Light-Activated ROS Production Induces Synaptic Autophagy.
The regulated turnover of synaptic vesicle (SV) proteins is thought to involve the ubiquitin-dependent tagging and degradation through endo-lysosomal and autophagy pathways. Yet, it remains unclear which of these pathways are used, when they become activated, and whether SVs are cleared en masse together with SV proteins or whether both are degraded selectively. Equally puzzling is how quickly these systems can be activated and whether they function in real-time to support synaptic health. To address these questions, we have developed an imaging-based system that simultaneously tags presynaptic proteins while monitoring autophagy. Moreover, by tagging SV proteins with a light-activated ROS generator, Supernova, it was possible to temporally control the damage to specific SV proteins and assess their consequence to autophagy-mediated clearance mechanisms and synaptic function. Our results show that, in mouse hippocampal neurons of either sex, presynaptic autophagy can be induced in as little as 5-10 min and eliminates primarily the damaged protein rather than the SV en masse. Importantly, we also find that autophagy is essential for synaptic function, as light-activated damage to, for example, Synaptophysin only compromises synaptic function when autophagy is simultaneously blocked. These data support the concept that presynaptic boutons have a robust highly regulated clearance system to maintain not only synapse integrity, but also synaptic function.SIGNIFICANCE STATEMENT The real-time surveillance and clearance of synaptic proteins are thought to be vital to the health, functionality, and integrity of vertebrate synapses and are compromised in neurodegenerative disorders, yet the fundamental mechanisms regulating these systems remain enigmatic. Our analysis reveals that presynaptic autophagy is a critical part of a real-time clearance system at synapses capable of responding to local damage of synaptic vesicle proteins within minutes and to be critical for the ongoing functionality of these synapses. These data indicate that synapse autophagy is not only locally regulated but also crucial for the health and functionality of vertebrate presynaptic boutons.


Oxytocin receptor dynamics in the brain across development and species.
Oxytocin (OXT) signaling through the OXT receptor plays a significant role in a variety of physiological processes throughout the lifespan. OXT's effects depend on the tissue distribution of the receptor. This tissue specificity is dynamic and changes across development, and also varies with sex, experience, and species. The purpose of this review is to highlight these themes with examples from several life stages and several species. Important knowledge gaps will also be emphasized. Understanding the effective sites of action for OXT via its receptor will help refine hypotheses about the roles of this important neuropeptide in the experience-dependent development and expression of species-typical social behavior. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 143-157, 2017.


circMTND5 Participates in Renal Mitochondrial Injury and Fibrosis by Sponging MIR6812 in Lupus Nephritis.
Recent studies have focused on nuclear-encoded circular RNAs (circRNAs) in kidney diseases, but little is known about mitochondrial circRNAs. Differentially expressed circRNAs were analyzed by RNA deep sequencing from lupus nephritis (LN) biopsies and normal human kidneys. In LN renal biopsies, the most downregulated circRNA was circMTND5, which is encoded in the mitochondrial genome. We quantitated circMTND5 by qPCR and localized by fluorescence in situ hybridization (FISH). Mitochondrial abnormalities were identified by electron microscopy. The expression of mitochondrial genes was decreased, and the expression of profibrotic genes was increased on qPCR and immunostaining. RNA binding sites for MIR6812 and circMTND5 were predicted. MIR6812 expression was increased by FISH and qPCR. In HK-2 cells and its mitochondrial fraction, the role of circMTND5 sponging MIR6812 was assessed by their colocalization in mitochondria on FISH, RNA immunoprecipitation, and RNA pulldown coupled with luciferase reporter assay. circMTND5 knockdown upregulated MIR6812, decreased mitochondrial functional gene expression, and increased profibrotic gene expression. Overexpression of circMTND5 reversed these effects in hTGF-β stimulated HK-2 cells. Similar effects were observed in HK-2 cells with overexpression and with knockdown of MIR6812. We conclude that circMTND5 alleviates renal mitochondrial injury and kidney fibrosis by sponging MIR6812 in LN.


Covid-19 Effects on Psychological Outcomes: How Do Gender Responses Differ?
The study aims at understanding the relationships between the fear of COVID-19 and perceived stress, wellbeing, and life satisfaction. The study also analyses the role of gender on the relationship of fear of COVID-19 with these study variables. For this, a cross-sectional study was conducted among 1125 participants in India, comprising 638 men and 487 women. Structural equation model was used to analyse the data. It was found that the fear of COVID-19 is positively related to perceived stress and negatively related to wellbeing and life satisfaction. It was also found that, these relationships are stronger among women than among men. The study shows the importance of psychiatric assessment during pandemic times and alerts policy makers and society in general, to take measures for ensuring mental health among people during times of crisis. Future studies can include longitudinal research for a comprehensive understanding of the psychological impacts of the pandemic.


A rapid purification of rat alpha 1-foetoprotein by phase partition.
The phase partition system dextran/polyethylene glycol (2 : 1, w/w) was chosen to separate rat alpha 1-foetoprotein from rat serum albumin, which is its main contaminant due to their having close physicochemical properties. The optimization of this method necessitated a systematic study of the behaviour of rat serum albumin in the system under consideration. This article describes the optimum conditions, in terms of pH, ionic strength and the concentration of polymer solutions, for the purification and recovery of alpha 1-foetoprotein. After a prepurification of rat foetal serum by CM-cellulose chromatography, a single partition step permitted the recovery of 15% of the total alpha 1-foetoprotein present in the rat serum. The purity of this alpha 1-foetoprotein was demonstrated by its binding parameters and by analytical gel electrophoresis.


Early concurrent and longitudinal symptoms of ADHD and ODD: relations to different types of inhibitory control and working memory.
The aim of the present study was to investigate how three different types of inhibitory control - interference control within task, interference control outside task, and prepotent response inhibition - and two types of working memory - verbal and spatial - would relate to early symptoms of attention deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), both concurrently and longitudinally. Seventy-two preschoolers, 1/3 who had been identified as being at risk for developing ADHD and/or ODD, completed neuropsychological tasks designed to measure inhibitory control and working memory. Behavioral symptoms were measured through parental and teacher ratings of the DSM-IV criteria for ADHD and ODD. Our results suggest distinct types of inhibitory control as being good predictors of concurrent and longitudinal symptoms of ADHD, rather than ODD. However, no associations were obtained between working memory and ADHD or ODD symptoms either concurrently or longitudinally. This study emphasizes the need to isolate complex executive processes and break them down into components in order to properly understand the neuropsychological roots involved in ADHD and ODD.


How does the introduction of a new year three GP curriculum affect future commitment to teach? An evaluation using a realist approach.
In western countries, there is a trend towards increasing amounts of undergraduate medical education being delivered in General Practice (GP). However, many medical schools report difficulties with the recruitment and retainment of GP clinical teachers. Newcastle University recently introduced a new year three GP curriculum, involving an increased quantity of community-based teaching and changes to the responsibilities of GP clinical teachers. We sought to explore and explain how this curricular change affects the future teaching commitment of year three GP clinical teachers. We adopted a realist approach. We firstly developed a candidate theory of how the new curriculum may affect future teaching commitment. Data collection and analysis then involved interviews of 10 GP teachers to refine this theory and produce a final Programme Theory. The results suggest that different teachers are affected in different ways, influenced by practice and individual contexts. Some parts of the new curriculum tend to reduce future teaching commitment, whereas other aspects tend to increase commitment. Mechanisms include changes to autonomy and sense of value. The results allow medical schools to better understand how GP teacher retention can be facilitated during curricular change. We make numerous recommendations, including advocating a team-based approach to teaching, paying attention to teacher autonomy, and considering patient contact in relation to generalist, primary care-orientated medicine as a core component of GP teaching.


FRAX and mandibular sparse trabeculation as fracture predictors: a longitudinal study from 1980 to 2002.
The fracture assessment tool (FRAX) is widely used for predicting fractures, but better methods are needed. The aim of this study was to determine whether visual assessments of mandibular trabecular bone could improve FRAX predictions. Three age-cohorts of women were examined twice - 499 women in 1980/1981 and 412 women in 1992/1993; 397 participated in both examinations. Information on 10-yr fracture events was available, and bone trabeculation was assessed in radiographs as 'dense', 'mixed', or 'sparse'. Fracture assessment tool values, without bone mineral density (BMD), were calculated twice. Both sparse trabeculation and FRAX >15% were associated with a twofold higher risk for future fracture in the younger group and with a three- to fourfold higher risk for future fracture in the older group. For those with both FRAX >15% and sparse trabeculation, the relative risk (RR) for a fracture in the next 10 yr was 5.9 (95% CI: 3.5-9.8) in the younger group and 22.7 (95% CI: 5.6-92) in the older group. If either FRAX >15% or sparse trabeculation was present, the RR was 2.6 (95% CI: 1.7-4.1) in the younger group and 15.7 (95% CI: 3.9-6.4) in the older group. We concluded that FRAX >15%, without BMD measurements, was an effective fracture predictor, and mandibular sparse trabeculation had a substantial additive effect. Together, FRAX plus mandibular sparse trabeculation predicts major osteoporotic fractures to approximately the same extent as does FRAX with BMD measurements.


Head and neck diffuse large B cell lymphomas (HN-DLBCL) in human immunodeficiency virus (HIV) positive patients: long-term results in the highly active antiretroviral therapy (HAART) era.
To report long-term outcomes and toxicity rates after chemotherapy (CHT) followed by radiotherapy (RT) in the highly active antiretroviral therapy (HAART) era in human immunodeficiency virus (HIV) positive patients with head and neck diffuse large B cell lymphomas (HN-DLBCL). Clinical data concerning consecutive HIV patients treated for DLBCL located in head and neck region with CHT and RT were retrospectively reviewed. Systemic treatment consisted of combination CHT agents given with concomitant HAART and regimen was left to oncologists' discretion. Involved field RT was delivered at a total dose of 30-36 Gy (2 Gy per fraction). Survival rates were estimated using the Kaplan-Meier method. Toxicity was evaluated using National Cancer Institute's Common Terminology Criteria for Adverse Events. Overall, 13 patients were included. There were no missing data. Eight patients had advanced disease (stage III-IV = 8; 61.5%). The most common primary tumor location was oral cavity (n = 7) with large mass at presentation. All patients completed the programmed treatment. Severe acute toxicity was observed in one patient, only. Overall, three patients had died and no treatment-related deaths occurred. After a median follow-up of 152 months, the 20-year overall survival and disease-free survival rates were 65.9 and 41.5%, respectively. Globally, there were no RT-related late complications. This data analysis suggested that CHT followed by RT can be safety proposed in the management of patients with HIV-related HN-DLBCL in the HAART era. Further investigations are necessary to validate our results.


