,9,10 are isolated from this genus for the first time, compounds 1 ~ 6,9,10 are isolated from this plant for the first time.


68Ga-FAPI-46 PET/MR Detects Recurrent Cholangiocarcinoma and Intraductal Papillary Mucinous Neoplasm in a Patient Showing Increasing CEA with Negative 18F-FDG PET/CT and Conventional CT.
A patient with intrahepatic cholangiocarcinoma who underwent hepatic resection with completed neoadjuvant chemotherapy presented with increased CEA levels. Previous whole abdominal and chest CT scan revealed no evidence of local recurrence or metastasis. 68 Ga-FAPI-46 PET showed significantly higher tumor-to-background contrast of recurrent tumor and nodal metastasis, which were undetectable in the FDG PET or conventional CT scan. These findings changed patient management. Larger studies with histopathological correlation and comparisons with other imaging modalities are required to validate the diagnostic performance. Moreover, a cystic lesion with FAPI uptake at the neck to the proximal body of the pancreas without FDG uptake is also incidentally noted. Differential diagnoses include sided branch IPMN and serous cystadenoma.


Prostate cancer antigen-1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancer.
A novel gene, prostate cancer antigen (PCA)-1, was recently reported to be expressed in the prostate; however, its biological roles remain unclear. Knockdown of the PCA-1 gene by small interfering RNA transfection induced apoptosis through reducing the expression of the anti-apoptotic molecule Bcl-xl and cytoplasmic release of cytochrome c in the androgen-independent prostate cancer cell line PC3. Moreover, in vitro matrigel and in vivo chorioallantoic membrane assays showed that silencing of PCA-1 significantly downregulated discoidin receptor (DDR)-1 expression, resulting in suppression of cancer-cell invasion. Transfection with PCA-1 increased the levels of both Bcl-xl and DDR1, which made the cells more invasive through the upregulation of matrix metalloproteinase 9 in DU145. Interestingly, long-term culture using androgen-free medium increased the level of PCA-1 and the related expression of Bcl-xl and DDR-1 in the androgen-sensitive cancer cell line LNCaP, suggesting that PCA-1 signaling is associated with androgen independence. Immunohistochemical analysis in a series of 169 prostate carcinomas showed that PCA-1 and DDR1 were strongly expressed in prostate cancer cells, including preneoplastic lesions, but there was little or no expression in normal epithelium. Moreover, the expression of PCA-1 and DDR-1 was associated with a hormone-independent state of prostate cancer. Taken together, we propose that PCA-1-DDR-1 signaling is a new important axis involved in malignant potential prostate cancer associated with hormone-refractory status.


Quality and safety aspects in the development and fabrication of transcutaneous sensors.
The safe and reliable application of transcutaneous sensors requires their construction and fabrication to be embedded in a system of external regulation and internal rules.


Development and validation of COVID-19 Impact Scale.
As the COVID-19 (Coronavirus disease 2019) pandemic is prolonged, psychological responses to the pandemic have changed, and a new scale to reflect these changes needs to be developed. In this study, we attempt to develop and validate the COVID-19 Impact Scale (CIS) to measure the psychological stress responses of the COVID-19 pandemic, including emotional responses and difficulty with activities of daily living. We recruited 2152 participants. Participants completed the CIS, the Fear of COVID-19 Scale (FCV-19S), and other mental health related measures. The factor structure, reliability, and validity of the CIS were analyzed. In addition, the validity of the scale was confirmed by its relationships to the existing measures assessing fear of COVID-19, depression, anxiety, subjective well-being, and suicidal ideation. Using exploratory factor analysis (N1 = 1076), we derived a one-factor structure. In confirmatory factor analysis (N2 = 1076), the one-factor model showed good to excellent fitness. The CIS was positively correlated with depression, anxiety, suicidal ideation, fear of COVID-19 and negatively correlated with subjective well-being. The FCV-19S did not show significant correlations with subjective well-being or suicidal ideation, and FCV-19S's explanatory powers on depression and anxiety were lower than those of the CIS. These results support that the CIS is a valid assessment of emotional problems and deterioration of the quality of life caused by the COVID-19 pandemic. Finally, the limitations of this study and future research directions are discussed.


