Treatment of water-based metalworking fluids to prevent hypersensitivity pneumonitis associated with Mycobacterium spp.
To prevent further outbreaks of hypersensitivity pneumonitis (HP), biocides are required which are capable of protecting water-based coolants from proliferating mycobacteria. The aim of this study was therefore, to test different biocide preparations on their mycobactericidal activity. Minimal inhibitory concentration values were determined for Mycobacterium chelonae and Mycobacterium immunogenum for triazine-based, methyloxazolidine-based, N/O-formal-based biocidal formulations. All biocides were effective already at a low dosage (<0.05%) irrespective of the presence or absence of organic soiling, except for one N/O-formal-based formulation containing Kathon 886 (CMI). Quenching of CMI in the presence of organic soiling was found to account for loss in efficacy as determined by high-performance liquid chromatography measurement. Preservation tests were carried out to investigate the efficacy of the biocidal preparations under practical conditions. Results indicate that methyloxazolidine-based biocidal preparations were most effective to prevent coolants from microbial contamination including rapidly growing mycobacteria. Furthermore, it could be demonstrated that common dipslides can be used to easily monitor coolants for contamination by mycobacteria. Our data does not support the hypothesis that mycobacterial proliferation is enhanced by the reduction of competitive microbial population by biocides such as triazines as described earlier but rather suggests a protective effect of biocides regarding mycobacteria in the presence of competitive microbial flora, thereby preventing further outbreaks of HP.


Correction: Tang et al. Vitamin K2 Modulates Mitochondrial Dysfunction Induced by 6-Hydroxydopamine in SH-SY5Y Cells via Mitochondrial Quality-Control Loop. Nutrients 2022, 14, 1504.
In the original publication [...].


Adenine nucleotide translocase mediates the K(ATP)-channel-openers-induced proton and potassium flux to the mitochondrial matrix.
KATP channel openers have been shown to protect ischemic-reperfused myocardium by mimicking ischemic preconditioning, although their mechanisms of action have not been fully clarified. In this study we investigated the influence of the adenine nucleotide translocase (ANT) inhibitors--carboxyatractyloside (CAT) and bongkrekic acid (BA)--on the diazoxide- and pinacidil-induced uncoupling of isolated rat heart mitochondria respiring on pyruvate and malate (6 + 6 mM). We found that both CAT (1.3 microM) and BA (20 microM) markedly reduced the uncoupling of mitochondrial oxidative phosphorylation induced by the K(ATP) channel openers. Thus, the uncoupling effect of diazoxide and pinacidil is evident only when ANT is not fixed by inhibitors in neither the C- nor the M-conformation. Moreover, the uncoupling effect of diazoxide and pinacidil was diminished in the presence of ADP or ATP, indicating a competition of K(ATP) channel openers with adenine nucleotides. CAT also abolished K+-dependent mitochondrial respiratory changes. Thus ANT could also be involved in the regulation of K(ATP)-channel-openers-induced K+ flux through the inner mitochondrial membrane.


Pros, cons, and organization of prehospital thrombolysis.
Early initiation of reperfusion therapy in ST-segment elevation myocardial infarction improves outcome. Prehospital thrombolysis (PHT) is 1 strategy to deliver earlier reperfusion. The goal of this study was to discuss the pros and cons of PHT and to describe the implementation of a program of PHT in the Hunter Region of Australia. Recent literature on PHT was reviewed to present a critical assessment of the evidence to support PHT. Different models of PHT are presented including the experience of the introduction of the Hunter program. Meta-analyses of clinical trials and registries have shown that PHT significantly decreases the time to thrombolysis, with reduction in the incidence of cardiogenic shock and a trend to a mortality benefit. The STREAM study reinforces current policy, which favors primary percutaneous coronary intervention (PCI) over thrombolysis, providing that PCI can be performed within an appropriate time interval; emphasizes that timely thrombolysis linked to an early invasive strategy provides an equivalent outcome when timely primary PCI is not possible; and supports other published experience that early-rescue PCI can be performed safely after administration of PHT. Although PHT can be implemented by trained paramedics working with on-board physicians, the Hunter Region has successfully used paramedics and ECG telemetry in consultation with hospital-based physicians. When the time to open the artery is ≤90 minutes, primary PCI is preferred. When the time to open the artery is >90 minutes, PHT with immediate transport postthrombolysis to a PCI-capable hospital is feasible and effective. PHT delivered by trained paramedics with telemetery backup to assist ECG interpretation is feasible and delivers the prospect of early reperfusion.


Severe resistance to weight gain, lack of stored triglycerides in adipose tissue, hypoglycaemia, and increased energy expenditure: a novel disorder of energy homeostasis.
Growth during childhood is a consequence of the equilibrium of energy balance. Obesity results from a shift of the equilibrium towards increased energy intake over expenditure. A clinical description of extreme leanness and failure to thrive secondary to a shift of the equilibrium towards increased energy expenditure over energy intake has not been previously described in the medical literature. We report the case of a female child born premature with a birth weight of 1.1 kg who presented with extreme failure to thrive, persistent hypoglycaemia, paucity of fat in the adipose tissue with increased brown fat and increased resting energy expenditure. Complete cessation of weight and height was noted between 3 months to 3.5 years of age. Hypoglycaemia was secondary to depleted energy stores and increased insulin sensitivity. Increased resting energy expenditure was demonstrated on indirect calorimetric assessment. Biopsy of adipose tissue demonstrated paucity of stored fat with increase in brown fat. No gain in weight and height was demonstrated despite high calorie intake of enteral and parenteral feeds. We describe a unique case of extreme failure to thrive with increased energy expenditure and severe hypoglycaemia. Unravelling the molecular basis of this novel disorder has the potential to provide insights into the prevention of obesity.


Clinical profile and factors associated with mortality in hospitalized patients with HIV/AIDS: a retrospective analysis from Tripoli Medical Centre, Libya, 2013.
In Libya, little is known about HIV-related hospitalizations and in-hospital mortality. This was a retrospective analysis of HIV-related hospitalizations at Tripoli Medical Centre in 2013. Of 227 cases analysed, 82.4% were males who were significantly older (40.0 versus 36.5 years), reported injection drug use (58.3% versus 0%) and were hepatitis C virus co-infected (65.8% versus 0%) compared with females. Severe immunosuppression was prevalent (median CD4 count = 42 cell/μL). Candidiasis was the most common diagnosis (26.0%); Pneumocystis pneumonia was the most common respiratory disease (8.8%), while cerebral toxoplasmosis was diagnosed in 8.4% of patients. Current HAART use was independently associated with low risk of in-hospital mortality (OR 0.33), while central nervous system symptoms (OR 4.12), sepsis (OR 6.98) and low total lymphocyte counts (OR 3.60) were associated with increased risk. In this study, late presentation with severe immunosuppression was common, and was associated with significant in-hospital mortality.


Evidence-based practice.
The following document is a position statement of The Society of Pediatric Nurses (SPN) that pertains to evidence-based practice (EBP). This document was developed by the Clinical Practice Committee of SPN, and it includes an overview of EBP basics and SPN recommendations with regards to EBP.


Sacral Fractures and Sacroplasty.
Sacral fractures result from high-impact trauma or in the form of insufficiency or pathologic fractures, resulting from osteoporosis, radiation therapy, or malignancy. In the emergency setting, the escalating use of computed tomography has substantially increased diagnosis of sacral fractures, which are frequently occult on radiographs. Radiologists should be familiar with and create reports using the most current fracture classification systems, because this improves communication with the treatment team and optimizes patient care. Sacroplasty is a safe, minimally invasive treatment option for many types of sacral fractures. It provides rapid and durable pain relief, with a low incidence of complications.


Plasma N-terminal pro-brain natriuretic peptide concentration predicts coronary events in men at work: a report from the BELSTRESS study.
Increased levels of neurohormonal markers, including the N-terminal fragment of pro-brain natriuretic peptide (NT-pro-BNP), have been shown to be of prognostic significance in patients with heart failure or coronary heart disease (CHD). The aim of this study was to study the predictive value of NT-pro-BNP for coronary events in a middle-aged population of men at work. A nested case-control study was performed in a large cohort of over 10 000 men at work (aged 35-59) after a median follow-up of 2.66 years. In total, 66 individuals who developed coronary events were matched on a 3-to-1 basis to 198 controls free of coronary events during follow-up. Besides clinical characteristics and conventional cardiac risk factors, NT-pro-BNP (electrochemiluminiscence assay, Roche diagnostics) and serum creatinine levels were determined. In univariable analysis, cases were more frequently current smokers and diabetics, had more frequently a history of CHD, and had higher levels of total cholesterol and systolic blood pressure (SBP), and lower levels of HDL cholesterol. A highly significant difference (P < 0.0001) was noted for NT-pro-BNP levels between cases (median 48.5 pg/mL, interquartile range 26.4-116.6 pg/mL) and controls (30.0 pg/mL, 19.5-47.6 pg/mL). In multivariable conditional logistic regression analysis, NT-pro-BNP remained strongly associated with risk for coronary events [third vs. first tertile, odds ratio (95% CI) 3.24 (1.18-8.85)], independent of body mass index, smoking, diabetes, SBP, total and HDL cholesterol, creatinine, and previous CHD. NT-pro-BNP is a strong predictor of coronary events in men at work after a relatively short period, even after adjustment for conventional risk factors.


Mineral and collagen content of human ossicles.
With increased use of human otologic homograft tissue for implantation, different preservation techniques and products are used for storing and preserving the grafts before surgery. Preserved ossicles may, according to some authors, already exhibit signs of decalcification after 2 weeks. Therefore, the mineral (calcium, phosphorus) and collagen content of human ossicles (incus) and mastoid cortex and the influence of different storage techniques was biochemically investigated. No significant mineral or collagen-concentration changes were observed after a 6-week storage in pH-7 formaldehyde or in cialit, in either the ossicles or in the cortical bone. These biochemical findings are in agreement with histologic observations and with similar experiments using the photon absorptiometry technique.


Quantitative myocardial T2 mapping adds value to Japanese circulation society diagnostic criteria for active cardiac sarcoidosis.
Noninvasive identification of active myocardial inflammation in patients with cardiac sarcoidosis plays a key role in management but remains elusive. T2 mapping is a proposed solution, but the added value of quantitative myocardial T2 mapping for active cardiac sarcoidosis is unknown. Retrospective cohort analysis of 56 sequential patients with biopsy-confirmed extracardiac sarcoidosis who underwent cardiac MRI for myocardial T2 mapping. The presence or absence of active myocardial inflammation in patients with CS was defined using a modified Japanese circulation society criteria within one month of MRI. Myocardial T2 values were obtained for the 16 standard American Heart Association left ventricular segments. The best model was selected using logistic regression. Receiver operating characteristic curves and dominance analysis were used to evaluate the diagnostic performance and variable importance. Of the 56 sarcoidosis patients included, 14 met criteria for active myocardial inflammation. Mean basal T2 value was the best performing model for the diagnosis of active myocardial inflammation in CS patients (pR2 = 0.493, AUC = 0.918, 95% CI 0.835-1). Mean basal T2 value > 50.8 ms was the most accurate threshold (accuracy = 0.911). Mean basal T2 value + JCS criteria was significantly more accurate than JCS criteria alone (AUC = 0.981 vs. 0.887, p = 0.017). Quantitative regional T2 values are independent predictors of active myocardial inflammation in CS and may add additional discriminatory capability to JCS criteria for active disease.