Signal sequence of preproglycinin affects production of the expressed protein in Escherichia coli.
The effect of the signal peptide portion on the bacterial production of preproglycinin, a precursor of soybean storage protein, was examined. Nucleotide sequences corresponding to the signal peptide and the mature N-terminal region were deleted stepwise from the cDNA encoding the glycinin A1aB1b subunit precursor, and the deleted cDNAs were placed under the control of trc promoter in an expression vector pKK233-2. When the amounts of the protein products in Escherichia coli from each expression plasmid were determined, no accumulation of preproglycinin was observed from the plasmids with the full length or the five amino acids of the signal sequence. However, significant accumulation of the preproglycinin homologue proteins was noted from the plasmids retaining less than three amino acids of the signal sequence depending on the extent of deletion. N-terminal amino acid sequences of the products coincided with those predicted from the deleted cDNAs. The preproglycinin homologue proteins expressed from the mutant plasmids assembled into trimers of about 8S.


Association Between Internet Use and Sleep Problems in Adolescents.
Sleep problems are commonly encountered in adolescents. It has been shown that electronic media have a negative influence on the sleep quality and daytime functioning in adolescents. This study aims to investigate the association between internet use and sleep problems in adolescents. A total of 1212 adolescents were recruited to the study. Self-report study questionnaire included two main parts: Young's Internet Addiction Scale (IAS) and a semi-structured inquiry on sleep habits/problems. Of the study sample, 16% (n=198) reported their sleep quality as bad or very bad. One-fourth of the sample reported using internet everyday and 27% of them reported spending more than one hour when online. The mean IAS total score was 35.56±13.87. Adolescents with a higher IAS score reported getting to bed later in the night, needing more time to fall asleep and having an increased number of awakenings in the night than the adolescents with lower IAS score (p=.001). They were also found to have higher frequencies of several sleep problems including difficulty in initiating and sustaining sleep, difficulty in waking up and feelings of sleepiness in day. In addition, sleep quality of them was worse when compared to the adolescents with a lower IAS score (p=.001). Problematic sleep habits and sleep problems were found to be more frequent in adolescents with a higher IAS total score. Health care providers must be aware of the possible negative impact of excessive and uncontrolled internet use on adolescents' sleep habits.


The separation of aluminum(III) ions from the aqueous solution on membrane filter using Alizarin Yellow R.
The membrane filtration was examined as an effective and selective method for collection of Al(III) ions from aqueous solutions using Alizarin Yellow R, one of a pH-indicator, as a precipitating reagent. For preparation of aqueous solutions without precipitate or turbidity, a non-ionic surfactant, Triton X-100, was used as a solubilizing reagent for insoluble materials. Three metal ions, Al(III), V(III) and Cu(II) ions, were able to be collected as yellow-orange precipitates from aqueous solutions controlled in a range of pH 4-7, pH 4-9, and pH 5.5-12, respectively, on a membrane filter by filtration under suction. Hydrogen peroxide and o-phenanthroline were found to be capable of masking V(III) and Cu(II) ions in a range of pH 5.5-8 in which Al(III) ions were collected. This membrane filtration was applied to selective separation and determination of Al(III) ions in tap water.


Masculinizing genitoplasty in intersex patients.
We reviewed cosmetic and functional outcome of masculinizing genitoplasty (MPG) in intersex patients assigned as a male performed in our service for more than 12 years. A total of 57 patients underwent MPG in our department during a 20-year period. Of these cases MPG was performed using modern 1-stage surgical techniques from 1991 to 2003 in 39 (68%). Of the 39 children 8 (21%) had 17beta-hydroxysteroid dehydrogenase deficiency, 2 (5%) had 3beta-hydroxysteroid dehydrogenase deficiency, 8 (21%) had 5alpha-reductase deficiency, 2 (5%) had mixed gonadal dysgenesis, 1 (2.6%) was a true hermaphrodite, 1 (2.6%) had Klinefelter's syndrome, 1 (2.6%) had partially androgen insensitivity syndrome and 16 (41%) had idiopathic male pseudohermaphroditism. The presenting disease was severe proximal penoscrotal hypospadias in 30 cases (77%), perineal hypospadias in 9 (23%) and müllerian duct opening in the perineum along with the urethral meatus in 16 (28%). Median patient age at surgery was 1.8 years. MPG was performed with a transverse pedicled preputial island flap as an onlay in 29 cases (74%). The remaining 10 patients (26%) underwent tubularization of the mucosa in the perineal area and end-to-end anastomosis to a tube made from the pedicled prepuce. Scrotal transposition as well as orchiopexy was performed in some patients as an independent operation so as not to jeopardize the perineal and preputial flaps. In 23 (59%) of the 39 children 1 operation achieved satisfactory cosmetic and functional results in terms of good urinary stream and straight phallus during erection. Three (7%) children presented with various degrees of breakdown of the urethroplasty and required a repeat operation. In 5 patients (12.8%) a small urethral fistula developed and closure was performed. A 1-stage male genitoplasty for male pseudohermaphroditism is accompanied by a reasonable incidence of major complications. It should be performed in early childhood to avoid psychological and social anxiety by the child and parents.


Intermittent calcitriol therapy and growth in children with chronic renal failure.
Intermittent calcitriol (1,25D) therapy has been used for the management of secondary hyperparathyroidism in children with chronic renal failure; however, the development of adynamic bone has been demonstrated in up to 40% of pediatric patients after 12 months of intermittent 1,25D therapy. To assess its effect on linear growth, we compared growth and biochemical data from 16 prepubertal patients with biopsy-proven secondary hyperparathyroidism during 12 months of intermittent 1,25D therapy and the preceding year of daily 1,25D therapy. While Z-scores for height remained stable during daily therapy, values decreased from -1.8 +/- 0.32 to -2.0 +/- 0.33, p < 0.01, during intermittent 1,25D therapy; the largest reductions were seen in those who developed adynamic bone. Reductions in growth may be due to the direct inhibitory effects of large intermittent doses of calcitriol on chondrocyte activity.


Platelet-Derived Growth Factor Receptor-Positive Pericytic Cells of White Adipose Tissue from Critical Limb Ischemia Patients Display Mesenchymal Stem Cell-Like Properties.
The pericytes in the blood vessel wall have recently been identified to be important in regulating vascular formation, stabilization, remodeling, and function. We isolated and identified pericyte-like platelet-derived growth factor receptor beta-positive (PDGFRβ+) cells from the stromal vascular fraction (SVF) of adipose tissue from critical limb ischemia (CLI) patients and investigated their potential as a reliable source of stem cells for cell-based therapy. De-identified subcutaneous fat tissues were harvested after amputation in CLI patients. Freshly isolated SVF cells and culture-expanded adipose-derived stem cells (ADSCs) were quantified using flow cytometry. A matrigel tube formation assay and multi-lineage differentiation were performed to assess pericytic and mesenchymal stem cell (MSC)-like characteristics of PDGFRβ+ ADSCs. PDGFRβ+ cells were located in the pericytic area of various sizes of blood vessels and coexpressed mesenchymal stem cell markers. PDGFRβ+ cells in freshly isolated SVF cells expressed a higher level of stem cell markers (CD34 and CXCR4) and mesenchymal markers (CD13, CD44, CD54, and CD90) than PDGFRβ- cells. In vitro expansion of PDGFRβ+ cells resulted in enrichment of the perivascular mesenchymal stem-like (PDGFRβ+/CD90+/CD45-/CD31-) cell fractions. The Matrigel tube formation assay revealed that PDGFRβ+ cells were located in the peritubular area. PDGFRβ+ ADSCs cells demonstrated a good multilineage differentiation potential. Pericyte-like PDGFRβ+ cells from the SVF of adipose tissue from CLI patients had MSC-like characteristics and could be amplified by in vitro culture with preservation of their cell characteristics. We believe PDGFRβ+ cells in the SVF of adipose tissue can be used as a reliable source of stem cells even in CLI patients.


Morphology dependence of the thermal transport properties of single-walled carbon nanotube thin films.
The thermal transport properties of random network, single-walled carbon nanotube (SWNT) films were assessed using Raman spectroscopy. Two types of SWNT films were investigated: single-layer and stacked. The single-layer films were fabricated by aerosol chemical vapour deposition and subsequent direct dry deposition, while the stacked films were prepared by placing the single-layer films on top of one another. The anisotropy of the network structures of each of these films was evaluated based on the angular dependence of the optical absorbance spectra. The results show that the anisotropy of the films decreases with increasing film thickness in the case of the single-layer films, and that the film anisotropy is preserved during the stacking process. The sheet thermal conductance is proportional to the SWNT area density in the case of stacked films, but is reduced with increasing thickness in the case of single-layer films. This effect is explained by a change in the network morphology from a two-dimensional anisotropic structure to the more isotropic structure. This work demonstrates the fabrication of low-density films with high sheet thermal conductance through the stacking of thin SWNT films.


Correlation between frequency doubling technology and heidelberg retina tomograph.
To evaluate the association between Heidelberg Retina Tomograph (HRT) parameters and the Frequency Doubling Technology (FDT) indices in ocular hypertension or primary open angle glaucoma patients. One eye was randomly chosen from 85 patients with primary open angle glaucoma (abnormal visual field and/or abnormal optic nerve and untreated IOP > 21 mm Hg) and ocular hypertension (normal visual field and normal optic nerve and untreated IOP > 21 mm Hg). All the patients were examined with Humphrey Perimeter program 30-2 full threshold, FDT program C 20-5, and HRT. Findings were analyzed using Pearson's correlation coefficient and linear regression. Within the entire sample of studied subjects we found a statistically significant correlation (Pearson's r) (P < 0.05) between FDT mean deviation and RA, CA, RV, CSM, RNFLt, and RNFLc of HRT, and between FDT pattern standard deviation and RA, CA, VOLC, CV, RV, CSM, RNFLt, and RNFLc of HRT. Linear regression analysis showed that cup shape measure was the most predictive parameter for FDT MD. No correlation was found between HRT parameters and FDT PSD indices in the glaucoma subgroup; in the ocular hypertensive subgroup some correlation was found between FDT PSD and some of the HRT parameters. In the entire group, cup shape measure showed to be the most significant factor correlating functional and morphologic changes. The presence of significant correlations between some HRT parameters and visual field indices in the ocular hypertensive and glaucoma subgroup suggested that HRT parameters and FDT indices could detect glaucoma damage differently.