Anterior pontomesencephalic vein and basilar artery in exophytic brainstem gilioma.
The angiographic differentiation of an intrinsic exophytic brainstem glioma from an extra-axial posterior fossa tumor is not always easy. The location of the basilar artery alone may not be significant. Displacement of the anterior pontomesencephalic vein anterior to the basilar artery appears to be a reliable indicator of an intrinsic exophytic brainstem glioma.


Natural enemy-herbivore networks along local management and landscape gradients in urban agroecosystems.
Ecological networks can provide insight into how biodiversity loss and changes in species interactions impact the delivery of ecosystem services. In agroecosystems that vary in management practices, quantifying changes in ecological network structure across gradients of local and landscape composition can inform both the ecology and function of productive agroecosystems. In this study, we examined natural-enemy-herbivore co-occurrence networks associated with Brassica oleracea (cole crops), a common crop in urban agricultural systems. Specifically, we investigated how local management characteristics of urban community gardens and the landscape composition around them affect (1) the abundance of B. oleracea herbivores and their natural enemies, (2) the natural-enemy : herbivore ratio, and (3) natural-enemy-herbivore co-occurrence network metrics. We sampled herbivores and natural enemies in B. oleracea plants in 24 vegetable gardens in the California, USA central coast region. We also collected information on garden characteristics and land-use cover of the surrounding landscape (2 km radius). We found that increased floral richness and B. oleracea abundance were associated with increased parasitoid abundance, non-aphid herbivore abundance, and increased network vulnerability; increased vegetation complexity suppressed parasitoid abundance, but still boosted network vulnerability. High agricultural land-use cover in the landscape surrounding urban gardens was associated with lower predator, parasitoid, and non-aphid herbivore abundance, lower natural-enemy : herbivore ratios, lower interaction richness, and higher trophic complementarity. While we did not directly measure pest control, higher interaction richness, higher vulnerability, and lower trophic complementarity are associated with higher pest control services in other agroecosystems. Thus, if gardens function similarly to other agroecosystems, our results indicate that increasing vegetation complexity, including trees, shrubs, and plant richness, especially within gardens located in intensively farmed landscapes, could potentially enhance the biodiversity and abundance of natural enemies, supporting ecological networks associated with higher pest control services.


Structural characterization and discrimination of Chinese medicinal materials with multiple botanical origins based on metabolite profiling and chemometrics analysis: Clematidis Radix et Rhizoma as a case study.
Traditional Chinese medicines (TCMs)-based products are becoming more and more popular over the world. To ensure the safety and efficacy, authentication of Chinese medicinal materials has been an important issue, especially for that with multiple botanical origins (one-to-multiple). Taking Clematidis Radix et Rhizoma (CRR) as a case study, we herein developed an integrated platform based on metabolite profiling and chemometrics analysis to characterize, classify, and predict the "one-to-multiple" herbs. Firstly, the predominant constituents, triterpenoid saponins, in three Clematis CRR were rapid characterized by a novel UPLC-QTOF/MS-based strategy, and a total of 49 triterpenoid saponins were identified. Secondly, metabolite profiling was performed by UPLC-QTOF/MS, and 4623 variables were extracted and aligned as dataset. Thirdly, by using pattern recognition analysis, a clear separation of the three Clematis CRR was achieved as well as a total number of 28 variables were screened as the valuable variables for discrimination. By matching with identified saponins, these 28 variables were corresponding to 10 saponins which were identified as marker compounds. Fourthly, based on the relative intensity of the marker compounds-related variables, genetic algorithm optimized support vector machines (GA-SVM) was employed to predict the species of CRR samples. The obtained model showed excellent prediction performance with a prediction accuracy of 100%. Finally, a heatmap visualization was employed for clarifying the distribution of identified saponins, which could be useful for phytochemotaxonomy study of Clematis herbs. These results indicated that our proposed platform was a powerful tool for chemical profiling and discrimination of herbs with multiple botanical origins, providing promising perspectives in tracking the formulation processes of TCMs products.


