Fate and effect of the antioxidant ethoxyquin on a mixed methanogenic culture.
The potential inhibitory effect of ethoxyquin, an antioxidant commonly used as a preservative in the food processing industry (e.g., for stabilizing dissolved air flotation residuals), was evaluated at concentrations up to 300 mg/L using a mixed, mesophilic (35 degrees C) methanogenic culture and dextrin, peptone and methanol as the carbon source. A batch assay conducted with a range of ethoxyquin concentrations did not result in any inhibition up to an ethoxyquin concentration of 75 mg/L, but severe inhibition of methanogenesis was observed at concentrations higher than 150 mg/L. Ethoxyquin addition to a batch reactor with the same mixed, methanogenic culture, at ethoxyquin concentrations gradually increasing over 100 days, resulted in a transient and a complete inhibition of methanogenesis at ethoxyquin concentrations of 150 and 300 mg/L, respectively. Acidogens were not significantly impacted, whereas aceticlastic and methanol degrading methylotrophic methanogens were impacted the most. Acclimation of the methanogenic culture to ethoxyquin was not observed over an incubation period of more than 100 days. Long-term (>100 days) incubation at sub-inhibitory ethoxyquin concentrations did not result in ethoxyquin biotransformation. Similarly, ethoxyquin biotransformation was not evident over an 8-day aeration period in a laboratory-scale activated sludge reactor operated under fully aerobic conditions. Ethoxyquin phase distribution tests conducted with the mixed, methanogenic culture at 1.61 g/L volatile solids concentration and nominal ethoxyquin concentrations equal to or higher than 300 mg/L resulted in solid phase/liquid phase ethoxyquin ratios equal to or higher than 1.0. The combined effect of ethoxyquin recalcitrance under anaerobic conditions along with its phase distribution, which favors biosolids, will result in ethoxyquin accumulation in anaerobic treatment systems used by the food processing industry. Such accumulation may pose concerns relative to inhibitory effects in these treatment systems and the disposal of ethoxyquin-bearing biosolids.


Involvement of neutrophils in machineries underlying the rupture of intracranial aneurysms in rats.
Subarachnoid hemorrhage due to rupture of an intracranial aneurysm has a quite poor prognosis after the onset of symptoms, despite the modern technical advances. Thus, the mechanisms underlying the rupture of lesions should be clarified. To this end, we obtained gene expression profile data and identified the neutrophil-related enriched terms in rupture-prone lesions using Gene Ontology analysis. Next, to validate the role of neutrophils in the rupture of lesions, granulocyte-colony stimulating factor (G-CSF) was administered to a rat model, in which more than half of induced lesions spontaneously ruptured, leading to subarachnoid hemorrhage. As a result, G-CSF treatment not only increased the number of infiltrating neutrophils, but also significantly facilitated the rupture of lesions. To clarify the mechanisms of how neutrophils facilitate this rupture, we used HL-60 cell line and found an enhanced collagenolytic activity, corresponding to matrix metalloproteinase 9 (MMP9), upon inflammatory stimuli. The immunohistochemical analyses revealed the accumulation of neutrophils around the site of rupture and the production of MMP9 from these cells in situ. Consistently, the collagenolytic activity of MMP9 could be detected in the lysate of ruptured lesions. These results suggest the crucial role of neutrophils to the rupture of intracranial aneurysms; implying neutrophils as a therapeutic or diagnostic target candidate.


Conversion of aqueous ammonia-treated corn stover to lactic acid by simultaneous saccharification and cofermentation.
Treatment of corn stover with aqueous ammonia removes most of the structural lignin, whereas retaining the majority of the carbohydrates in the solids. After treatment, both the cellulose and hemicellulose in corn stover become highly susceptible to enzymatic digestion. In this study, corn stover treated by aqueous ammonia was investigated as the substrate for lactic acid production by simultaneous saccharification and cofermentation (SSCF). A commercial cellulase (Spezyme-CP) and Lactobacillus pentosus American Type Culture Collection (ATCC) 8041 (Spanish Type Culture Collection [CECT]-4023) were used for hydrolysis and fermentation, respectively. In batch SSCF operation, the carbohydrates in the treated corn stover were converted to lactic acid with high yields, the maximum lactic acid yield reaching 92% of the stoichiometric maximum based on total fermentable carbohydrates (glucose, xylose, and arabinose). A small amount of acetic acid was also produced from pentoses through the phosphoketolase pathway. Among the major process variables for batch SSCF, enzyme loading and the amount of yeast extract were found to be the key factors affecting lactic acid production. Further tests on nutrients indicated that corn steep liquor could be substituted for yeast extract as a nitrogen source to achieve the same lactic acid yield. Fed-batch operation of the SSCF was beneficial in raising the concentration of lactic acid to a maximum value of 75.0 g/L.


Investigation of the Ligand-Field States of the Hexaammine Cobalt(III) Ion with Quantum Chemical Methods.
The ligand-field (LF) transition energies of the Co(NH3)6(3+) ion have been computed with multiconfiguration quasidegenerate second-order perturbation theory (MCQDPT2). The water solvent was treated with the polarizable continuum model (PCM), and the environment in crystals was modeled by the Co(NH3)6·Cl4(-) complex. The Co-N bond lengths, calculated for the hydrated cation and the Co(NH3)6·Cl4(-) model compound, agree with those in the crystal structures. The vertical transition energies agree with experiment, whereby those based on Co(NH3)6·Cl4(-) are more accurate than those for the hydrated ion. The 0-0 transitions were based on the OPBE geometries of ground and excited (1)T1g, (3)T1g, (5)T2g states of the hydrated ion. The (3)T1g state is the lowest excited state; the (5)T2g state lies higher by >0.6 eV.


Methodology governing the assessment of myocardial glucose metabolism by positron emission tomography and fluorine 18-labeled fluorodeoxyglucose.
Positron emission tomography (PET) with fluorine 18-labeled fluorodeoxyglucose (FDG) has provided important insights into the alterations in myocardial glucose metabolism associated with normal cardiac physiology and pathophysiology. In patients with left ventricular dysfunction caused by coronary artery disease, PET-FDG studies have identified certain patterns of myocardial glucose metabolism relative to flow that are associated with viable myocardium. Consequently, in many centers, PET-FDG imaging is being used to identify patients with left ventricular dysfunction who are likely to benefit from coronary revascularization. However, myocardial glucose metabolism (and thus myocardial uptake of FDG) is markedly dependent on a variety of factors, particularly the substrate environment and level of myocardial perfusion. These and other factors must be considered to obtain and interpret myocardial FDG images accurately with respect to the underlying pathophysiologic process. In this review the impact of these factors on myocardial FDG imaging, as well as the relative advantages and disadvantages of approaches designed to optimize myocardial PET-FDG studies, will be discussed.


A photoelastimetric analysis of stress induced by root-end resection.
The aim of this study was to place into perspective some factors that played an important role in the healing of periapical lesions after surgical endodontic procedures. Root-ends were sectioned at different angulations on models and analyzed by photoelastimetry. Results showed that a section of the root-end through a plane perpendicular to the long axis of the tooth offers a better distribution of the stresses exerted on the apical region that the use of an inclined plane. The biological implications of these results have led the authors to propose a plan of resection that is perpendicular to the long axis of the tooth instead of the inclined plane commonly used.