Long-term survivors of childhood malignancies--aeromedical dilemmas and implications.
Survival rates from childhood cancer have dramatically improved over the past three decades; average overall 5-yr survival rates are now > 75%. However, this has been achieved by treatments associated with significant morbidity that may present many years later. This review seeks to delineate the basic information necessary to evaluate flight-training candidates with a history of childhood cancer. We performed a literature review using the Medline database with appropriate search terms related to delayed morbidity and mortality associated with childhood cancer; we did not attempt to evaluate the risk of recurrent cancer. The neurological, cardiovascular, and pulmonary systems were identified areas of aeromedical concern. Central nervous disease and treatment-related effects may increase the risk of seizures or other neurocognitive sequelae. The cardiac toxicity of chemotherapeutic agents such as anthracyclines and radiation may cause late-occurring arrhythmia, cardiac failure, and sudden death, while available screening modalities are of limited value. Pulmonary disease and related treatment effects may cause a 9-fold increase of late-occurring pulmonary fibrosis and lung cancer, with increasing prevalence as long as 25 yr following the cancer diagnosis. Additionally, second malignancies may occur in up to 12.5% of cancer survivors at 25 yr after cancer diagnosis, affecting medical clearance for flight training. In summary, this review discusses the relevant aeromedical issues, including disabilities with specific relevance to the flying environment, risk estimation of late-occurring treatment complications, and possible interactions with occupational exposures in aircrew.


Interleukin-10-1082A/G and -592C/A polymorphisms with risk of Parkinson's disease: a meta-analysis.
Several studies have been conducted in recent years to evaluate the risk of Parkinson's disease (PD) and polymorphisms of interleukin-10 (IL-10). However, the results were conflicting. Therefore, we performed this meta-analysis of published case-control studies to assess this association. Systematic searches of electronic databases PubMed Web of Science, BIOSIS Previews, Science Direct, Chinese Biomedical Database, WANFANG Database, and Chinese National Knowledge Infrastructure with hand searching of the references of identified articles were conducted. Data were extracted using a standardized form and pooled odd ratios with 95% confidence intervals were calculated to evaluate the strength of the association. A total of seven case-control studies involving 1912 PD cases and 1740 controls were included, concerning two polymorphisms (-1082A/G and -592C/A) of IL-10 gene. No significant associations were found in the overall analysis for both -1082A/G and -592C/A polymorphisms with PD risk. Similar lacking associations were observed in subgroup analysis based on ethnicity and age of onset. In conclusion, there is no enough evidence for association between IL-10 polymorphisms (-1082A/G and -592C/A) and risk of PD at present. Well-designed studies with larger sample size and multi-ethnicity studies are warranted in the future.


Cu-catalyzed asymmetric allylic alkylation of phosphonates and phosphine oxides with Grignard reagents.
An efficient and highly enantioselective copper-catalyzed allylic alkylation of phosphonates and phosphine oxides with Grignard reagents and Taniaphos or phosphoramidites as chiral ligands is reported. Transformation of these products leads to a variety of new phosphorus-containing chiral intermediates.


Altering the response to radiation: sensitizers and protectors.
A number of agents are used clinically to enhance the efficacy of radiotherapy today, many of which are cytotoxic chemotherapies. Agents that enhance radiation induced tumor cell killing or protect normal tissues from the deleterious effects of ionizing radiation are collectively termed radiation modifiers. A significant effort in radiobiological research is geared towards describing and testing radiation modifiers with the intent of enhancing the therapeutic effects of radiation while minimizing normal tissue toxicity. In this review, we discuss the characteristics of these agents, the testing required to translate these agents into clinical trials, and highlight some challenges in these efforts.


The Relationship between the Experience of Hypomimia and Social Wellbeing in People with Parkinson's Disease and their Care Partners.
Though hypomimia, also called facial masking, is experienced by many people with Parkinson's disease (PD), little is known about how the experience of this motor impairment relates to their own and their care partners' (CP) social life and relationship quality. To test if the experience of facial masking relates to social wellbeing in people with PD and their CPs. Forty individuals with PD and their CPs rated PD's difficulty showing facial expression (facial masking), and completed questionnaires about their own social wellbeing and depression. PD-reported and CP-reported facial masking of PD were positively correlated with experience of social rejection in both partners, though this relationship was diminished when controlling for depression. CPs' rating of their partner's facial masking was negatively associated with enjoyment interacting with their partner. This relationship remained when controlling for CP and PD depression. The findings suggest that the experience of facial masking is negatively associated with social wellbeing particularly for the CPs, and especially so for the quality of CPs interpersonal relationship with their partner with PD.


Atrial fibrillation and obstructive sleep apnea in African populations: uncovering a neglected association.
Atrial fibrillation (AF), the most common sustained arrhythmia, is one of the risk factors with the largest relative increase in attributed cardiovascular mortality in Africa. There are important knowledge gaps in the epidemiology of AF in Africa, along with inadequate service provision for cardiac arrhythmias including AF. This paper comments on the available data on the prevalence and correlates of obstructive sleep apnea (OSA) in patients with AF in Africa. Two studies from Tunisia revealed a high prevalence of OSA based on polysomnography (77% and 90%) among patients with AF. Patients with OSA were more likely to report snoring, were older and had longer AF duration compared to those without OSA. The implications of these findings are discussed. Furthermore, key points on the mechanisms underlying the association between AF and OSA, the impact of OSA on AF-related outcomes and the screening and management of OSA in patients with AF are highlighted.


Expression, purification, and structural analysis of intracellular C-termini from metabotropic glutamate receptors.
Glutamate is the most important excitatory neurotransmitter in the mammalian central nervous system (CNS). Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors (GPCRs) that guide several intracellular signal cascades thereby controlling multiple physiological tasks, such as neuronal excitability, learning, and memory. Consequently, these receptors are discussed in the context of several CNS-associated diseases, including addiction for drugs, Alzheimer's disease, Fragile X syndrome, night blindness, or schizophrenia. Although increasing structural information is available for the extracellular and transmembrane domains of GPCRs, data describing the nature of intracellular receptor domains are largely missing. Indeed, in all available crystal structures of neurotransmitter receptors, their intracellular domains were omitted. Most intracellular mGluR C-termini are alternatively spliced and contain multiple binding sites for interacting proteins. Therefore, analyzing their structure can identify molecular mechanisms of receptor regulation. Recently, we analyzed the conformation of the intracellular C-termini of mGluR6, mGluR7a, and mGluR8a. Here, we describe an array of biochemical, biophysical, and computational techniques suited to elucidate the nature of these highly interesting receptor domains.


Screening and identification of the nucleic acid aptamers in nasopharyngeal carcinoma.
To screen the nucleic acid aptamers of the EB virus-positive nasopharyngeal carcinoma cells, we used SELEX technology and synthesized in vitro a 78-nucleotide random DNA library. We used normal nasopharyngeal epithelial cells and EB virus-positive low differentiated nasopharyngeal carcinoma cells as target to conduct 10 cycles of screening, cloning, sequencing, and identification of the aptamers. The fluorescence produced by the combination of the sub-library and the target cells gained intensity gradually with the increase in the number of screening cycles, indicating elevated binding capacity. The cluster analysis showed that the aptamers can be divided into three families, with two of the families having the common conserved sequence. In this study, by screening nucleic acid aptamers for affinity and specificity, we established an initial aptamer library for EB virus-positive nasopharyngeal carcinoma cells.


Efficacy and safety of a new power toothbrush in a population with mild to moderate gingivitis.
To evaluate the efficacy and safety of a novel ultrasound power toothbrush over a 30-day period in a population with mild to moderate gingivitis. A 30-day, randomized, examiner-blind, parallel-arm study was conducted to evaluate the safety and efficacy of a ultrasound novel power toothbrush (Ultreo - ULT) as compared to a control manual toothbrush (Oral-B 35-MTB). Fifty-three subjects (n = 26 ULT, n = 27 MTB) with a minimum of 18 natural teeth and a Löe and Silness Gingival Index of > or = 1.5 were enrolled. An intraoral examination (oral soft and hard tissues, restorations) was performed, and Löe and Silness Gingival Index scores were recorded at baseline and 30 days. Subjects were instructed to brush at home twice per day with their assigned toothbrush and study toothpaste. A product evaluation questionnaire was also completed at the 30-day study visit. Oral examinations indicated normal findings at all time points for both groups, and no adverse events were reported during the study. There were no significant differences in gingivitis scores at baseline between the toothbrush groups (p > 0.05). From baseline, each treatment group demonstrated a significant reduction in gingivitis over the 30-day period (p < 0.001). However, subjects in the ULT group demonstrated a significantly greater reduction in gingivitis compared to those using the manual toothbrush (p = 0.010). Results from the questionnaire, on average, indicated subjects in the ULT group scored their device higher with respect to the clean feeling after brushing and perceived improvements in gingival health. The novel Ultreo ultrasound power toothbrush significantly reduced gingivitis over the 30-day study, and resulted in a significantly greater reduction in gingivitis than a manual toothbrush. No adverse events or safety concerns were identified with either the power or manual toothbrush.


[Effects of norepinephrine on proliferation and apoptosis of neonatal cardiac fibroblasts in rats].
To investigate the effects of different concentrations of norepinephrine (NE) on proliferation and apoptosis of cultured cardiac fibroblasts (CFBs) from neonatal mice and to elucidate related mechanisms. CFBs of Sprague-Dawley (SD) rats were isolated and cultured and divided into normal control group and different concentration of NE intervention groups (0.1, 1, 10, 50, and 100 µmol/L). Water soluble tetrazolium-1 (WST-1) assay was carried out to detect the viability of CFBs. Morphology of apoptosis cells was evaluated by fluorescence microscope with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expressions of collagen I, collagen III, pro-oncogene c-myc in CFBs were detected by reverse transcription-polymerase chain reaction (RT-PCR). The phospho-mitogen activated protein kinase (p-p38MAPK) and caspase3 protein levels were examined by Western blot. Proliferation was significantly increased in 1 µmol/L and 10 µmol/L groups compared with the normal control group (1.05 ± 0.05 and 1.09 ± 0.02 vs. 1.00 ± 0.03, all P < 0.05).CFBs apoptosis was significantly enhanced in 50 µmol/L and 100 µmol/L groups ((22.69 ± 2.18)% and (36.40 ± 6.80)% vs.(4.50 ± 1.08)%, all P < 0.05). Expression of Collagen I peaked in 10 µmol/L group, expression of collagen III and c-myc increased dose-dependently in proportion to increasing NE concentrations (all P < 0.05 vs. control group). The expression of p-p38MAPK and caspase3 was also significantly upregulated in a dose-dependent manner in NE groups (all P < 0.05 vs. control group). Low concentration NE induces CFBs proliferation and high concentration NE promotes CFBs apoptosis. p38MAPK phosphorylation may be a major mediator of NE-induced effects on CFBs.