Low incidence of adverse events following varenicline initiation among opioid dependent smokers with comorbid psychiatric illness.
Most drug treatment patients smoke cigarettes, yet few data exist on the prevalence and outcomes of varenicline treatment among smokers with comorbid substance use and psychiatric disorders. We reviewed all patient charts of opioid-dependent smokers prescribed varenicline between May 2006 and December 2009 in two urban methadone clinics that also provide on-site medical and psychiatric care. We assessed prevalence, adverse events, and effectiveness of varenicline treatment in this cohort. We identified 575 smokers among 690 patients (83.3%), and assessed 82 courses of varenicline treatment prescribed to 70 smokers. Both cardiovascular risk factors and psychiatric illness were highly prevalent among those prescribed varenicline: hypertension, 51%; hyperlipidemia, 23%; diabetes, 20%; depression, 53%; anxiety, 30%; psychotic disorders, 10%; bipolar disorder, 8.6%. Of 82 varenicline courses, nine (11%) were discontinued due to adverse events and two due to depressive symptoms. One patient initiated new psychiatric medications within six months of initiating varenicline, but did not discontinue varenicline. There were no reports of suicidal ideation, agitation prompting clinical intervention, or psychiatric hospitalization. There were no incident cardiac or vascular events within six months of varenicline prescription. Some (8.6%) varenicline-treated smokers quit smoking, and cessation was significantly associated with varenicline treatment duration. Despite substantial comorbidity, opioid-dependent smokers receiving integrated substance abuse, medical and psychiatric care had few documented adverse events with varenicline treatment. Methadone patients will likely experience little harm and a great deal of benefit from treatment with varenicline for smoking cessation.


Thymosin β4 Prevents Angiotensin II-Induced Cardiomyocyte Growth by Regulating Wnt/WISP Signaling.
Thymosin beta-4 (Tβ4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. However, the role of Tβ4 in cardiomyocyte hypertrophy is currently unknown. The purpose of this study was to determine the cardio-protective effect of Tβ4 in angiotensin II (Ang II)-induced cardiomyocyte growth. Neonatal rat ventricular cardiomyocytes (NRVM) were pretreated with Tβ4 followed by Ang II stimulation. Cell size, hypertrophy marker gene expression and Wnt signaling components, β-catenin, and Wnt-induced secreted protein-1 (WISP-1) were evaluated by quantitative real-time PCR, Western blotting and fluorescent microscopy. Pre-treatment of Tβ4 resulted in reduction of cell size, hypertrophy marker genes and Wnt-associated gene expression, and protein levels; induced by Ang II in cardiomyocyte. WISP-1 was overexpressed in NRVM and, the effect of Tβ4 in Ang II-induced cardiomyocyte growth was evaluated. WISP-1 overexpression promoted cardiomyocytes growth and was reversed by pretreatment with Tβ4. This is the first report which demonstrates that Tβ4 targets Wnt/WISP-1 to protect Ang II-induced cardiomyocyte growth. J. Cell. Physiol. 231: 1737-1744, 2016. © 2015 Wiley Periodicals, Inc.


The inferences of common causes reduced to common origins.
This paper advocates the reduction of the inference of common cause to that of common origins. It distinguishes and subjects to critical analysis thirteen interpretations of "the inference of common cause" whose conclusions do not follow from their assumptions. Instead, I introduce six types of inferences of common origins of information signals from their receivers to reduce, in the sense of supersede and replace, the thirteen inferences of common causes. I show how the paradigmatic examples of inferences of common cause, as well as a broader scope of inferences in the historical sciences, are better explained by inferences of origins. Inferences of origins from information rich coherences between receivers of information signals both fit more closely and explain better the range of examples that have traditionally been associated with inferences of common causes, as well as a broader scope of examples from the historical sciences. Shannon's concept of information as reduction in uncertainty, rather than physicalist concepts of information that relate it to entropy or waves, simplifies the inferences, preempts objections, and avoids the underdetermination of conclusions that challenge models of inferences of common causes. In the second part of the paper I model inferences of common origins from information preserved in their receivers. I distinguish information poor inferences that there were some common origins of receivers from the information richer inferences of ranges of possible common origins and the information transmission channels by which they transmitted signals to receivers. Lastly and most information rich, I distinguish the inference of the defining properties of common origins. The information transmission model from origins to receivers allows the reconceptualization of the concepts of "independence" as absence of intersections between information channels and "reliability" as the preservation of information from origins in receivers. Finally, I show how inferences of origins form the epistemic basis of the historical sciences.


Effect of olive leaf extract marination on heterocyclic aromatic amine formation in pan-fried salmon.
In this study, the reducing effects of varying levels of olive leaf extract (0%, 0.25%, 0.5%, 1% and 2%) on the formation of heterocyclic aromatic amines (HAAs) in pan-cooked salmon at 180 and 220 °C were examined. All salmon samples were analyzed for ten HAAs: IQx, IQ, MeIQx, MeIQ, 4,8-DiMeIQx, 7,8-DiMeIQx, PhIP, AαC, MeAαC and Trp-P-2. The most abundant HAA was MeIQ (≤2.98 ng g-1 ) followed by Trp-P-2 (≤2.40 ng g-1 ), MeIQx (≤0.83 ng g-1 ), IQ (≤0.41 ng g-1 ), 7,8-DiMeIQx (≤0.29 ng g-1 ), 4,8-DiMeIQx (≤0.16 ng g-1 ) and IQx (≤0.06 ng g-1 ). However, PhIP, AαC and MeAαC were undetectable in all samples. In the control samples, HAAs were found at levels ranging from not detected to 2.40 ng g-1 . Total HAA content was between 0.81 and 4.03 ng g-1 . The olive leaf extracts reduced the total HAA levels at all certain concentration levels at 180 °C and the reducing effects were found to be 32.78-77.69%. The current study displayed that olive leaf extracts could be efficient when added in up to 1% concentration prior to cooking for reducing HAA formation without changing organoleptic characteristics of salmon. © 2021 Society of Chemical Industry.


Exploring the Masculine Identity in the Context of HIV Prevention in Chile.
This study aims to describe human immunodeficiency virus (HIV)-related knowledge and beliefs, as well as understanding attitudes towards masculinity in the context of HIV prevention, held among Chilean men. This study reports the qualitative findings of a sequential qualitative-quantitative mixed methodology study: Bringing men into HIV Prevention in Chile, NIH R01 TW007674-03. Twenty in-depth interviews using a qualitative, descriptive approach to elicit information for the study were conducted among men residing in two communities of low socio-economic status in Santiago, Chile. Content analysis of interviews revealed three main themes regarding machismo and how it relates to HIV: sexuality and machismo, the changing nature of machismo, and violence against women. Addressing HIV and intimate partner violence through developing education programs tailored to meet the needs of Chilean men are needed to include men in HIV prevention efforts. Specifically, incorporating ideas of what men consider healthy masculinity and working to destigmatize men who have sex with men are important steps in addressing the negative aspects of machismo.


A 3-year natural history of orthostatic blood pressure dysregulation in early Parkinson's disease.
In Parkinson's disease (PD), cardiovascular dysautonomia accumulates with disease progression, but studies are lacking on the natural history behind each subtype except orthostatic hypotension. This study investigated the early natural history of orthostatic blood pressure (BP) subtypes in PD. Two hundred sixty-seven early PD patients were included. Their cardiovascular functions were assessed by head-up tilt-test and 123I-metaiodobenzylguanidine scintigraphy. All patients were classified as having supine hypertension (SH), orthostatic hypertension (OHT), delayed orthostatic hypotension (dOH), or orthostatic hypotension (OH) according to consensus criteria. The patients were assigned to one of three groups: extreme BP dysregulation (BPextreme), mild BP dysregulation (BPmild), and no BP dysregulation (BPnone) according to their orthostatic BP subtypes. The autonomic functions of 237 patients were re-assessed after approximately 3 years. Among initially enrolled subjects, 61.8% of the patients showed orthostatic BP dysregulation: 29.6% in the BPextreme group and 32.2% in the BPmild group. At follow-up, the BPextreme group increased in number, while the BPmild group diminished. Two-thirds of the initial BPextreme patients maintained their initial subtype at follow-up. In comparison, 40.7% of the initial BPmild patients progressed to the BPextreme group, and 32.4% and 14.7% of the initial BPnone group progressed to BPextreme and BPmild groups, respectively. Cardiac denervation was most severe in the BPextreme group, and a linear gradient of impairment was observed across the subtypes. In conclusion, various forms of positional BP dysregulation were observed during the early disease stage. SH and OH increased with disease progression, while OHT and dOH decreased, converting primarily to SH and/or OH.


Evaluation of thermal formation and air ventilation inside footwear during gait: The role of gait and fitting.
Comfort is an important concept in footwear design. The microclimate inside footwear contributes to the perception of thermal comfort. To investigate the effect of ventilation on microclimate formation inside footwear, experiments with subjects were conducted at four gait speeds with three different footwear sizes. Skin temperature, metabolism, and body mass were measured at approximately 25 °C and 50% relative humidity, with no solar radiation and a calm wind. The footwear occupancy and ventilation rate were also estimated, with the latter determined using the tracer gas method. The experimental results revealed that foot movement, metabolism, evaporation, radiation, convection, and ventilation were the main factors influencing the energy balance for temperature formation on the surface of the foot. The cooling effect of ventilation on the arch temperature was observed during gait. The significance of the amount of air space and ventilation on the improvement in the thermal comfort of footwear was clarified.