Pharmacological preconditioning with simvastatin protects liver from ischemia-reperfusion injury by heme oxygenase-1 induction.
The protective role of heme oxygenase-1 (HO-1) against liver ischemia-reperfusion (I/R) injury in models of hypoxic and remote preconditioning has been proved. The feasible candidates who induce HO-1 and thorough which exert the protective effects are under investigation. The aim was to study the role of HO-1 in pharmacological preconditioning by simvastatin in a rat model. Pharmacological preconditioning by intraperitoneal injection of simvastatin (5 mg/kg) was tested on a partial liver I/R model on rats. The expression of HO-1 protein and enzyme activities in livers, serum alanine transaminase (ALT) levels, and TUNEL staining of liver after I/R injury were measured in rats with and without simvastatin preconditioning. HO-1 was induced and persistently overexpressed in the hepatocytes 24 hr after simvastatin treatment. Simvastatin preconditioning diminished the elevation of serum ALT levels 4 hr after I/R injury (69.6+/-26.3 U/L) (P<0.05 vs. other groups) when compared with control (403.8+/-261.9 U/L) and zinc protoporphyrin (ZnPP)-pretreated (717.5+/-205.6 U/L) groups. Simvastatin preconditioning diminished the apoptosis after I/R injury as well (apoptosis index: 26.4+/-8 for Simvastatin, 78+/-7 for control, and 85.3+/-2 for ZnPP group; P<0.05). The addition of ZnPP negated the protective effects of simvastatin as evidenced in the ALT level (406.2+/-243.0 U/L) and apoptosis index (75.6+/-6). The heme oxygenase activity in treated rats correlated with these results. The induction of HO-1 by simvastatin preconditioning played a protective role against hepatic I/R injury.


[Psychotropic drugs dispensed on the island of Bonaire].
Up till now little is known about psychiatric disorders in relation to the use of psychotropics drugs on the Dutch Antilles, with the exception of Curaçao. To map the quantity and type of psychotropics prescribed for Bonairians in 2009. We performed a retrospective data analysis of the antipsychotics dispensed by the pharmacies on Bonaire in 2009. Our analysis focused on the benzodiazepines and related compounds, antipsychotics, lithium, antidepressants and ADHD- and narcolepsy-medication. With regard to antipsychotics and antidepressants, we also investigated 'the age distribution of the persons to whom the psychotropics were dispensed'. In addition, we mapped the frequency with which the drugs were dispensed: once only, infrequently, regularly. At least one psychotropic drug was delivered to 18.37% of (N=2365) Bonairians in 2009. Benzodiazepines and related compounds in particular were the most commonly dispensed drugs. One in five Bonairians received at least one prescription for psychotropic drugs in 2009.


Ischaemic stroke patients present sex differences in gut microbiota.
Gut microbiota plays a role in the pathophysiology of ischaemic stroke (IS) through the bidirectional gut-brain axis. Nevertheless, little is known about sex-specific microbiota signatures in IS occurrence. A total of 89 IS patients and 12 healthy controls were enrolled. We studied the taxonomic differences of the gut microbiota between men and women with IS by shotgun metagenomic sequencing. To evaluate the causal effect of several bacteria on IS risk, we performed a two-sample Mendelian randomisation (MR) with inverse-variance weighting (IVW) using genome-wide association analysis (GWAS) summary statistics from two cohorts of 5959 subjects with genetic and microbiota data and 1,296,908 subjects with genetic and IS data, respectively. α-Diversity analysis measured using Observed Species (p = 0.017), Chao1 (p = 0.009) and Abundance-based Coverage Estimator (p = 0.012) indexes revealed that IS men have a higher species richness compared with IS women. Moreover, we found sex-differences in IS patients in relation to the phylum Fusobacteria, class Fusobacteriia, order Fusobacteriales and family Fusobacteriaceae (all Bonferroni-corrected p < 0.001). MR confirmed that increased Fusobacteriaceae levels in the gut are causally associated with an increased risk of IS (IVW p = 0.02, β = 0.32). Our study is the first to indicate that there are gut microbiome differences between men and women with IS, identifying high levels of Fusobacteriaceae in women as a specific risk factor for IS. Incorporating sex stratification analysis is important in the design, analysis and interpretation of studies on stroke and the gut microbiota.


Relationships Between Reproductive History and Mortality From Cardiovascular Diseases Among Japanese Women: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC) Study.
Reproductive history has been addressed as a risk factor for cardiovascular disease (CVD). We examined the relationship between reproductive history and CVD mortality in Japanese women. We followed 53,836 women without previous CVD or cancer history from 1988-1990 to 2009 in a prospective cohort study. Hazard ratios (HRs) and 95% confidence intervals (CIs) of CVD mortality were estimated according to the number of deliveries and maternal age at first delivery. During the follow-up, 2,982 CVD-related deaths were identified. There was U-shaped association between the number of deliveries and risk of CVD mortality with reference to three deliveries, although the excess risk of CVD mortality associated with ≥5 deliveries was of borderline statistical significance. The corresponding multivariable HRs were 1.33 (95% CI, 1.12-1.58) and 1.11 (95% CI, 0.99-1.24). In addition, higher CVD mortality was associated with maternal age ≥28 years at first delivery than maternal age of 24-27 years at first delivery. The multivariable HRs were 1.22 (95% CI, 1.10-1.36) for 28-31 years at first delivery and 1.26 (95% CI, 1.04-1.52) for ≥32 years at first delivery. Moreover, among women with ≥3 deliveries, maternal age ≥28 years at first delivery was associated with 1.2- to 1.5-fold increased CVD mortality. The number of deliveries showed a U-shaped association with risk of CVD mortality. Higher maternal age at first delivery was associated with an increased risk of CVD mortality, and excessive risk in women aged ≥28 years at first delivery was noted in those with ≥3 deliveries.


Three-dimensional/four-dimensional transperineal ultrasound: clinical utility and future prospects.
During the last decade, there has been a huge advancement in the use of transperineal ultrasound (TPU) in the field of obstetrics and gynecology. Its main applications in obstetrics include the monitoring of fetal progression in labor and recently the assessment of maternal pelvic dimensions, whereas in gynecology, TPU is at present widely used for the evaluation of the female pelvic floor, opening new boundaries for the assessment of pelvic floor disorders. The association of volumetric three-dimensional techniques has largely contributed to the remarkable progress that has occurred in the use of TPU. The aim of this paper is to offer an overview of the advantages, challenges and future perspectives of the use of TPU for women's imaging.


Blood transfusion and overall quality of life after hip fracture in frail elderly patients--the transfusion requirements in frail elderly randomized controlled trial.
We examined possible associations between different red blood cell (RBC) transfusion strategies, overall quality of life (OQoL), and recovery of activities of daily living (ADL) in operated frail elderly hip fracture patients, and the possibility that OQoL was related to ADL recovery. A prospective, assessor-blinded, randomized controlled trial was carried out among 157 elderly residents (≥65 years) from nursing homes and sheltered housing facilities with Mini-Mental State Examination scores ≥5 points. Patients were assigned to either a restrictive RBC transfusion strategy [hemoglobin (Hb) < 9.7 g/dL, 6 mmol/L] or a liberal strategy (Hb < 11.3 g/dL, 7 mmol/L) during the first 30 days after surgery. An interview-based questionnaire, the depression list (DL) assessing OQoL, and the modified Barthel Index (MBI) assessing ADL performance, were conducted on day 30 and 1 year after hip fracture surgery. Sum-scores of DL, MBI, and their changes from day 30 until 1 year (expressing recovery) were compared between RBC transfusion groups. Possible associations between changes of DL and MBI sum-scores were tested for across total patient population. There was no association between OQoL and RBC transfusion strategies on day 30 or at 1 year. The DL sum-score changes were similar for both groups, (ie, 1.06 points) [95% confidence interval (CI) -0.62, 2.76)] P = .21. The MBI sum-scores increased at 1 year following the liberal transfusion strategy (ie, by 6.86 points) (95% CI 0.41, 13.3) P = .03. Recoveries of OQoL and ADL were associated: β = -0.06 (95% CI -0.11, -0.01) P = .02. According to our Hb threshold criteria, OQoL and RBC transfusion strategies for frail elderly hip fracture patients are not associated. However, for survivors with less severe dementia, ADL recovery after 1 year is greater following a liberal transfusion strategy than a restrictive strategy. OQoL progress and ADL recovery were associated.