Intracisternal tubules in a case of chronic lymphocytic leukaemia.
In a case of chronic lymphocytic leukaemia we found that a few (less than 5%) of the circulating leukaemic lymphocytes contained inclusions of a type which do not appear to have been reported in the literature. The inclusions presented as solitary tubules or aggregates of parallel tubules lying within dilated cisternae of the rough endoplasmic reticulum and the perinuclear cistern. Some of the tubules were bounded by a single wall, others by a double wall. We also found a tubule bounded by three walls and another where a segment of the tubular profile was triple-walled and the remainder double-walled. We are inclined to think that the walls of these tubules are composed of membranes. The aetiogenic agent or agents responsible for the production of intracisternal tubules and their mode of formation are obscure.


Precuneus magnetic stimulation for Alzheimer's disease: a randomized, sham-controlled trial.
Repetitive transcranial magnetic stimulation (rTMS) is emerging as a non-invasive therapeutic strategy in the battle against Alzheimer's disease. Alzheimer's disease patients primarily show alterations of the default mode network for which the precuneus is a key node. Here, we hypothesized that targeting the precuneus with TMS represents a promising strategy to slow down cognitive and functional decline in Alzheimer's disease patients. We performed a randomized, double-blind, sham-controlled, phase 2, 24-week trial to determine the safety and efficacy of precuneus stimulation in patients with mild-to-moderate Alzheimer's disease. Fifty Alzheimer's disease patients were randomly assigned in a 1:1 ratio to either receive precuneus or sham rTMS (mean age 73.7 years; 52% female). The trial included a 24-week treatment, with a 2-week intensive course in which rTMS (or sham) was applied daily five times per week, followed by a 22-week maintenance phase in which stimulation was applied once weekly. The Clinical Dementia Rating Scale-Sum of Boxes was selected as the primary outcome measure, in which post-treatment scores were compared to baseline. Secondary outcomes included score changes in the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental State Examination and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale. Moreover, single-pulse TMS in combination with EEG was used to assess neurophysiological changes in precuneus cortical excitability and oscillatory activity. Our findings show that patients that received precuneus repetitive magnetic stimulation presented a stable performance of the Clinical Dementia Rating Scale-Sum of Boxes score, whereas patients treated with sham showed a worsening of their score. Compared with the sham stimulation, patients in the precuneus stimulation group also showed also significantly better performances for the secondary outcome measures, including the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental State Examination and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale. Neurophysiological results showed that precuneus cortical excitability remained unchanged after 24 weeks in the precuneus stimulation group, whereas it was significantly reduced in the sham group. Finally, we found an enhancement of local gamma oscillations in the group treated with precuneus stimulation but not in patients treated with sham. We conclude that 24 weeks of precuneus rTMS may slow down cognitive and functional decline in Alzheimer's disease. Repetitive TMS targeting the default mode network could represent a novel therapeutic approach in Alzheimer's disease patients.


Basic psychopharmacology of antidepressants, part 2: Estrogen as an adjunct to antidepressant treatment.
Estrogen exerts profound effects upon behavior by interacting with neuronal estrogen receptors. Changes in estrogen levels over a woman's life cycle are linked not only to behavioral fluctuations, but potentially to the onset or recurrence of mood disorders. The modern psychiatric evaluation of women requires obtaining a complete reproductive history, including details of hormone treatments, while identifying reproductive events as triggers of affective disorder episodes. While guidelines for the use of reproductive hormones in psychiatry are just evolving, administration of estrogen as an adjunct to antidepressants is an exciting possibility for expanding the frontiers of psychiatry into the field of women's health.


Effect of vitrification technique and assisted hatching on rabbit embryo developmental rate.
The aim of the study was to determine the efficiency of two vitrification techniques followed by two assisted hatching (AH) techniques based on post-thaw developmental capacity of precompacted rabbit embryos and their ability to leave the zona pellucida (hatching) during in vitro culture. The total cell number and embryo diameter as additional markers of embryo quality after warming were evaluated. In vivo fertilized, in vitro cultured 8-12-cell rabbit embryos obtained from superovulated rabbit does were cryopreserved by two-step vitrification method using ethylene glycol (EG) as cryoprotectant or by one-step vitrification method with EG and Ficoll (EG+Ficoll). Thawed embryos were subjected to enzymatic or mechanical AH. Vitrified EG group showed significantly lower (P < 0.05) blastocyst rate (22.5%) and hatching rate (15%) than those vitrified with EG + Ficoll (63 and 63% resp.) and that of control (97 and 97% respectively). Significantly lower values of total cell number (P < 0.05) as well as embryo diameter (P < 0.01) in EG group compared with EG + Ficoll and control group were recorded. No significant difference was found in developmental potential of warmed embryos treated by either mechanical or enzymatic AH. The present study demonstrates that the EG + Ficoll vitrification protocol provides superior embryo survival rates over the EG vitrification protocol for 8-12-cell stage precompacted rabbit embryos. No positive effect of either mechanical or enzymatic AH on the post-thaw viability and quality of rabbit embryos in vitro was observed.


Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia.
Symptomatic interventions for patients with dementia involve anti-dementia drugs to improve cognition, psychotropic drugs for the treatment of behavioral disorders (BDs), and different categories of drugs for concomitant disorders. Demented patients may take >6-10 drugs/day with the consequent risk for drug-drug interactions and adverse drug reactions (ADRs >80%) which accelerate cognitive decline. The pharmacoepigenetic machinery is integrated by pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes redundantly and promiscuously regulated by epigenetic mechanisms. CYP2D6, CYP2C9, CYP2C19, and CYP3A4/5 geno-phenotypes are involved in the metabolism of over 90% of drugs currently used in patients with dementia, and only 20% of the population is an extensive metabolizer for this tetragenic cluster. ADRs associated with anti-dementia drugs, antipsychotics, antidepressants, anxiolytics, hypnotics, sedatives, and antiepileptic drugs can be minimized by means of pharmacogenetic screening prior to treatment. These drugs are substrates, inhibitors, or inducers of 58, 37, and 42 enzyme/protein gene products, respectively, and are transported by 40 different protein transporters. APOE is the reference gene in most pharmacogenetic studies. APOE-3 carriers are the best responders and APOE-4 carriers are the worst responders; likewise, CYP2D6-normal metabolizers are the best responders and CYP2D6-poor metabolizers are the worst responders. The incorporation of pharmacogenomic strategies for a personalized treatment in dementia is an effective option to optimize limited therapeutic resources and to reduce unwanted side-effects.


Lessons learned from first-principles calculations of transition metal oxides.
Transition metal oxides (TMOs) are an important class of materials with diverse applications, ranging from memristors to photoelectrochemical cells. First-principles calculations are critical for understanding these complex materials at an atomic level and establishing relationships between atomic and electronic structures, particularly for probing quantities difficult or inaccessible to experiment. Here, we discuss computational strategies used to understand TMOs by focusing on two examples, a photoanode material, BiVO4, and an oxide for low-power electronics, La1-xSrxCoO3. We highlight key aspects required for the modeling of TMOs, namely, the descriptions of how oxygen vacancies, extrinsic doping, the magnetic state, and polaron formation impact their electronic and atomic structures and, consequently, many of the observed properties.


Existence of genetic lineages within Asian genotype of Taenia solium-Genetic characterization based on mitochondrial and ribosomal DNA markers.
Taenia solium cysticercosis is a potentially eradicable neglected zoonotic disease with public health importance. The genetic lineages of T. solium in Asia and Africa/America are distinct and the genetic composition of the parasite was found to influence the clinical symptoms in patients with cysticercosis. In the present study, the Cysticerci collected from pigs of two southern states of India (Karnataka and Andhra Pradesh) were genetically characterized based on mitochondrial (COX 1 and Cyt b) and ribosomal (ITS-1 and TBR) DNA markers. The study confirms the existence of two mitochondrial lineages of the parasite as Asian and African/American. Cytochrome oxidase 1 (COX 1) based analysis revealed the existence of two sub-lineages of the parasite within the Asian lineage based on the polymorphism at 994 position as 994A/G. In India, both the sub-lineages were identified and genetic divergence among different Indian isolates was evident. Further, the sequence analysis of Cytochrome B (Cyt b) revealed the existence of six sub-lineages of T. solium in India as 69T/69G, 97A/97G as well as 264T/264C. The analysis of nucleotide sequence of large subunit ribosomal DNA (TBR) revealed the existence of two sub-lineages in India based on the deletion of a nucleotide at 624th position. The cysts collected in the present study were more closely related to those of China and Indonesia than with other Indian isolates. Further, the sequence analysis did not indicate the presence of Taenia asiatica in the examined pigs and African/American lineages of T. solium. The results of the present study help to better understand the genetic diversity of T. solium in India.