Change in Red Blood Cell Distribution width During the Last Years of Life in Geriatric Patients.
Most of the studies that evaluate the association between red blood cell distribution width (RDW) and mortality assess it on a single occasion instead of doing so through serial measurements. Very few studies have investigated repeated measurements of RDW and its prognostic value, and most of them are focused on patients with cardiovascular diseases. RDW is a dynamic value so we aimed at determining the prognostic value of sequential RDW assessment in the last years of life in patients enrolled in a Department of Geriatrics. This work is part of a prospective study derived from a cohort of 122 patients over 75 years hospitalized in 2005 for the purpose of assessing the prognostic significance of several comorbidity and prognostic indices. Patients were consecutively recruited for the study at admission in a tertiary hospital and then followed up for at least 5 years. A total of 55 patients with repeated RDW assessments during all the five years before their death were selected from the total cohort of 122 patients. We found a strong correlation between progressive rise in RDW and mortality risk, especially during the last year of life. There was a gradual significant increase in the RDW values along the last five years of life, with means growing up from 14,8 (95% CI: 13,98-15.62) to 16,37 (15,80-16,94). In our cohort of geriatric patients, RDW is a dynamic variable that is modified during the last five years of life, irrespective of their age, and especially during the last year.


The application of honey in wound care of raw surface at spontaneous rupture submandibular abscess that extends to submental and right neck: A case report.
Honey has been reported to accelerate wound healing. The use of honey in wound care mostly uses medicated (Manuka) honey. There are still few who report using Nusantara honey, local honey from Indonesia, as a wound dressing. We report wound care using Nusantara honey in patients with a remarkably open wound due to a ruptured submandibular abscess extending to the submental and right neck. A 67 years old male patient came with a ruptured submandibular abscess that extends to the submental and right neck. On the right submandibular region, an ulcer extends to submental with a size of 10 × 4 × 3 cm, hyperemic, edema around the wound, fluctuating, with pus and tenderness. The isolated bacteria were Staphylococcus aureus. The patient received combination antibiotic therapy, blood sugar management, necrotomy debridement, tooth extraction, and wound care using Nusantara honey on the sixth day after surgery. An improvement was seen on the 10th day after necrotomy. The use of honey for wound care is based on thousands of years of history. Honey can accelerate wound healing and show different effects depending on the phase of wound healing. In addition, honey also has antibacterial properties. Applying Nusantara honey to treat raw surfaces can help speed up wound healing and provide cost-efficiency. There were no allergic reactions or secondary bacterial infections after using honey in this patient.


Laparoscopic resection of a primary diaphragmatic schwannoma: a case report and literature review.
Schwannomas are nerve sheath tumors that commonly originate from the stomach and small intestine. A primary schwannoma of the diaphragm is rare and does not show any symptoms until it grows to a certain size. Hence, it is extremely rare that it was found at a size that allowed resection under videoscopic surgery. A 77-year-old woman was referred to our department for surgical treatment of a tumor located near the gastric fornix. She underwent a routine esophagogastroduodenoscopy 2 years and 7 months prior to the referral. It was suspected that she had a submucosal tumor measuring 10 mm, located in the fornix, and was then referred to her previous physician. During her follow-up, endoscopic ultrasonography (EUS) revealed that the cystic structure had continued to grow toward the gastric wall, and she was then referred to the endoscopy division of our hospital. She continued to be followed-up, and it was noted that the tumor was gradually increasing in size. Therefore, she requested surgical resection, and was finally referred to our division. Since the tumor was rather small, we planned a laparoscopic surgery. An initial examination during the operation revealed that the tumor was located on the left diaphragm. Since the tumor was relatively small and visibility was good, we decided to continue with the laparoscopic surgery. Partial diaphragmectomy with complete inclusion of the tumor was performed, and the defect of the diaphragm was directly closed by a running suture. Pathological examination revealed a benign schwannoma that had originated from the diaphragm. To support our findings, we also reviewed the scientific literature on diaphragmatic schwannoma cases reported up to April 2020. In this extremely rare case, we successfully resected the diaphragmatic schwannoma using laparoscopic surgery.