Structural and evolutionary characteristics of fish-specific TLR19.
Toll-like receptors (TLRs) are important pattern recognition receptors in the innate immune system of fish. Although ten years have passed since the first identification, the systematic knowledge about fish-specific TLR19 is still far insufficient. In present study, a phylogenetic analysis showed that TLR19 belonged to family 11, and clustered with TLR20 and TLR11/12 on the evolutionary tree. TLR20 is the closest paralogue of TLR19. The ectodomain of TLR19 contains 24 leucine-rich repeat (LRR) modules. The electrostatic surface potential analysis indicated that the modeled structure of TLR19 ectodomain showed much stronger polarity on the ascending lateral surface than on the descending lateral surface. The ascending lateral surface with strong electrostatic surface potential possibly mainly participates in the ligand binding of TLR19 ectodomain. The quite small dN/dS value at the TLR19 locus showed that TLR19 was very conserved. Approximately one third codons in the coding sequence of TLR19 were subjected to significantly negative selection, whereas only 5 codons underwent significantly positive selection. Overall, these findings possibly help in deepening the understanding to fish-specific TLR19.


Micellar nanoparticle formation via electrostatic interactions for delivering multinuclear platinum(II) drugs.
Nanoparticles formed via electrostatic interactions between methoxy-polyethylene glycol-block-poly(glutamic acid) (MPEG-PGA) and a multinuclear platinum(II) drug, di-cisPt, exhibit efficient platinum loading, improved cellular uptake, in vitro cytotoxicity, and enhanced in vivo efficacy.


Dietary nitrate intake in relation to the risk of dementia and imaging markers of vascular brain health: a population-based study.
Nitric oxide is a free radical that can be produced from dietary nitrate and positively affects cardiovascular health. With cardiovascular health playing an important role in the etiology of dementia, we hypothesized a link between dietary nitrate intake and the risk of dementia. This study aimed to find the association of total, vegetable, and nonvegetable dietary nitrate intake with the risk of dementia and imaging markers of vascular brain health, such as total brain volume, global cerebral perfusion, white matter hyperintensity volume, microbleeds, and lacunar infarcts. Between 1990 and 2009, dietary intake was assessed using food-frequency questionnaires in 9543 dementia-free participants (mean age, 64 y; 58% female) from the prospective population-based Rotterdam Study. Participants were followed up for incidence dementia until January 2020. We used Cox models to determine the association between dietary nitrate intake and incident dementia. Using linear mixed models and logistic regression models, we assessed the association of dietary nitrate intake with changes in imaging markers across 3 consecutive examination rounds (mean interval between images 4.6 y). Participants median dietary nitrate consumption was 85 mg/d (interquartile range, 55 mg/d), derived on average for 81% from vegetable sources. During a mean follow-up of 14.5 y, 1472 participants developed dementia. A higher intake of total and vegetable dietary nitrate was associated with a lower risk of dementia per 50-mg/d increase [hazard ratio (HR): 0.92; 95% confidence interval (CI): 0.87, 0.98; and HR: 0.92; 95% CI: 0.86, 0.97, respectively] but not with changes in neuroimaging markers. No association between nonvegetable dietary nitrate intake and the risk of dementia (HR: 1.15; 95% CI: 0.64, 2.07) or changes in neuroimaging markers were observed. A higher dietary nitrate intake from vegetable sources was associated with a lower risk of dementia. We found no evidence that this association was driven by vascular brain health.


Haplotype analysis of endothelial nitric oxide synthase (NOS3) genetic variants and tardive dyskinesia in patients with schizophrenia.
Several studies have indicated the involvement of nitric oxide (NO) in the pathogenesis of tardive dyskinesia (TD), an incapacitating adverse movement disorder associated with long-term antipsychotic treatment. In human brain, the NO could be generated by endothelial nitric oxide synthase (NOS3). In this study, we studied whether the genetic variants in human NOS3 gene is associated with TD in patients with schizophrenia. Two hundred and eighty-two chronic inpatients with schizophrenia treated with typical antipsychotics were recruited in this study. The patients were further grouped by the presence of TD or not according to the Research and Diagnostic Criteria for TD. The genetic variants in the NOS3 gene investigated in this study were -786T > C in the promotor region, 27-bp variable number of tandem repeats (27-bp VNTR) in intron 4, and Glu298Asp in exon 7. The frequencies of genotypes, alleles and haplotypes of the three markers were compared between the TD (n = 153) and non-TD (n = 129) groups. There were no significant associations between the genotypes and alleles of the three markers and TD. However, in the haplotype-based case-control analysis, the frequency of haplotype T-4b-Glu was significantly higher in non-TD than in TD group (TD vs. non-TD = 72.7% vs. 81.0%, permutation P value = 0.021, OR = 0.648, 95% CI = 0.432-0.973). We found that the haplotype T-4b-Glu represents a protective haplotype against TD after long-term antipsychotic treatment. This finding suggests that human NOS3 gene may be involved in the pathogenesis of TD.


Radiologic features of a metastatic carcinoma to the ureter.
2 cases of metastasis to the ureter from carcinoma of the stomach are presented. The clinical and radiologic features are reviewed. Metastasis to the ureter is rare. A plea for vigorous evaluation and early detection of this entity is made.


Trabeculectomy according to cairns combined with extracapsular lens extraction and intraocular lens implant in the posterior chamber.
The authors report 20 cases of patients in which a trabeculectomy, an extracapsular cataract extraction and implant in posterior chamber are performed. The early long-term postoperative complications and final results are described.


Association of change in brain structure to objectively measured physical activity and sedentary behavior in older adults: Age, Gene/Environment Susceptibility-Reykjavik Study.
Many studies have examined the hypothesis that greater participation in physical activity (PA) is associated with less brain atrophy. Here we examine, in a sub-sample (n=352, mean age 79.1 years) of the Age, Gene/Environment Susceptibility-Reykjavik Study cohort, the association of the baseline and 5-year change in magnetic resonance imaging (MRI)-derived volumes of gray matter (GM) and white matter (WM) to active and sedentary behavior (SB) measured at the end of the 5-year period by a hip-worn accelerometer for seven consecutive days. More GM (β=0.11; p=0.044) and WM (β=0.11; p=0.030) at baseline was associated with more total physical activity (TPA). Also, when adjusting for baseline values, the 5-year change in GM (β=0.14; p=0.0037) and WM (β=0.11; p=0.030) was associated with TPA. The 5-year change in WM was associated with SB (β=-0.11; p=0.0007). These data suggest that objectively measured PA and SB late in life are associated with current and prior cross-sectional measures of brain atrophy, and that change over time is associated with PA and SB in expected directions.