The clinical use of disulfiram (Antabuse): a review.
Disulfiram is a potent alcohol-sensitizing drug, the effectiveness of which remains unproven in the treatment of alcoholism after 40 years of use. Its clinical utility is more closely associated with nonspecific, nonpharmacological factors (such as social class, patient compliance, patient personality characteristics, and treatment structure) than with its aversive biochemistry. Disulfiram is not effective as a sole alternative to a structured treatment program. Disulfiram retains a place in standard alcoholism treatment programs because clinicians have found this agent useful for selected alcoholic patients. Clinical studies and clinical lore describe these patients as older, relapse-prone, socially stable, cognitively intact, not depressed, compulsive, capable of following rules, and tolerant of dependence. Another distinctly responsive (but evasive) group is court-probated patients. These characteristics also describe patients who are well-known to have good outcomes without disulfiram, thus they do not help clinicians to select suitable patients for this medication. Consequently, this article proposes the following selection criteria: (1) patients who can tolerate a treatment relationship; (2) patients who are relapse-prone (but in treatment); (3) patients who have failed with less structured approaches; (4) patients in early abstinence who are in crisis or under severe stress; (5) patients in established recovery for whom individual or group psychotherapy is a relapse risk; and (6) patients who specifically request it. With or without disulfiram, a treatment program needs to be highly structured and predictable in order to be useful to newly recovering patients. Recovery is a process with discernible phases of development, and the provision of structure is the core of early treatment, where behavior change is more important than insight. A well-structured program will have phases through which a patient may progress. Generally speaking, disulfiram is most useful early to establish sobriety and to allow time for other support structures, such as AA, therapist-patient relationships, and new personal relationships, to take hold. Disulfiram is best given to patients with prior treatment failures, early in treatment, briefly during crises in established sobriety, or to support unusual stresses, such as psychotherapy. Prescriptions should be short-term and not allow automatic refills. It should be necessary to attend a treatment program in order to obtain them. Supervision and monitoring dramatically increase compliance.(ABSTRACT TRUNCATED AT 400 WORDS)


Trichloroethylene, tetrachloroethylene, nitrates, and other chemicals in well water in the Fresno-Clovis Metropolitan Area.
In this study, the author examined the spatial and temporal distribution of tetrachloroethylene, trichloroethylene, nitrate, and several other organic and inorganic chemicals in large community wells in the Fresno-Clovis Metropolitan Area and estimated the lifetime cancer risk associated with exposure to tetrachloroethylene and trichloroethylene. By 1992-1993, investigators found the industrial solvent tetrachloroethylene in 34 wells and found trichloroethylene in 16 wells. All wells had detectable levels of nitrate. In addition, investigators found radon, arsenic, cadmium, iron, manganese, trihalomethanes, and several other volatile organic chemicals in the wells, but only radon and arsenic posed a significant health risk. In 1995, 16 wells were closed because chemicals were found in them. Twenty-six of 248 (10.5%) active wells and 24 of 43 (55.8%) closed wells contained multiple contaminants, excluding nitrate. Between 1988 and 1993, concentrations of trichloroethylene, tetrachloroethylene, and nitrates increased in selected wells. Daily, monthly, and bimonthly variations in the concentrations of tetrachloroethylene, trichloroethylene, and nitrate were often considerable. Granulated activated carbon filtration reduced trichloroethylene levels in well water by 91%-95%, and the author examined its usefulness as a remedial measure. Estimated lifetime cancer risks for tetrachloroethylene and trichloroethylene were 1 excess cancer death per 9.5 million people and 1 excess death per 250 million, respectively. The author also included recommendations for the conduct of further epidemiological and environmental studies.


Bone turnover after bariatric surgery.
The aim of the present study was to evaluate parameters of bone and mineral metabolism after bariatric surgery. This sectional study included data from medical records from 61 bariatric surgery (BS) patients (minimum period of 6 months after the procedure) and from 30 class II and III obese patients as a control group (Cont), consisting of daily dietary intake of macronutrients, calcium and sodium, serum 25(OH)D and parathyroid hormone (PTH) and other biochemical serum and urinary parameters. Bone alkaline phosphatase (BAP), leptin, fibroblast growth factor-23 (FGF-23) and deoxypyridinoline (DPYD) were determined from available banked serum and urinary samples. Mean body mass index (BMI), median energy, carbohydrate, protein and sodium chloride consumption were significantly lower in the BS versus Cont, but calcium and lipids were not. No significant differences were found in ionized calcium, 25(OH)D, PTH and fibroblast growth factor 23 (FGF-23) between groups. Mean serum BAP was significantly higher for BS versus Cont and had a positive correlation with time after the surgical procedure. Mean serum leptin was significantly lower and median urinary DPYD higher in BS versus Cont. The present study showed an increase in bone markers of both bone formation and resorption among bariatric patients up to more than 7 years after the surgical procedure, suggesting that an increased bone turnover persists even at a very long-term follow-up in such patients.


The players may change but the game remains: network analyses of ruminal microbiomes suggest taxonomic differences mask functional similarity.
By mapping translated metagenomic reads to a microbial metabolic network, we show that ruminal ecosystems that are rather dissimilar in their taxonomy can be considerably more similar at the metabolic network level. Using a new network bi-partition approach for linking the microbial network to a bovine metabolic network, we observe that these ruminal metabolic networks exhibit properties consistent with distinct metabolic communities producing similar outputs from common inputs. For instance, the closer in network space that a microbial reaction is to a reaction found in the host, the lower will be the variability of its enzyme copy number across hosts. Similarly, these microbial enzymes that are nearby to host nodes are also higher in copy number than are more distant enzymes. Collectively, these results demonstrate a widely expected pattern that, to our knowledge, has not been explicitly demonstrated in microbial communities: namely that there can exist different community metabolic networks that have the same metabolic inputs and outputs but differ in their internal structure.


Total Synthesis of (-)-Chanoclavine I and an Oxygen-Substituted Ergoline Derivative.
An efficient and direct route to ergot alkaloid (-)-chanoclavine I (3) is described using the inexpensive compound (2R)-(+)-phenyloxirane (15) as a chiral pool in 13 steps with 17% overall yield. Key features of the synthesis include a palladium-catalyzed intramolecular aminoalkynylation of terminal olefin and a rhodium-catalyzed intramolecular [3 + 2] annulation. An oxygen-substituted ergoline derivative (-)-25 was also achieved by using the same strategy.


Preoperative and perioperative care for patients with suspected or established aortic stenosis facing noncardiac surgery.
Current medicine has displayed a trend toward less interfering techniques but more invasive surgical approaches in older patients with more comorbidities. In this population, the prevalence of symptomatic cardiac disease including aortic stenosis is increased. More than 25 years have elapsed since severe aortic stenosis was identified as an independent, important risk factor for patients undergoing general anesthesia for noncardiac surgery. Despite impressive advances in anesthesiologic and surgical techniques, morbidity and mortality in patients with severe aortic stenosis remains high. Published study results clearly show that adverse perioperative risk in patients with aortic stenosis depends on the interaction of factors such as the severity of valve disease, concomitant coronary artery disease, and the severity and/or urgency of the surgical procedures. The mainstay of preoperative evaluation remains the obtaining of a comprehensive preoperative medical history and a physical examination, while transthoracic echocardiography is necessary to establish or exclude hemodynamically relevant aortic stenosis in selected patients. Perioperative care is established in patients with asymptomatic aortic stenosis and/or those undergoing low-risk surgery. However, further preoperative testing or aortic valve replacement prior to noncardiac surgery should be discussed individually with the patients awaiting urgent surgical procedures who are at medium or high risk. At this point, decisions should be made in an interdisciplinary manner, including the opinions/wishes of the patient and the patient's family.


Exploring the criticality hypothesis using programmable swarm robots with Vicsek-like interactions.
A widely mentioned but not experimentally confirmed view (known as the 'criticality hypothesis') argues that biological swarm systems gain optimal responsiveness to perturbations and information processing capabilities by operating near the critical state where an ordered-to-disordered state transition occurs. However, various factors can induce the ordered-disordered transition, and the explicit relationship between these factors and the criticality is still unclear. Here, we present an experimental validation for the criticality hypothesis by employing real programmable swarm-robotic systems (up to 50 robots) governed by Vicsek-like interactions, subject to time-varying stimulus-response and hazard avoidance. We find that (i) not all ordered-disordered motion transitions correspond to the functional advantages for groups; (ii) collective response of groups is maximized near the critical state induced by alignment weight or scale rather than noise and other non-alignment factors; and (iii) those non-alignment factors act to highlight the functional advantages of alignment-induced criticality. These results suggest that the adjustability of velocity or directional coupling between individuals plays an essential role in the acquisition of maximizing collective response by criticality. Our results contribute to understanding the adjustment strategies of animal interactions from a perspective of criticality and provide insights into the design and control of swarm robotics.


The optical trocar in gynecological surgery: clinical and technical outcomes.
Optical trocars have been introduced as an alternative technique for obtaining access to the peritoneal cavity. The advantage is that each layer of the abdominal wall can be identified avoiding inadvertent injuries due to a lack of vision. From March 2010 to March 2011, 138 women underwent laparoscopy for benign diseases. They were submitted to gynecological laparoscopy for direct optical access. There was no evidence of vascular injuries. This study confirms that the optical trocar is a safe, rapid, and effective method, that offers a real perception of the safety of the entrance into the abdomen.


Facile Synthesis of NH-Free 5-(Hetero)Aryl-Pyrrole-2-Carboxylates by Catalytic C-H Borylation and Suzuki Coupling.
A convenient two-step preparation of NH-free 5-aryl-pyrrole-2-carboxylates is described. The synthetic route consists of catalytic borylation of commercially available pyrrole-2-carboxylate ester followed by Suzuki coupling without going through pyrrole N-H protection and deprotection steps. The resulting 5-aryl substituted pyrrole-2-carboxylates were synthesized in good- to excellent yields. This synthetic route can tolerate a variety of functional groups including those with acidic protons on the aryl bromide coupling partner. This methodology is also applicable for cross-coupling with heteroaryl bromides to yield pyrrole-thiophene, pyrrole-pyridine, and 2,3'-bi-pyrrole based bi-heteroaryls.


A trifocal perspective on medicine as a moral enterprise: towards an authentic philosophy of medicine.
The fundamental claim that the practice of medicine is essentially a moral enterprise remains highly contentious, not least among the dominant traditional moral theories. The medical profession itself is today characterized by multicultural pluralism and moral relativism that have left the Hippocratic moral tradition largely in disarray. In this paper, I attempt to clarify the ambiguity about practicing medicine as a moral enterprise and echo Pellegrino's call for a phenomenologically and teleologically derived philosophy of medicine. I proffer a realistic trifocal matrix in which the virtuous moral agency and the teleologically derived moral imperative of the physician are comprehensively integrated with an action-guiding practical analytical framework for the resolution of ethical dilemmas in medicine. I argue that this trifocal perspective points us towards an authentic philosophy of medicine that is not only verifiable through Lonerganian self-appropriation, but also authentically objective through the possible moral self-transcendence of the good physician.


Promoting positive outcomes in obese patients.
Obese patients are seen in every practice setting. Obesity is a chronic disease that may lead to physical and emotional problems, which may have an impact on the social and psychological functioning of the patient. With appropriate preoperative, intraoperative, and postoperative precautions; monitoring; and restructuring the environment to promote care and safety, the incidence of poor surgical outcomes can be minimized. This paper will address the significance of obesity, related diseases, and proper care of the obese patient.


