Heart failure biomarkers.
Biomarker testing in patients with heart failure (HF) is rapidly expanding. With high-quality research indicating its diagnostic and prognostic capabilities, biomarkers are excellent adjuncts to manage patients with HF. Their superiority lies mainly in their reflection of ongoing pathophysiological events at a cellular level. Monitoring biomarker levels has been shown to provide incremental information on the progression of disease, thus allowing to better tailor treatment and management. Several biomarkers have gained attention in the past decade and continuing research demonstrates the specificity of each biomarker to be used on its own or in combination to improve diagnostic accuracy. This review will provide an insight into the role of such biomarkers, which are widely studied in the setting of HF so as to delineate their role in diagnosing, prognosticating, and titrating HF therapy.


Immunohistochemical alterations in invasive adenocarcinoma in endoscopically resected adenoma and factors associated with risk of residual or recurrent disease.
We determined the pattern of immunohistochemical expression in invasive adenocarcinoma in endoscopically resected adenoma, its relationship with the risk of residual or recurrent disease and the related factors. We included individuals with malignant polyps resected endoscopically in the period 1999-2009. Clinical and endoscopic data were collected. All histological specimens were re-analysed. CD44, matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor-β (VEGF-β), β-catenin, laminin and cyclooxygenase 2 (COX-2) expression were determined by immunohistochemistry. A multivariate logistic regression was performed to determine variables independently associated with the risk of residual or recurrent disease. One-hundred and fifty-one malignant polyps (114 pedunculated; mean size ± SD=22.61 ± 10.86 mm) were resected endoscopically. Resection was fragmented and incomplete in 26.5% and 8.6% of patients, respectively. Surgical resection was performed on 71 (47%) patients. After a median follow-up of 44 months, residual (n=12) or recurrent (n=6) disease was detected in 17 patients. Conventional histology showed that 32.1% met high-risk histological criteria. Immunohistochemical expression was positive for CD44, MMP-9, VEGF-β, β-catenin, laminin and COX-2 in 63.3%, 25.3%, 45%, 38.8%, 79% and 34.5% of specimens, respectively, with no differences between both groups. Variables associated with residual or recurrent disease in the univariate analysis were: nonpedunculated morphology (P=0.07); fragmented (P<0.001) or incomplete resection (P<0.001); margin infiltration (P=0.04); and histological high-risk lesion (P=0.003). Finally, incomplete resection (OR=12.16, 95% CI=3.15-46.98; P<0.001) and histological high risk (OR=4.73, 95% CI=1.33-16.74; P=0.002) were independently associated with the risk of residual or recurrent disease. Immunohistochemistry could not predict residual or recurrent disease. Only incomplete excision and histological high risk did so. The factors independently associated were histological high-risk lesion and incomplete resection.


Eye-head coupling in humans. I. Simultaneous recording of isolated motor units in dorsal neck muscles and horizontal eye movements.
A tonic coupling between the horizontal component of eye position and dorsal neck muscle activity has been demonstrated in the cat and monkey. In order to demonstrate this synergy in humans and study its characteristics, we have measured the relation between the firing rate of individual motor unit of the splenius muscle and voluntary horizontal shifts of gaze using 5 degrees steps, in head-fixed subjects. Eye movement recording was achieved by conventional binocular electro-oculography and the activity of the right splenius muscle was recorded with Bronks coaxial bipolar electrodes inserted manually at the C4-C5 intervertebral level. The activity of 51 motor units in 10 subjects has been recorded. For all subjects, motor units firing rate increased when the gaze shifted to the ipsilateral side, and both increase in firing rate and recruitment were observed. These results demonstrate that the tonic eye head synergy is also present in man.


Synergistic effect of cigarette smoke and saliva on lymphocytes--the mediatory role of volatile aldehydes and redox active iron and the possible implications for oral cancer.
Oral squamous cell carcinoma (SCC) is most induced by exposure of the oral epithelial cells to tobacco products such as cigarette smoke. This exposure always occurs in the presence of saliva and presumably is induced by free radicals. To explore the effects of CS on cells in the presence of saliva, we used peripheral blood lymphocytes (PBL) and exposed them to CS, alone or in the presence of saliva. We discovered that after 80min, exposure of the lymphocytes to CS alone resulted in a time-dependent cellular loss with a survival rate of 56%, while following lymphocyte exposure to CS in the presence of saliva, less than 15% of the cells survived. This was accompanied by concomitant accumulation of cellular protein carbonyls which could be protected by the exogenous addition of uric acid or glutathione, but not by the addition of ascorbate (Asc), N-acetyl-l-cystein (NAC) or desferal (DES). Exposure of the lymphocytes to aldehydes present in CS, such as acrolein and croton-aldehyde, also resulted in the elevation of protein carbonyls, which was ameliorated primarily by the addition of glutathione. However, lymphocyte exposure to acroline in the presence of saliva did not show the same synergism in cell death observed as when the lymphocytes were exposed to CS and saliva. Thus, we postulated the existence of another mechanism and examined the role of redox active iron as an additional explanation for this synergism. In fact, it was found that in the presence of saliva and ascorbate there was a marked decrease in the lymphocyte survival rate; this was reversed by the addition of the iron chelator desferal. In light of these results, a comprehensive mechanism for the induction of oral cancer by cigarette smoke is suggested, stressing the role of a pivotal player in the process leading to oral cancer which has never been previously considered in this regard - the saliva.


Draft genomes, phylogenomic reconstruction and comparative genome analysis of three Xenorhabdus strains isolated from soil-dwelling nematodes in Kenya.
As a proven source of potent and selective antimicrobials, Xenorhabdus bacteria are important to an age plagued with difficult-to-treat microbial infections. Yet, only 27 species have been described to date. In this study, a novel Xenorhabdus species was discovered through genomic studies on three isolates from Kenyan soils. Soils in Western Kenya were surveyed for steinernematids and Steinernema isolates VH1 and BG5 were recovered from red volcanic loam soils from cultivated land in Vihiga and clay soils from riverine land in Bungoma respectively. From the two nematode isolates, Xenorhabdus sp. BG5 and Xenorhabdus sp. VH1 were isolated. The genomes of these two, plus that of X. griffiniae XN45 - this was previously isolated from Steinernema sp. scarpo that also originated from Kenyan soils - were sequenced and assembled. Nascent genome assemblies of the three isolates were of good quality with over 70 % of their proteome having known functions. These three isolates formed the X. griffiniae clade in a phylogenomic reconstruction of the genus. Their species were delineated using three overall genome relatedness indices: an unnamed species of the genus, Xenorhabdus sp. BG5, X. griffiniae VH1 and X. griffiniae XN45. A pangenome analysis of this clade revealed that over 70 % of species-specific genes encoded unknown functions. Transposases were linked to genomic islands in Xenorhabdus sp. BG5. Thus, overall genome-related indices sufficiently delineated species of two new Xenorhabdus isolates from Kenya, both of which were closely related to X. griffiniae . The functions encoded by most species-specific genes in the X. griffiniae clade remain unknown.


Rhodopseudomonas blastica atp operon. Nucleotide sequence and transcription.
The nucleotide sequence has been determined of a 12,368 base-pair region of DNA cloned from the non-sulphur photosynthetic bacterium Rhodopseudomonas blastica. It contains a cluster of six genes of which five encode the subunits of F1-ATPase; the sixth codes for an unknown protein. The genes are arranged in the same order as in the Escherichia coli unc operon, except that the unknown gene is placed between those for gamma and beta subunits. Neither the genes for F0 subunits, nor a homologue of the E. coli uncI gene is associated with this locus. The six genes are transcribed from a single promoter and we have designated this region the R. blastica atp operon. The two distal genes, beta and epsilon, may also be transcribed from a second promoter. Initiation and termination points for transcription have been identified by primer extensions and S1 nuclease mapping experiments. Signals involved in initiation of translation (Shine and Dalgarno sequences) and termination of transcription in the photosynthetic bacterium resemble those in E. coli. However, no common features can be identified in these two bacteria between 5' regions adjacent to sites of initiation of transcription. The sequence also contains a gene that encodes a protein homologous to discoidin, a cell surface lectin of Dictyostelium discoideum thought to be involved in cell--cell aggregation. Seven other reading frames have not been identified.


Dissolved organic carbon, a critical factor to increase the bioavailability of phosphorus during biochar-amended aerobic composting.
Considerable research efforts have been devoted to increase phosphorus (P) availability during aerobic composting. However, there is little discussion weather the dissolved organic carbon (DOC) controls the transformation among P-fractions. Thus, we investigated the changes in DOC compositions and P-fractions during biochar-amended composting (wet weight basis, 5% and 10%). TP content continuously increased since the 'concentration effect' during aerobic composting. NaHCO3-Pi, NaOH-Pi and HCl-Pi were main P-fractions, and biochar can improve P-bioavailability by transforming NaOH-Pi and HCl-Pi into NaHCO3-Pi. Structure equation models (SEMs) indicated that biochar enhanced the P-bioavailability through regulating the decomposition of DOC. Our results at least hint that the activation mechanism on P under the influence of DOC during biochar-amended composting.


MurC ligase of multi-drug resistant Salmonella Typhi can be inhibited by novel Curcumin derivative: Evidence from molecular docking and dynamics simulations.
Emerging multi-drug resistance in recent Salmonella Typhi isolates, causative agent of enteric Typhoid fever, compelled us to investigate alternative therapeutic strategies. The present study encompassed virtual screening, ADMET screening as well as antibacterial activity prediction to shortlist potent lead molecules whose binding affinities (BAs) were checked against major druggable S. Typhi targets. BA profile revealed a deoxy-tetradeutero- curcumin derivative to be novel bioactive compound having high BA towards UDP-N-acetylmuramate-L-alanine ligase (MurC) protein involved in peptidoglycan synthesis. Molecular docking indicated that our lead {Binding energy (BE)= -8.00 ± 0.02 kcal/mol}could competitively bind to MurC with respect to its natural ligand ATP (BE= -7.65 ± 0.19 kcal/mol). The lead also possessed superior binding and inhibition profile against MurC than other commercial antibiotics. This BE was contributed by Hydrogen (H-) bonds and numerous non-canonical interactions with the evolutionary conserved active-site residues. From molecular docking and coarse-grained dynamics simulations, it was inferred that the novel curcumin derivative was predicted to be potential competitive inhibitor of ATP for MurC-catalytic domain having low relative RMSF (0.59 Å) to inhibit MurC-induced peptidoglycan biosynthesis. The inferences drawn from the study can open new portals for designing efficient therapeutic strategies against S. Typhi.