Effects of Gluten Intake on Risk of Celiac Disease: A Case-Control Study on a Swedish Birth Cohort.
Early nutrition may affect the risk of celiac disease. We investigated whether amount of gluten in diet until 2 years of age increases risk for celiac disease. We performed a 1-to-3 nested case-control study of 146 cases, resulting in 436 case-control pairs matched for sex, birth year, and HLA genotype generated from Swedish children at genetic risk for celiac disease. Newborns were annually screened for tissue transglutaminase autoantibodies (tTGA). If tested tTGA positive, time point of seroconversion was determined from frozen serum samples taken every 3 months. Celiac disease was confirmed by intestinal biopsies. Gluten intake was calculated from 3-day food records collected at ages 9, 12, 18 and 24 months. Odds ratios (OR) were calculated through conditional logistic regression. Breastfeeding duration (median, 32 wk) and age at first introduction to gluten (median, 22 wk) did not differ between cases and tTGA-negative controls. At the visit before tTGA seroconversion, cases reported a larger intake of gluten than controls (OR, 1.28; 95% confidence interval [CI], 1.13-1.46; P = .0002). More cases than controls were found in the upper third tertile (ie, >5.0 g/d) before they tested positive for tTGA seroconversion than controls (OR, 2.65; 95% CI, 1.70-4.13; P < .0001). This finding was similar in children homozygous for DR3-DQ2 (OR, 3.19; 95% CI, 1.61-6.30; P = .001), heterozygous for DR3-DQ2 (OR, 2.24; 95% CI, 1.08-4.62; P = .030), and for children not carrying DR3-DQ2 (OR, 2.43; 95% CI, 0.90-6.54; P = .079). The amount of gluten consumed until 2 years of age increases the risk of celiac disease at least 2-fold in genetically susceptible children. These findings may be taken into account for future infant feeding recommendations.


Transport and cellular uptake of polychlorinated biphenyls (PCBs)--II. Changes in vivo in plasma lipoproteins and proteins of pigeons in response to PCBs, and a proposed model for the transport and cellular uptake of PCBs.
The complex distribution of polychlorinated biphenyl (PCB) isomers and congeners amongst plasma fractions of the pigeon suggests that the lipid and apolipoprotein components of lipoproteins, as well as plasma proteins, may be important in transporting PCBs to tissues (Borlakoglu et al., Biochem. Pharmac. 40, 265 (1990]. Pigeons were injected with the commercial PCB mixture Aroclor 1254 (1.5 mmol/kg body weight). After 120 hr triacylglycerol-like droplets accumulated in hepatocytes ('fatty liver syndrome'), there was proliferation of the hepatic smooth endoplasmic reticulum, and plasma concentrations of triacylglycerol and total cholesterol increased. This was accompanied by significant decreases in plasma concentrations of total protein, total apolipoproteins of the low density lipoprotein (LDL) and the high density lipoprotein (HDL) fractions, and albumin and by a significant increase in that of urea, indicating increased protein breakdown. These results suggest that Aroclor 1254 increased hepatic lipid synthesis, but decreased hepatic production of albumin and apolipoproteins. This would explain the accumulation of triacylglycerol in the liver and the increase in the proportion of triacylglycerol to apolipoprotein in the total lipoproteins. From the evidence presented, a model is proposed based on the association of PCBs with hydrophobic domains of lipids and proteins for the transport of PCBs by plasma fractions, their uptake into cells and intracellular metabolism, and their accumulation in adipose tissue.


Prognostic value of electroencephalograms in asphyxiated newborns treated with hypothermia.
Previous studies described how early electroencephalogram patterns in neonatal hypoxic-ischemic encephalopathy seem to correlate with the severity of the clinical picture and provide prognostic information. This study evaluated whether electroencephalograms of newborns with severe perinatal hypoxic-ischemic encephalopathy, treated with hypothermia, provide information on clinical outcomes. Twenty-three newborns treated with hypothermia underwent electroencephalogram monitoring within 48 hours of age, and were enrolled in a follow-up with sequential electroencephalogram and neurologic controls (at ages 1 week, 1 month, 3-6 months, and 1 year). An inactive electroencephalogram pattern in the first 48 hours of age was associated with death or major neurologic sequelae. At age 1 week, a low-voltage, continuous pattern indicated a worse prognostic value when compared with other patterns. The persistence of electroencephalogram abnormalities at age 1 month was associated with a higher risk of neurologic sequelae. Background electroencephalogram abnormalities, detected in the first days of life after hypoxic-ischemic encephalopathy, can provide prognostic information, even in patients treated with hypothermia. After 1 month of age, the information on clinical outcomes provided by electroencephalograms usually decreases because of the natural trend toward electroencephalogram normalization.


Implementation of residue-level coarse-grained models in GENESIS for large-scale molecular dynamics simulations.
Residue-level coarse-grained (CG) models have become one of the most popular tools in biomolecular simulations in the trade-off between modeling accuracy and computational efficiency. To investigate large-scale biological phenomena in molecular dynamics (MD) simulations with CG models, unified treatments of proteins and nucleic acids, as well as efficient parallel computations, are indispensable. In the GENESIS MD software, we implement several residue-level CG models, covering structure-based and context-based potentials for both well-folded biomolecules and intrinsically disordered regions. An amino acid residue in protein is represented as a single CG particle centered at the Cα atom position, while a nucleotide in RNA or DNA is modeled with three beads. Then, a single CG particle represents around ten heavy atoms in both proteins and nucleic acids. The input data in CG MD simulations are treated as GROMACS-style input files generated from a newly developed toolbox, GENESIS-CG-tool. To optimize the performance in CG MD simulations, we utilize multiple neighbor lists, each of which is attached to a different nonbonded interaction potential in the cell-linked list method. We found that random number generations for Gaussian distributions in the Langevin thermostat are one of the bottlenecks in CG MD simulations. Therefore, we parallelize the computations with message-passing-interface (MPI) to improve the performance on PC clusters or supercomputers. We simulate Herpes simplex virus (HSV) type 2 B-capsid and chromatin models containing more than 1,000 nucleosomes in GENESIS as examples of large-scale biomolecular simulations with residue-level CG models. This framework extends accessible spatial and temporal scales by multi-scale simulations to study biologically relevant phenomena, such as genome-scale chromatin folding or phase-separated membrane-less condensations.


In light or dark grown Euglena gracilis cells, the DPG content, in contrast to the PG content, is dependent on the carbon source. These results are closely related to the electron microscopy observations, showing structural changes in mitochondria varying with the carbon source of the media.Two media have been used: the first one contains L-glutamic and DL-malic acid and the second contains DL-lactic acid. The phospholipidic analysis shows that PC and PE are the two main phospholipids.


Identification and characterization of IL-1 receptor-associated kinase-4 (IRAK-4) in half-smooth tongue sole Cynoglossus semilaevis.
As a crucial component in TLR/IL-1R signaling pathways, IRAK-4 plays a central role in innate and adaptive immunity. In the present study, the cDNA of IRAK-4 was cloned for the first time from half-smooth tongue sole (Cynoglossus semilaevis). The full-length cDNA of csIRAK-4 was 2149 bp and contained a 168 bp 5' UTR, a 580 bp 3' UTR and a 1401 bp CDS. The predicted protein sequence of csIRAK-4 had two typical domains, a death domain (DD) at the N terminus and a serine/threonine/tyrosine protein kinase domain (STYKc) at the C terminus. RT-PCR showed that csIRAK-4 mRNA was detected in all tested tissues, especially in immune-related organs, gonads and brain. After injected with inactivated Vibrio anguillarum, the expressions of csIRAK-4 were up-regulated significantly (P<0.05) in spleen and head kidney. During development, csIRAK-4 was expressed at all selected stages and low-level expression was detected at metamorphosis. Taken together, the present study indicated that csIRAK-4 played a crucial role in immune responses and might be involved in the process of development.


Nd:YAG laser pleurodesis through thoracoscopy: new curative therapy in spontaneous pneumothorax.
From January 1986 to May 1987, 14 patients with spontaneous pneumothorax were treated in our department with a new endoscopic method using neodymium:yttrium-aluminum-garnet laser photocoagulation through thoracoscopy. The 10 male and 4 female patients ranged in age from 14 to 59 years (mean age, 29 years). In all patients, the procedure was performed under general anesthesia. The thoracoscope was introduced through a 1- to 1.5-cm incision in the anterior axillary line of the fourth intercostal space. The fiber of the laser was advanced through the operative channel of the thoracoscope. In all patients, the bleb (or blebs) detected in the apex of the upper lobe was successfully coagulated with low-power laser pulses. Then the parietal pleura of the first five ribs was partially scarified to achieve pleurodesis. There were no side effects. Thirteen patients were successfully treated without recurrence (maximum follow-up, 29 months). We conclude that this new therapy can play an important role in select patients with spontaneous pneumothorax.


Synthesis, anti-inflammatory, and antiproliferative activity evaluation of isoindole, pyrrolopyrazine, benzimidazoisoindole, and benzimidazopyrrolopyrazine derivatives.
A number of isoindole (3x, 3y, 6xa-6ye), pyrrolopyrazine (3z, 6za-6ze), benzimidazoisoindole (4x, 4y, 7xa-7ye), and benzimidazopyrrolopyrazine (4z, 7za-7ze) derivatives has been synthesized in excellent yields. All these compounds were fully characterized and evaluated against five human cancer cell lines for their anti-inflammatory and antiproliferative activity. Compounds 6yc and 7zd exhibited good anti-inflammatory activity whereas compounds 6zc, 7zd (lung NCl H-522), 6ye, 7xd, 7yd, 7zc, 7zd (colon HCT-15), 6xc, 7zc (ovary PA-1), 6xc, 6yb, 6zc (liver HepG-2) exhibited good antiproliferative activity.


Selective analysis for adenosine using reversed-phase high-pressure liquid chromatography.
A high-pressure liquid chromatographic procedure for the selective determination of adenosine in the presence of other nucleic acid components is reported. Reversed-phase microparticle columns and an isocratic elution mode of dilute potassium dihydrophosphate and anhydrous methanol were used. The analysis is specific for adenosine and is achieved in less than 10 min. An example of the use of this analysis in a biomedical study is reported.


Mesenchymal chondrosarcoma. A cytogenetic, immunohistochemical and ultrastructural study.
A case of mesenchymal chondrosarcoma was studied. The tumor was near-tetraploid and the clonal structural chromosomal abnormalities included add(7)(p13), add(22)(q13), markers, and double minutes. The ultrastructural and immunohistochemical findings were consistent with the diagnosis. Strong immunoreactivity for desmin was an unusual, not previously reported, feature of the neoplasm.


Facial onset sensory and motor neuropathy in a pain clinic outpatient: a case report.
Facial onset sensory and motor neuropathy is a very rare sensorimotor disorder characterized by facial onset and gradual progression, with approximately 100 cases reported worldwide in 2020. We report on our experience with a facial onset sensory and motor neuropathy case in our outpatient pain clinic. A 71-year-old Japanese man with a previous diagnosis of trigeminal nerve palsy complained of facial paresthesia, cervical pain, and arm numbness. Cervical facet arthropathy was diagnosed initially, but neither pharmacotherapy nor nerve blocking alleviated his symptoms. We suspected bulbar palsy based on the presence of tongue fasciculation, which prompted referral to a neurologist. Based on a series of neurological examinations, facial onset sensory and motor neuropathy was ultimately diagnosed. Pain clinicians must be mindful of rare diseases such as facial onset sensory and motor neuropathy; if they are unable to make a diagnosis, they should consult with other competent specialists.