Genetically engineered fusion of allergen and viral-like particle induces a more effective allergen-specific immune response than a combination of them.
Chimeric virus-like particles (VLPs) were developed as a candidate for allergen-specific immunotherapy. In this study, hepatitis B core antigen (HBcAg) that genetically fused to Chenopodium album polcalcin (Che a 3)-derived peptide was expressed in E. coli BL21, purified, and VLP formation was evaluated using native agarose gel electrophoresis (NAGE) and transmission electron microscopy (TEM). Chimeric HBc VLPs were characterized in terms of their reactivity to IgE, the induction of blocking IgG and allergen-specific IgE, basophil-activating capacity, and Th1-type immune responses. Results from IgE reactivity and basophil activation test showed that chimeric HBc VLPs lack IgE-binding capacity and basophil degranulation activity. Although chimeric HBc VLPs induced the highest level of efficient polcalcin-specific IgG antibody in comparison to those induced by recombinant Che a 3 (rChe a 3) mixed either with HBc VLPs or alum, they triggered the lowest level of polcalcin-specific IgE in mice following immunization. Furthermore, in comparison to the other antigens, chimeric HBc VLPs produced a polcalcin-specific Th1 cell response. Taken together, genetically fusion of allergen derivatives to HBc VLPs, in comparison to a mix of them, may be a more effective way to induce appropriate immune responses in allergen-specific immunotherapy. KEY POINTS: • The insertion of allergen-derived peptide into major insertion region (MIR) of hepatitis B virus core (HBc) antigen resulted in nanoparticles displaying allergen-derived peptide upon its expression in prokaryotic host. • The resultant VLPs (chimeric HBc VLPs) did not exhibit IgE reactivity with allergic patients' sera and were not able to degranulate basophils. • Chimeric HBc VLPs dramatically improved protective IgG antibody response compared with those induced by allergen mixed either with HBc VLPs or alum. • Chimeric HBc VLPs induced Th1 responses that were counterparts of Th2 responses (allergic). • Chimeric HBc VLPs increased IgG2a/ IgG1 ratio and the level of IFN-γ compared to those induced by allergen mixed with either HBc VLPs or alum. Graphical Abstract.


Prospective analysis of factors associated with work reentry in patients with accident-related injuries.
The objective of this study was to investigate the influence of accidents, the physical and psychological consequences, the patient's predisposition as well as work-related cognitions on return to work (RTW) post accident. Despite the costs of time-off from work after accidental injuries, very few investigations have been carried out so far. In a consecutive sample, 163 patients were investigated directly and 12 months after an accident. 32% of the patients had a poor occupational integration 12 months after an accident. As predictors for return to work were found type of prior work: laborer (OR = 4.34; 1.79-10.50 CI 95%), type of accident: recreational (OR = 0.27; 0.11-0.69 CI 95%) and subjective perception of the accident severity (OR = 0.98; 0.96-0.99 CI 95%). Laborers after a traffic or work accident, who estimate the accident as severe, are at greater risk of developing long-term disability. Future efforts should be conducted especially for this target group.


Innovations in healthcare delivery: Human papilloma virus self sampling diagnostics and participatory innovations for CCS.
Human papillomavirus (HPV) infection is a major contributor to the development of cervical cancer, resulting in over 500,000 cases and 266,000 deaths annually worldwide. Previous cervical cancer screening programs have been successful in reducing cervical cancer rates, but have faced challenges such as low acceptance and adherence rates. Innovations in screening technology, such as the HerSwab self-sampling test, have the potential to increase awareness, acceptance, and participation in cervical cancer screening programs. This literature review examines the effectiveness of HerSwab and participatory innovations in increasing adherence to cervical cancer screening. This manuscript comprised a comprehensive narrative literature review encompassing the years 2006-2022. The review process adhered to the PRISMA diagram as a guiding framework. Among the search terms utilized, a total of 200 articles were initially retrieved. However, after applying the predefined inclusion criteria, only 57 articles were included. The HerSwab self-sampling test is described, including how it is performed, challenges, and facilitators, and evaluation and assessment of its effectiveness. While the HerSwab diagnostic test is not currently widely available, studies should assess its feasibility in less developed countries where cervical cancer mortality rates are high. By increasing awareness and availability of innovative screening techniques, such as HerSwab, we can work toward reducing the incidence of cervical cancer and improving outcomes for women worldwide.