Evaluation of the Ruditapes decussatus immune response after differential injected doses of Perkinsus olseni.
Ruditapes decussatus is a highly appreciated clam species, with a high demand, especially in European countries. However, natural populations of this species have been affected by over-exploitation, abiotic factors and also by diseases mainly caused by bacteria, virus and protozoans. Within the latter group of pathogens, Perkinsus spp. has been attracting attention for causing relevant mortality rates on bivalves around the world. From all species of this genus, Perkinsus olseni is one of the most impactful for R. decussatus, as it may cause chronic infection with fatal consequences under adverse conditions. Therefore, in this study, naïve clams were injected with two doses of P. olseni in order to better understand the response of R. decussatus against this parasite. So, one of the main goals of this experiment was to evaluate the differential response of the clams at gene expression level after injection and also to monitor the possible mortalities related to parasite. Results indicated that the methods applied for injection and detection of parasite load are effective. Furthermore, altogether, R. decussatus gene expression studies indicate differences on expression of some of the addressed genes among distinct levels of infection over time, which require further studies to confirm if these genes could be used as molecular markers of P. olseni infection. According to the results obtained, Adiponectin-C1q seems to be a promising gene to be used as molecular marker of chronic infection in claḿs haemolymph.


[Evaluation of the implementation of the Care Network for People with Disabilities in the Brazilian Unified National Health System: a multiple case study].
The Care Network for People with Disabilities (RCPCD) was implemented in 2012 as a consequence of the actions of the Viver sem Limite (Living without Limits) plan and has been the research object of recent studies. However, no published studies address the degree of implementation of this network. This study aimed to evaluate the degree of implementation of the RCPCD in eight states in the five regions of Brazil. This multiple case study performed evaluative research of the degree of implementation of the RCPCD in the states of Amazonas, Bahia, Espírito Santo, Mato Grosso do Sul, Minas Gerais, Paraíba, Rio Grande do Sul, and São Paulo. A logical model of the policy and a measurement matrix were developed. The degree of implementation of seven states was moderate, but Amazonas had an incipient degree of implementation. The evaluation of each stage of the process showed important differences, as the regional diagnosis and network adhesion stages presented moderate to advanced degrees of implementation in most states. In the service contracting stage, no state had an advanced degree of implementation, and the stage of follow-up and monitoring of the RCPCD was not even reached. The measurement matrix helps evaluate the degree of implementation of the RCPCD, and, by recognizing its results, the state steering groups and technical area recommend its use. Actions to improve this implementation, such as strengthening regionalization, establishing regional steering groups, ensuring contracting mechanisms, and defining criteria for certification of the care points, are necessary.


Identifying dominant factors of waterlogging events in metropolitan coastal cities: The case study of Guangzhou, China.
Urban waterlogging disasters are affected by environmental conditions and human activities. Previous studies had explored the effect of land-use type on waterlogging in relatively small watersheds. Few, however, have comprehensively revealed the relative contributions of the environmental and anthropogenic factors to urban waterlogging concerning different scales of analysis. Indeed what is less known, are the dominant factors and the appropriate scale of analysis. To overcome this limitation, a novel method that integrates the stepwise regression model with hierarchical partitioning analysis is presented. The purpose is to investigate the complex mechanism of urban waterlogging by identifying the relative contribution of each environmental and anthropogenic factor and the stability linking waterlogging to influencing factors at multiple scales of analysis (i.e. 1 km, 2 km, 3 km, 4 km, and 5 km). We consider waterlogging events in the central urban districts of Guangzhou (PR China) from 2009 to 2015 as a case study. The results show that the spatial distribution of waterlogging events in the central urban area presents a strong agglomeration pattern. The waterlogging hot spots are mainly concentrated in the historical area of Guangzhou. Under all analysis scales, we find that the percent cover of urban green spaces (44.74%), percent cover of residential area (41.03%), and slope.std (36.85%) both have a dominant contribution to urban waterlogging, which suggests the importance of land cover composition in determining urban waterlogging. However, the relative contribution and dominant factors of waterlogging varied across different analysis scales, presenting a strong scale effect. Under a small analysis scale (1 km), the topography factors (slope.std and relative elevation) are confirmed as the dominant variables; however, with the increase of analysis scale, the influence of land cover composition (greenspace, residence area, grassland) and land cover spatial configuration (LPI, AI, Cohesion index) on waterlogging magnitude is greater than other factors. This finding provides additional insights that the urban waterlogging can be alleviated by balancing the relative composition of land cover features as well as by optimizing their spatial configuration. Since the optimal statistical scale for urban waterlogging studies only worked for specific influencing factors, the appropriate analysis scale for urban waterlogging study should be determined by the characteristics of study areas. This study has the capability to extend our scientific understanding of the complex mechanisms of waterlogging in the highly urbanized coastal city, providing useful support for the prevention and management of urban waterlogging.


Effects of acute high-altitude exposure on working memory: A functional near-infrared spectroscopy study.
Inadequate oxygen availability may lead to impairment of neurocognitive functions. The aim of the present study was to investigate the effect of acute high-altitude exposure on the cerebral hemodynamic response and working memory. The same subjects performed working memory exercises with forward and backward digit span tasks both under normal oxygen conditions and in large simulated hypobaric hypoxia chambers, and a series of physiological parameters were evaluated. Functional near-infrared spectroscopy was used to measure cerebral blood flow changes in the dorsolateral prefrontal cortex (DLPFC) during the tasks. Compared with normoxic conditions, under hypoxic conditions, the heart rate and blood pressure increased, blood oxygen saturation decreased significantly, and the forward task had similar accuracy and response time, while the backward task had lower accuracy and longer response time. Neuroimaging analysis showed increased activation in the DLPFC during the forward task and deactivation during the backward task under hypobaric hypoxia conditions. Acute high-altitude exposure leads to physiological adaptations. The abnormal hemodynamic responses of the DLPFC to hypoxia at low pressure reveal the disruption of neurocognitive function by acute high-altitude exposure, which compromises complex cognitive functions, and provides a promising application for functional near infrared spectroscopy in the exploration of neural mechanisms in the brain during high-altitude exposure.


A case control study of factors and infections associated with clinically apparent respiratory disease in UK Thoroughbred racehorses.
A matched case control study was used to determine infections and other factors associated with clinically apparent respiratory disease in young racehorses in training in the UK. A total of 170 cases, defined as horses with sudden onset coughing, nasal discharge or pyrexia, were identified and matched to 632 non-affected controls by trainer and time period. Factors examined included age, sex, time since entry into the training yard, time since last race and different infections including tracheal and nasopharyngeal (NP) bacteria and viruses. Multivariable conditional logistic regression (CLR) modelling was used to evaluate the risk of being a case for variables after adjustment for other factors. Three analyses were conducted using clinical cases as outcomes, which were compared with: (i) controls without evidence of subclinical inflammatory airway disease (IAD) (ii) controls with evidence of subclinical IAD and (iii) all controls irrespective of IAD status. A fourth analysis was conducted comparing the two groups of controls, i.e. those with and without IAD. Younger horses and those that had entered training more recently were at increased risk of suffering episodes of clinically apparent respiratory disease. Among the infections, increasing numbers of Pasteurella/Actinobacillus spp. in tracheal washes were associated with increasing risk of clinical disease. Tracheal infection with Streptococcus zooepidemicus was associated with both clinical respiratory disease and subclinical IAD when compared with controls with no evidence of IAD. This explained the lack of association between clinical cases and S. zooepidemicus when all controls were used. Tracheal isolation of Mycoplasma felis was also associated with clinical disease after controlling for other factors. An inverse association was identified between risk of clinically apparent disease and isolation from tracheal washes of the transient, non-pathogenic bacteria Staphylococcus and Acinetobacter spp. There was no significant association identified between clinical disease and infection with equine herpesviruses-1 and -4, rhinoviruses-1 and -2 or adenovirus. Equine influenza was significantly associated with clinical respiratory disease but it was a very rare infection in this well-vaccinated population, only occurring in three cases.


Self-help therapy for insomnia: a meta-analysis.
Insomnia is a prevalent problem which often leads to a reduced quality of life and diminished work productivity. Only a minority of patients are treated with effective non-pharmacological therapies. A self-help intervention might offer an inexpensive and more accessible alternative to face-to-face treatment. We conducted a meta-analysis of randomized controlled studies examining the effects of self-help interventions for insomnia, identified through extensive searches of bibliographical databases. We examined the effects of self-help on different sleep outcomes, in comparison with both waiting lists controls and face-to-face treatments. Ten studies with a total of 1000 subjects were included. The intervention did improve sleep efficiency (d=0.42; p<0.05), sleep onset latency (d=0.29; p<0.05), wake after sleep onset (d=0.44; p<0.05) and sleep quality (d=0.33; p<0.05) but not total sleep time (d=0.02; p>0.05). The sleep improvements were maintained over the longer term. Symptoms of anxiety and depression also decreased after self-help (d=0.28; p<0.05 and d=0.51; p<0.05, respectively). Although based on a very limited number of studies, the face-to-face treatments did not show statistically significant superiority to the self-help treatments. The effect sizes associated with self-help treatments might be overestimated due to publication bias. The effects of self-help treatments are small to moderate. Nevertheless, they might constitute a useful addition to existing treatment options especially when integrated in a stepped care approach.


Genecialist manifesto: overcoming the "class struggle" in medicine.
Generalists and specialists are often considered two completely distinct species, which culminates in the establishment of a concept of dichotomy. However, these dichotomy can at times fuel tension and even erupt into open conflict. In order to resolve this issue, the author herein proposes the concept of a "genecialist." The genecialist refers to a hybrid comprising elements inherent to both generalists and specialists. This potentially overcomes the multitude of issues associated with both generalists and specialists in the practical aspects of medicine. The coalescence of these two contrarieties may hold the key to improving the future of health care. Mediating and integrating both categories into one consolidated entity carries the potential to stem the tide of class warfare between generalists and specialists.