Drivers of overall satisfaction with primary care: evidence from the English General Practice Patient Survey.
To determine which aspects of primary care matter most to patients, we aim to identify those aspects of patient experience that show the strongest relationship with overall satisfaction and examine the extent to which these relationships vary by socio-demographic and health characteristics. Data from the 2009/10 English General Practice Patient Survey including 2,169,718 respondents registered with 8362 primary care practices. Linear mixed-effects regression models (fixed effects adjusting for age, gender, ethnicity, deprivation, self-reported health, self-reported mental health condition and random practice effect) predicting overall satisfaction from six items covering four domains of care: access, helpfulness of receptionists, doctor communication and nurse communication. Additional models using interactions tested whether associations between patient experience and satisfaction varied by socio-demographic group. Doctor communication showed the strongest relationship with overall satisfaction (standardized coefficient 0.48, 95% CI = 0.48, 0.48), followed by the helpfulness of reception staff (standardized coefficient 0.22, 95% CI = 0.22, 0.22). Among six measures of patient experience, obtaining appointments in advance showed the weakest relationship with overall satisfaction (standardized coefficient 0.06, 95% CI = 0.05, 0.06). Interactions showed statistically significant but small variation in the importance of drivers across different patient groups. For all patient groups, communication with the doctor is the most important driver of overall satisfaction with primary care in England, along with the helpfulness of receptionists. In contrast, and despite being a policy priority for government, measures of access, including the ability to obtain appointments, were poorly related to overall satisfaction.


Dermoid cyst of the floor of the mouth--a case report.
We report a case of a 30-year-old, previously healthy man who presented at our clinic with complaints of increasing dysphagia and globus sensation for about 2 years. In addition, he noticed an increasing submental swelling. On examination, the patient revealed a massive swelling of the floor of the mouth, which had displaced the tongue cranially. MRI imaging showed the lesion to be a homogeneous, cystic lesion, clearly at a distance from the surrounding mucous tissue. Surgery was performed, and the tumor was resected completely. Histologic examination of the resected tissue was consistent with a dermoid cyst located in the floor of the mouth. Although dermoid cysts are rarely located in the oral cavity, it should be included in differential diagnosis. Surgery is the treatment of choice.


18-Ethynyl-deoxycorticosterone inhibition of steroid production is different in freshly isolated compared to cultured calf zona glomerulosa cells.
The inhibiting effects of 18-ethynyl-deoxycorticosterone (18-E-DOC) as a mechanism-based inhibitor on the late-steps of the aldosterone biosynthetic pathway were examined in calf adrenal zona glomerulosa cells in primary culture and in freshly isolated calf zona glomerulosa cells. 18-E-DOC inhibited the stimulated secretion of aldosterone and 18-hydroxycorticosterone in a similar dose-response and time fashion. No significant differences were found between the inhibition in cultured and freshly isolated cells (Ki of 0.25 vs 0.26 microM) Corticosterone secretion stimulated by ACTH or angiotensin II was also cultured in freshly isolated zona glomerulosa and fasciculata cells, but was not inhibited in cultured calf adrenal cells. Cortisol secretion stimulated by ACTH was not inhibited by 18-E-DOC in cultured zona fasciculata adrenal cells, but was inhibited in freshly isolated zona fasciculata cells with a Ki of 48 microM. The secretion of 18-hydroxyDOC or 19-hydroxyDOC stimulated by ACTH was not inhibited by 18-E-DOC. The bovine adrenal has been reported to have cytochrome P-450 11 beta-hydroxylases that can perform the various hydroxylations required for the synthesis of cortisol and aldosterone in the different areas of the adrenal. In other species a distinct 11 beta-hydroxylase which participates in the biosynthesis of aldosterone and is located in the zona glomerulosa has been described. These studies with the mechanism-based inhibitor, 18-E-DOC, suggest that the bovine adrenal functions in a manner very similar to that of other species and raises the possibility that a distinct 11 beta-hydroxylase with aldosterone synthase activity might be present, but has not been cloned as yet.


Identification of dominant lactic acid bacteria and yeast in rice sourdough produced in New Zealand.
This study characterised a commercial New Zealand gluten free (GF) rice sourdough and its starter culture composition. Acidity of the mother sourdough, dough before proofing and dough after proofing was determined during the production of rice sourdough bread, and colour was measured for the baked bread. Yeast and lactic acid bacteria (LAB) were enumerated in the rice sourdough samples and representative colonies characterised using API kits and sequenced by the Internal Transcribed Spacer and 16 S rRNA region. Sourdough LAB isolates were identified as Lactobacillus (L.) papraplantarum DSM 10667 and L. fermentarum CIP 102980 and the yeast isolates as Saccharomyces (S.) cerevisiae CBS 1171. Dough acidity increased significantly (p < 0.05) during fermentation due to the metabolic activities of the sourdough cultures. After baking, the colour of the rice sourdough bread crust was similar to that of unleavened wheat bread (golden brown). The improved colour of the rice sourdough bread crust may be a result of combined use of sourdough technique and optimal baking conditions. The results of this study may allow bakers to improve the overall quality of GF rice sourdough baked bread by selecting suitable fermentation and baking parameters.


Hantzsch pyrrole synthesis on solid support.
An efficient method for solid-phase synthesis of pyrroles is described. Polystyrene Rink amide resin is acetoacetylated and converted into polymer bound enaminones upon treatment with primary amines. These then undergo a Hantzsch reaction with alpha-bromoketones to yield pyrroles. After cleavage with 20% trifluoroacetic acid in dichloromethane pyrrole-3-carboxamides are obtained in excellent purity.


Collagen synthesis by human glomerular cells in culture.
Collagen synthesis was studied in three subcultured human glomerular cell types, by radiolabeled incorporation of [14C]proline and [3H]lysine. The epithelioid circular glomerular cells secrete a collagen with a single size of chain (possibly type IV) with a high ratio of hydroxyproline to proline, hydroxylysine to lysine, and 11--17% of hydroxyproline as the 3-isomer. The smooth muscle-like rhomboid glomerular cells secrete collagen with a chain pattern suggesting types III and I collagen, distinct from that found in the media of fibroblasts. Small ovoid glomerular cells are morphologically and biochemically intermediate between circular glomerular cells and rhomboid glomerular cells, and may represent an in vitro modification of either circular glomerular cells or rhomboid glomerular cells.


The Benefit of a General, Systematic Use of Mapping Systems During Electrophysiological Procedures in Children and Teenagers: The Experience of an Adult EP Laboratory.
Standard imaging during electrophysiological procedures (EPs) uses fluoroscopy. The aim of this study was to evaluate the feasibility, efficacy, safety and effect of an extended use of non-fluoroscopic mapping systems (NMSs) for imaging during paediatric EPs in an adult EP laboratory focusing on the amount of X-ray exposure. This study is a retrospective analysis that includes consecutive young patients (83 pts, aged between 8 and 18) who underwent EPs from March 2005 to February 2015. We compare the fluoroscopy data of two groups of pts: Group I, pts who underwent EPs from 2005 to 2008 using only fluoroscopy and Group II, pts who underwent EPs from 2008 to 2015 performed also using NMSs. The use of an NMS resulted in reduced fluoroscopy time in Group II {median value 0.1 min (95 % CI [0.00-1.07])} compared to Group I {median value 3.55 min (95 % CI [1.93-7.83]) (MW test, P < 0.05)}. There was a complementary reduction in the total X-ray exposure from 2.53 Gy cm(2) (95 % CI [1.51-4.66]) in Group I to 0.05 Gy cm(2) in Group II (95 % CI [0.00-1.22]) (MW test, P < 0.05). Regarding ablation procedures, the median effective dose decreased from 3.04 mSv (95 % CI [1.22-6.89]) to 0.25 mSv (95 % CI [0.00-0.60]) (MW test, P < 0.05). The use of an NMS dramatically reduces fluoroscopy time and total X-ray exposure during EPs in children and teenagers in an adult EP laboratory. In our experience, this reduction is mainly related to the systematic day-to-day use of NMSs.