Vancomycin dosing and target attainment in children.
The aim of this study is to determine the best dosing strategy for vancomycin by studying the associated factors and examining correlations between the area under the plasma concentration-time curve (AUC) values and trough concentrations in children. Children aged 3 months to 18 years were included if they received vancomycin for more than three doses between January 1, 2010 and December 31, 2012 and had one or more serum vancomycin trough concentrations. Vancomycin clearance (CL) was calculated using the following model: CL = 0.248*Wt0.75*(0.48/serum creatinine)0.361*[ln (age)/7.8]0.995. The AUC (mg-h/L) was calculated by 24-hour dose (mg/kg/d)/CL(L/h). The value of AUC divided by the minimum inhibitory concentration (MIC) of vancomycin was AUC/MIC. A total of 218 children were included. The mean age was 6.0 ± 5.1 years and the mean body weight was 20 ± 11.7 kg. Vancomycin trough concentrations were moderately correlated with AUC values (r2 = 0.232, p < 0.01). Dosing of 15 mg/kg/dose q6h produced significantly higher AUC values (p < 0.001) and vancomycin trough concentrations (p < 0.001) compared to dosing of 10 mg/kg/dose q6h. In children receiving a 10-mg/kg/dose q6h, 5.6% (5/90) achieved the target trough concentrations of 15-20 μg/mL and 9.5% (5/90) achieved the goal AUC/MIC ≥ 400. In children receiving a 15-mg/kg/dose q6h, 13% (6/46) achieved the target trough concentrations of 15-20 μg/mL, whereas 54.3% (25/46) achieved the goal AUC/MIC ≥ 400. A 15-mg/kg/dose q6h compared to a 10-mg/kg/dose q6h is more likely to achieve target trough concentrations of 15-20 μg/mL and the goal AUC/MIC ≥ 400.


Modulation of pain transmission by G-protein-coupled receptors.
The heterotrimeric G-protein-coupled receptors (GPCR) represent the largest and most diverse family of cell surface receptors and proteins. GPCR are widely distributed in the peripheral and central nervous systems and are one of the most important therapeutic targets in pain medicine. GPCR are present on the plasma membrane of neurons and their terminals along the nociceptive pathways and are closely associated with the modulation of pain transmission. GPCR that can produce analgesia upon activation include opioid, cannabinoid, alpha2-adrenergic, muscarinic acetylcholine, gamma-aminobutyric acidB (GABAB), groups II and III metabotropic glutamate, and somatostatin receptors. Recent studies have led to a better understanding of the role of these GPCR in the regulation of pain transmission. Here, we review the current knowledge about the cellular and molecular mechanisms that underlie the analgesic actions of GPCR agonists, with a focus on their effects on ion channels expressed on nociceptive sensory neurons and on synaptic transmission at the spinal cord level.


Effects of konjac glucan-nan/low-acyl gellan edible coatings loaded thymol-β-cyclodextrin microcapsules on postharvest blueberry.
This study developed an edible antimicrobial coating using a blend of konjac glucomannan (KGM) and low acyl gellan gum (LAG) hydrogel to incorporate thymol nanoparticles (TKL). The optimized TKL formulation (TKL60) comprised 0.22% thymol microcapsules (TMs), 0.075% total polysaccharide content (KGM:LAG = 1:2), and 99.63% distilled water. When applied to blueberries, TKL60 significantly extended their shelf life to 42 d at 2 ± 0.5 °C, tripling that of control fruit. TKL60 reduced decay rate, weight loss, and respiration rate, delayed softening and senescence during cold storage. It preserved the outer epidermis by retaining cuticular waxes, curbing lipid oxidation, and sustaining defense-related enzyme activities. Flavor analysis revealed altered volatile compound concentrations in TKL60-treated berries, including decreased terpenes and benzaldehyde, and increased esters and aldehydes like 2-methylbutanol, 3-methylbutanol, and linalool. Discriminant Analysis highlighted TKL60's efficacy in delaying aroma deterioration by over 21 d. TKL60 exhibits potential as a substitute for synthetic coatings and chemical insecticides.


Enlarging amniotic fluid 'sludge' in preterm labor associated with severe course of sepsis and recurrent tension pneumothorax in the infant.
Amniotic fluid 'sludge' (AFS) is defined as the presence of dense aggregates of hyperechogenic material in close proximity to the internal cervical os. The presence of AFS is an independent risk factor for impending preterm delivery, histological chorioamnionitis, and microbial invasion of the amniotic cavity in patients with spontaneous preterm labor with intact membranes, and preterm prelabor rupture of membranes. We describe a case showing enlarging AFS on transvaginal ultrasound in a patient with impending preterm labor, followed by chorioamnionitis and emergency cesarean section at 28 weeks of gestation, resulting in a severe course of sepsis and recurrent tension pneumothorax in the infant. Such a case has not been reported as far as we know. Based on our case, sonographic findings of enlarging AFS may be a predictor of severe neonatal outcomes in a case with preterm labor even though the maternal symptoms of inflammation are not obvious.


Nurses' perception regarding patient safety climate and quality of health care in general hospitals in Japan.
To clarify perceptions of nurses towards patient safety climate and quality of health care in Japan. Nurses' perceptions of patient safety climate and quality of health care services are not well-known. The survey was conducted at general hospitals with 200 beds or more using the Patient Safety Climate Scale and the Modified multiple-item scale for consumer perceptions of health care service quality. Significant positive correlations were found among nurses' perception towards patient safety and health care service quality. The experience of nurses as members of the committee on patient safety and their employment position did not show any significant difference in the perception towards patient safety and health care services quality. Perceptions of health care service quality were lower among those with 6- to 10-year experience than with over 21 years. In the perception of nurses and nurse managers' continuous improvement, perceptions towards patient safety were related to reliability, assurance, responsiveness and empathy in health care service quality. Generalist nurses with 21 years or more experiences in multiple departments showed high perception towards health care service quality. Experienced nurses' perceptions of activities to improve patient safety and quality of health care services are important.


The electrochemical and fluorescence detection of nitric oxide in the cochlea and its increase following loud sound.
A nitric oxide (NO)-selective sensor (tip diameter 30 microm) was inserted into the perilymph of the basal turn of the guinea pig cochlea. The basal level and stimulation-induced changes of NO were measured. The mean (+/-S.E.M.) basal level of NO was 273+/-42.9 nM. Following perilymphatic perfusion of the artificial perilymph containing NO synthase (NOS) substrate L-arginine (100 microM) combined with cofactor (6R)-5,6,7,8-tetrahydrobiopterin dihydrochloride (100 microM), a rapid and significant increase of NO to a mean concentration of 392+/-32.3 nM (P < 0.01, n = 10) was recorded. In contrast, a significant decrease of mean NO concentration to 180+/-32.7 nM (P < 0.01, n = 10) was observed following the perfusion of the NOS-inhibiting agent N(G)-nitro-L-arginine methyl ester (100 microM). No change in the NO concentration was found following the perfusion of either artificial perilymph or N(G)-monomethyl-D-arginine (100 microM) solution employed as controls. Broadband noise exposure (3 h/day at 120 dBA SPL) for three consecutive days produced an increase in NO concentration to 618+/-60.7 nM (P < 0.05, n = 10) in the perilymph. In addition, by using specific dyes for NO, 4,5-diaminofluoresceine diacetate and for the reactive oxygen species (ROS), dihydrorhodamine 1,2,3, the distribution of NO in the whole mounts of the organ of Corti and the production of ROS in vivo in the organ of Corti were investigated in both control (n = 5) and noise-exposed (n = 5) animals. The more intense NO and ROS fluorescence was observed in both the inner and outer hair cells in the noise-exposed groups. It is proposed that both the basal level and the increase in NO concentration following the addition of substrate (L-arginine) are produced by the constitutive NOS while the elevated NO and ROS following noise exposure indicate that NO may be involved in noise-induced hearing loss.


Dense-gas chromatography of nonvolatile substances of high molecular weight.
Working at pressures of up to 2000 atmospheres, more than ten times higher than in previous gas chromatography, we used the solvent power of dense gases to enable migration of chromatographic substances of molecular weights as high as 400,000. Carotenoids, corticol steroids, sterols, nucleosides, amino acids, carbohydrates, and several polymers have been caused to migrate, separated, and detected in NH(3) and CO(2) carrier gases at temperatures of 140 degrees and 40 degrees C, just above the respective critical points. Previously such compounds either defied separation by gas chromatography or had to be chromatographed as their more volatile derivatives.


Coronary computed tomography angiography (CCTA): effect of bolus-tracking ROI positioning on image quality.
The aim of the study was to evaluate the effect of bolus-tracking ROI positioning on coronary computed tomography angiography (CCTA) image quality. In this retrospective monocentric study, all patients had undergone CCTA by step-and-shoot mode to rule out coronary artery disease within a cohort at intermediate risk. Two groups were formed, depending on ROI positioning (left atrium (LA) or ascending aorta (AA)). Each group contained 96 patients. To select pairs of patients, propensity score matching was used. Image quality with regard to coronary arteries as well as pulmonary arteries was evaluated using quantitative and qualitative scores. In terms of the coronary arteries, there was no significant difference between both groups using quantitative (SNR AA 14.92 vs. 15.46; p = 0.619 | SNR LM 19.80 vs. 20.30; p = 0.661 | SNR RCA 24.34 vs. 24.30; p = 0.767) or qualitative scores (4.25 vs. 4.29; p = 0.672), respectively. With regard to pulmonary arteries, we found significantly higher quantitative (SNR RPA 8.70 vs. 5.89; p < 0.001 | SNR LPA 9.06 vs. 6.25; p < 0.001) and qualitative scores (3.97 vs. 2.24; p < 0.001) for ROI positioning in the LA than for ROI positioning in the AA. ROI positioning in the LA or the AA results in comparable image quality of CT coronary arteriography, while positioning in the LA leads to significantly higher image quality of the pulmonary arteries. These results support ROI positioning in the LA, which also facilitates triple-rule-out CT scanning. • ROI positioning in the left atrium or the ascending aorta leads to comparable image quality of the coronary arteries. • ROI positioning in the left atrium results in significantly higher image quality of the pulmonary arteries. • ROI positioning in the left atrium is feasible to perform triple-rule-out CTA.


Acute and chronic clinical performance comparison of a porous and a solid electrode design.
The long-term performance of porous and solid ring-tipped electrodes was compared in clinical use over a one-year period. Each of the two electrode designs was implanted in 22 patients in conjunction with an output-programmable pacemaker. Implant evaluation included impedance, height of sensed R wave, and a strength-duration curve. Threshold determination by pulse-width programming was performed at the time of implant and at one week, two weeks, two months, six months, and one year. There were no dislodgements with either electrode. No significant differences were noted in the acute parameters or in chronic thresholds.