Prostaglandin E2-Induced AKT Activation Regulates the Life Span of Short-Lived Plasma Cells by Attenuating IRE1α Hyperactivation.
The mechanism regulating the life span of short-lived plasma cells (SLPCs) remains poorly understood. Here we demonstrated that the EP4-mediated activation of AKT by PGE2 was required for the proper control of inositol-requiring transmembrane kinase endoribonuclease-1α (IRE1α) hyperactivation and hence the endoplasmic reticulum (ER) homeostasis in IgM-producing SLPCs. Disruption of the PGE2-EP4-AKT signaling pathway resulted in IRE1α-induced activation of JNK, leading to accelerated death of SLPCs. Consequently, Ptger4-deficient mice (C57BL/6) exhibited a markedly impaired IgM response to T-independent Ags and increased susceptibility to Streptococcus pneumoniae infection. This study reveals a highly selective impact of the PGE2-EP4 signal on the humoral immunity and provides a link between ER stress response and the life span of SLPCs.


Autistic and alexithymic traits modulate distinct aspects of face perception.
Atypical face processing is a prominent feature of autism spectrum disorder (ASD) but is not universal and is subject to individual variability. This heterogeneity could be accounted for by reliable yet unidentified subgroups within the diverse population of individuals with ASD. Alexithymia, which is characterized by difficulties in emotion recognition and identification, serves as a potential grouping factor. Recent research demonstrates that emotion recognition impairments in ASD are predicted by its comorbidity with alexithymia. The current study assessed the relative influence of autistic versus alexithymic traits on neural indices of face and emotion perception. Capitalizing upon the temporal sensitivity of event-related potentials (ERPs), it investigates the distinct contributions of alexithymic versus autistic traits at specific stages of emotional face processing in 27 typically developing adults (18 female). ERP components reflecting sequential stages of perceptual processing (P100, N170 and N250) were recorded in response to fear and neutral faces. The results indicated that autistic traits were associated with structural encoding of faces (N170), whereas alexithymic traits were associated with more complex emotion decoding (N250). These findings have important implications for deconstructing heterogeneity within ASD.


Preoperative electromagnetic navigation bronchoscopy-guided one-stage multiple-dye localization for resection of subsolid nodules: A single-center pilot study.
Electromagnetic navigation bronchoscopy (ENB)-guided transbronchial dye marking and video-assisted thoracoscopic surgery (VATS) is an emerging technique that enables successful resection of multiple small subsolid pulmonary nodules. The aim of this study was to evaluate the accuracy and safety of preoperative ENB-guided transbronchial multiple dye localization for VATS resection of subsolid pulmonary nodules. As a single-center pilot study, we recruited patients with at least two small or subsolid pulmonary nodules. Multiple-dye localization was performed by intraoperative ENB-guided transbronchial injection of an indigo carmine dye. The patients underwent VATS for sublobar resection immediately after localization. The accuracy of ENB-guided dye marking was checked. ENB-guided one-stage multiple dye localization was conducted for 18 pulmonary nodules in seven patients between September 2018 and December 2019. The mean diameter of the pulmonary nodules was 9.3 mm (range, 4-18) and the mean distance from the pleura to pulmonary nodule was 6 mm (range, 1-17 mm). ENB-guided transbronchial multiple dye localization was successfully performed in 94.4% (17/18), and the accuracy of ENB-guided dye marking was 88.2% (15/17). When two nodules were not seen in intraoperative fields, anatomical sublobar resection was performed. There was no conversion to thoracotomy and operative mortalities. Among the seven patients, only one patient showed mild intrabronchial bleeding but stopped spontaneously. The changes in lung function after multiple wedge resections (-1.6% to 24.8%) were tolerable level. ENB-guided one-stage transbronchial dye localization showed accurate and safe intraoperative identification of multiple subsolid pulmonary nodules. A large scale prospective clinical study is warranted.


Structural characterization and immunomodulatory activity of a novel polysaccharide from Pueraria lobata (Willd.) Ohwi root.
A novel polysaccharide with a molecular weight of 12.3 kDa, was isolated from the root of Pueraria lobata (Willd.) Ohwi using cold water extraction method. Methylation analysis, Periodate oxidation, Smith degradation, and nuclear magnetic resonance analysis showed that 1,4-α-D-Glcp and 1,3,6-α-D-Glcp were the main linkage types of this polysaccharide. It exhibited immunomodulatory activity by enhancing the pinocytic and phagocytic capacities and promoting the secretion of nitric oxide, interleukin (IL)-6, and tumor necrosis factor alpha by RAW 264.7 cells. The beta glucan receptor, scavenger receptor I, and toll-like receptor 4 were identified as the main receptors of the polysaccharide on the membrane of RAW 264.7 cells. These results suggested that this polysaccharide is a candidate functional food supplement for hypoimmune populations.


Urethral caruncle in a male: a case report.
Urethral caruncle in a 60-year-old male labourer is being reported. Its occurrence in male urethra has not been reported so far in the literature.


Analysis and implementation of semi-automatic model for vulnerability exploitations of threat agents in NIST databases.
Proactive security plays a vital role in preventing the attack before entering active mode. In the modern information environment, it depends on the vulnerability management practitioners of an organization in which the critical factor is the prioritization of threats. The existing models and methodology follow the traditional approaches of a Common Vulnerability Scoring System (CVSS) to prioritize threats and vulnerabilities. The CVSS is not able to provide effectiveness to the security of the business of an organization. In contrast, the vulnerability analysis needs a model which can give significance to the prioritization policies. The model depends on the CVSS score of threats and compares various features of vulnerability like threat vectors, inputs, environments used by threat agent's groups, and potential outputs of threat agents. Therefore, the research aims to design a semi-automatic model for vulnerability analysis of threats for the National Institute of Standards and Technology (NIST) database of cyber-crime. We have developed a semi-automatic model that simulates the CVE (Common Vulnerabilities and Exposures) list of the NIST database between 1999 and 2021, concerning the resources used by the threat agents, pre-requisites input, attack vectors, and dormant results. The semi-automatic approach of the model to perform the vulnerability analysis of threat agent groups identified in a network makes the model more efficient and effective to addresses the profiling of threat agents and evaluating the CTI (Critical Threat intelligence feed). Our experimental results imply that the semi-automatic model implements the vulnerability prioritization based on the CVSS score and uses the comparative analysis based on the threat agent's vectors identified. It also provides potency and optimized complexity to an organization's business to mitigate the vulnerability identified in a network.


Successful femoral vessel puncture facilitated by using a J-tipped hydrophilic guidewire in pediatric cardiac catheterization.
Vascular access is an important part of cardiac catheterization, but it is extremely difficult in some cases. We present two cases in which a J-tipped hydrophilic guidewire inserted from the contralateral vessel facilitated successful vascular access after initial access failure by conventional method using anatomical landmark.


Depressed mood and anxiety as risk factors for hypertensive disorders of pregnancy: a systematic review and meta-analysis.
Psychosocial factors have been implicated as both a cause and consequence of hypertension in the general population but are less understood in relation to hypertensive disorders of pregnancy (HDP). The aims of this review were to (1) synthesize the existing literature examining associations between depression and/or anxiety in pregnancy and HDP and (2) assess if depression and/or anxiety in early pregnancy was a risk factor for HDP. A comprehensive search of Medline, Embase, CINAHL, and PsycINFO was conducted from inception to March 2020 using terms related to 'pregnancy', 'anxiety', 'depression', and 'hypertensive disorders'. English-language cohort and case-control studies were included if they reported: (a) the presence or absence of clinically significant symptoms of depression/anxiety, or a medical record diagnosis of depression or an anxiety disorder in pregnancy; (b) diagnosis of HDP; and/or (c) data comparing the depressed/anxious group to the non-depressed/anxious group on HDP. Data related to depression/anxiety, HDP, study characteristics, and aspects related to study quality were extracted independently by two reviewers. Random-effects meta-analyses of estimated pooled relative risks (RRs) were conducted for depression/anxiety in pregnancy and HDP. In total, 6291 citations were retrieved, and 44 studies were included across 61.2 million pregnancies. Depression and/or anxiety were associated with HDP [RR = 1.39; 95% confidence interval (CI) 1.25-1.54]. When measurement of anxiety or depression preceded diagnosis of hypertension, the association remained (RR = 1.27; 95% CI 1.07-1.50). Women experiencing depression or anxiety in pregnancy have an increased prevalence of HDP compared to their non-depressed or non-anxious counterparts.


Heparin-glutathione III: study with fluorescent probes as indicators of membrane status of bull sperm.
Sperm obtained from bull epididymes were used to validate in vitro the effect of heparin and reduced glutathione on sperm membrane status, with the use of sodium dodecyl sulfate (SDS) and Triton X-100 in the presence of propidium iodide (IP) and diacetate fluorescein (FDA). The metabolic activities of treated sperm were qualitatively monitored using an alamar Blue Redox fluorescence indicator. Heparin did not damage the sperm plasma membrane, whereas GSH and SDS at 26 h of incubation dissolved the plasma membrane and the acrosome. On the other hand, at time zero, Triton X-100 showed 75% of sperm stained with IP, indicating plasma membrane damage. Results validated by electron microscopy of thin sections of treated sperm showed complete lack of the membrane, acrosome, and postacrosomal membrane system with 0.01% Triton X-100. Extracellular 15 mM GSH completely disappeared the plasma membrane over the sperm nucleus, leaving the postacrosomal membrane system and nucleus without apparent damage. The metabolic activity was supported over 52 h of incubation in any of the incubation systems tested, including Triton X-100, which showed a spermaticide effect. The authors propose that membrane damage does not mean they are dead, no matter the vital stain employed, and also that FDA-IP staining can be used as a fluorescent marker of sperm plasmatic membrane permeabilization and nuclear swelling.


Unveiling Modifications of Biomass Polysaccharides during Thermal Treatment in Cholinium Chloride : Lactic Acid Deep Eutectic Solvent.
A deep analysis upon the chemical modifications of the cellulose and hemicelluloses fractions that take place during biomass delignification with deep eutectic solvents (DES) is lacking in literature, being this a critical issue given the continued research on DES for this purpose. This work intends to fill this gap by disclosing a comprehensive study on the chemical modifications of cellulose (microcrystalline cellulose and bleached kraft pulp) and hemicelluloses (xylans) during thermal treatment (130 °C) with cholinium chloride/lactic acid ([Ch]Cl/LA) at molar ratio 1 : 10, one of the best reported DES for biomass delignification. The obtained data revealed that [Ch]Cl/LA (1 : 10) has a negative impact on the polysaccharides fractions at prolonged treatments (>4 h), resulting on substantial modifications including the esterification of cellulose with lactic acid, shortening of fibers length, fibers agglomeration and side reactions of the hemicelluloses fraction (e. g., humin formation, lactic acid grafting). Wood delignification trials with [Ch]Cl/LA (1 : 10) at the same conditions also corroborate these findings. Moreover, the DES suffers degradation, including the formation of lactic acid derivatives and its polymerization. Therefore, short time delignification treatments are strongly recommended when using the [Ch]Cl/LA DES, so that a sustainable fractionation of biomass into high quality cellulose fibers, isolated lignin, and xylose/furfural co-production along with solvent recyclability could be achieved.