Income Inequality, Economic Growth and Stroke Mortality in Brazil: Longitudinal and Regional Analysis 2002-2009.
Stroke accounts for more than 10% of all deaths globally and most of it occurs in low- and middle-income countries (LMIC). Income inequality and gross domestic product (GDP) per capita has been associated to stroke mortality in developed countries. In LMIC, GDP per capita is considered to be a more relevant health determinant than income inequality. This study aims to investigate if income inequality is associated to stroke mortality in Brazil at large, but also on regional and state levels, and whether GDP per capita modulates the impact of this association. Stroke mortality rates, Gini index and GDP per capita data were pooled for the 2002 to 2009 period from public available databases. Random effects models were fitted, controlling for GDP per capita and other covariates. Income inequality was independently associated to stroke mortality rates, even after controlling for GDP per capita and other covariates. GDP per capita reduced only partially the impact of income inequality on stroke mortality. A decrease in 10 points in the Gini index was associated with 18% decrease in the stroke mortality rate in Brazil. Income inequality was independently associated to stroke mortality in Brazil.


Population of the ictal-interictal zone: The significance of periodic and rhythmic activity.
Seizures contribute to patient mortality and are usually treated aggressively. Rhythmic and periodic patterns - the "ictal-interictal continuum" - are often associated with seizures, yet the optimum method of treating these patterns is not known: should they be aggressively suppressed, or monitored without treatment? Understanding which patterns are more strongly associated with seizures and which are highly associated with mortality is important to help the clinician decide how to treat these findings. We present an overview of the etiologies, association with seizures, and mortality of periodic and rhythmic patterns, and one approach to treatment.


Genetic control of dormancy in a Triumph/Morex cross in barley.
Seed dormancy in barley ( Hordeum vulgare L.) is one of the most important parameters affecting malting. Seed dormancy is quantitatively inherited and variously influenced by the environment. The objectives of the present study were to determine the genome location and effects of quantitative trait loci (QTLs) involved in the expression of seed dormancy in a barley cross between two varieties derived from different germplasm pools. Using a doubled-haploid population of 107 lines of the cross between the malting types Triumph (two-row, dormant) and Morex (six-row, non-dormant), seed dormancy phenotypic data sets from five environments and a 147-marker linkage map were developed in order to perform QTL analyses with simple interval mapping and simplified composite interval mapping procedures. Two different types of variables were considered for seed dormancy characterization: (1) level of dormancy induced during seed development, which was indirectly measured as germination percentage at 3 days and 7 days, GP3 and GP7 respectively; (2) rate of dormancy release in the course of a period after seed harvest (after-ripening). Different mechanisms of genetic control were detected for these two types of dormancy-related traits. A major and consistent dormancy QTL near the centromere on chromosome 7(5H) was associated with the establishment of dormancy during seed development and accounted for 52% and 33% of the variability for GP3 and GP7, respectively. Two other QTLs located in the vicinity of the vrs1 locus on chromosome 2(2H) and near the long arm telomere on chromosome 7(5H) explained 9% and 19% of variation, respectively, for the rate of dormancy release during after-ripening. Likewise, seed dormancy was assessed in an F(2) population derived from the cross between two dormant types of distinct germplasm groups, Triumph (European, two-row, malt) and Steptoe (North American, six-row, feed), which showed similar but not identical genetic control for dormancy. Interestingly, there is remarkable dormancy QTL conservation in both regions on chromosome 7(5H) identified in this study and among other barley mapping populations. These widely conserved QTLs show potential as targets for selection of a moderate level of seed dormancy in breeding programs.