Pre-microRNA binding aminoglycosides and antitumor drugs as inhibitors of Dicer catalyzed microRNA processing.
Over-expressions of miRNAs are being increasingly linked with many diseases including different types of cancer. In this study, the role of some known small molecular therapeutics has been investigated for their ability to bind with the pre-miRNA target (hsa-mir-155) and thereby to interfere with the Dicer catalyzed miRNA processing. Potential binding and inhibition effects have been demonstrated by some of these analogs. They can be used as leads for further development of potent small molecular miRNA-antagonists.


Cerebral angiogenesis and expression of VEGF after subarachnoid hemorrhage (SAH) in rats.
Subarachnoid hemorrhage (SAH) leads to the development of vasospasm in which endothelin-1 plays a very important role. The effect of its vasoconstricting action is hypoxia of the nervous tissue, which stimulates the release of growth factors. Vascular endothelial growth factor (VEGF) released in excessive amounts from hypoxically altered cerebrovascular endothelial cells is the most potent angiogenic factor and may enhance angiogenesis after SAH. If endothelin-1 is mainly responsible for vasospasm after SAH, it is possible that early administration of endothelin converting enzyme inhibitor or endothelin receptor antagonist may protect neurons against. The aim of the study was to establish whether prolonged vasospasm and endothelial cell hypoxia stimulate VEGF expression and, in consequence, promote angiogenesis in the central nervous system after subarachnoid hemorrhage. Investigations were also performed to determine whether the administration of phosphoramidon, an endothelin-converting enzyme (ECE) inhibitor, and BQ-123, an endothelin receptor ET(A) antagonist, suppresses angiogenesis and VEGF expression. Experiments were carried out in male Wistar rats injected with phosphoramidon or BQ-123 into the cisterna magna following the induction of subarachnoid hemorrhage. The brains were removed 48 h after the hemorrhage for histopathological and immunohistochemical examinations of VEGF expression and angiogenesis in the cerebral hemispheres, brainstem, and cerebellum. Statistical analysis was performed using nonparametric Wilcoxon test (P<0.05). The results obtained have shown for the first time a close correlation between endothelial hypoxia after SAH in cerebral microvessels and enhanced angiogenesis. There is also an increase in VEGF expression in cerebral vessels and neurons within the cerebral hemispheres, brainstem, and cerebellum. The administration of phosphoramidon or BQ-123 has been found to inhibit angiogenesis. Angiogenesis in the chronic phase of SAH-induced vasospasm is the result of prolonged narrowing of vessels due to excessive secretion of endothelin by damaged endothelial cells. Present results obtained indicate that it is possible to reduce or prevent the late effects of SAH, i.e., neuronal hypoxia and cerebral edema, through the inhibition of endothelin-1 induced vasospasm.


Rationale, experimental data, and emerging clinical evidence on early and preventive use of levosimendan in patients with ventricular dysfunction.
Acute ventricular dysfunction (AVD) is a complex condition with substantial morbidity and mortality, still featuring unique therapeutic challenges. Levosimendan is a calcium sensitizer and ATP-dependent potassium channel opener that was developed as an inodilating drug for the treatment of acute heart failure and cardiogenic shock. Differently from other more widely used inotropic agents, levosimendan has some exclusive characteristics, in terms of mechanisms of action, pharmacodynamic profile, and haemodynamic effects. This may have important clinical implications. In particular, in patients with AVD or in patients with pre-existing severe ventricular impairment undergoing planned myocardial stress, the administration of levosimendan before the onset of overt symptoms or before cardiovascular therapeutic procedures may have the potential to bridge the patient through the critical phase. In this review, we will focus on the rationale, the existing experimental data, and the emerging clinical experience supporting an early, even preventive use of levosimendan in severe ventricular dysfunction, beyond its recognized indications.


IgA nephropathy after COVID-19 vaccination and analysis of reported cases.
Immunoglobin A nephropathy (IgAN) is one of the most common forms of chronic glomerulonephritis and has been shown to occur in association with vaccinations. While various vaccines against COVID-19 have become widely used, their side effects, especially on IgAN following COVID-19 vaccines are still unclear. In this report, we describe the clinical courses and histopathologic findings of a newly diagnosed case of IgAN after receiving the mRNA-1273 (Moderna) COVID-19 vaccination. This study presents a case of new-onset IgAN following mRNA-1273 COVID-19 (Moderna) vaccination. In addition, we review and analyze similar cases previously reported in the literature up to October 2022. Of the 52 cases reviewed, including our own, the majority of patients were female, and 64% of patients had initial onset IgAN. The most common manifestation was gross hematuria (87%), other associated symptoms were fever (44%), myalgia (8%), arthralgia (4%), and edema (4%). Many of these cases occurred after receiving Pfizer products as the second vaccination. Oral corticosteroids were used to 16 cases, and steroid pulse therapy was used to treat 7 cases. While this is not a controlled study, it is important for physicians to consider the possibility that COVID-19 vaccines may provoke a flare of IgAN. Several therapeutic agents may be useful for treating COVID-19 vaccine-induced IgAN, although a specific mechanism or pathophysiological association cannot be confirmed without further research.


Integration of microfluidic and cantilever technology for biosensing application in liquid environment.
Microcantilever based oscillators have shown the possibility of highly sensitive label-free detection by allowing the transduction of a target mass into a resonant frequency shift. Most of such measurements were performed in air or vacuum environment, since immersion in liquid dramatically deteriorates the mechanical response of the sensor. Besides, the integration of microcantilever detection in a microfluidic platform appears a highly performing technological solution to exploit real time monitoring of biomolecular interactions, while limiting sample handling and promoting portability and automation of routine diagnostic tests (Point-Of-Care devices). In the present paper, we report on the realization and optimization of a microcantilever-based Lab-on-Chip, showing that microplates rather than microbeams exhibit largest mass sensitivity in liquid, while pirex rather than polymers represents the best choice for microfluidic channels. Maximum Q factor achieved was 140 (for fifth resonance mode of Pirex prototype), as our knowledge the highest value reported in literature for cantilever biosensors resonating in liquid environment without electronic feedback. Then, we proved the successfully detection of Angiopoietin-1 (a putative marker in tumor progression), showing that the related frequency shifts coming from non-specific interactions (negative controls) are roughly one order of magnitude lower than typical variations due to specific protein binding. Furthermore, we monitored the formation of antibody-antigen complex on MC surface in real-time. The proposed tool could be extremely useful for the comprehension of complex biological systems such as angiogenic machinery and cancer progression.


Revealing the role of peroxisome proliferator-activated receptor β/δ in nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD), a form of chronic liver disease that occurs in individuals with no significant alcohol abuse, has become an increasing concern for global health. NAFLD is defined as the presence of lipid deposits in hepatocytes and it ranges from hepatic steatosis (fatty liver) to steatohepatitis. Emerging data from both preclinical studies and clinical trials suggest that the peroxisome proliferator-activated receptor (PPAR)β/δ plays an important role in the control of carbohydrate and lipid metabolism in liver, and its activation might hinder the progression of NAFLD. Here, we review the latest information on the effects of PPARβ/δ on NAFLD, including its capacity to reduce lipogenesis, to alleviate inflammation and endoplasmic reticulum stress, to ameliorate insulin resistance, and to attenuate liver injury. Because of these effects, activation of hepatic PPARβ/δ through synthetic or natural ligands provides a promising therapeutic option for the management of NAFLD.