Variants inducible for glutamine synthetase in V79-56 cells.
V79-56 cells have an absolute requirement for exogenous glutamine and are not inducible for glutamine synthetase. Prototrophs arise spontaneously at approximately 1.0 X 10(-5) per cell per generation as measured by fluctuation tests. Higher frequencies of glutamine-independent variants may be obtained by treatment with the mutagen ethyl methane sulfonate, as well as by exposure to 5-azacytidine and sodium butyrate, which act primarily by affecting gene expression. Variants of all types show marked elevation of glutamine synthetase activity. Although this activity declines toward constitutive levels in the presence of glutamine, it is still inducible in variant cells. These populations, after a lag, regain the ability for progressive growth in glutamine-free medium. Thus, the stable variation seen here is in the potential for induction, rather than steady-state expression of glutamine synthetase at a higher level.


Do internalized age stereotypes mediate the relationship between volunteering and social connectedness for adults 50+?
The productive aging literature describes a wide range of psychosocial benefits of volunteerism for older adults. A growing, compelling body of research drawing from stereotype embodiment theory identifies significant, negative public health impacts of internalized age stereotypes. Yet, little research explores which activities may reduce internalized ageism and enhance psychosocial health as people age. This cross-sectional parallel mediation study examines whether internalized age stereotypes mediate the relationship between volunteering and social connectedness for adults over 50. A convenience sample of volunteers (n = 165) 50+ years of age in the U.S. Mountain West completed an online survey primarily during the COVID-19 pandemic. The independent variable is volunteer hours per week (M = 6.45, SD = 5.38). The dependent variable is social connectedness measured by five positively worded items from the UCLA loneliness scale (M = 4.32, SD = 0.63, and α = 0.86). The indirect effects of five internalized positive (e.g., "wise" and "capable") (M = 4.85, SD = 0.68, α = 0.72) and five negative (e.g., "grumpy" and "helpless") (M = 1.20, SD = 1.02, α = 0.74) age stereotypes were tested. Results (n = 154) indicate that increased internalized positive, but not negative, age stereotypes partially mediate the relationship between volunteer hours and increased social connectedness, while holding constant relevant covariates. Although positive age stereotypes have long been considered a form of ageism, the results of this study suggest that internalizing positive age stereotypes may function as a form of esteem (particularly during the pandemic) to promote enhanced psychosocial health as people age.


Deprotonated N-(2,4-Dinitrophenyl)amino Acids Undergo Cyclization in Solution and the Gas Phase.
The collisionally activated mass spectral fragmentations of N-(2,4-dinitrophenyl)alanine and phenylalanine [M - H](-) may be gas-phase analogs of the base-catalyzed cyclization of N-(2,4-dinitrophenyl)amino acids in aqueous dioxane. This latter reaction is one source of the 2-substituted 5-nitro-1H-benzimidazole-3-oxides, which are antibacterial agents. The fragmentation of both compounds, established by tandem mass spectrometric experiments and supported by molecular modeling using DFT methods, indicate that the [M - H](-) ions dissociate via sequential eliminations of CO(2) and H(2)O to produce deprotonated benzimidazole-N-oxide derivatives. The gas-phase cyclization reactions are analogous to the base-catalyzed cyclization in solution, except that in the latter case, the reactant must be a dianion for the reaction to occur on a reasonable time scale. The cyclization of N-(2-nitrophenyl)phenylalanine, which has one less nitro group, requires a stronger base for the cyclization than the compound with a second nitro group at the 4-position. Following losses of CO(2) and H(2)O are expulsions of both neutral molecules and free radicals, the latter being examples of violations of the even-electron ion rule.


Gene response upon illumination in forming mRNA encoding peroxisomal glycollate oxidase.
Glycollate oxidase is a constituent of leaf peroxisomes. Its biosynthesis is, like the biosynthesis of many chloroplastic proteins, controlled by light, via phytochrome. The level of mRNA coding for glycollate oxidase was determined at different stages of greening of etiolated plant cells. The appearance of glycollate oxidase mRNA in the cytoplasm was measured by hybridization with cDNA containing part of the coding sequence for glycollate oxidase. cDNA was prepared from enriched mRNA, inserted into the Pst I site of pBR 322, and cloned in Escherichia coli DH-1. By differential colony hybridization and hybrid selection, a clone containing a 670 bp sequence complementary to mRNA encoding glycollate oxidase was selected and identified. Northern blot hybridization was used to investigate mRNA levels induced by light. It was found that continuous light affected the formation of glycollate oxidase mRNA. When a large population of microbodies was present in the cells being induced, the immediate mRNA increase was very pronounced, and was detectable as little as 20 min after the beginning of the light treatment. In contrast, a lag period in the mRNA increase was observed when the induction was performed with etiolated leaves which are characterized by the occurrence of a rather small population of microbodies. For comparison, we measured the time-course of formation of mRNA coding for a light-induced chloroplastic protein, i.e., a protein of the light-harvesting complex. The time-courses of levels of the two mRNAs indicate that the program of gene expression differs between the two particular proteins destined either for chloroplasts or for peroxisomes. The formation of glycollate oxidase mRNA could also be stimulated by a short pulse of light, a treatment of 15 s being a sufficient trigger.


The role of non-coding RNAs in diabetes-induced osteoporosis.
Diabetes mellitus (DM) and osteoporosis are two major health care problems worldwide. Emerging evidence suggests that DM poses a risk for osteoporosis and can contribute to the development of diabetes-induced osteoporosis (DOP). Interestingly, some epidemiological studies suggest that DOP may be at least partially distinct from those skeletal abnormalities associated with old age or postmenopausal osteoporosis. The increasing number of DM patients who also have DOP calls for a discussion of the pathogenesis of DOP and the investigation of drugs to treat DOP. Recently, non-coding RNAs (ncRNAs) have received more attention due to their significant role in cellular functions and bone formation. It is worth noting that ncRNAs have also been demonstrated to participate in the progression of DOP. Meanwhile, nano-delivery systems are considered a promising strategy to treat DOP because of their cellular targeting, sustained release, and controlled release characteristics. Additionally, the utilization of novel technologies such as the CRISPR system has expanded the scope of available options for treating DOP. Hence, this paper explores the functions and regulatory mechanisms of ncRNAs in DOP and highlights the advantages of employing nanoparticle-based drug delivery techniques to treat DOP. Finally, this paper also explores the potential of ncRNAs as diagnostic DOP biomarkers.


The fate of parental nucleosomes during SV40 DNA replication.
The fate of parental nucleosomes during the replication of chromatin templates was studied using a modification of the cell-free SV40 DNA replication system. Plasmid DNA molecules containing the SV40 origin were assembled into chromatin with purified core histones and fractionated assembly factors derived from HeLa cells. When these templates were replicated in vitro, the resulting progeny retained a nucleosomal organization. To determine whether the nucleosomes associated with the progeny molecules resulted from displacement of parental histones during replication followed by reassembly, the replication reactions were performed in the presence of control templates. It was observed that the progeny genomes resulting from the replication of chromatin templates retained a nucleosomal structure, whereas the progeny of the control DNA molecules were not assembled into chromatin. Additional experiments, involving direct addition of histones to the replication reaction mixtures, confirmed that the control templates were not sequestered in some form which made them unavailable for nucleosome assembly. Thus, our data demonstrate that parental nucleosomes remain associated with the replicating molecules and are transferred to the progeny molecules without displacement into solution. We propose a simple model in which nucleosomes ahead of the fork are transferred intact to the newly synthesized daughter duplexes.


Gene control in germinal differentiation: RNF6, a transcription regulatory protein in the mouse sertoli cell.
In mouse Sertoli cells, transcription of the Inha gene encoding the alpha subunit of inhibin, which acts locally as a tumor suppressor, is down-regulated in tumors and in normal cells during aging. Previous studies suggested that regulation of Inha transcription involves the binding of a protein(s) to a repeat of the GGGGC motif in the promoter. Expression screening identified a cDNA encoding a protein that binds this sequence. Of the RING-H2 family, it is the mouse homologue of a human protein of unknown function, RNF6. The mouse gene, Rnf6, is predominantly expressed in two interacting cell types of the testis, Sertoli cells and pachytene spermatocytes. In Sertoli cells, it colocalizes with the PML and Daxx proteins in punctate nuclear bodies. In transient and stable transfectants, Rnf6 expression from a heterologous promoter increased the expression of reporter genes driven by the Inha promoter. In a Sertoli tumor cell line in which expression of both Inha and Rnf6 was reduced, reexpression of the latter restored the level of Inha while, concomitantly, the cells reverted to normal growth control in culture.


The effect of dichloroacetate and hydroxypyruvate on the entry of 14C from [1-14C]alanine into urea in rat hepatocytes.
Entry of metabolic 14CO2 into urea is shown to be decreased by dichloroacetate although the production of 14CO2 is stimulated 2-fold. Hydroxypyruvate, a product of dichloroacetate metabolism, increases the incorporation of metabolic 14CO2 into urea. It is proposed that these effects result from changes in the cytoplasmic-mitochondrial pH gradient.


Increasing Awareness for Peripheral Artery Disease through the Identification of Novel Biomarkers.
Peripheral artery disease (PAD) is a chronic atherosclerotic disorder that involves the lower extremity arteries, manifesting in claudication, rest pain, and tissue loss [...].


Targets for neuroprotection in Parkinson's disease.
Current therapies for Parkinson's disease significantly improve the quality of life for patients suffering from this neurodegenerative disease, yet none of the current therapies has been convincingly shown to slow or prevent the progression of disease. Much has been learned about the pathophysiology of Parkinson's disease in recent years, and these discoveries offer a variety of potential targets for protective therapy. Mechanisms implicated in the disease process include oxidative stress, mitochondrial dysfunction, protein aggregation and misfolding, inflammation, excitotoxicity, and apoptosis. At the same time, the involvement of these diverse processes makes modeling the disease and evaluation of potential treatments difficult. In addition, available clinical tools are limited in their ability to monitor the progression of the disease. In this review, we summarize the different pathogenic mechanisms implicated in Parkinson's disease and neuroprotective strategies targeting these mechanisms currently under clinical study or under preclinical development, with a view towards strategies that seem most promising.