Cytostatic and reverse-transforming therapies of cancer - a brief review and future prospects.
Cytostatic cancer therapies are defined as those which retard cancer growth by intervening selectively in the disordered control mechanisms responsible for malignant behavior, without producing direct cytotoxicity. A number of possible approaches to cytostatic therapy are now under investigation and are briefly reviewed here - cyclic AMP congeners and promoters, prostaglandin precursors, thioproline, benzaldehyde, retinoids, interferon, chalones, antineoplastons, protease inhibitors, polar solvents. Suggestions for the further development of cytostatic therapies are offered, and a role for cytostatic therapy within a broad global concept of cancer therapy is proposed.


MCA/MR syndrome with hypocholesterolemia related to familial dominant hypobetalipoproteinemia.
Recent reports have emphasized the role of cholesterol in vertebrate embryonic development. The RSH or so-called Smith-Lemli-Opitz syndrome (SLOS) was the first multiple congenital anomalies/mental retardation syndrome related to a cholesterol synthesis disturbance. Familial hypobetalipoproteinemia is a well-known dominantly inherited entity in which affected individuals usually are free of symptoms. We report on the unusual association of a malformation syndrome with mental retardation resembling SLOS and profound hypocholesterolemia related to familial hypobetalipoproteinemia. We discuss the possible causal relationship between the two conditions and the current understanding of the role of cholesterol in normal embryogenesis.


[A tongue biopsy led to the diagnosis].
A 76-year-old patient in otherwise good health presented with a 2-year history of bilateral painless submandibular swelling and macroglossia. A standard ENT examination revealed no additional symptoms. Tongue biopsy led to the diagnosis of amyloidosis, serum immunofixation identified AL amyloidosis and a kappa light chain gammopathy resulting from multiple myeloma as the underlying cause.


Persistent tardive dyskinesia and neuroleptic effects on glucose tolerance.
The relations of persistent tardive dyskinesia (TD) to glucose tolerance and family history of type 2 diabetes mellitus (FH-NIDDM) were examined in 22 schizophrenic patients. All patients underwent a standard oral glucose tolerance test (GTT) while receiving haloperidol, and 15 patients also underwent a GTT when drug free. Fasting blood glucose (FBS) was significantly higher in the TD group than in the non-TD group in the medicated condition, but not in the drug-free state. TD and non-TD groups did not differ significantly in postload glucose levels either in the drug-free or in the medicated condition. However, relative to the drug-free state, haloperidol-treated TD patients showed decreased glucose tolerance while non-TD patients showed increased glucose tolerance. Seven (32%) of the 22 patients had an FH-NIDDM. A positive FH-NIDDM was significantly associated with the presence of TD and with higher drug-free FBS. A possible role of melatonin in mediating the TD-augmenting effects of FH-NIDDM and the neuroleptic-induced decrease in glucose tolerance has been proposed.


In-line monitoring of a pharmaceutical blending process using FT-Raman spectroscopy.
FT-Raman spectroscopy (in combination with a fibre optic probe) was evaluated as an in-line tool to monitor a blending process of diltiazem hydrochloride pellets and paraffinic wax beads. The mean square of differences (MSD) between two consecutive spectra was used to identify the time required to obtain a homogeneous mixture. A traditional end-sampling thief probe was used to collect samples, followed by HPLC analysis to verify the Raman data. Large variations were seen in the FT-Raman spectra logged during the initial minutes of the blending process using a binary mixture (ratio: 50/50, w/w) of diltiazem pellets and paraffinic wax beads (particle size: 800-1200 microm). The MSD-profiles showed that a homogeneous mixture was obtained after about 15 min blending. HPLC analysis confirmed these observations. The Raman data showed that the mixing kinetics depended on the particle size of the material and on the mixing speed. The results of this study proved that FT-Raman spectroscopy can be successfully implemented as an in-line monitoring tool for blending processes.


Specific surface modification of the acetylene-linked glycolipid vesicle by click chemistry.
A novel glycolipid with a terminal acetylene was synthesized and used to prepare unilamellar vesicles. Using these vesicles, a convenient method was developed for the specific modification of the vesicle surface using the photoresponsive copper complex [Cu(OH(2))(cage)] as the catalyst for a click reaction.


Characterization of NDM-1- and OXA-23-producing Acinetobacter baumannii isolates from inanimate surfaces in a hospital environment in Algeria.
Investigation of several outbreaks of multidrug-resistant Acinetobacter baumannii infection has demonstrated that contamination of the inanimate hospital environment could be implicated in the spread of these multidrug-resistant strains. To investigate the occurrence of carbapenem-resistant A. baumannii on inanimate surfaces and possible dissemination in the hospital environment in Algeria as a potential source of infection in humans. A. baumannii strains were isolated from the hospital environment and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined using disc diffusion and E-test methods. Carbapenemase activity was detected using microbiological tests, including modified Hodge test, modified Carba NP test, and EDTA test. Carbapenem resistance determinants were studied by polymerase chain reaction (PCR) and sequencing. Clonal relatedness was determined using multi-locus sequence typing (MLST). A total of 67 A. baumannii isolates were obtained from 868 environmental samples and identified by MALDI-TOF MS. Among them, 61 isolates were resistant to imipenem with minimum inhibitory concentration >32 μg/mL and positive by the modified Hodge test and modified Carba NP test. In addition, the activity of carbapenemase was inhibited by EDTA in 32 strains. PCR and sequencing showed the presence of blaOXA-23 gene in 29 strains, and the blaNDM-1 gene in 32 isolates. MLST demonstrated the presence of five types of ST (ST19, ST2, ST85, ST98, and ST115). Our study demonstrated the dissemination of carbapenemase-producing A. baumannii strains recovered from inanimate surfaces in a hospital environment, surrounding patients, healthcare workers and visitors, in Algeria as a potential source for nosocomial infection.


Insulin-like growth factor I (IGF-I)-induced chronic gliosis and retinal stress lead to neurodegeneration in a mouse model of retinopathy.
Insulin-like growth factor I (IGF-I) exerts multiple effects on different retinal cell types in both physiological and pathological conditions. Despite the growth factor's extensively described neuroprotective actions, transgenic mice with increased intraocular levels of IGF-I showed progressive impairment of electroretinographic amplitudes up to complete loss of response, with loss of photoreceptors and bipolar, ganglion, and amacrine neurons. Neurodegeneration was preceded by the overexpression of genes related to retinal stress, acute-phase response, and gliosis, suggesting that IGF-I altered normal retinal homeostasis. Indeed, gliosis and microgliosis were present from an early age in transgenic mice, before other alterations occurred, and were accompanied by signs of oxidative stress and impaired glutamate recycling. Older mice also showed overproduction of pro-inflammatory cytokines. Our results suggest that, when chronically increased, intraocular IGF-I is responsible for the induction of deleterious cellular processes that can lead to neurodegeneration, and they highlight the importance that this growth factor may have in the pathogenesis of conditions such as ischemic or diabetic retinopathy.


Availability and use of services for maternal and child health care in rural Nigeria.
A personal in-home interview was conducted in four rural towns in Nigeria. The aims of the interview were to describe the content of Maternal and Child Health (MCH) care in these rural towns and to assess how patterns of prenatal, delivery and postnatal service use are related to a variety of demographic and socioeconomic variables in the population. Findings from data analysis indicate that services available are deficient in terms of the number of centers and content of care. Variables found to be statistically significant (P less than 0.01) for use of services are maternal education, occupation, distance and previous use of a physician. Husband's occupation was significant only for prenatal registration, but not for subsequent use of services. Recommendations include a reorganization of rural MCH services and an introduction of female literacy programs, especially at the rural level.


Phenylephrine to increase blood flow in the radial artery used as a coronary bypass conduit.
The radial artery has more smooth muscle in its wall than the other arterial conduits and is known to be vasospastic. Because it is frequently necessary to use vasoconstrictors early after coronary bypass surgery we investigated the effects of phenylephrine on conduit flow in this setting. Thirty patients undergoing coronary artery bypass with all arterial conduits in which the radial artery was used as a T-graft were randomly assigned to receive intravenous infusions of normal saline (n = 10); nitroglycerin, 0.5 microg x kg x min (n = 11); or nicardipine, 0.5 microg x kg x min (n = 9), beginning early in the operation. After discontinuation of cardiopulmonary bypass and achievement of stable hemodynamics, control measurements were obtained, and this was followed by phenylephrine infusion to achieve a 20% increase in mean arterial pressure, after which the measurements were repeated. Mean radial artery flow increased similarly in all groups: normal saline, 40% +/- 25%; nicardipine, 37% +/- 27%; nitroglycerin, 48% +/- 36% (P = .533). Comparable changes occurred in arterial pressure and systemic vascular resistance, whereas the cardiac index remained unchanged. Radial artery blood flow increases when the mean arterial pressure is increased with phenylephrine. There was no evidence of a conduit vasoconstrictive effect, which could limit or reduce conduit flow. Vasoconstriction with phenylephrine is appropriate to provide adequate perfusion pressure for radial artery grafts.


Burden, predictors, and outcome of unconsciousness among under-five children hospitalized for community-acquired pneumonia: A retrospective study from a developing country.
Despite the reduction of death from pneumonia over recent years, pneumonia has still been the leading infectious cause of death in under-five children for the last several decades. Unconsciousness is a critical condition in any child resulting from any illness. Once it occurs during a pneumonia episode, the outcome is perceived to be fatal. However, data on children under five with pneumonia having unconsciousness are scarce. We've retrospectively analyzed the data of under-five children admitted at the in-patient ward of Dhaka Hospital of icddr,b during 1 January 2014 and 31 December 2017 with World Health Organization classified pneumonia or severe pneumonia. Children presented with or without unconsciousness were considered as cases and controls respectively. Among a total of 3,876 children fulfilling the inclusion criteria, 325 and 3,551 were the cases and the controls respectively. A multivariable logistic regression analysis revealed older children (8 months vs. 7.9 months) (adjusted odds ratio, aOR 1.02, 95% CI: 1.004-1.04, p = 0.015), hypoxemia (aOR 3.22, 95% CI: 2.39-4.34, p<0.001), severe sepsis (aOR 4.46, 95% CI: 3.28-6.06, p<0.001), convulsion (aOR 8.90, 95% CI: 6.72-11.79, p<0.001), and dehydration (aOR 2.08, 95% CI: 1.56-2.76, p<0.001) were found to be independently associated with the cases. The cases more often had a fatal outcome than the controls (23% vs. 3%, OR 9.56, 95% CI: 6.95-13.19, p<0.001). If the simple predicting factors of unconsciousness in children under five hospitalized for pneumonia with different severity can be initially identified and adequately treated with prompt response, pneumonia-related deaths can be reduced more effectively, especially in resource-limited settings.