Anaerobic Mesophilic Codigestion of Rice Straw and Chicken Manure: Effects of Organic Loading Rate on Process Stability and Performance.
To investigate the effects of organic loading rate (OLR) on performance and stability of mesophilic co-digestion of rice straw (RS) and chicken manure (CM), benchtop experiments (40 L) were carried out at OLRs of 3.0, 3.6, 4.2, 4.8, 6.0, 8.0, and 12.0 kg volatile solid (VS)/(m(3)·day) with volatile solid (VS) ratio of 1:1 (RS/CM) which was based on batch tests. Anaerobic co-digestion was slightly and severely inhibited by the accumulation of ammonia when the digester was overloaded at an OLR of 6 and 12 kg VS/(m(3)·day), respectively. The recommended OLR for co-digestion is 4.8 kg VS/(m(3)·day), which corresponds to average specific biogas production (SBP) of 380 L/kg VS and volumetric biogas production rate (VBPR) of 1.8 m(3)/(m(3)·day). An OLR of 6-8 kg VS/(m(3)·d) with SBP of 360-440 L/kg VS and VBPR of 2.1-3.5 m(3)/(m(3)·day) could be considered, if an Anaerobic digestion (AD) system assisted by in situ removal of ammonia was adopted.


Bayesian transfer in a complex spatial localization task.
Prior knowledge can help observers in various situations. Adults can simultaneously learn two location priors and integrate these with sensory information to locate hidden objects. Importantly, observers weight prior and sensory (likelihood) information differently depending on their respective reliabilities, in line with principles of Bayesian inference. Yet, there is limited evidence that observers actually perform Bayesian inference, rather than a heuristic, such as forming a look-up table. To distinguish these possibilities, we ask whether previously learned priors will be immediately integrated with a new, untrained likelihood. If observers use Bayesian principles, they should immediately put less weight on the new, less reliable, likelihood ("Bayesian transfer"). In an initial experiment, observers estimated the position of a hidden target, drawn from one of two distinct distributions, using sensory and prior information. The sensory cue consisted of dots drawn from a Gaussian distribution centered on the true location with either low, medium, or high variance; the latter introduced after block three of five to test for evidence of Bayesian transfer. Observers did not weight the cue (relative to the prior) significantly less in the high compared to medium variance condition, counter to Bayesian predictions. However, when explicitly informed of the different prior variabilities, observers placed less weight on the new high variance likelihood ("Bayesian transfer"), yet, substantially diverged from ideal. Much of this divergence can be captured by a model that weights sensory information, according only to internal noise in using the cue. These results emphasize the limits of Bayesian models in complex tasks.


Spinal osteomyelitis: an unusual complication in aortic graft surgery.
The case history of a patient with vertebral osteomyelitis due to a contiguous paraprosthetic aortic abscess is reported. This unusual complication may be associated with the indolent nature of paraprosthetic aortic infections. The diagnostic as well as therapeutic value of computerised tomography in this condition is emphasized.


Impact of socio-economic growth on desalination in the US.
In 2013, around 1336 desalination plants in the United States (US) provided purified water mainly to municipalities, the industry sector and for power generation. In 2013 alone, ∼200 million m(3) of water were desalinated; the amount that could satisfy annual municipal water consumption of more than 1.5 million people in the US. Desalination has proven to be a reliable water supply source in many countries around the world, with the total global desalination capacity of ∼60 million m(3)/day in 2013. Desalination has been used to mitigate water scarcity and lessen the pressure on water resources. Currently, data and information about desalination are still limited, while extensive socio-economic analyses are missing. This paper presents an econometric model to fill this gap. It evaluates the impact of selected socio-economic variables on desalination development in the US in the time span 1970-2013. The results show that the GDP and population growth have significantly impacted the desalination sector over the analyzed time period. The insights into the economics of desalination provided with this paper can be used to further evaluate cost-effectiveness of desalination both in the US and in other countries around the world.