Glucocorticoids decrease the numbers and activation of mast cells by inducing the transactivation receptors of AGEs.
Glucocorticoids (GCs) are potent anti-allergic compounds that function, at least in part, by inhibiting signaling pathways in mast cells. We hypothesized that the GC-induced mastocytopenia and suppression of mast cell activation are mediated by the advanced glycation end products (AGEs)/receptors of AGEs (RAGEs) signaling axis. We evaluated the role of AGEs in GC-mediated mastocytopenia and impaired mast cell degranulation in male Wistar rats and Swiss-Webster mice subcutaneously injected with dexamethasone or prednisolone (0.1 mg/kg) once a day for 21 consecutive days. The animals were treated with either the AGE inhibitor aminoguanidine (250 mg/kg), the RAGE antagonist FPS-ZM1 (1 mg/kg) or the galectin-3 antagonist GSC-100 (1 mg/kg) daily for 18 days, starting 3 days following GC treatment. Aminoguanidine inhibited GC-induced mast cell apoptosis and restored mast cell numbers in the pleural cavity of GC-treated rats. Aminoguanidine also reversed the GC-induced reduction in histamine release triggered by allergens or compound 48/80 in vitro. GC treatment induced RAGE and galectin expression in mast cells, and blocking these agents by FPS-ZM1 or GSC-100 significantly reversed mast cell numbers in the peritoneal cavity and mesenteric tissue of GC-treated mice. In addition, the combination of GC and AGE-induced mast cell apoptosis in vitro was inhibited by both FPS-ZM1 and GSC-100. We concluded that the GC-induced mastocytopenia and suppression of mast cell stimulation are associated with the gene transactivation of RAGE and galectin-3.


Square wave jerks in Friedreich's ataxia.
We observed a brother and sister with Friedreich's ataxia during steady fixation. They both had abnormal eye movements consisting of randomly occurring, small amplitude, conjugate horizontal saccades away from the fixation target. The saccades were followed by maintenance of this eccentric position for a brief period, and finally, a corrective saccade back to the original position. Electro-oculographic recordings showed these eye movements to be square wave jerks. They had an amplitude ranging from 1.5 to 10.7 degrees and a duration averaging less than 200 msec. Square wave jerks were also superimposed on pursuit movements in both patients. Square wave jerks are an additional ocular finding that may signify chronic cerebellar dysfunction. More specifically, they are an additional neuro-ophthalmological finding that may be observed in Friedreich's ataxia.


Revealing de novo pyrimidine synthesis as a key vulnerability in brain tumors.
Brain tumors are notoriously difficult to treat. Three recent Cancer Cell articles aim to uncover novel druggable targets in IDH mutant gliomas, diffuse midline gliomas, and medulloblastomas, respectively, and show that these brain tumor types shift their metabolism to become reliant on de novo pyrimidine synthesis.


Increased risk of additional cancers among patients with gastrointestinal stromal tumors: A population-based study.
Most gastrointestinal stromal tumors (GISTs) are considered nonhereditary or sporadic. However, single-institution studies suggest that GIST patients develop additional malignancies at increased frequencies. It was hypothesized that greater insight could be gained into possible associations between GISTs and other malignancies with a national cancer database inquiry. Patients diagnosed with GISTs (2001-2011) in the Surveillance, Epidemiology, and End Results database were included. Standardized prevalence ratios (SPRs) and standardized incidence ratios (SIRs) were used to quantify cancer risks incurred by GIST patients before and after GIST diagnoses, respectively, in comparison with the general US population. There were 6112 GIST patients, and 1047 (17.1%) had additional cancers. There were significant increases in overall cancer rates: 44% (SPR, 1.44) before the GIST diagnosis and 66% (SIR, 1.66) after the GIST diagnosis. Malignancies with significantly increased occurrence both before and after diagnoses included other sarcomas (SPR, 5.24; SIR, 4.02), neuroendocrine-carcinoid tumors (SPR, 3.56; SIR, 4.79), non-Hodgkin lymphoma (SPR, 1.69; SIR, 1.76), and colorectal adenocarcinoma (SPR, 1.51; SIR, 2.16). Esophageal adenocarcinoma (SPR, 12.0), bladder adenocarcinoma (SPR, 7.51), melanoma (SPR, 1.46), and prostate adenocarcinoma (SPR, 1.20) were significantly more common only before the GIST diagnosis. Ovarian carcinoma (SIR, 8.72), small intestine adenocarcinoma (SIR, 5.89), papillary thyroid cancer (SIR, 5.16), renal cell carcinoma (SIR, 4.46), hepatobiliary adenocarcinoma (SIR, 3.10), gastric adenocarcinoma (SIR, 2.70), pancreatic adenocarcinoma (SIR, 2.03), uterine adenocarcinoma (SIR, 1.96), non-small cell lung cancer (SIR, 1.74), and transitional cell carcinoma of the bladder (SIR, 1.65) were significantly more common only after the GIST diagnosis. This is the first population-based study to characterize the associations and temporal relations between GISTs and other cancers by both site and histological type. These associations may carry important clinical implications for future cancer screening and treatment strategies.


Pelvic ultrasonography in girls with precocious puberty, congenital adrenal hyperplasia, obesity, or hirsutism.
Real-time ultrasonography of the pelvic organs was performed on 151 girls with various complete and incomplete forms of precocious puberty, 20 girls with congenital adrenal hyperplasia, 20 with hirsutism, 18 with obesity, and 133 age-matched normal girls. Uterine and ovarian volumes were calculated and the ovarian morphologic picture was classified as homogeneous, nonhomogeneous (less than three small cystic areas), microcystic (four or more small cystic areas less than 9 mm in diameter), follicular (at least one cystic area greater than 9 mm), and macrocystic (large cystic area greater than 20 mm). Ultrasound imaging allowed an easy distinction between true precocious puberty and premature thelarche or idiopathic premature adrenarche. It was also helpful in the diagnosis of transient sexual precocity, although in these cases the differential diagnosis of precocious puberty can be difficult. In postmenarcheal patients with congenital adrenal hyperplasia, ultrasound study showed a low uterine volume and, frequently, a macrocyst in the ovary. In hirsute girls and in a few obese patients, ovaries had an increased volume and a microcystic structure, similar to those in polycystic ovary syndrome. Pelvic ultrasonography can be useful not only in diagnosing disorders in sexual development but also for greater understanding of the pathogenesis of these and other disorders.


Simultaneous quantification of twenty Amadori products in soy sauce using liquid chromatography-tandem mass spectrometry.
A liquid chromatography-tandem mass spectrometry method using a pentafluorophenylpropyl-bonded silica column was developed to simultaneously quantify twenty Amadori products (APs), including N-(1-Deoxy-d-fructosyl-1-yl)-l-isoleucine (Fru-Ile) and N-(1-Deoxy-d-fructosyl-1-yl)-l-leucine (Fru-Leu), in soy sauce, without the need for an ion-pairing reagent or sample derivatization. The method was applied to six types of soy sauce, to determine the total AP levels and the levels of individual APs. The level of total APs widely varied between the eight samples, from 358mg/L to 24347mg/L. The concentrations of N-ε-(1-deoxy-d-fructosyl-1-yl)-l-lysine (Fru-Lys) and N-(1-deoxy-d-fructosyl-1-yl)-l-pyroglutamic acid (Fru-pGlu) were the highest among the APs and the level of Fru-pGlu was similar to that of Fru-Lys. Furthermore, fermentation periods of up to six months greatly influenced AP levels in soy sauce but the levels remained constant thereafter. Thermal treatment of soy sauce had little effect on AP levels.