Identification of novel monoclonal antibodies targeting the outer membrane protein C and lipopolysaccharides for Escherichia coli O157:H7 detection.
To identify and evaluate the application of two novel monoclonal antibody (mAb) 2G12 against outer membrane protein (Omp) C and mAb 12B1 targeting the O chain of the lipopolysaccharides (LPS) of Escherichia coli O157:H7 (ECO157). The sensitivity and specificity of these two antibodies were evaluated with eight ECO157 strains and 68 untargeted strains. mAb 2G12 and 12B1 had no detectable binding with any of the non-O157 strains at 6·0 log10 CFU per ml, while its high specificity and affinity remained with all ECO157 strains. When a higher level (8·0 log10 CFU per ml) was tested, 2G12 and 12B1 did not react with 82·35 and 97·06% of the non-O157 strains respectively. Based on the pair of two antibodies, the sandwich enzyme-linked immunosorbent assay detected 100% (8/8) of ECO157 strains and none of the non-ECO157 strains. The detection limit of ECO157 strains in pure culture were 4·2 ± 0·2 log10 CFU per ml. When the developed test was applied to artificially inoculated beef samples, the detection limit was 6·0 log10 CFU per gram without enrichment and 1·0 log10 CFU per gram after 12 h of enrichment. The two novel antibodies identified in this study served as great candidates for the recovery, and detection of ECO157 from different environmental and food samples. ECO157-specific detection was improved by a combination of the novel OmpC mAb and LPS mAb with defined target antigen and good specificity.


Degos disease - malignant atrophic papulosis or cutaneointestinal lethal syndrome: rarity of the disease.
Degos disease is a very rare syndrome with a rare type of multisystem vasculopathy of unknown cause that affects the skin, gastrointestinal tract, and central nervous system. Other organs such as the kidneys, lungs, pleura, liver, heart, and eyes, can also be involved. To highlight the incidence of Degos disease with regard to age and sex, discuss the necessity of its accurate and early diagnosis, and demonstrate the most current techniques for its diagnosis; to discuss whether early therapeutic intervention can impact patient prognosis; and to present a literature review about this disease. With a retrospective, observational, nonrandomized trial, we described the evolution of the different forms of Degos disease and referenced the literature. Research on rare documented cases in the literature, including two cases of potentially lethal form of the disease involving the skin and gastrointestinal system and, possibly, the lungs, kidneys, and central nervous system. A case of the benign form of the disease involving the skin was observed by the authors. Differences between outcomes in patients with the cutaneointestinal form and skin-only form of the disease. There was one fatal outcome. We reviewed possible new approaches to diagnosis and treatment. The study demonstrated the rapid evolution of the aggressive and malignant form of the disease. It also described newly accessible Phase I diagnostic tools being currently researched as well as new therapeutic approaches. The rarity of the disease, with only eleven cases throughout the literature. The gastrointestinal form of Degos disease can be lethal. Its vascular etiology has finally been confirmed; however, new and more accurate early diagnostic modalities need to be developed. There are new therapeutic possibilities, but the studies of them are still in the early stages and have not yet shown the full effectiveness of these new therapies.


[Anhedonia as target symptom in personalized therapy of patients with mood disorders and alcohol use disorder comorbidity].
To estimate the efficacy of antidepressants in the treatment of anhedonia in mood disorders (MD) comorbid with alcohol use disorder (AUD), considering melatonin concentration in the patient's blood serum. Seventy patients, aged 18-65 years old, with MD, including patients with- (group F3+F10, n=36) or without comorbid AUD (group F3, n=34), were examined. Control group consisted of 26 healthy volunteers. Clinical-dynamic evaluation was carried out using SIGH-SAD and SHAPS-C. Melatonin concentration was measured with MAGPIX analyzer (Luminex, USA). The statistical analysis was carried out using the SPSS (V. 23.0) standard package. In the case of MD/AUD comorbidity anhedonia symptom does not respond well to psychopharmacotherapy during four weeks (p=0.192, Wilcoxon test) whereas anhedonia in «pure» MD does (p=0.007, Wilcoxon test). At the same time, only patients with «pure» MD have a statistically significant decrease in melatonin concentration in blood serum compared with the control group (p=0.025, p=0.031, Mann-Whitney test), on the contrary, in the case of MD/AUD comorbidity, a relative increase in melatonin concentration (p>0.05 Mann-Whitney test) was demonstrated. The relatively low response of anhedonia symptom in the case of MD/AUD comorbidity compared with the «pure» MD, makes perspective using antidepressants with prodophaminergic mechanism of action in this cohort of patients. Furthermore, in MD/AUD comorbidity, contrary to «pure» MD, a relative increase in melatonin concentration in blood serum was detected, therefore it could be a limitation to prescribing antidepressants directly or indirectly modulating melatoninergic system.


At least 104 nucleotides are transposed from the 5' terminus of the avian sarcoma virus genome to the 5' termini of smaller viral mRNAs.
Cells producing avian sarcoma virus (ASV) contain at least three virus-specific mRNAs, two of which are encoded within the 3' half of the viral genome. Each of these viral RNAs can hybridize with single-stranded DNA(cDNA5') that is complementary to a sequence of 101 nucleotides found at the 5' terminus of the ASV genome, but not within the 3' half of the genome. We proposed previously (Weiss, Varmus and Bishop, 1977) that this nucleotide sequence may be transposed to the 5' termini of viral mRNAs during the genesis of these RNAs. We now substantiate this proposal by reporting the isolation and chemical characterization of the nucleotide sequences complementary to cDNA5' in the genome and mRNAs of the Prague B strain of ASV. We isolated the three identified classes of ASVmRNA (38, 28 and 21S) by molecular hybridization; each class of RNA contained a "capped" oligonucleotide identical to that found at the 5' terminus of the ASV genome. When hybridized with cDNA5', each class of RNA gave rise to RNAase-resistant duplex hybrids that probably encompassed the full extent of cDNA5'. The molar yields of duplex conformed approximately to the number of virus-specific RNA molecules in the initial samples; hence most if not all of the molecules of virus-specific RNA could give rise to the duplexes. The duplexes prepared from the various RNAs all contained the capped oligonucleotide found at the 5' terminus of the viral genome and had identical "fingerprints" when analyzed by two-dimensional fractionation following hydrolysis with RNAase T1. In contrast, RNA representing the 3' half of the ASV genome did not form hybrids with cDNA5'. We conclude that a sequence of more than 100 nucleotides is transposed from the 5' end of the ASV genome to the 5' termini of smaller viral RNAs during the genesis of these RNAs. Transposition of nucleotide sequences during the production of mRNA has now been described for three families of animal viruses and may be a common feature of mRNA biogenesis in eucaryotic cells. The mechanism of transposition, however, and the function of the transposed sequences are not known.


In vivo regulation of the chicken cardiac troponin T gene promoter in zebrafish embryos.
The chicken cardiac troponin T (cTnT) gene is representative of numerous cardiac and skeletal muscle-specific genes that contain muscle-CAT (MCAT) elements within their promoters. We examined the regulation of the chicken cTnT gene in vivo in zebrafish embryos, and in vitro in cardiomyocyte, myoblast, and fibroblast cultures. Defined regions of the cTnT promoter were linked to the green fluorescent protein (GFP) gene for in vivo analysis, and the luciferase gene for in vitro analysis. Injection of the cTnT promoter constructs into fertilized zebrafish eggs resulted in GFP expression in both heart and skeletal muscle cells reproducing the pattern of expression of the endogenous cTnT gene in the chicken embryo. Promoter deletion analysis revealed that the cis-regulatory regions responsible for cardiac and skeletal muscle-specific expression functioned in an equivalent manner in both in vitro and in vivo environments. In addition, we show that mutation of the poly-ADP ribose polymerase-I (PARP-I) binding site adjacent to the distal MCAT element in the chicken cTnT promoter produced a non-cell-specific promoter in vitro and in the zebrafish. Thus, the PARP-I transcriptional regulatory mechanism that governs muscle specificity of the chicken cTnT promoter is conserved across several chordate classes spanning at least 350 million years of evolution.


Survival, momentum, and things that make me "me": patients' perceptions of goal setting after stroke.
Goal setting and patient-centredness are considered fundamental concepts in rehabilitation. However, the best way to involve patients in setting goals remains unclear. The purpose of this study was to explore patient experiences of goal setting in post-acute stroke rehabilitation to further understanding of its application to practice. Thematic analysis was used to analyse interview transcripts from 10 stroke survivors, recruited from 4 rehabilitation units as part of a pilot study investigating the effects of a structured means of eliciting patient-centred goals in post-acute stroke rehabilitation. Three key themes emerged: (1) "A Day by Day Momentum", comprising subordinate themes of "Unpredictability" and "Natural Progression" in which daily progress forwards was seen as an integral part of rehabilitation; (2) "Battle versus Alliance" in which issues of struggle versus support influenced participants' advancement; and (3) "The Special Things", consisting of subordinate themes of "What Makes Me 'Me'" and "Symbolic Achievements" concerning issues defining individuals and their rehabilitation experiences. Patients' discourse around goal setting can differ from the discourse conventionally used by clinicians when describing "best practice" in rehabilitation goal setting. Understanding patients' non-conventional views of goals may assist in supporting and motivating them, thus providing drive for their rehabilitation. Stroke patients think about goals very differently from health professionals. Individual patients have diverse ideas about goals within the context of the uncertainty of stroke, their life as a whole and recovery after formal rehabilitation is completed. To meet these diverse needs, health professionals need to communicate fully with patients to gain an understanding of their experiences of stroke and wider views on goals.


dTap vaccination uptake during pregnancy: Pregnant women-focused and health professionals-focused predictors in the Veneto Region (Italy).
Despite recommendations, the uptake of dTap maternal vaccination is still low in many countries. The reasons for this must be investigated both on the patient's and the healthcare professionals' sides. A record linkage study was performed linking Birth Assitance Certificates and dTap mothers' vaccination records (5183 deliveries) to describe the influence of socioeconomical and obstetrical-gynecological factors after the recommendations concerning dTap vaccination in pregnancy issued by the Italian Ministry of Health (August 2018). An interview was also administered to a subgroup of 656 new mothers on the occasion of the first vaccination of their newborns, in order to assess the dTap vaccination advice received from maternal care providers during pregnancy. A generalized linear model (binomial family, log link) was implemented to give a correct estimate of the mother's relative risk of being vaccinated. Several pregnant women-focused factors are evident, but the most important ones are related to maternal care providers' practices: after mutual adjustment, the explicit advice towards dTap maternal vaccination given by the Obstetrician-Gynecologist or the Midwife is associated with a 12-fold increase in the dTap coverage. Multiprofessional training is essential to make Obstetricians-Gynecologists and Midwives more confident in recommending dTaP maternal immunization.