Smad7 inhibits differentiation and mineralization of mouse osteoblastic cells.
The transforming growth factor (TGF)-β family members, bone morphogenetic protein (BMP)-2 and TGF-β that signal via the receptor-regulated Smads (R-Smads) induce bone formation in vivo. The inhibitory Smads (I-Smads), Smad6 and Smad7, negatively regulate TGF-β family ligand signaling by competing with R-Smads for binding to activated type I receptors, and preventing R-Smad activation, Hence, the I-Smads potentially act as suppressors of bone formation although their effects on phenotypic changes in mature osteoblasts are unclear. While Smad7 inhibits both BMP and TGF-β signaling, Smad6 is less effective in inhibiting TGF-β signaling. The present study was performed to examine the role of Smad7 on the phenotype of mouse osteoblastic MC3T3-E1 cells. We employed stable Smad7-transfected MC3T3-E1 cells to examine the role of Smad7 in osteoblast proliferation, differentiation and mineralization. Stable Smad7 overexpression significantly inhibited the absorbance in the MTT-dye assay and inhibited the levels of PCNA compared with those in empty vector-transfected cells. Smad7 overexpression suppressed the type 1 collagen mRNA and protein levels. Moreover, Smad7 inhibited ALP activity and mineralization of osteoblastic cells. The effects of stable overexpression of Smad6 were similar to those of Smad7 suggesting the changes mediated by either I-Smad occurred by inhibition of BMP rather than TGF-β signaling. In addition, PTH-(1-34) elevated the levels of Smad7 in parental MC3T3-E1 cells. In conclusion, the present study demonstrated that Smad7, as well as Smad6, inhibits proliferation, differentiation and mineralization of mouse osteoblastic cells. Therefore, I-Smads are important molecular targets for the negative control of bone formation.


Investigative therapy for advanced esophageal cancer using the option for combined immunotherapy and chemotherapy.
Aim: Advanced esophageal cancer has limited therapeutic options and a poor outcome. The efficacy of immunotherapy, as the first-line treatment of advanced esophageal cancer, is uncertain. Results: A stage IV advanced esophageal cancer patient received the first-line treatment with a combination of pembrolizumab and chemotherapy. Partial response (PR) was achieved after three cycles, and the efficacy was evaluated as stable after six cycles of immunochemotherapy and two cycles of maintenance monotherapy. Immune-related adverse events (irAEs) were not obvious. The patient was followed up till November 2019 when he died of gastrointestinal hemorrhage. Conclusion: The combination of an immune checkpoint inhibitor and chemotherapy is effective and safe for the initial treatment of advanced esophageal cancer. To confirm the evidence from this case, larger clinical trials are required in the future.


Self-reported attitudes versus actual practice of oxygen therapy by ICU physicians and nurses.
High inspiratory oxygen concentrations are frequently administered in ventilated patients in the intensive care unit (ICU) but may induce lung injury and systemic toxicity. We compared beliefs and actual clinical practice regarding oxygen therapy in critically ill patients. In three large teaching hospitals in the Netherlands, ICU physicians and nurses were invited to complete a questionnaire about oxygen therapy. Furthermore, arterial blood gas (ABG) analysis data and ventilator settings were retrieved to assess actual oxygen practice in the same hospitals 1 year prior to the survey. In total, 59% of the 215 respondents believed that oxygen-induced lung injury is a concern. The majority of physicians and nurses stated that minimal acceptable oxygen saturation and partial arterial oxygen pressure (PaO2) ranges were 85% to 95% and 7 to 10 kPa (52.5 to 75 mmHg), respectively. Analysis of 107,888 ABG results with concurrent ventilator settings, derived from 5,565 patient admissions, showed a median (interquartile range (IQR)) PaO2 of 11.7 kPa (9.9 to 14.3) [87.8 mmHg], median fractions of inspired oxygen (FiO2) of 0.4 (0.4 to 0.5), and median positive end-expiratory pressure (PEEP) of 5 (5 to 8) cm H2O. Of all PaO2 values, 73% were higher than the upper limit of the commonly self-reported acceptable range, and in 58% of these cases, neither FiO2 nor PEEP levels were lowered until the next ABG sample was taken. Most ICU clinicians acknowledge the potential adverse effects of prolonged exposure to hyperoxia and report a low tolerance for high oxygen levels. However, in actual clinical practice, a large proportion of their ICU patients was exposed to higher arterial oxygen levels than self-reported target ranges.


Prevalence of malaria among acute febrile patients clinically suspected of having malaria in the Zeway Health Center, Ethiopia.
Malaria diagnosis is a common challenge in developing countries with limited diagnostic services. Common febrile illnesses were assessed in 280 malaria-suspected patients, and each case was subjected to clinical and laboratory examinations for malaria, relapsing fever, typhoid fever, typhus, and brucellosis. Data were entered and analyzed using Epi Info version 3.1 software. Malaria accounted for 17% (CI, 12.6-21.4%) of febrile illnesses. The remaining cases were associated with typhoid fever (18.5%; CI, 13.95-23.05%), typhus (17.8%; CI, 13.32-22.28%), brucellosis (1%; CI, -0.17-2.17%), relapsing fever (2%; CI, 0.36-3.64%), and unknown causes (44%). Approximately 7% of patients had coinfections, and 2% of patients treated as monoinfections. Approximately 1.4% of the nonmalarial patients received antimalarial treatment. The sensitivity and specificity of the CareStart Pf/pan rapid diagnostic tests in comparison with those of microscopy were 100% and 91%, respectively, with positive- and negative-predictive values of 94% and 100%, respectively. Compared with microscopy, the positive-predictive value of each malaria symptom was much lower than that of the symptoms combined: fever, 17%; sweating, 30%; headache, 18%; general body ache, 22%; loss of appetite, 21%. The study findings revealed a high proportion of nonmalarial illnesses were clinically categorized as malaria. Parasite-based diagnosis is recommended for the management of malarial and nonmalarial cases.


Phosphoglycolate has profound metabolic effects but most likely no role in a metabolic DNA response in cancer cell lines.
Repair of a certain type of oxidative DNA damage leads to the release of phosphoglycolate, which is an inhibitor of triose phosphate isomerase and is predicted to indirectly inhibit phosphoglycerate mutase activity. Thus, we hypothesized that phosphoglycolate might play a role in a metabolic DNA damage response. Here, we determined how phosphoglycolate is formed in cells, elucidated its effects on cellular metabolism and tested whether DNA damage repair might release sufficient phosphoglycolate to provoke metabolic effects. Phosphoglycolate concentrations were below 5 µM in wild-type U2OS and HCT116 cells and remained unchanged when we inactivated phosphoglycolate phosphatase (PGP), the enzyme that is believed to dephosphorylate phosphoglycolate. Treatment of PGP knockout cell lines with glycolate caused an up to 500-fold increase in phosphoglycolate concentrations, which resulted largely from a side activity of pyruvate kinase. This increase was much higher than in glycolate-treated wild-type cells and was accompanied by metabolite changes consistent with an inhibition of phosphoglycerate mutase, most likely due to the removal of the priming phosphorylation of this enzyme. Surprisingly, we found that phosphoglycolate also inhibits succinate dehydrogenase with a Ki value of <10 µM. Thus, phosphoglycolate can lead to profound metabolic disturbances. In contrast, phosphoglycolate concentrations were not significantly changed when we treated PGP knockout cells with Bleomycin or ionizing radiation, which are known to lead to the release of phosphoglycolate by causing DNA damage. Thus, phosphoglycolate concentrations due to DNA damage are too low to cause major metabolic changes in HCT116 and U2OS cells.


Divry-Van Bogaert syndrome. Clinical and ultrastructural findings.
A case of a progressive disease with epilepsy, marble skin, and roentgenographic evidence of tapering of the distal carotid branches with corticomeningeal angiomatosis was studied. The clinical course, angiographic findings, and skin biopsy results justified the diagnosis of noncalcifying venous capillary angiomatosis, or Divry-Van Bogaert syndrome.


Clinical characteristics, treatment, and outcome of primary rectal lymphoma: a single center experience of 16 patients.
The rectum is a relatively uncommon site for lymphoma compared with other gastrointestinal sites; no consensus regarding management of primary rectal lymphoma (PRL) has been formed due to its limited frequency. We aimed to investigate clinical characteristics and treatment outcomes in patients with PRL in a single center patient cohort. We retrospectively analyzed the results of 16 consecutive patients with PRL, identified and treated at the Asan Medical Center, Seoul, Korea between January 1993 and December 2014. These 16 patients with PRL constituted 0.8% of all non-Hodgkin's lymphoma patients (N=1,984). B-cell lymphomas (N=14) made up the majority of the series, and half of these were extranodal marginal zone lymphomas (ENMZL, N=7). Ten patients received systemic chemotherapy with (N=3) or without rituximab (N=7), and 4 of these received additional local therapy. The others received radiotherapy (N=3) or endoscopic mucosal resection (N=3). Twelve patients (75%) achieved complete response (CR) after first-line treatment. Event-free survival (EFS) and overall survival (OS) in stages IE and IIE were significantly longer compared with stages IVE (P=0.001 and P=0.001, respectively). All patients with ENMZL (N=7) achieved CR during or after initial treatment. PRL is very rare and seems to present mostly as B-cell type. Stage is the most important prognostic factor, with significantly better survival associated with localized diseases. ENMZL may be one of the most common types of PRL with favorable treatment outcomes.


An exemplar model of performance in the artificial grammar task: holographic representation.
We apply a multitrace model of memory to explain performance in the artificial grammar task. The model blends the convolution method for representation from Jones and Mewhort's BEAGLE model (Jones, M. N., & Mewhort, D. J. K. (2007). Representing word meaning and order information in a composite holographic lexicon. Psychological Review, 114, 1-37) of semantic memory with the multitrace storage and retrieval model from Hintzman's MINERVA 2 model (Hintzman, D. L. (1986). "Schema abstraction" in a multiple-trace memory model. Psychological Review, 93, 411-428) of episodic memory. We report an artificial grammar experiment, and we fit the model to those data at the level of individual items. We argue that performance in the artificial grammar task is best understood as a process of retrospective inference from memory.