Improved interval methods for solving circle packing problems in the unit square.
In this work computer-assisted optimality proofs are given for the problems of finding the densest packings of 31, 32, and 33 non-overlapping equal circles in a square. In a study of 2005, a fully interval arithmetic based global optimization method was introduced for the problem class, solving the cases 28, 29, 30. Until now, these were the largest problem instances solved on a computer. Using the techniques of that paper, the estimated solution time for the next three cases would have been 3-6 CPU months. In the present paper this former method is improved in both its local and global search phases. We discuss a new interval-based polygon representation of the core local method for eliminating suboptimal regions, which has a simpler implementation, easier proof of correctness, and faster behaviour than the former one. Furthermore, a modified strategy is presented for the global phase of the search, including improved symmetry filtering and tile pattern matching. With the new method the cases n = 31 , 32 , 33 have been solved in 26, 61, and 13 CPU hours, giving high precision enclosures for all global optimizers and the optimum value. After eliminating the hardware and compiler improvements since the former study, the new proof technique became roughly about 40-100 times faster than the previous one. In addition, the new implementation is suitable for solving the next few circle packing instances with similar computational effort.


Honeybees control the gas permeability of brood and honey cappings.
Some bee species use wax to build their nests. They store honey and raise their brood in cells made entirely from wax. How can the bee brood breathe and develop properly when sealed in wax cells? We compared the chemical composition and structural properties of the honey cappings and worker brood cappings of the honeybee Apis mellifera carnica, measured the worker brood respiration, and calculated the CO2 gradients across the two types of cappings. We identified microscopic pores present in the brood cappings that allow efficient gas exchange of the developing brood. In contrary, honey cappings are nearly gas impermeable to protect honey from fermenting. Similar principles apply in bumble bees. Our data suggest the control of gas exchange of cappings as a selective pressure in the evolution of wax-building bees that drives their adaptation for using wax in two highly contrasting biological contexts.


A Practical Method for Continuous Production of sp3-Rich Compounds from (Hetero)Aryl Halides and Redox-Active Esters.
A practically useful coupling reaction between aromatic halides and redox-active esters was realized by nickel catalysis through the use of a packed zinc bed column in continuous flow. Multiple reuse of the column showed a negligible decrease in efficiency, affording high space/time yields. A wide range of substrates, including a number of heteroaryl halides and polyfunctional materials were coupled in generally good yields. Longer-time and larger-scale experiments further demonstrates the robustness of the system.


Hexaminolevulinate guided fluorescence cystoscopy reduces recurrence in patients with nonmuscle invasive bladder cancer.
We assessed the impact that improved detection of nonmuscle invasive bladder cancer with hexaminolevulinate fluorescence cystoscopy may have on early recurrence rates. This prospective, randomized study enrolled 814 patients suspected of having bladder cancer at increased risk for recurrence. All patients underwent white light cystoscopy and mapping of lesions, followed by transurethral resection of the bladder when indicated. Patients in the fluorescence group also received intravesical hexaminolevulinate solution at least 1 hour before cystoscopy to induce fluorescence of cancerous lesions, and underwent additional inspection with blue light before and after transurethral resection of the bladder. Adjuvant intravesical therapy was based on risk. Followup cystoscopy at 3, 6 and 9 months was conducted with white light. Detection was performed as a within patient comparison in the fluorescence group. In this group 286 patients had at least 1 Ta or T1 tumor (intent to treat). In 47 patients (16%) at least 1 of the tumors was seen only with fluorescence (p = 0.001). During the 9-month followup (intent to treat) there was tumor recurrence in 128 of 271 patients (47%) in the fluorescence group and 157 of 280 (56%) in the white light group (p = 0.026). The relative reduction in recurrence rate was 16%. Hexaminolevulinate fluorescence cystoscopy significantly improves the detection of Ta and T1 lesions and significantly reduces the rate of tumor recurrence at 9 months.


Exposure to ambient air pollution and executive function among Chinese primary schoolchildren.
Evidence on the associations between particulate matter (PM) and nitrogen dioxide (NO2) exposure with executive function in children is scarce in developing countries. Moreover, few studies investigated ozone (O3) and sulfur dioxide (SO2). This study aimed to investigate the associations between long-term exposure to air pollution and executive function in Chinese children. In 2017, we randomly recruited 5028 children aged 6-12 years from 5 schools in Guangzhou city, southern China. Each of 5028 children's executive function were assessed using parent filled questionnaire. We further randomly selected 522 children to take computerized tests to assess working memory, inhibitory control, and cognitive flexibility. The 1-year average residence-based exposure to PM with diameters ≤2.5 (PM2.5) or 10 μm (PM10), NO2, O3, and SO2 exposures were estimated by using an inverse-distance weighting approach. Associations were evaluated by mixed linear regression models. The 1-year average concentrations of PM2.5, PM10, NO2, SO2, and O3 was 39.06 ± 1.12 μg/m3, 60.95 ± 3.49 μg/m3, 53.64 ± 4.44 μg/m3, 12.33 ± 0.79 μg/m3, and 90.07 ± 7.96 μg/m3, respectively. Each interquartile range increment in PM2.5 was associated with 48.04 ms [95% confidence interval (CI): 2.18 to 93.89] increase in inhibitory control and 0.72 (95% CI: -1.14 to -0.29) points decrease in forward recall. PM10 exposure was associated with 0.55 (95% CI: -1.04 to -0.06) and 0.67 points (95% CI: -1.09 to -0.25) reduction in forward and backward recall, respectively. SO2 exposure was associated with 0.69 (95%CI: 0.37 to 1.02) and 0.73 (95%CI: 0.40 to 1.05) high scores of behavioral regulation index and metacognition index, respectively. Significant association was found between O3 exposure and metacognition index (estimate, 95%CI: 0.87, 0.45 to 1.29). No associations for cognitive flexibility were observed. Stratified analyses did not yield any significant modification effects of sex, physical activity, screen time, and parental smoking. Long-term exposures to PM2.5, PM10, SO2, and O3 were associated with poorer performance in working memory, inhibitory control, behavioral regulation, and metacognition in children.


Intracellular staining of physiologically identified neurons and axons in the somatosensory thalamus of the cat.
Neurons and axons responding to somesthetic stimulation in the thalamic ventrobasal complex (VB) were characterized electrophysiologically by intracellular recording and then individually injected with horseradish peroxidase. Two types of thalamocortical relay neuron were identified, primarily on the basis of dendritic morphology and axon diameter. Types with cutaneous or deep receptive fields were found in each class. Neither type had collateral axons in VB but each gave branches to the thalamic reticular nucleus (RTN). Small putative interneurons in VB and RTN neurons with somatosensory receptive fields were also injected. The RTN neurons had profusely branched widely ramifying axons in VB and adjoining nuclei. Injected medial lemniscal axons in VB had a range of receptive field properties and conduction velocities and ended in elongated anteroposterior domains with one or more dense concentrations of terminal boutons of varying size and with varying numbers of boutons.


Characterization of extracellular neuraminidase produced by Actinomyces pyogenes.
Extracellular neuraminidase from Actinomyces pyogenes could be isolated by ammonium sulfate precipitation, ion exchange chromatography with DEAE cellulose and gel filtration on Ultrogel ACA 54. The purified enzyme had a molecular weight of approximately 50,000 Dalton, a pH optimum at pH 6.0, a temperature optimum at 55 degrees C and a Km value of 1.4 X 10(-4) mol/l with N-acetyl-neuraminlactose as substrate. Preparative isoelectric focussing of the culture supernatant revealed neuraminidase activity mainly at pH 6.5. The enzyme activity was not influenced by metalions or EDTA.


Clinical Simulation Training in Geriatric Medicine: A Review of the Evidence and Lessons for Training in Psychiatry of Old Age.
Clinical simulation encompasses a broad range of methods and techniques that allow clinical skills to be rehearsed and practiced away from the clinic before being applied to real patients. As such, preparation of doctors and other healthcare professionals for safe clinical practice is one of its main aims. The objective of this paper was to review the evidence regarding the use of clinical simulation training in geriatric medicine education and consider how the findings may be translated to education in the closely related field of psychiatry of old age. Original papers and descriptive case studies of clinical simulation training programs for medical professionals were considered for inclusion. Papers were grouped according to the participants' level of training: (1) undergraduate medical education; (2) postgraduate medical education; and (3) multiple levels of medical learners. A diverse range of effective simulation modalities for teaching geriatric medicine was identified across all levels of learning. The evidence suggests that there is much fertile ground for trainees in geriatric medicine and psychiatry of old age to participate in joint simulation training programs, thereby maximising their reach while minimising associated resource requirements and financials costs. Given the prominent position of psychiatry of old age at the interface between psychiatry and medicine, old age psychiatrists potentially have much to offer in advancing the field of clinical simulation while simultaneously improving patient care.


Ecological typologies of large areas. An application in the Mediterranean Sea.
One approach to identifying and mapping the state of marine biophysical conditions is the identification of large-scale ecological units for which conditions are similar and the strategies of management may also be similar. Because biological processes are difficult to directly record over large areas, abiotic characteristics are used as surrogate parameters. In this work, the Mediterranean Sea was classified into homogeneous spatial areas based on abiotic variables. Eight parameters were selected based on salinity, sea surface temperature, photosynthetically active radiation, sea-wave heights and depth variables. The parameters were gathered in grid points of 0.5° spatial resolution in the open sea and 0.125° in coastal areas. The typologies were obtained by data mining the eight parameters throughout the Mediterranean and combining two clustering techniques: self-organizing maps and the k-means algorithm. The result is a division of the Mediterranean Sea into seven typologies. For these typologies, the classification recognizes differences in temperature, salinity and radiation. In addition, it separates coastal from deep areas. The influence of river discharges and the entrance of water from other seas are also reflected. These results are consistent with the ecological requirements of the five studied seagrasses (Posidonia oceanica, Zostera marina, Zostera noltei, Cymodocea nodosa, Halophila stipulacea), supporting the suitability of the resulting classification and the proposed methodology. The approach thus provides a tool for the sustainable management of large marine areas and the ability to address not only present threats but also future conditions, such as climate change.