Clozapine and haloperidol differentially alter the constitutive activity of central serotonin2C receptors in vivo.
Central serotonin2C (5-HT2C) receptors are known to play a role in the mechanism of action of the antipsychotic drugs (APDs) clozapine and haloperidol. However, evidence for the involvement of the constitutive activity of 5-HT2C receptors in the dopamine (DA)ergic effects of APDs is lacking in vivo. Using in vivo microdialysis in halothane-anesthetized rats, we assessed the ability of selective 5-HT2C compounds to modulate the release of DA induced by haloperidol and clozapine in the nucleus accumbens and striatum. Both APDs induced a dose-dependent increase in accumbal and striatal DA extracellular levels. The effect of .01 mg/kg haloperidol was potentiated by the 5-HT2C inverse agonist SB 206553 (5 mg/kg) but unaltered by the 5-HT2C antagonists SB 243213 and SB 242084 (1 mg/kg). Conversely, the effect of 1 mg/kg clozapine, a dose able to reverse the decrease in DA outflow induced by the 5-HT2C agonist Ro 60-0175 (3 mg/kg), was unaffected by SB 206553 but blocked by SB 243213 (1 mg/kg) and SB 242084 (.3 and 1 mg/kg). These results show that clozapine and haloperidol differentially alter the constitutive activity of 5-HT2C receptors and suggest that clozapine behaves as a 5-HT2C inverse agonist in vivo.


MicroRNA-206 regulates cell proliferation by targeting G6PD in skeletal muscle.
Skeletal muscle is a major component of body mass and plays a central role in the control of whole-body metabolism in humans and animals. Therefore, elucidation of the underlying mechanisms of skeletal growth and development are expected to lead to the discovery of novel genes and pathways related to muscle disease. miR-206, a skeletal muscle-specific microRNA, plays a crucial role in myogenesis; however, miR-206 is known to function in myogenic differentiation, whether or not it affects muscle cells' proliferation, and the underlying mechanisms are unknown. In this study, we investigated the effect of miR-206 on muscle cell proliferation and differentiation, as well as its effect on myofiber type conversion using mouse C2C12 myoblasts. The results showed that overexpression of miR-206 inhibited cell proliferation and promoted muscle cell differentiation, but it did not affect myofiber type conversion. Intriguingly, we found that overexpression of miR-206 suppressed muscle cell proliferation and induced cell cycle arrest in G0/G1 phase by inhibiting the glucose-6-phosphate dehydrogenase (G6PD) gene. Taken together, we demonstrated that the miR-206-G6PD pathway suppresses muscle cell proliferation, and these findings may facilitate the treatment of muscle diseases.-Jiang, A., Dong, C., Li, B., Zhang, Z., Chen, Y., Ning, C., Wu, W., Liu, H. MicroRNA-206 regulates cell proliferation by targeting G6PD in skeletal muscle.


The Paxillin-like protein AgPxl1 is required for apical branching and maximal hyphal growth in A.gossypii.
The development from young, slowly growing hyphae to fast growing hyphae in filamentous fungi is referred to as hyphal maturation. We have identified the Paxillin-like protein AgPxl1 in Ashbyagossypii as a developmental protein that is specifically required for hyphal maturation. The early development of A.gossypii strains lacking AgPxl1 is indistinguishable from wild-type. However, at later developmental stages the maximal hyphal extension rate is less than half compared to wild-type and apical branching is affected. Apical branching is characterised as the symmetric division of fast growing hyphal tips resulting in two sister hyphae. In Agpxl1Delta strains two thirds of the apical branching events lead to asymmetric sister hyphae where growth of one branch is either completely aborted or slowed down while extension of the other branch is not affected. This suggests that AgPxl1 plays a role in the organisation of growth and efficient division of growth upon apical branching in mature mycelia. The conserved C-terminal LIM domains are necessary for AgPxl1 function and also contribute to tip localisation. AgCLA4, a PAK-like kinase, is epistatic to AgPXL1 and robust localisation of AgPxl1 depends on AgCla4. This suggests that AgCla4 acts upstream of AgPxl1.


Conversion surgery after combination chemotherapy of docetaxel, cisplatin and S-1 (DCS) for far-advanced gastric cancer.
A triplet regimen of docetaxel, cisplatin, and S-1(DCS) is highly effective against metastatic gastric cancer. We performed this study to clarify the safety and efficacy of surgical resection in patients with initially unresectable gastric cancer, after down-staging or disease control was achieved by DCS chemotherapy. The subjects of this retrospective study were 31 consecutive patients with initially unresectable gastric cancer, who underwent surgical resection between October, 2006 and December, 2012, after down-staging or disease control was achieved by DCS chemotherapy. We evaluated the clinicopathological factors and clinical outcomes and assessed radiographic response based on the RECIST criteria, not by central review. Before DCS chemotherapy, 18 patients had extra-regional lymph node metastasis, 5 had liver metastasis, 8 had macroscopic peritoneal metastasis, and 8 had pancreatic head invasion. Twenty-three (74.2%) of the 31 patients underwent R0 resection. Postoperative morbidity and mortality rates were 16.1 and 0%. During chemotherapy, grade 3/4 toxicities included neutropenia (54.8%), leukopenia (32.3%), and anemia (16.1%). Median progression-free survival and median overall survival (OS) were 42.1 and 56.1 months, respectively. These results were similar for all patients, except those with locally advanced disease alone. In the multivariate analysis for OS, ypN remained an independent negative prognostic factor (p = 0.018). Surgical resection after DCS chemotherapy for initially unresectable gastric cancer was safe and provided a reasonable R0 resection rate and good mid-term survival.


Odontogenic skin sinus: a commonly overlooked skin presentation.
Facial skin lesions present routinely to clinic and are largely dermatological in origin. Odontogenic infections are an unusual cause of facial lesion and are well-described in the dental literature; however they are regularly overlooked and mismanaged, often to considerable aesthetic detriment. We present such a case and highlight important avoidable pitfalls.


Monosynaptic striatal inputs to the nigrotegmental neurons: an electron microscopic study in the cat.
The cat substantia nigra (SN) pars reticulata (SNR) has been observed electron microscopically after ibotenic acid injections into the caudate nucleus (Cd) and horseradish peroxidase injections into the nucleus tegmenti pedunculopontinus pars compacta (TPC). As a result, degenerating striatal terminals were found to make symmetric synaptic contacts on retrogradely labeled SNR neurons. The present findings, together with our previous study on the tegmentonigrostriatal projection (Tokuno et al., Neurosci. Lett. 85 (1988) 1-4), confirm that the Cd has indirect reciprocal connections with the TPC via the SN.


Urinary microRNA-192 and microRNA-21 as potential indicators for liver fluke-associated cholangiocarcinoma risk group.
Opisthorchis viverrini infection induces chronic inflammation in the bile ducts, leading to periductal fibrosis (PDF), which possibly associates to cholangiocarcinoma (CCA). Patients with CCA have a poor prognosis, which is linked to asymptomatic disease and late diagnosis. Hence, detecting early stage CCA is essential. Secretory miRNAs have been promoted as biomarkers for pathological changes associated with parasitic infections, fibrosis and/or cancer. We aimed to determine levels of miR-192 and miR-21 in the urine of O. viverrini infected, periductal fibrosis (PDF) and CCA groups using qRT-PCR. We found that miR-192 was significantly higher in O. viverrini infected, PDF and also CCA groups (p<0.05) than in healthy controls. By utilizing the Receiver Operation Characteristics (ROC) analysis, miR-192 differentiated patients with opisthorchiasis (the area under the curve; AUC=0.766), PDF subjects (AUC=0.781) and CCA patients (AUC=0.682) from healthy controls. MiR-21 was significantly higher in PDF and CCA groups (p<0.05) than in healthy controls. MiR-21 discriminated PDF subjects (AUC=0.735) and CCA patients (AUC=0.682) from healthy controls. Combined levels of these two miRNAs revealed an increased AUC of 0.812 for separating opisthorchiasis, AUC of 0.815 in discriminating PDF subjects, and AUC of 0.849 in differentiating CCA from healthy controls. Odds ratios (OR) indicated high levels of miR-192/miR-21 as risk predictors for opisthorchiasis, PDF and CCA. Levels of these miRNAs declined significantly for patients following praziquantel treatment. In conclusion, urinary miR-192/miR-21 have potential as risk indicators for opisthorchiasis and PDF-associated CCA in the endemic region.


Efficient Suppression of Abdominal Aortic Aneurysm Expansion in Rats through Systemic Administration of Statin-Loaded Nanomedicine.
Abdominal aortic aneurysm (AAA) is a life-threatening disease. However, no systemically injectable drug has been approved for AAA treatment due to low bioavailability. Polymeric micelles are nanomedicines that have the potential to improve therapeutic efficacy by selectively delivering drugs into disease sites, and research has mainly focused on cancer treatments. Here, we developed a statin-loaded polymeric micelle to treat AAAs in rat models. The micelle showed medicinal efficacy by preventing aortic aneurysm expansion in a dose-dependent manner. Furthermore, the micelle-injected group showed decreased macrophage infiltration and decreased matrix metalloproteinase-9 activity in cases of AAA.


Infusion of calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in colorectal cancer: a systematic review and meta-analysis.
It is hypothesised that infusion of calcium and magnesium (Ca/Mg) can reduce the occurrence of oxaliplatin-related sensory neurotoxicity. However, more recent data have drawn a controversial picture concerning this topic. A comprehensive literature search was performed using Medline, Embase, Cochrane Library and Google Scholar database up to 1st August 2011. Keywords for the search were: calcium, magnesium and oxaliplatin. The odd ratio (OR) for neurotoxicity and relative risk (RR) for tumour response rate were calculated. Seven studies (four randomised controlled trials (RCTs) and three cohorts) including a total of 1238 participants met our criteria. Meta-analysis of three RCT studies that reported in National Cancer Institute-Common Toxicity Criteria (NCE-CTC) showed that OR for neurotoxicity of Grade ~2 was not significant (OR 0.47; 95%confidence interval (CI) 0.22-1.00, P homogeneity = .729). The OR was also not significant in All Grades (OR 3.15, 0.32-31.35, P homogeneity = .952) and Grade 3 subgroup (OR 1.64, 0.30-9.00, P homogeneity = .656). No statistically significant difference was observed in RR for tumour response rate. (RR = 0.91, 0.78-1.06, P homogeneity = .33) This meta-analysis does not support the hypothesis that infusion of Ca/Mg reduces the occurrence of neurotoxicity in oxaliplatin-treated patients with colorectal cancer measuring with NCE-CTC criteria. On the other hand, our results support the hypothesis that administrations of Ca/Mg do not impair the efficacy of oxaliplatin-based chemotherapy. However, large-scale randomised, controlled clinical trials will be required to confirm these hypotheses.