Melatonin Mediates Protective Effects against Kainic Acid-Induced Neuronal Death through Safeguarding ER Stress and Mitochondrial Disturbance.
Kainic acid (KA)-induced neuronal death is linked to mitochondrial dysfunction and ER stress. Melatonin is known to protect hippocampal neurons from KA-induced apoptosis, but the exact mechanisms underlying melatonin protective effects against neuronal mitochondria disorder and ER stress remain uncertain. In this study, we investigated the sheltering roles of melatonin during KA-induced apoptosis by focusing on mitochondrial dysfunction and ER stress mediated signal pathways. KA causes mitochondrial dynamic disorder and dysfunction through calpain activation, leading to neuronal apoptosis. Ca2+ chelator BAPTA-AM and calpain inhibitor calpeptin can significantly restore mitochondrial morphology and function. ER stress can also be induced by KA treatment. ER stress inhibitor 4-phenylbutyric acid (PBA) attenuates ER stress-mediated apoptosis and mitochondrial disorder. It is worth noting that calpain activation was also inhibited under PBA administration. Thus, we concluded that melatonin effectively inhibits KA-induced calpain upregulation/activation and mitochondrial deterioration by alleviating Ca2+ overload and ER stress.


Effects of combined dopamine and nitroprusside therapy in patients with severe pump failure and hypotension complicating acute myocardial infarction.
In severe pump failure with hypotension complicating acute myocardial infarction, dopamine has been useful in raising arterial pressure by increasing myocardial performance and augmenting peripheral resistance. Once adequate blood pressure are obtained, vasodilators may be used to reduce peripheral resistance and thus enhance pump performance. Accordingly, the hemodynamic effects of dopamine and nitroprusside administration were monitored in eight patients who developed hypotension following an acute myocardial infarction. With dopamine therapy alone, mean arterial pressure averaged 84 +/- 3.6 mm Hg and mean left ventricular filling pressure 32 +/-7.9 mm Hg. The addition of nitroprusside, at doses ranging from 0.5 to 1.6 micrograms/kg/min, resulted in a decrease in arterial pressure to 75 +/- 2.4 mm Hg (p less than 0.01) and in left ventricular filling pressure to 23 +/- 7.2 mm Hg (p less than 0.001). Cardiac index increased modestly from 1.81 +/- 0.61 to 2.01 +/- 0.60 liters/min/m2 (p less than 0.05), while systemic vascular resistance fell from 1,967 +/- 707 to 1,586 +/- 634 dynes-sec-cm-5 (p less than 0.01). Heart rate did not change significantly. Seven of eight patients died in the hospital within 4 days of admission. It appears that despite a beneficial hemodynamic response effected by combined dopamine-nitroprusside administration, the prognosis of this group of patients may not be favorably altered because of the extensive destruction of myocardium.


Predicting primary treatment failure using interim FDG-PET scanning in diffuse large B-cell lymphoma.
Interim FDG-PET (iPET) in diffuse large B-cell lymphoma (DLBCL) is increasingly practised and used in clinical trials to adapt further therapy. However, the optimum timing and methodology of iPET remains controversial. We retrospectively analysed the iPET results and outcomes of 200 DLBCL patients where FDG-PET was routinely performed at baseline, after 2 cycles (iPET2) and at completion of chemoimmunotherapy. iPET was also performed after 4 cycles (iPET4) where at iPET2, Deauville score (DS) was ≥4. Scans were assessed by blinded expert lymphoma PET physicians for DS, maximum standard uptake value (SUVmax), total metabolic tumour volume (TMTV) and total lesion glycolysis (TLG). Treatment failure was defined as death, progression or refractory disease. 95.5% of patients received R-CHOP. No baseline PET parameter was predicted for EFS or OS independent of the NCCN-IPI. The multivariable analysis at iPET2 showed DS5 (19.5% of cases) predicted treatment failure (HR 6.29, 95% CI 3.01-13.17, P < .001), but DS4 was equivalent to DS1-3. At iPET4, ΔSUVmax < 66% predicted treatment failure (HR 5.49, 95% CI 3.03-9.99, P < .001). By multivariable analysis of all time points, high NCCN-IPI and DS5 at iPET2 were negative predictors of survival. These findings were independent of novel prognostic markers.


Severe Glomerular Endothelial Injury Associated with a Short D4Z4 Repeat on Chromosome 4q35.
The short D4Z4 repeat on chromosome 4q35 is a confirmatory genetic cause of facioscapulohumeral muscular dystrophy (FSHD), which presents with no renal complications. We herein report a five-year-old girl previously diagnosed with Coat's-like retinopathy, deafness, and mental retardation, who was found to have early-onset, severe FSHD. Despite the absence of muscle weakness, a Southern blot analysis showed a short D4Z4 repeat on chromosome 4q35. She presented with steroid-resistant nephrotic syndrome, and her renal histopathological findings were severe glomerular endothelial injury, which is a new complication associated with this genetic abnormality. Screening of renal complications may be necessary for FSHD patients. This patient requires close follow-up for her muscle symptoms.


Amino terminus of outer membrane PhoE protein: localization by use of a bla-phoE hybrid gene.
Expression of a recently constructed bla-phoE hybrid gene results in synthesis and incorporation into the outer membrane of PhoE protein containing an amino-terminal extension of 158 amino acid residues of beta-lactamase (Tommassen et al., EMBO J. 2:1275-1279, 1983). As the PhoE protein part of this hybrid protein is apparently normally incorporated into the outer membrane, the beta-lactamase part of the protein can be considered as a label of the amino terminus of PhoE protein. By using trypsin accessibility experiments, this beta-lactamase part was shown to be located at the periplasmic side of the membrane. Therefore, the amino terminus of PhoE protein most likely faces the periplasm.


Altered states of consciousness: review of experimental data obtained with a multiple techniques approach.
To investigate the psychophysiologic mechanisms of an altered state of consciousness (ASC) produced via systematic mental training by correlating the results of multiple computerized bioelectrographic measurements. All subjects were tested, using a set of modern computerized techniques comprising digital electroencephalography, measurement of the low-frequency bilateral activity of the brain, evoked bioelectrographic signals measured by computerized Kirlian photography (otherwise called gas discharge visualization [GDV]), self-reporting by subjects, linguistic testing, and profiling of mood states. Sweden and Russia from 1996 to 1999. Young volunteers (61) who underwent systematic mental training for not less than 7 weeks. Members of the control group (56) were not engaged in mental training. All participants involved in the systematic mental training showed significant positive changes in their psychoemotional status after 7 weeks of mental training. All of the techniques showed specific changes that might be associated with an ASC in the subjects. The Kirlian (GDV) patterns showed a form of "explosive activation," which was stable, reproducible, and correlated with an ASC. This led the authors to introduce the concept of short-term activation of the induced bioelectrographic processes and enabled the properties of this ACS to be determined for the first time. There were practically no changes in the control group. ASC activation took place with harmonization of the biopotential field of the brain, the psychic state, and the bioenergy fields. This is attributed to changes in both the psychosomatic and psychoenergetic autoregulation. This conclusion is of vital importance for understanding what happens in systematic mental training and understanding the fundamentals of bioenergetic and psychosomatic medicine.


[Ultrasonographic findings in 22 cattle with pericarditis traumatica].
The goal of the present study was to describe the ultrasonographic findings in 22 cattle with traumatic pericarditis. A 5.0 MHz linear transducer or a 5.0 MHz convex transducer was used to examine the thorax, reticulum and liver. There was severe pleural effusion in 17 heifers and severe pericardial effusion in 13 animals. Echogenic deposits and strands of fibrin were seen on the epicardium of 7 animals. Eighteen cattle had signs of traumatic reticuloperitonitis, and 11 had ascites. Because of cardiac insufficiency, 14 cattle had a markedly enlarged liver due to congestion and 15 had dilatation of the caudal vena cava. Ultrasonography is a useful diagnostic aid for visualisation and characterisation of thoracic and abdominal lesions in cattle with traumatic pericarditis.


[Diagnosis of infectious pancreatic necrosis (IPN) of trout using immunofluorescence].
Until recently, demonstration of infectious pancreatic necrosis was conditioned by the isolation of virus. By means of the immunofluorescence method it is possible to make a rapid and accurate diagnosis, as well as to determine the development of infection. In acute cases, the virus in fry was demonstrated mainly in the cytoplasm of epithelial cells of guts; in Pd1-2 trout, the virus was proved in the cytoplasm of epithelial cells of primary kidney tubules and in the cytoplasm of epithelial cells of pancreatic acini. In all cases the virus occurrence demonstrated by immunofluorescence was in correlation with the results achieved by cultivation methods.


Biodegradation of high concentrations of halomethanes by a fermentative enrichment culture.
A fermentative enrichment culture (designated DHM-1) that grows on corn syrup was evaluated for its ability to cometabolically biodegrade high concentrations of chloroform (CF), carbon tetrachloride (CT), and trichlorofluoromethane (CFC-11). When provided with corn syrup and vitamin B12 (0.03 mol B12 per mol CF), DHM-1 grew and biodegraded up to 2,000 mg/L of CF in 180 days, with only minor transient accumulation of dichloromethane and chloromethane. CT (15 mg/L) and CFC-11 (25 mg/L) were also biodegraded without significant accumulation of halomethane daughter products. The rate of CF biodegradation followed a Michaelis-Menten-like pattern with respect to the B12 concentration; one-half the maximum rate (66 mg CF/L/d) occurred at 0.005 mol B12 per mol CF. DHM-1 was able to biodegrade 500 mg/L of CF at an inoculum level as low as 10(-8) mg protein/L. The highest rate of CF biodegradation occurred at pH 7.7; activity decreased substantially below pH 6.0. DHM-1 biodegraded mixtures of CT, CFC-11, and CF, although CFC-11 inhibited CF biodegradation. Evidence for compete defluorination of CFC-11 was obtained based on a fluoride mass balance. Overall, the results suggest that DHM-1 may be effective for bioaugmentation in source zones contaminated with thousands of milligrams per liter of CF and tens of milligrams per liter of CT and CFC-11.


The Fast Lane of Hypoxic Adaptation: Glucose Transport Is Modulated via A HIF-Hydroxylase-AMPK-Axis in Jejunum Epithelium.
The intestinal epithelium is able to adapt to varying blood flow and, thus, oxygen availability. Still, the adaptation fails under pathologic situations. A better understanding of the mechanisms underlying the epithelial adaptation to hypoxia could help to improve the therapeutic approach. We hypothesized that the short-term adaptation to hypoxia is mediated via AMP-activated protein kinase (AMPK) and that it is coupled to the long-term adaptation by a common regulation mechanism, the HIF-hydroxylase enzymes. Further, we hypothesized the transepithelial transport of glucose to be part of this short-term adaptation. We conducted Ussing chamber studies using isolated lagomorph jejunum epithelium and cell culture experiments with CaCo-2 cells. The epithelia and cells were incubated under 100% and 21% O2, respectively, with the panhydroxylase inhibitor dimethyloxalylglycine (DMOG) or under 1% O2. We showed an activation of AMPK under hypoxia and after incubation with DMOG by Western blot. This could be related to functional effects like an impairment of Na+-coupled glucose transport. Inhibitor studies revealed a recruitment of glucose transporter 1 under hypoxia, but not after incubation with DMOG. Summing up, we showed an influence of hydroxylase enzymes on AMPK activity and similarities between hypoxia and the effects of hydroxylase inhibition on functional changes.