Integration of gene expression and DNA methylation identifies epigenetically controlled modules related to PM2.5 exposure.
Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p < 0.05) associated with exposure to particulate matter < 2.5 µm in diameter (PM2.5) at birth, one of them mapping to the MIR1296 gene. Further, by integrating gene expression with DNA methylation using Functional Epigenetic Modules algorithms, we identified 9 and 6 modules in relation to PM2.5 exposure at birth and at current address, respectively (including NR1I2, MAPK6, TAF8 and SCARA3). In conclusion, PM2.5 exposure at birth was linked to differential gene expression in children and adolescents. Importantly, we identified several significant interactome hotspots of gene modules of relevance for complex diseases in relation to PM2.5 exposure.


The alveolar type II epithelial cell: a multifunctional pneumocyte.
The epithelial surface of the alveoli is composed of alveolar type I and type II cells. Alveolar type I cells comprise 96% of the alveolar surface area. These cells are extremely thin, thus, minimizing diffusion distance between the alveolar air space and pulmonary capillary blood. Type II cells are spherical pneumocytes which comprise only 4% of the alveolar surface area, yet they constitute 60% of alveolar epithelial cells and 10-15% of all lung cells. Four major functions have been attributed to alveolar type II cells: (1) synthesis and secretion of surfactant; (2) xenobiotic metabolism; (3) transepithelial movement of water; and (4) regeneration of the alveolar epithelium following lung injury. Therefore, alveolar type II cells play important roles in normal pulmonary function and in the response of the lung to toxic compounds which may cause lung damage. Techniques have now been developed to isolate and purify alveolar type II epithelial cells from lung tissue. Such cellular preparations afford bioassay systems to monitor the effects of occupational or environmental pollutants on alveolar pneumocytes and should yield important information concerning the etiology of pulmonary disease in the alveolar region of the lung.


Spasm of the near reflex mimicking deteriorating accommodative esotropia.
To describe a patient with accommodative esotropia who developed spasm of the near reflex. A 6-year-old girl with a history of successfully treated refractive, accommodative esotropia suddenly developed spasm of the near reflex after the death of a relative. The condition resolved after 2 months. Spasm of the near reflex should be considered in children with accommodative esotropia who seem to deteriorate and become esotropic once again while wearing their hyperopic glasses.


Plug inguinal hernia repair mimicking nodal spread of prostate cancer on PSMA-PET/CT.
A variety of non-prostatic or non-malignant findings exhibiting prostate specific membrane antigen (PSMA) tracer uptake and resemble metastatic disease on positron emission tomography (PET) imaging. In this case, a 72-year-old man presenting for initial staging of prostate cancer was found to have PSMA tracer uptake along the left external iliac vessels corresponding to a structure resembling a lymph node on computed tomography (CT). This finding was initially concerning for nodal spread of the patient's primary neoplasm. However, chart review revealed a remote history of left inguinal hernia plug repair with location corresponding to the area of PSMA activity. This case highlights PSMA uptake related to surgical mesh from inguinal hernia plug repair as a mimic of nodal metastatic disease on PSMA PET.


On the diagnostic value of the hypoosmotic sperm swelling test in an in vitro fertilization (IVF) program.
The ability of the hypoosmotic sperm swelling (HOS) test to identify nonfertilizing sperm samples in a group of 50 couples undergoing in vitro fertilization (IVF) was investigated. The findings indicate that the HOS test is not significantly more useful than any of the standard semen variables for this purpose.


The Variations in Deviation of Nasal Septum and their Impact on Maxillary Sinus Volume and Occurrence of Sinusitis.
To study the effect of variations in deviation of the nasal septum and their impact on maxillary sinus volume and occurrence of sinusitis. This prospective observational study was conducted in the department of ENT, Head &Neck surgery GMC Jammu from August 2021 to November 2022. 130 patients (90 males, 40 females), with age range of 18-47 years with DNS were included in the study. Grade of DNS was classified according to Mladina's classification and volume of maxillary sinus was calculated using geometric formula by performing 256 slice CT Scan. In our study mean age of the males was 32.8 ± 6.99 years and females was 33.7 ± 7.26 years with Male: Female ratio of 9:4.Patients with grade 1 DNS had mean maxillary sinus volume of 9.9 ± 1.97 cu mm while patients with grade 7 DNS had mean maxillary sinus volume of 3.8 ± 1.47 cu mm. Thus, with the increasing grade of DNS, the OMC blockage increased towards the side of DNS and so the occurrence of maxillary sinusitis. The study showed that with high grade DNS, the maxillary sinus volume decreases on the side of septum deviation and there is association of blocked OMC with increasing grade of DNS. The incidence of maxillary sinusitis findings on the side of septum deviation was significantly increased.


The incidence of contrast-induced nephropathy in trauma patients.
We measured the incidence and risk factors for contrast-induced nephropathy (CIN) in trauma patients. We conducted a retrospective review of a prospectively collected trauma database. We studied injured patients who received a contrast-enhanced computer tomography with an initial and repeat serum creatinine after 48 h. Exclusion criteria were patients on dialysis. CIN was defined as a 25% rise in creatinine or an increase in creatinine > or =0.5 mg/dl from baseline 48 h after contrast. Data were reported as means+/-SD. Group comparisons were made by Fisher's exact test or Student's t-test (alpha=0.05, two tails). In total, 235 patients were studied with an average age of 44+/-20 (13-92 years) (80% men), 79% of whom had blunt injuries. CIN incidence was 5.1% [95% confidence interval (CI), 2.9-8.8%]. No patients in the CIN or non-CIN groups died, or required in-patient/chronic dialysis. CIN patients were significantly (P=0.003) older (61 vs. 43 years). For age > or =75 years, the relative risk was 7.7 and the number needed to harm was 5. An elevated creatinine (more than 1.5 mg/dl) was significantly (P=0.007) associated with CIN. For creatinine greater than 1.5 mg/dl, the relative risk was 6.4 and the number needed to harm was 6. CIN was significantly (P=0.02) more likely in patients with glomerular filtration rate less than 60 ml/min/1.73 m. We found no significant (P>0.05) difference in base-deficit, lactate, and Injury Severity Score between CIN and non-CIN patients. We found a 5.1% incidence of CIN in trauma patients exposed to intravenous contrast. Elderly and trauma patients with low glomerular filtration rate were especially predisposed to CIN.


Underreporting of robotic surgery complications.
Since its Food and Drug Administration (FDA) approval, robot-assisted laparoscopic surgery has grown with expanding indications. One factor used to expand indications is device-related complications. We designed a study to evaluate device-related robotic surgery complications reported to FDA. We searched the FDA device-related complication database, LexisNexis, and PACER (Public Access to Court Electronic Records) to identify robotic surgery-related complications over a 12-year period (January 1, 2000 to August 1, 2012). Cases from LexisNexis and PACER were cross-referenced with the FDA database to determine cases where an FDA report was inaccurate, filed late or not filed. A total of 245 events were reported to the FDA during the study period, including 71 deaths and 174 nonfatal injuries. Median time to report an event to the FDA was 30 days (range = 0-930 days). Eight cases were identified from the LexisNexis and PACER searches where FDA reports were improperly filed. In five of these, no report was filed with a mean follow-up of 4.1 years (range = 2.3-5.8 years). In the three cases where a report was filed, the mean time between the event and the FDA report was 20.4 months (611 days, range = 292-930 days). It is important that the true incidence of complications with robotic-assisted laparoscopic surgery be known to ensure continued safe innovation.


Creation and Validation of the Select Medical Patient Reported Experience Measure for Physical and Occupational Therapy Outpatient Clinics.
This study describes the creation and examination of the internal consistency, content validity, construct/structural validity, and criterion/concurrent validity of the Select Medical Patient Reported Experience Measure (SM-PREM). Observational study design. 1054 Outpatient physical and occupational therapy locations in North America. The study included 89,205 patients with various musculoskeletal disorders (N=89,205). Not applicable. Content validity was described, and internal consistency, construct/structural validity (factor analysis), and criterion/concurrent validity were analyzed, with concurrent validity compared against patient reported outcomes (PROM), the Net Promoter Scale, and the Orebro Musculoskeletal Screening Questionnaire-12. Exploratory and confirmatory factor analysis of the SM-PREM yielded 3 dimensions, each with a very strong internal consistency (>.850). The SM-PREM yielded statistically significant results in all areas, with values that reflected minimal to fair association with PROMs. The SM-PREM appears to capture a unique construct compared to PROMs. The 11-item tool has 3 definitive dimensions and exhibits strong internal consistency. The tool may be useful in examining patient experience in patients with musculoskeletal injuries seen by physical and occupational therapists.


Computer Vision Syndrome: Prevalence and Associated Risk Factors Among Computer-Using Bank Workers in Pakistan.
The aim of this study was to investigate the prevalence of symptoms of computer vision syndrome (CVS) and identify its associated risk factors among computer-using bank workers in Pakistan. This cross-sectional study was conducted on computer-using bank workers. The data collection procedure included a self-administered questionnaire and comprehensive ocular health examination. The prevalence of CVS and its associated risk factors were investigated. The chi-square test was used to study the significance of the association of CVS with potential risk factors. Of 127 participants, 95 (74.8%) were men. Most of the participants (n=53; 41.7%) were in the 30-40 years age group. A total of 101 participants (79.5%) reported any ocular symptom, with burning eyes being the most frequent ocular symptom (77.2%). General body fatigue was the most common non-ocular symptom of CVS (92.9%), followed by headache (83.5%). Out of 127 participants, 71 men and 30 women had some degree of CVS. Female participants had significantly higher risk of CVS than male participants (p=0.01). Total duration of computer use per day and duration of uninterrupted computer use were significantly associated with the occurrence of CVS (p=0.001 and p=0.008, respectively). No significant association was found between CVS and distance from computer screen (p=0.89), frequency of breaks (p=0.18), or font size (p=0.12). A high prevalence of CVS-related symptoms was observed among computer-using bank workers. Non-ocular symptoms associated with computer use were more common than ocular symptoms (92.9% vs. 77.2%).