Penetration of benzene, toluene and xylenes contained in gasolines through human abdominal skin in vitro.
Few studies are available in literature on the risk for humans from skin exposure to gasolines. This work is focused on the in vitro skin penetration of benzene (carcinogenic substance), toluene and xylenes. We examined three commercial gasolines using the Franz diffusion cells and human abdominal full thickness skin. Gasoline composition was determined using a multi-dimensional gas chromatographic (MDGC) technique. Aromatic compounds into the receptor fluid, consisting of saline solution were quantitated by a gas chromatography technique equipped with a flame ionization detector (GC-FID) and coupled with a headspace-solid phase micro extraction system (HS-SPME). Among the three substances, benzene showed the highest average apparent permeability coefficient (K(p)=43.8x10(-5)cmh(-1)) compared to toluene (K(p)=6.48x10(-5)cmh(-1)) and xylenes (K(p)=0.84x10(-5)cmh(-1)). This value could be explained by the lower boiling point and higher water solubility of benzene. Lag times were about 1h for benzene and 2h for toluene and xylenes. Averaged total recoveries in the receptor fluid were 0.43% of dose for benzene, 0.06% for toluene and 0.008% for xylenes. A statistical significative difference (Student's t-test, P<0.05) between the fluxes calculated for the three gasolines are noted only for xylene and for toluene between gasolines #1 (richer in aromatic compounds) and #3. The obtained apparent permeability coefficient are useful for determining the permeability of these aromatics components from gasolines of a different composition. Hands exposure risk, calculated using RfD and RfC as defined by US EPA, is critical for benzene. The risk of skin permeation of gasoline, and, in particular, of benzene, should be better evaluated for those workers who have a large potential for exposure. Adequate personal protective equipment should be used in the high exposure jobs, mainly for hands and forearms.


Ankle fusion in hemophilic patients.
Hemophilic arthropathy is painful and disabling. We report a retrospective study of ankle fusion with intra- and peri-operative clotting factor perfusion. The objective was to assess the efficacy of maintaining perioperative clotting factor rates close to 100%, and report long-term results. The study hypothesis was that results would be good, without early hemorrhagic complications. Between 2000 and 2013, 12 ankle fusions were performed in 9 patients, with a mean age of 39years (range, 19-58years). Anti-hemophilic factor perfusion was controlled by the reference physician of the Regional Hemophilia Treatment Center. Clinical AOFAS and Olerud scores and the Pettersson radiologic score were used for assessment. Mean preoperative AOFAS score was 22 (range, 2-55) and mean Olerud score 7 (range, 5-12). Mean preoperative factor VIII concentration was <1% (range, <1-3%). Mean follow-up was 8years (range, 2-16years). Mean AOFAS score at follow-up was 69 (range, 35-92) and mean Olerud score 70 (range, 30-100). Improvement mainly concerned the Pain dimension. Statistical analysis found a significant difference between pre- and post-operative clinical scores (AOFAS, P=0.004; Olerud, P=0.004). Mean factor VIII concentration at surgery was 90% (range, 24-117%), and 109% (range, 75-152%) the day following surgery. There were no cases of hematoma or surgical site infection. Radiologic fusion was systematic at a mean 3.5 months (range, 3-4months). The study hypothesis was confirmed. Ankle fusion in advanced hemophilic arthropathy improved function and quality of life. Perioperative clotting factor perfusion contributed to these good results, providing supplementary prevention of hemorrhagic risk. IV, retrospective study.


His bundle block.
In patients with narrow QRS complexes, atrioventricular block is usually localized to the AV node, and it is frequently benign. The more distal intra-His bundle blocks are rare, potentially malignant, and difficult to recognize. This case report illustrates how His bundle block can be diagnosed by analyzing the effects of certain maneuvers on the heart rate. Paradoxically, exercise and atropine tend to provoke His bundle block, whereas carotid massage may release it. Implantation of a permanent pacemaker is generally indicated.


Unusual primary central nervous system lymphoma location involving the fourth ventricle and hypothalamus.
A previously healthy 65-year-old man presented with a two-week history of weight loss, headaches, blurred vision, asthenia and quickly worsening walking impairment. He denied photophobia, neck stiffness, fever, nausea or vomiting.Neurological examination showed global motor slowing, tendency to fall asleep during the clinical examination, generalized weakness against resistance to head and limbs, and osteotendon reflexes present in the upper limbs, but not evoked in the lower limbs. No sensitive deficit or focal neurologic sign was recognizable.Non-contrast multislice computed tomography (MSCT) of the head was performed in the emergency department, showing diffuse periventricular white matter and thalamic mild hyperdensity.Lumbar puncture, blood tests, including serology for HIV and other infections, were negative.On the third day the patient, showing decreased consciousness, underwent magnetic resonance imaging (MRI) with contrast medium injection. MRI revealed the presence of multiple pseudonodular avidly enhancing lesions, supra and infratentorial, crossing the midline, involving the ventricular system, including the fourth ventricle, with extension into the surrounding white matter, the corpus callosum, the thalamus and the hypothamalus.A stereotactic biopsy led to a diagnosis of diffuse large B-cell lymphoma, primarily located in the central nervous system (PCNSL).After the completion of the first phase of treatment (immunotherapy with intravenous Rituximab and corticosteroid), the MRI showed a marked regression of tumor masses.


IgM-lambda paraproteinemia with associated cutaneous lymphoplasmacytic infiltrate in a patient who meets diagnostic criteria for POEMS syndrome.
POEMS is a rare multisystem paraneoplastic syndrome featuring polyneuropathy, organomegaly, endocrinopathy, a monoclonal protein, and skin changes. In the relatively few reported biopsies of POEMS-associated cutaneous hyperpigmentation, the most common skin finding seen in patients with the disorder, only a non-specific inflammatory infiltrate has been demonstrated histologically. We present the case of a 79-year-old man with polyneuropathy, autoimmune thyroiditis, pancytopenia, and a history of lymphadenopathy who presented to the inpatient dermatology service with cutaneous hyperpigmentation. A skin biopsy of a hyperpigmented area showed a cutaneous lymphoplasmacytic infiltrate, prompting further investigation. A monoclonal IgM-lambda paraprotein was subsequently identified, leading to administration of combination chemotherapy for a diagnosis of POEMS syndrome. The novel finding of a lymphoplasmacytic infiltrate in POEMS-associated hyperpigmentation suggests a diagnostic role for skin biopsy in these patients.


Immunoadsorption for collagen and rheumatic diseases.
The field of therapeutics has seen remarkable progress in the recent years, which has made mainstream drug treatment possible for collagen and rheumatic diseases. However, treatment of intractable cases where drug effectiveness is poor is a challenge. Furthermore, organ damage, concurrent illnesses or allergic reactions make adequate drug therapy impossible. For such cases, therapeutic apheresis is very significant, and it is important how this should be valued related to drug therapies. Therapeutic apheresis for collagen and rheumatic diseases involves the removal of factors that cause and exacerbate the disease; the aim of immunoadsorption, in particular, is to improve the clinical condition of patients with autoimmune disease by selectively removing pathogenic immune complexes and autoantibodies from their plasma. Immunoadsorption, in particular, unlike plasma exchange and DFPP, utilizes a high-affinity column that selectively removes autoantibodies and immune complexes, leaving other plasma components intact. There is no need to replenish fresh frozen plasma or blood products such as albumin and gamma globulin preparations. Immunoadsorption is thus superior in terms of safety, as the risk of infection or allergic reaction relating to these preparations can be avoided. We anticipate future investigations of application of synchronized therapy using drugs and therapeutic apheresis, most notably immunoadsorption, in combination to treat intractable clinical conditions such as collagen and rheumatic diseases. In this paper, our discussion includes the indications for immunoadsorption such as collagen and rheumatic diseases, the relevant conditions and types, as well as the latest understanding related to methods and clinical efficacy.


Protective mechanism of gallic acid and its novel derivative against ethanol-induced gastric ulcerogenesis: Involvement of immunomodulation markers, Hsp70 and Bcl-2-associated X protein.
Some phytochemicals demonstrate gastroprotective effects by inhibiting gastric acid secretion or through antioxidant action. One of these antioxidant phytochemicals which have been studied is gallic acid. However, its mechanism in the treatment and prevention of gastric ulcer remains unclear. This study evaluated the anti-ulcerogenic mechanism(s) of gallic acid (GA) and its novel synthetic derivative (GD). Adult male Sprague Dawley rats were orally pretreated with GA and GD and 30min later exposed to acute gastric ulcerogenesis induced by 95% ethanol (5ml/kg). Potential gastric chemoprevention of GA and GD were assessed using qualitative and quantitative evaluation of gastric lesions, gastric juice acidity, mucus production, histolopathology, PAS histochemistry, immunostaining of Hsp70 and Bax, nitric oxide, prostaglandin E2, TNF-α and thiobarbituric acid reactive substances (TBARS) assay. Oral administration of GA and GD (25 and 50mg/kg) inhibited significantly (P<0.05) ethanol-induced gastric lesions. Treatment with the compounds protected rat's stomach and modulated remarkably the levels of PAS-reactive substances, gastric pH, TBARS, immunological and apoptosis marker. The in vivo antioxidant properties, immunomodulator proteins and inhibition of mitochondrial apoptosis may contribute to the gastroprotective activity of gallic acid (GA) and its novel derivative (GD).


The role of fish in distribution and germination of seeds of the submerged macrophytes Najas marina L. and Ruppia maritima L.
The effects of three species of fish (tilapia, grass carp and common carp) on the seeds of Najas marina L. and of Ruppia maritima L. were investigated. Practically all the seeds that were injested by the common carp were digested. The two other fish were less affective: they digested seeds with soft seed-coats but excreted a good portion of the hard ones. Germination of the excreted seeds was improved. Seeds have been retained in the digestion tracts of the fish for up to 65 h. It is thus suggested that tilapias and grass-carps play a role in the distribution and the improvement of reproduction of Najas and Ruppia.


Analysis of cataract and keratotic damage induced by 4-diethylaminoethoxy-alpha-ethyl-benzhydrol (RGH-6201) in rats.
RGH-6201 (4-diethylaminoethoxy-alpha-ethyl-benzhydrol) in the first dose-range finding study on rats produced severe, irreversible ophthalmic damage. The underlying mechanism was studied in a series of experiments with daily doses of 50, 100 and 200 mg/kg in rats by gavage. Lenticular damage appeared as a moderate nuclear degeneration during Week 4 of treatment with 50 mg/kg RGH-6201. This could be detected in the isolated eye and in histological examination but not by ophthalmoscopy. Keratitis and iridocyclitis developed about the 2nd week of treatment followed by epithelial proliferation in the lens under the anterior capsule in the higher dose groups. Nuclear and total cataract developed from the 2nd week on in the 200 mg/kg group and from the 3rd week on in the 100 mg/kg group. Further gross pathological changes in the high dose group were characterized by marked hairloss, desquamation in the cardiac region of the stomach and diarrhoea. It has to be emphasized that fine lenticular changes were unrelated to keratitis and iridocyclitis. Since other benzhydrol derivatives such as 2,5-dimethyl-alpha-ethylbenzhydrol and 3-trifluoro-methyl-alpha-ethyl-benzhydrol do not induce similar changes, the diethyl-amino-ethoxy group was assumed to be the toxic part of the molecule. Intravenous studies with equimolar doses of diethyl-aminoethanol revealed no similar symptoms.