Ultrastructure of the Lewis lung carcinoma.
ELectron microscopic observations were made on the Lewis lung carcinoma, which has frequently been used in various experiments. Although the tumor cells had desmosomes, interdigitation, microvilli and basement membranes which were of epithelial nature, they did not show either squamous or adenomatous differentiation. On the basis of microscopic and ultrastructural findings, this tumor falls into the category of large cell carcinomas. At the periphery of the tumor, sinusoidal clefts between the strands of tumor cells contained many red blood cells without fibrin. While perfect blood vessels were observed towards the center of the tumor, large necrotic areas were observed. Dilated large vessels possessed some endothelial fenestrations. Light endothelial cells were also observed, which were penetrated by red blood cells. Interstitial components were very scant and collagen fibres were frequently observed to be dissolved.


Serum lectin with known structure activates complement through the classical pathway.
Serum mannan-binding protein (MBP), a lectin specific for mannose and N-acetylglucosamine, was revealed to activate the complement system as measured by passive hemolysis using sheep erythrocytes coated with yeast mannan. In contrast, rat liver MBP, which shares many properties in common with serum MBP, could not activate complement at all. The activation by serum MBP was inhibited effectively by the presence of haptenic sugars and dependent absolutely upon the presence of C4, indicating that the activation is initiated by the sugar binding activity of MBP and proceeds through the classical pathway. The 25 NH2-terminal amino acid sequence of rat serum MBP determined in this study was completely matched with that of MBP-A deduced from cDNA sequence by Drickamer et al. (Drickamer, K., Dordal, M. S., and Reynolds, L. (1986) J. Biol. Chem. 261, 6878-6887), revealing that MBP-A is in fact identical with serum MBP. On the basis of the knowledge of primary structures and physicochemical properties of rat serum and liver MBPs, a possible mechanism of the complement activation by serum MBP is discussed with reference to close similarity in the gross structures of serum MBP and C1q.


Regulation of alternative splicing of Bcl-x by BC200 contributes to breast cancer pathogenesis.
BC200 is a long non-coding RNA (lncRNA) that has been implicated in the regulation of protein synthesis, yet whether dysregulation of BC200 contributes to the pathogenesis of human diseases remains elusive. In this study, we show that BC200 is upregulated in breast cancer; among breast tumor specimens there is a higher level of BC200 in estrogen receptor (ER) positive than in ER-negative tumors. Further experiments show that activation of estrogen signaling induces expression of BC200. To determine the significance of ER-regulated BC200 expression, we knockout (KO) BC200 by CRISPR/Cas9. BC200 KO suppresses tumor cell growth in vitro and in vivo by expression of the pro-apoptotic Bcl-xS isoform. Mechanistically, BC200 contains a 17-nucleotide sequence complementary to Bcl-x pre-mRNA, which may facilitate its binding to Bcl-x pre-mRNA and recruitment of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, a known splicing factor. Consequently, hnRNP A2/B1 interferes with association of Bcl-x pre-mRNA with the Bcl-xS-promoting factor Sam68, leading to a blockade of Bcl-xS expression. Together, these results suggest that BC200 plays an oncogenic role in breast cancer. Thus, BC200 may serve as a prognostic marker and possible target for attenuating deregulated cell proliferation in estrogen-dependent breast cancer.


Towards large-scale identification of HLA-restricted T cell epitopes from four vaccine candidate antigens in a malaria endemic community in Ghana.
Sterile protection against clinical malaria has been achieved in animal models and experimental human challenge studies involving immunization with radiation attenuated Plasmodium falciparum sporozoite vaccines as well as by live sporozoites under chloroquine prophylaxis. Parasite-specific IFN-γ and granzyme B-secreting CD8 + T cells have been identified as key mediators of protection. Although the exact parasite targets of protective CD8 + T cell responses are not fully defined, responses against a handful of vaccine candidate antigens have been associated with protection. Identifying the T cell targets in these antigens will facilitate the development of simpler, cost-effective, and efficacious next generation multi-epitope vaccines. The aim of this study was to identify immunodominant portions of four malaria vaccine candidate antigens using peripheral blood mononuclear cells (PBMCs) from adults with life-long exposure to malaria parasites. Cryopreserved PBMCs from 291 HLA-typed subjects were stimulated with pools of overlapping 15mer peptides spanning the entire sequences of P. falciparum circumsporozoite protein (CSP, 9 pools), apical membrane antigen 1 (AMA1, 12 pools), thrombospondin related anonymous protein (TRAP, 6 pools) and cell traversal for ookinetes and sporozoites (CelTOS, 4 pools) in FluoroSpot assays. 125 of 291 subjects made IFN-γ responses to 30 of the 31 peptide pools tested and 22 of 291 made granzyme B responses, with 20 making dual responses. The most frequent responses were to the CSP C-terminal region and the least frequent responses were to TRAP and CelTOS. There was no association between FluoroSpot responses and active malaria infection, detected by either microscopy, RDT, or PCR. In conclusion, CSP and AMA1 have relatively higher numbers of epitopes that trigger IFN-γ and granzyme B-secreting T cells in adults with life-long malaria parasite exposure compared to the other two antigens tested, and highlights the continued relevance of these two antigens as vaccine candidates.


Meckel's diverticulitis: a rare etiology of an acute abdomen during pregnancy.
Perforated Meckel's diverticulum (MD) is a rare complication of pregnancy. Its diagnosis, however, must be considered in all cases of intra-abdominal disease, as its presentation is similar to appendicitis. Prompt diagnosis and appropriate treatment is imperative in these cases due to the high rate of perforation leading to fetal and maternal morbidity and mortality. The usual lesion affecting a patient with MD and a review of the literature on other unusual causes of an acute abdomen in pregnancy is presented in the following report.


Staging and management of localized non-Hodgkin's lymphomas: variations among experts in radiation oncology.
To examine the opinions of radiation oncology experts on the management of lymphomas with respect to staging procedures, treatment plan, radiation target volume, and dose prescription. Our aim was to identify the patterns of practice and areas of controversy that may need to be resolved and be amenable to prospective clinical trials. Radiation oncology experts in lymphoma management were identified from academic centers in the United States, Europe, and Canada. A sample of individuals with a publication record and/or participation in the design and execution of lymphoma clinical trials (n = 33) were mailed a questionnaire of five case scenarios. The experts were asked to specify their approaches to staging investigations, treatment plan, radiation target volume, and dose prescription for each scenario. Radiation fields were indicated by the respondents on a schematic anatomy diagram on the questionnaire. The response rate to the survey was 82% (27/33). Staging of lymphomas relied on the use of imaging, because computed tomography of the abdomen and pelvis was recommended in all cases, and computed tomography of the uninvolved thorax was advocated by 70% of respondents. A lymphangiogram and a gallium scan were suggested by, respectively, 26% and 25% of respondents. The overall treatment plan was uniform for the four cases of localized presentations of lymphoma. However, the details of chemotherapy and radiation target volume varied significantly. Variations were observed in recommendations regarding the number of courses of chemotherapy and the extent of radiotherapy. The survey documented significant differences in the recommended radiation therapy (RT) dose (30-50 Gy). The scenario of leptomeningeal relapse in diffuse large B-cell lymphoma documented the most diverse treatment recommendations. These varied from whole-brain radiation alone to systemic and intrathecal chemotherapy, radiation with craniospinal coverage, and high-dose chemotherapy with bone marrow transplantation. This survey demonstrated a high degree of consensus regarding the overall management plan of localized lymphomas among the sampled expert radiation oncologists. However, the recommendations regarding the specifics of chemotherapy and RT remain variable. There is clearly no agreement on the most appropriate RT dose and volume. The large variation in the treatment of leptomeningeal relapse of diffuse large B-cell lymphoma suggests that the optimal treatment in this situation is poorly defined, and the clinical outcome with RT, as well as the rationale for decision making, should be examined in more detail.