Sleep apnea severity in patients undergoing atrial fibrillation ablation: Home sleep apnea-test and polysomnography comparison.
Sleep apnea (SA) is highly prevalent and should be treated in patients referred for catheter ablation (CA) of atrial fibrillation (AF). Watch-type peripheral arterial tonometry (WP) for home SA testing has demonstrated a high correlation of the apnea-hypopnea index (AHI) with Polysomnography (PSG), but the evidence of its accuracy in AF patients is not adequate. This study was conducted under a retrospective, single-center, observational design. We included 464 consecutive AF patients (age 65 ± 11 years, 76.5% male, 45.0% paroxysmal-AF) who received both WP and PSG during the periprocedural period of the CA. We compared the AHI using the WP (WP-AHI) to that using PSG (PSG-AHI). The WP-AHI was 25.9 ± 12.7 and PSG-AHI 31.4 ± 18.9 (r = .48). Among 325 patients with a WP-AHI < 30, 116 (35.7%) exhibited a PSG-AHI ≥ 30. Only 12.5% of the patients were indicated for continuous positive airway pressure (CPAP) treatment only by the WP-AHI, while 70.9% were indicated for CPAP by the PSG-AHI according to the Japanese health insurance system. The best cut-off value of the WP-AHI was 18.1 to predict a PSG-AHI ≥ 20 with an area under the curve of 0.72 (95% confidence interval, 0.67-0.76). The WP-AHI and PSG-AHI were weakly correlated in AF patients receiving CA. About one-third of the patients with moderate SA using the WP was diagnosed with severe SA evaluated by PSG. The majority required PSG for the CPAP indication.


Rationale and study design of a randomized controlled trial to investigate the renoprotective effect of canagliflozin assessed by test of renal hemodynamics in diabetic kidney disease (the FAGOTTO study).
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are considered to have the potential to maintain renal function by correcting glomerular hypertension in patients with diabetic kidney disease (DKD). The aim of this study is to demonstrate the renoprotective effect of SGLT2i by measuring renal hemodynamics, including glomerular filtration fraction (FF), in type 2 diabetic patients with moderate renal dysfunction. Renoprotective effect of canagliflozin derived from test of renal hemodynamics in diabetic kidney disease (FAGOTTO) study is a 12-week multicenter, open-label, randomized (1:1), parallel-group trial of type 2 diabetic patients with diabetic kidney disease (30 ≤ estimated glomerular filtration rate [eGFR] ≤ 60 mL/min/1.73 m2). A total of 110 patients are to be randomly allocated to receive once-daily canagliflozin 100 mg or control (standard therapy). FF will be calculated by dividing the measured GFR (mGFR) by the effective renal plasma flow (eRPF). mGFR and eRPF will be measured by the clearance of inulin and para-aminohippuric acid (PAH), respectively. The primary endpoint of this trial is the percentage change in FF after 4 weeks of treatment in the canagliflozin and control groups. The FAGOTTO study will elucidate the mechanism of the renoprotective action of SGLT2i. The background, rationale, and study design of this trial are presented. To date, > 80 patients have been enrolled in this trial. The study will end in 2025. jRCT (Japan Registry Of Clinical Trials) jRCTs041200069. Date of registration: November 27, 2020.


Hematopoietic colony stimulatory factor formation by murine mesangial cells: gene expression and biological activity.
This study examined the ability of mesangial cells to synthesize colony-stimulating factors (CSF), cytoregulatory peptides associated with the differentiation and proliferation of hematopoietic cells. Conditioned media obtained from SV-40 transformed murine mesangial cells stimulated the growth of murine bone marrow progenitor cells of the myeloid series. Differential analysis of these cells showed the presence of both macrophages and granulocytes. Cellular identification of bone marrow colonies stimulated in response to mesangial cell conditioned media was examined by flow cytometric analysis and revealed the presence of F4/80 antigen positive macrophages (67%) and Gran-1 antigen positive granulocytes (21%). Neutralizing antibodies to macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) but not antibody to interleukin-3 (IL-3), or stem cell factor (SCF) significantly inhibited the growth of the progenitor cells induced by mesangial cell conditioned media. Utilizing Northern blot analysis, murine mesangial cells expressed mRNA transcripts for M-CSF, GM-CSF, and granulocyte colony-stimulating factor (G-CSF). Further studies were performed to determine optimal incubation conditions for mesangial cell CSF gene expression. These studies revealed that both GM-CSF and G-CSF mRNA were maximally expressed at early time points (4 and 8 h of incubation), while M-CSF mRNA expression remained unchanged during the incubation of mesangial cells from 4-48 h. Incubation of mesangial cells with various concentrations of fetal bovine serum (FBS, 0.5-15%) markedly increased the mRNA expression of M-CSF, GM-CSF and G-CSF in a dose-dependent manner. These studies indicated that transformed murine mesangial cells are able to synthesize and secrete biologically active CSF that are associated with the migration and proliferation of circulating mononuclear cells in the glomerulus. Furthermore, observations regarding the role of duration of incubation and the media concentration of FBS on mesangial cell CSF mRNA expression may provide useful data to understand the optimal conditions for studies that examine the gene expression of basal or inducible CSF in mesangial cells.


Acute dendrotoxic changes in the hippocampus of kainate treated rats.
Kainic acid (KA), a potent neuroexcitatory and neurotoxic analog of glutamate (Glu), induces a widespread pattern of brain damage when administered subcutaneously to adult rats. The hippocampus is among the brain regions most consistently and severely damaged. Here we describe acute swelling of certain spines and branchlets of dendrites as the first detectable sign of KA neurotoxic changes in the hippocampus. These swellings conform to a laminar pattern suggesting selective toxic interaction of KA at specific levels of the dendritic trees of hippocampal pyramidal and dentate granule neurons. The frequency and severity of involvement of each type of hippocampal neuron at each level of its dendritic tree was roughly estimated and neuronal types were ranked from the most to least extensively involved (CA3 greater than CA4 greater than CA1 greater than CA2 greater than dentate granules). The same rank order has been described for the vulnerability of these neurons to acute destruction following intraventricular KA administration. Because the pattern of dendritic dilatations observed corresponds well with the pattern of termination of putative glutamergic inputs to the hippocampus, we interpret the findings as being consistent with the hypothesis that the toxic effects of KA are mediated through glutamergic excitatory receptors. We propose that the sensitivity of a given neuron to the neurodestructive action of KA may be determined by the percentage of its dendritic surface occupied by Glu receptors. We suspect that most, if not all, hippocampal neurons receive some glutamergic input and, therefore, are sensitive to KA. That CA3 pyramids are substantially more sensitive than dentate granules may signify that the former receive many more Glu terminals than the latter, an assumption quite consistent with our observation that focal dendritic swellings were both more densely and more widely distributed over the dendritic surfaces of the former than the latter.


Isolation and characterization of a heat-resistant beef allergen: myoglobin.
Meat allergy is rarely reported. Most of the described cases are sensitizations to bovine serum albumin. The aim of the study was to describe a case of allergy to a new meat allergen and, after its characterization. A 35-year-old nonatopic female with allergic episodes after ingestion of several types of meat was studied. Skin tests (prick and prick-to-prick); total and specific immunoglobulin E (IgE) determination; sodium dodecyl sulphate-polyacrylamide gel electrophoresis and specific IgE determination by immunoblotting under different conditions were performed. A 17-kDa allergen was semipurified by ethanol fractionation and its amino-terminal sequence was determined. The existence of specific IgE directed to this protein was studied by immunoblot in 80 atopic patients. The patient showed specific IgE antibodies to a 17-kDa protein. During the isolation of this allergen it was found that a 70-90% (vol/vol) ethanol concentration was able to purify the protein. The characterization revealed that it was a heat-resistant protein without disulfide bonds. N-terminal amino acid sequence (16 residues) showed identity with myoglobin. The study of specific IgE to this allergen among atopic patients showed that it was recognized by about 1% of the subjects. We describe a case of meat allergy caused by myoglobin. This is the first described case of monosensitization to this protein.


Effect of a multimodality natural medicine program on carotid atherosclerosis in older subjects: a pilot trial of Maharishi Vedic Medicine.
Although the onset and progression of coronary heart disease (CHD) involve multiple risk factors, few intervention studies have attempted to modify these factors simultaneously. This pilot study tested the effect of a multimodality intervention involving dietary, exercise, herbal food supplement, and stress reduction approaches from a traditional system of natural medicine, Maharishi Vedic Medicine (MVM). The primary outcome measure was carotid intima-media thickness (IMT), a noninvasive measure of peripheral atherosclerosis and surrogate measure of coronary atherosclerosis. Comparison groups included modern medicine (conventional dietary, exercise, and multivitamin approaches) and usual care (no added intervention). Of 57 healthy seniors (mean age 74 years) randomized to the 3 treatment groups, 46 completed IMT post-testing. Carotid IMT was determined by B-mode ultrasound before and after 1 year of treatment. IMT decreased in a larger fraction of MVM subjects (16 of 20) than in the modern (5 of 9) and usual care (7 of 14) groups combined (i.e., 12 of 23; odds ratio 3.7, p = 0.05). For subjects with multiple CHD risk factors ("high-risk" subjects, n = 15), IMT decreased more in the MVM (-0.32 +/- 0.23 mm, mean +/- SD) than in the usual care (+0.022 +/- 0.085; p = 0.009) or modern (-0.082 +/- 0.095, p = 0.10) groups. Within-group reductions in IMT were significant for all MVM subjects (-0.15 +/- 0.21, n = 20, p = 0.004) and for high-risk MVM subjects (n = 6, p = 0.01). These results show that this multimodality traditional approach can attenuate atherosclerosis in older subjects, particularly those with marked CHD risk.


Children's adjustment in conflicted marriage and divorce: a decade review of research.
To review important research of the past decade in divorce, marital conflict, and children's adjustment and to describe newer divorce interventions. Key empirical studies from 1990 to 1999 were surveyed regarding the impact of marital conflict, parental violence, and divorce on the psychological adjustment of children, adolescents, and young adults. Recent studies investigating the impact of divorce on children have found that many of the psychological symptoms seen in children of divorce can be accounted for in the years before divorce. The past decade also has seen a large increase in studies assessing complex variables within the marriage which profoundly affect child and adolescent adjustment, including marital conflict and violence and related parenting behaviors. This newer literature provides provocative and helpful information for forensic and clinical psychiatrists in their work with both married and divorcing families. While children of divorced parents, as a group, have more adjustment problems than do children of never-divorced parents, the view that divorce per se is the major cause of these symptoms must be reconsidered in light of newer research documenting the negative effects of troubled marriages on children.