An Overview of Heavy Chain Ferritin in Cancer.
As a spherical protein that acts as a repository for intracellular iron, Ferritin is the most important iron storage form and is known to influence tumor immunity. Unbound ferritin is composed of 24 subunits, made up of ferritin light chain (FTL) and ferritin heavy chain (FTH). Ferritin can be automatically put together to form hollow nanocages that measure 12 nm around the outside and 8 nm around the inside. Cancer causes the second-most deaths worldwide, effective elimination of tumor cells while protecting normal cells is the foundation of modern tumor therapy. To this end, the innate tumor-targeting activity of human FTH1, first identified ten years ago, is highly appealing. Unmodified human FTH1 binds to its receptor, transferrin receptor 1 (TfR1), which is frequently overexpressed in cancer cells. FTH1-TfR1 binding permits improved drug efficacy by promoting ferritin-mediated targeted delivery. In addition, FTH is also associated with the prognosis of multiple typies of cancer. The level of FTH1 is significantly and positively correlated with the infiltration of tumor-associated macrophages. FTH1 also plays an important role in regulating the tumor immunity of solid cancer. As such, FTH1 has been extensively applied in the targeted delivery of anticancer drugs, diagnostic molecules (e.g., radioisotopes and fluorophones), and inorganic nanoparticles (NPs) to tumors.This article reviews the role of FTH in cancer and its potential as a therapeutic target.


"It's about our bodies… we have the right to know this stuff": A qualitative focus group study on Australian women's perspectives on breast density.
This study aimed to explore Australian women's current knowledge, perspectives and attitudes about breast density (BD); and information needs to inform effective evidence-based communication strategies. Fourteen online focus group sessions with a total of 78 women in New South Wales and Queensland, Australia aged 40-74 years without a personal diagnosis of breast cancer were conducted. Audio-recorded data was transcribed and analysed thematically. Women had a very limited knowledge of BD. Overall, women expressed a preference for more frequent mammograms and/or supplemental screening should they be told they had dense breasts, despite being presented with information on potential downsides of additional testing. The majority of women were supportive of the notion of BD notification, often suggesting they had a 'right to know' and they would prefer to be educated and informed about it. The potential of being informed and notified of BD is found to be of interest and importance to Australian women of breast screening age despite lacking current knowledge. This study highlights that policy makers and screening services need to consider how to weigh up these views and preferences of women with current evidence surrounding BD in deciding about implementing population-based BD notification.


Tuberculosis Genetic Epidemiology: A Latin American Perspective.
There are an estimated 10 million new cases of tuberculosis worldwide annually, with 282,000 new or relapsed cases each year reported from the Americas. With improvements in genome sequencing technology, it is now possible to study the genetic diversity of tuberculosis with much greater resolution. Although tuberculosis bacteria do not engage in horizontal gene transfer, the genome is far more variable than previously thought. The study of genome-wide variation in tuberculosis has improved our understanding of the evolutionary origins of tuberculosis, the arrival of tuberculosis in Latin America, the genetic determinants of drug resistance, and lineage-specific associations with important clinical phenotypes. This article reviews what is known about the arrival of tuberculosis in Latin America, the genetic diversity of tuberculosis in Latin America, and the genotypic determinants of clinical phenotypes.


An evaluation of coupling coordination between sports industry and health service industry in China.
Depending on the strategy of "Healthy China", more and more people pay attention to health issues. The integration and development of sports industry and health service industry is an inevitable outcome of industrial transformation and upgrading and healthy life in the new era. Through constructing the evaluation index system of the coupling and coordination development degree between sports industry and health service industry, using entropy evaluation method and coupling and coordination degree model, this paper explore the comprehensive level and coupling and coordination development status of sports industry and health service industry in thirty-one provinces, municipality cities and autonomous regions of China from 2013 to 2017. The results of this paper show that the comprehensive China's sports industry and health service industry both present an incremental development trend year by year, and are characterized by the distribution of "high in the east and low in the west" in space. The government's policy support provides superior industrial supporting conditions for the development of sports industry. However, it is not conducive to the promotion of industrial economic benefits. In the health service industry, the rapid development of health insurance is beneficial to the integration of industrial resources and the perfection of industrial chain. Whereas as the core content of health service industry, health service has greater space for development; the coupling and coordination degree between the two industries rises from mild maladjustment to basic coordination, which is characterized by the distribution of "high in the east and low in the west" in space; among provinces, with Beijing, the Yangtze River Delta and Guangdong as the three development center points, it shows the spatial evolutionary process from "dispersion-type plaques" to "gathering type scattered surfaces".


Prospective longitudinal study on quality of life in relapsed/refractory multiple myeloma patients receiving second- or third-line lenalidomide or bortezomib treatment.
Treatment advances for multiple myeloma (MM) that have prolonged survival emphasise the importance of measuring patients' health-related quality of life (HRQoL) in clinical studies. HRQoL/functioning and symptoms of patients with relapsed/refractory MM (RRMM) receiving second- or third-line lenalidomide or bortezomib treatment were measured in a prospective European multicentre, observational study at different time points. At baseline, patients in the lenalidomide cohort were frailer than in the bortezomib cohort with more rapid disease progression at study entry (more patients with Eastern Cooperative Oncology Group performance status >2, shorter time from diagnosis, more chronic heart failure, higher serum creatinine levels, more patients with dialysis required). About 40% of the patients receiving lenalidomide discontinued the study in <6 months while 55% in the bortezomib cohort discontinued. No substantial HRQoL deterioration was observed for the first 6 months in patients with RRMM receiving one or the other treatment. For patients still on treatment at study completion (month 6), only the European Organization for Research and Treatment of Cancer Quality-of-Life Core domains of Diarrhoea and Global Health Status/QoL had worsened in the lenalidomide and bortezomib cohorts, respectively. A clinically meaningful deterioration in HRQoL was more often observed for patients who discontinued the study prior to 6 months in the bortezomib cohort than in the lenalidomide cohort.


Interlocked Supramolecular Polymers Created by Combination of Halogen- and Hydrogen-Bonding Interactions through Anion-Template Self-Assembly.
We present the synthesis and oxoanion-assembling properties of a monomer with a naphthalene ring as a central core decorated with two arms containing iodotriazolium rings as anion binding sites. Interactions with SO42-, H2PO4-, and HP2O73- anions, via a cooperative mechanism, afforded new supramolecular materials stabilized by a combination of halogen- and hydrogen-bonding interactions. 1H NMR experiments and solid-state structure provided evidence for the initial formation of a supramolecular linear chain, nucleation step, and then two different supramolecular chains are interpenetrated with each other, elongation steps, involving the formation of hydrogen bonds between two oxygens of the anion from one of the chains and the naphthalene inner protons from the other chain. Scanning electron microscopy studies revealed that the morphology of the crystals changed dramatically with the nature of the anion added.


Screening merits of the Lang II, Frisby, Randot, Titmus, and TNO stereo tests.
Previous works show a pronounced disagreement on the reliability of stereo tests as screening tools for amblyopia and strabismus. This study's aim was to compare the ability of the Lang II, Frisby, Randot, Titmus, and TNO stereo tests to detect amblyopia and strabismus with visual acuity testing and cover testing. A total of 1035 school children aged 12 to 13 years were examined in a field study in Monterrey, Mexico. In addition to the 5 stereo tests, the examination included visual acuity, cover testing, refraction (skiascopy), and inspection of the red reflex and posterior pole. Sensitivity ranged from 17% to 47% (Frisby-Titmus-Lang II-Randot-TNO, in order of occurrence). Of the 60 subjects with strabismus and/or amblyopia, only 8 subjects were identified by all 5 stereo tests. A considerable number of subjects (25), the majority of whom were amblyopic (23 subjects), were not identified by any of the tests. All stereo tests showed higher sensitivities for strabismus than for amblyopia. None of the 5 stereo tests studied is suitable for screening for amblyopia or strabismus. The results of both ocularly normal subjects and subjects with strabismus and/or amblyopia are variable, and there is no way of separating normal response from abnormal response.


Syringocystadenoma Papilliferum: A Case Report and Review of the Literature.
Syringocystadenoma papilliferum is a very rare, benign adnexal tumor that originates from the apocrine sweat glands. Herein, we report a 25-year-old male who presented with a 10-year history of an asymptomatic slowly growing skin lesion on his face. Skin examination revealed a solitary rounded 3 × 3 cm erythematous plaque with central crustation on the right side of his face. Punch skin biopsy was taken from the lesion. The epidermis showed downward papillomatous extensions. The dermis showed multiple epithelial sheets and dilated ducts that were lined by columnar cells. On the basis of the above clinicopathological findings, the diagnosis of syringocystadenoma papilliferum was made. The patient was reassured and referred to a surgeon for surgical excision of the lesion.


Perfect people, happier lives? When the quest for perfection compromises happiness: the roles played by substance use and internet addiction.
Building on the Conservation of Resources Theory and the Stress-Coping Model, the present study explored the relationship between perfectionism (rigid, self-critical, narcissistic) and subjective happiness among youth. In this relationship, we also examined the mediating roles of substance use (i.e., drinking and smoking) and Internet addiction symptoms. Our sample comprised 431 Romanian university students aged 18-25 (M = 20.50, SD = 1.58), and most of them were females (79.81%, self-reported gender). Participants completed self-reported anonymous scales through a web-based survey at the beginning of 2023. Correlation analysis results indicated that all forms of perfectionism were associated with Internet addiction symptoms. Self-critical and narcissistic perfectionism and drinking, smoking, and Internet addiction symptoms were negatively associated with subjective happiness. Path analysis suggested that health-risk behaviors completely mediated the effect of perfectionism on subjective happiness. High levels of perfectionism were associated with high levels of health-risk behaviors, and high levels of addictive behaviors were associated with low levels of subjective happiness. We discuss the present findings considering their practical use regarding students' subjective happiness.