Sex Differences in Mitochondrial Function Following a Controlled Cortical Impact Traumatic Brain Injury in Rodents.
Traumatic brain injury (TBI) is a complex disease to study due to the multifactorial injury cascades occurring after the initial blow to the head. One of the most vital players in this secondary injury cascade, and therapeutic target of interest, is the mitochondrion. Mitochondria are important for the generation of cellular energy, regulation of cell death, and modulation of intracellular calcium which leaves these "powerhouses" especially susceptible to damage and dysfunction following traumatic brain injury. Most of the existing studies involving mitochondrial dysfunction after TBI have been performed in male rodent models, leaving a gap in knowledge on these same outcomes in females. This mini-review intends to highlight the available data on mitochondrial dysfunction in male and female rodents after controlled cortical impact (CCI) as a common model of TBI.


Clinical and genetic features of arrhythmogenic cardiomyopathy: diagnosis, management and the heart failure perspective.
Arrhythmogenic cardiomyopathy (ACM) is an emerging new concept of a life-threatening heart muscle disorder due not only to desmosome gene mutations, but also to non-desmosome genes, such as filamin C, lamin A/C, phospholamban, transmembrane protein 43, titin, SCN5A and RNA binding motif protein 20.Multi-modality imaging along with genetic testing are important tools for risk stratification to tailor treatment to a single patient. Cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE) is the gold standard for evaluating left and right ventricular structure and function, edema, and fibrosis. The identification of regional fibrosis with LGE has prognostic value. The management of ACM involves several aspects: treatment of arrhythmias and heart failure, risk stratification, implantable cardioverter-defibrillator (ICD) placement, exercise restrictions, and life-style changes. The decision for ICD placement in ACM patients is not well established and should be made weighing risks and benefits. However, the presence of specific genotypes can allow a precision medicine approach. In ACM patients with only mild left ventricular dysfunction but phospholamban, filamin C or lamin A/C mutations, an ICD is now considered a reasonable approach. We sought to provide an overview of clinical and genetic feature of arrhythmogenic cardiomyopathy providing epidemiology, imaging, diagnostic and treatment information, using a systematic genetic approach.


Salvaging the failing Fontan: lateral tunnel versus extracardiac conduit.
Since Fontan revision has been demonstrated to provide hemodynamic and symptomatic improvement in select patients with failing Fontan circulations, we now believe it is important to determine if one type of revision (lateral tunnel [LT] or extracardiac conduit [ECC]) provides superior outcomes. Thirty-five Fontan revisions were performed (Jun 1997 to Dec 2004): 19 ECC (54%) and 16 LT. Preoperative variables were similar: New York Heart Association (NYHA) IV (LT = 4 vs ECC = 2, p = not significant [NS]), preoperative arrhythmias (LT = 13 vs ECC = 16, p = NS) and systemic right ventricle (LT = 4 vs ECC = 2, p = NS). Twenty-eight patients (80%) underwent a modified maze procedure (LT = 12 vs ECC = 16, p = NS) and 29 (83%) had pacemaker placement (LT = 11 vs ECC = 18, p < 0.05). There were no hospital deaths and no arrhythmias at hospital discharge. There were no differences in mean duration of intubation (LT 0.6 vs ECC 0.9 days, p = NS), inotropic support (LT 1.5 vs ECC 2.1 days, p = NS), intensive care unit stay (LT 2.6 vs ECC 3.5 days, p = NS), hospital stay (LT 8.8 vs ECC 9.7 days, p = NS), or episodes of acute postoperative arrhythmias (LT = 2 vs ECC = 4, p = NS). On intermediate follow-up (29 +/- 22 months), the overall cohort had 94% survival, 97% of survivors in NYHA class I/II, 91% freedom from late arrhythmias requiring medication, and no patient required cardiac transplantation. Follow-up revealed no differences in NYHA I/II (LT = 14 vs ECC = 18, p = NS), mortality (LT = 2 vs ECC = 0, p = NS), or late arrhythmia (LT = 4 vs ECC = 4, p = NS). Both the LT and ECC revisions provide symptomatic benefit for a failing Fontan connection and have equivalent early and intermediate results including arrhythmia recurrence.