Monoamine metabolites in cerebrospinal fluid of depressed patients during treatment with mianserin or amitriptyline.
A group of 20 inpatients with moderate to severe primary affective disorder received 14 days of placebo treatment and were then randomly allocated to receive mianserin 10 mg 3 times daily or identical amitriptyline 25 mg 3 times daily for 1 week followed by 60 mg mianserin or 150 mg amitriptyline daily for a second week. Patients were rated for side-effects and depression (Hamilton Depression Scale) on days 0, 7, 14, 21 and 28. Probenecid 100 mg/kg was administered in 3 divided doses on days 13/14 and on days 27/28 of the trial, followed by collection of CSF. Blood samples for determination of antidepressant levels were collected on day 27. Both mianserin and amitriptyline produced a significant decrease in CSF levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), but only amitriptyline significantly lowered CSF levels of 5-hydroxyindole-3-acetic acid (5-HIAA). Neither drug affected CSF levels of homovanillic acid (HVA). Both mianserin and amitriptyline produced significant but indistinguishable improvement in mean Hamilton scores over 2 weeks of treatment. There was no relationship between therapeutic response and either plasma antidepressant levels or pre-treatment CSF monoamine metabolite levels in his small group of patients. The reductions of CSF levels of metabolites of NA (MHPG) and 5-HT (5-HIAA) are consistent with the known effects of amitriptyline on amine uptake. Mianserin may reduce CSF MHPG levels as a result of its effects upon NA release and/or uptake, but it appears to be devoid of influence upon central 5-HT metabolism.


Non-response to daclatasvir and asunaprevir therapy in patients co-infected with hepatitis C virus genotypes 1 and 2.
Direct-acting antiviral agents for hepatitis C virus (HCV) have been developed such as combined daclatasvir (DCV) and asunaprevir (ASV) treatment. This typically enables HCV serotype 1 patients to achieve a high sustained virological response rate, but a small number of such patients fail to respond to therapy. We investigated three HCV patients who showed no response to DCV and ASV therapy. Hepatitis C genotyping was undertaken in the three patients using nested polymerase chain reaction and polymerase chain reaction direct sequencing in the core region of the HCV genome. All three patients possessed HCV serotype 1, and no mutations were identified in either the non-structural protein 3 or 5A region. The three patients were shown to be co-infected with HCV genotypes 1 and 2 because genotypes 2a and 2b were also identified. This is the first report into failed response to DCV and ASV therapy in patients co-infected with HCV genotypes 1 and 2.


Physicochemical factors for cytotoxic activity in platinum dinuclear complexes with pyrimidine and imide ligands.
The relationship between cytotoxic activity of platinum dinuclear complexes toward cancer cells and their intrinsic properties (electrophilicity and hydrophobicity) have been examined. It is shown that the reactivity with chloride anion is a good index of the electrophilicity of the platinum complexes. By assuming a cell kill pharmacodynamic model, the relation between IC50 value and the electrophilicity is obtained. It is concluded that inside cells the reactivity of the platinum complexes having imide ligands is higher than that of CDDP. The other important factor which affects the cytotoxic activity is hydrophobicity. The log k' values (k': capacity factor) are found useful to estimate the hydrophobicity of platinum complexes. The accumulation of platinum into cells is dominated by the hydrophobicity and the charge of platinum complexes. Highly hydrophobic complexes are thought to be adsorbed in cell membranes, resulting in low cytotoxic activity since they cannot reach DNA. A schematic model of the interaction between platinum complexes and serum proteins reveals that more hydrophobic complexes tend to bind to serum proteins more stably. At least three possible paths of the cellular platinum accumulation are suggested: direct accumulation of the platinum complexes, incorporation in the form of CDDP produced from the complexes, and incorporation through protein-platinum complexes, although the contribution of the third one may be small.


Di-alkylated paromomycin derivatives: targeting the membranes of gram positive pathogens that cause skin infections.
A collection of paromomycin-based di-alkylated cationic amphiphiles differing in the lengths of their aliphatic chain residues were designed, synthesized, and evaluated against 14 Gram positive pathogens that are known to cause skin infections. Paromomycin derivatives that were di-alkylated with C7 and C8 linear aliphatic chains had improved antimicrobial activities relative to the parent aminoglycoside as well as to the clinically used membrane-targeting antibiotic gramicidin D; several novel derivatives were at least 16-fold more potent than the parent aminoglycoside paromomycin. Comparison between a di-alkylated and a mono-alkylated paromomycin indicated that the di-alkylation strategy leads to both an improvement in antimicrobial activity and to a dramatic reduction in undesired red blood cell hemolysis caused by many aminoglycoside-based cationic amphiphiles. Scanning electron microscopy provided evidence for cell surface damage by the reported di-alkylated paromomycins.


Epigenetic modification of H3K4 and oxidative stress are involved in MC-LR-induced apoptosis in testicular cells of SD rats.
Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide, produced by aquatic cyanobacteria such as microcystis, with strong reproductive toxicity which poses greater threat to the reproductive abilities of humans and animals. By exploring the role of trimethylation of histone H3 at lysine 4 (H3K4me3) and the role of oxidative stress in MC-LR-induced apoptosis in testicular Sertoli cells in Sprague-Dawley (SD) rats, this study indicated that MC-LR increased the expression levels of apoptosis-related genes by raising the levels of H3K4me3. 5'-Deoxy-5'-methylthioadenosine (MTA), the inhibitor of H3K4me3, reduced apoptosis, indicating for the first time that epigenetic modification is closely related to the testicular reproductive toxicity induced by MC-LR. MC-LR also induced oxidative stress by stimulating the generation of reactive oxygen species (ROS), and subsequently triggering mitochondria-mediated apoptotic pathway by decreasing mitochondrial membrane potential and increasing the levels of Bax, Bcl-2, Caspase-3, and so on. MC-LR-induced apoptosis of testicular cells could be decreased after pretreatment with oxidative stress inhibitor N-acetyl-cysteine (NAC). Furthermore, the pathological damage to mitochondria and testes were observed in SD rats. These results show that MC-LR can induce apoptosis by raising the levels of H3K4me3, and pretreatment with MTA can ameliorate the MC-LR-induced apoptosis of cocultured cells by lowering the levels of H3K4me3. Furthermore, NAC has a protective effect on MC-LR-induced apoptosis of testicular cells in SD rats by inhibiting the oxidative stress.


Oxygen-rich bismuth oxychloride Bi12O17Cl2 materials: construction, characterization, and sonocatalytic degradation performance.
In this study, a series of oxygen-rich bismuth oxychloride Bi12O17Cl2 samples were prepared at different calcination temperatures and characterized by X-ray diffraction patterns, UV-Vis diffuse reflectance spectra, scanning electron microscope, X-ray energy dispersion spectroscope, X-ray photoelectron spectroscopy, and photoluminescence spectroscopy. The calcination temperature greatly affected microstructures and band structures of as-prepared samples, further influencing sonocatalytic degradation efficiencies over dye Rhodamine B. Some dependant factors such as ultrasonic power, catalyst dosage, pH value, initial concentration of Rhodamine B, and reaction temperature were systematically investigated and the robust sample Bi12O17Cl2-550 with a favorable microstructure and band structure provided the best sonocatalytic removal efficiency around 90% at the optimal condition. Based upon reactive species entrapping and hydroxyl radical detection experiments, a primary sonocatalysis mechanism was eventually speculated.


Effects of high-intensity ultrasound on the structural, optical, mechanical and physicochemical properties of pea protein isolate-based edible film.
Pea protein is a promising alternative to animal-based protein and the interest in its application in food industry has been rapidly growing. In this study, pea protein isolates (PPI) were used to form protein-based edible films and the effect of ultrasound treatment on the structure of PPI and the structural, optical, mechanical and physicochemical properties of PPI-films were investigated. Ultrasound induced unfolding of PPI and exposed interior hydrophobic groups to protein surface while both PPI dissociation and formation of large aggregates were observed, as confirmed by measuring intrinsic emission fluorescence, surface hydrophobicity, surface charge, and particle size distribution and polydispersity index, respectively. FE-SEM showed that ultrasound decreased the cracks and protein aggregates at the surface of PPI-film. The film structure was also investigated by FTIR, which showed peak shift in amide I and II region and noticeable difference of protein secondary structure as affected by ultrasound. As a result of such structural changes caused by ultrasound, the properties of PPI-films were improved. Results showed that ultrasound greatly improved the film transparency, significantly increased film tensile strength but not elongation at break, and decreased moisture content and water vapor permeability of the film. This study provided structural data as evidence for utilizing ultrasound technique to develop PPI-films with improved optical, mechanical and water barrier properties.


Forces transmission to the skull in case of mandibular impact.
Forensic investigations have been reported regarding the loss of consciousness and cardiac arrests resulting from direct mandible impact. However, the mechanisms by which the forces are transferred to the skull through direct mandible impact remain unclear. We conducted a study regarding direct mandible impact on the level of energy required to create a mandible fracture and on the energy dispersion phenomenon to the skull and to the brain. This study combines an experimental and numerical approach. Mandible strike was studied using experimental trials performed on post-mortem human subjects. A finite element model of the head and face of a male was also developed based on tomodensitometry scans. The model was validated with literature data and experimental trials. A parametric study was then performed to study the effect of diverse variables such as the dentition integrity, cortical bone thickness, etc. The forces measured on our reference model were 3000 N on the chin, 1800 N at the condyles, and 970 N in the occiput. Of all the results, we observed a decrease of approximately one-third of the efforts from the chin to the base of the skull and a lower half of the still forces at the occiput, except in the edentulous and for the lateral and frontal impact where the force is transmitted directly to the skull base area. This study allowed us to create a 3D model of the mandible and face bones to better understand the force transfer mechanisms into and from the mandible. The parameters of the model may be modified to suit the individual characteristics for forensic investigations and legal matters.


A program running under MS-DOS for the analysis of epidemiologic stratified or matched data.
Breslow and Day's method for computing the conditional likelihood of the logistic model in case of stratified samples requires, at each iteration the generation, for each stratum, of all the permutations of nc elements drawn from a total of nc + nt elements, where nc and nt are respectively the numbers of the cases and of the controls. This procedure rapidly proves costly in time as nc and nt increase, and also when nc and nt differ from one stratum to the next. The use of this technique on microcomputers is therefore limited. Presented here is an algorithm written in FORTRAN, based on a binary representation of the possible permutations, which readily permits the implementation of Breslow and Day's model on a microcomputer.