Epigenetic Alterations in Keratinocyte Carcinoma.
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are both derived from epidermal keratinocytes but are phenotypically diverse. To improve the understanding of keratinocyte carcinogenesis, it is critical to understand epigenetic alterations, especially those that govern gene expression. We examined changes to the enhancer-associated histone acetylation mark H3K27ac by mapping matched tumor-normal pairs from 11 patients (five with BCC and six with SCC) undergoing Mohs surgery. Our analysis uncovered cancer-specific enhancers on the basis of differential H3K27ac peaks between matched tumor-normal pairs. We also uncovered biological pathways potentially altered in keratinocyte carcinoma, including enriched epidermal development and Wnt signaling pathways enriched in BCCs and enriched immune response and cell activation pathways in SCCs. We also observed enrichment of transcription factors that implicated SMAD and JDP2 in BCC pathogenesis and FOXP1 in SCC pathogenesis. On the basis of these findings, we prioritized three loci with putative regulation events (FGFR2 enhancer in BCC, intragenic regulation of FOXP1 in SCC, and WNT5A promoter in both subtypes) and validated our findings with published gene expression data. Our findings highlight unique and shared epigenetic alterations in histone modifications and potential regulators for BCCs and SCCs that likely impact the divergent oncogenic pathways, paving the way for targeted drug discoveries.


High Definition Lipoabdominoplasty.
To describe the author's experience with the high definition lipoabdominoplasty technique for the treatment of abdominal flaccidity and lipodystrophy, with correction of muscle diastasis and definition of body contours. This is a retrospective study analyzing the results of 146 patients operated on with the high definition lipoabdominoplasty procedure. The average age was 37.93 years (25 to 58). The average body mass index was 25.68 kg/m2 (19.6 to 29.9 kg/m2). Combined surgeries were associated in 76 cases (52%). The results obtained are demonstrated by comparing the pre and postoperative photos. With the advent of high definition liposuction, the results improved significantly, reaching a higher degree of definition and giving a more athletic and aesthetically pleasing contour. However, this procedure is not free of complications, and should be performed cautiously, while following specific protocols. With proper patient selection, this technique provides excellent outcomes when combined with abdominoplasty. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


CD95 ligand--death factor and costimulatory molecule?
The CD95 ligand is involved as a death factor in the regulation of activation-induced cell death, establishment of immune privilege and tumor cell survival. In addition, CD95L may serve as a costimulatory molecule for T-cell activation. Alterations in expression or shedding of membrane and soluble CD95L are associated with numerous diseases, and underscore the pathophysiological relevance of the CD95/CD95L system. In most cases, the causal link between altered CD95L expression and pathophysiology is unknown. Given the potency of the molecule to regulate death and survival of many different cell types, the control of CD95L production, transport, storage, shedding and inactivation is of tremendous biological and clinical interest. This review summarizes the current knowledge, hypotheses and controversies about CD95L as a multifunctional ligand and receptor. It considers the different roles of membrane and soluble forms of CD95L and the complex networks of intracellular dynamics of protein trafficking, as well as the potential bidirectional signal transduction capacity of CD95L, with a focus on molecular interactions that have been worked out over the past years.


Checklist of nematodes parasitizing fish in the Brazilian Amazon.
This study presents a list of parasitic fish nematodes from the Brazilian Amazon based on the previous Brazilian list including scientific assessments carried out between 2010 and 2021. A total of 16 families, 48 species and 28 undetermined species of nematodes associated with fish are included in the checklist, in addition to 93 host species and 15 geographical records.


Burn care costing: the Welsh experience.
It has been accepted for many years that the cost of care for the burn-injured patient is high. There is, however, little published data to show how "expensive" it is. At the Welsh Centre for burns we have undertaken a costing exercise in an attempt to define the true cost to the treatment of burns. Using our current cost base and activity, we established a cost per health related group (HRG) for burns and also prospectively calculated costs for three inpatients to determine whether HRG-based burn tariffs accurately represent these costs. The NHS is under increasing pressure to provide evidence to support budgetary requirements; we feel this paper offers a framework for burn care costing upon which calculations could be based.