Does hypoplasia of one pulmonary artery preclude a definitive repair in pulmonary atresia, intact ventricular septum, and hypoplastic right ventricle?
Twins with pulmonary atresia, intact ventricular septum, and hypoplastic right ventricle associated with underdeveloped and discontinuous left pulmonary artery are described. Operations to connect the left pulmonary artery to the main pulmonary trunk, with subsequent biventricular repair assisted by bidirectional cavopulmonary anastomosis and atrial fenestration were performed. Follow-up catheterization proved spontaneous closure of the fenestration in one patient. Both patients have been in a satisfactory condition for 3 years since operation.


Results of intertrochanteric femur fractures treated with a 135-degree sliding screw with a two-hole side plate.
To observe and report the clinical results of the treatment of intertrochanteric hip fractures treated with a 135-degree hip screw with a two-hole side plate. Prospective consecutive. Community private practice. A consecutive series of seventy primarily older patients with intertrochanteric hip fractures treated in a community hospital setting. Surgical treatment with a 135-degree sliding hip screw and a two-hole side plate. Healing rate and time, operative blood loss and time, incidence of hardware failure, and complications including loss of side plate fixation and amount of collapse. Sixty-nine patients, with seventy intertrochanteric hip fractures, underwent surgical treatment with a 135-degree sliding hip screw and a two-hole side plate. There were twenty-one (30 percent) A1.1, sixteen (23 percent) A1.2, twenty-one (30 percent) A2.1, and twelve (17 percent) A2.2 fractures in twenty-three (33 percent) men and forty-six (67 percent) women. Average age was seventy-nine years. The average estimated blood loss was seventy-seven cubic centimeters (range 10 to 300 cubic centimeters), and the average surgical time was thirty-one minutes (range 8 to 90 minutes). The average time to union was fifteen weeks (range 8 to 17 weeks). There were three failures: two from screw cut-out and one from screw plate dissociation. No cases failed due to loss of fixation of the two-hole side plate. Collapse was minimum in fifty-five patients (79 percent), moderate in twelve patients (17 percent), and severe in two patients (3 percent). Use of the 135-degree sliding hip screw with a two-hole side plate produces satisfactory healing and results in relatively low blood loss and short surgical times without the loss of side plate fixation.


RIP2-deficiency induces inflammation in response to SV40 Large T induced genotoxic stress through altered ROS homeostasis.
Deciphering signaling pathways that regulate the complex interplay between inflammation and cell death is a key challenge in understanding innate immune responses. Over recent years, receptor interacting protein (RIP) kinases have been described to regulate the interplay between inflammation and cell death. Whereas RIP1 and 3, the most well described members of the RIP kinase family, play important roles in necroptosis, RIP2's involvement in regulating inflammation, cell death processes and cancer is less well described and controversially discussed. Here, we demonstrate that RIP2 exerts immune regulatory functions by regulating mitochondrial damage and mitochondrial superoxide production in response to SV40 LT-induced genotoxic stress by the induction of ULK1-phosphorylation, therefore regulating the expression of interferon stimulated genes (ISGs) and NLRP3-inflammasome dependent IL-1β release. Because RIP2 is upregulated and/or activated in autoimmune/inflammatory disease and cancer, observations from this study promise implications of RIP kinases in human disease.


Maternal androgen excess inhibits fetal cardiomyocytes proliferation through RB-mediated cell cycle arrest and induces cardiac hypertrophy in adulthood.
Maternal hyperandrogenism during pregnancy is associated with adverse gestational outcomes and chronic non-communicable diseases in offspring. However, few studies are reported to demonstrate the association between maternal androgen excess and cardiac health in offspring. This study aimed to explore the relation between androgen exposure in utero and cardiac health of offspring in fetal and adult period. Its underlying mechanism is also illustrated in this research. Pregnant mice were injected with dihydrotestosterone (DHT) from gestational day (GD) 16.5 to GD18.5. On GD18.5, fetal heart tissue was collected for metabolite and morphological analysis. The hearts from adult offspring were also collected for morphological and qPCR analysis. H9c2 cells were treated with 75 μM androsterone. Immunofluorescence, flow cytometry, qPCR, and western blot were performed to observe cell proliferation and explore the underlying mechanism. Intrauterine exposure to excessive androgen led to thinner ventricular wall, decreased number of cardiomyocytes in fetal offspring and caused cardiac hypertrophy, compromised cardiac function in adult offspring. The analysis of steroid hormone metabolites in fetal heart tissue by ultra performance liquid chromatography and tandem mass spectrometry showed that the content of androgen metabolite androsterone was significantly increased. Mechanistically, H9c2 cells treated with androsterone led to a significant decrease in phosphorylated retinoblastoma protein (pRB) and cell cycle-related protein including cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin D1 (CCND1) in cardiomyocytes. This resulted in cell cycle arrest at G1-S phase, which in turn inhibited cardiomyocyte proliferation. Taken together, our results indicate that in utero exposure to DHT, its metabolite androsterone could directly decrease cardiomyocytes proliferation through cell cycle arrest, which has a life-long-lasting effect on cardiac health. Our study highlights the importance of monitoring sex hormones in women during pregnancy and the follow-up of cardiac function in offspring with high risk of intrauterine androgen exposure.


Modelling pathology from autolog fresh cadaver organs as a novel concept in neurosurgical training.
The aim of neurosurgical cadaver training for residents and fellows is not only to obtain a high level of skills, but also to keep the number of complications during the learning curve as low as possible. To move this process forward, we have worked out a novel method in further training. Tumours can be modelled from the autolog organs. We can then implant the modelled tumour from the opposite direction and a colleague can remove the pathology from the correct approach. We have experienced improving skills in difficult microsurgical operations. We have performed more than 800 fresh cadaver operations over the last 6 years. The last 70 cases have been performed with modelling pathology. In our department, we introduce a regular weekly program in our cadaver operating theatre. The consideration could be useful not only for the young neurosurgeons but also for experienced colleagues.


The lateral mobility and surface distribution of Lyt-1, Lyt-2 and Lyt-3 on mouse thymocytes.
Fluorescein-conjugated monoclonal antibodies were used to investigate the properties of the Lyt-1, Lyt-2 and Lyt-3 antigens on the murine lymphocyte cell surface. Monoclonal antibody to Lyt-1 patched and capped on the thymocyte cell surface, whereas an Fab fragment of the antibody gave a uniform distribution of fluorescence on most cells and diffused freely in the plane of the membrane. Fluorescence photobleaching measurements showed that the intact antibody was relatively immobile on the cell surface, whereas the Fab fragment was freely mobile. Monoclonal antibody to Lyt-2 or Lyt-3 (which are linked to one another by disulfide bonds) gave a uniform distribution of fluorescence and was mobile on the cell surface. When cells were incubated with antibodies to Lyt-2 and Lyt-3 simultaneously, cells appeared patched and the lateral mobility of the antibodies was greatly reduced. Treatment of cells with either sodium azide or 2-mercaptoethanol followed by N-ethyl maleimide to reduce and block sulfhydryl groups inhibited the patch formation caused by simultaneous incubation with both Lyt-2 and Lyt-3 antibodies.


Case report: mRNA-1273 COVID-19 vaccine-associated myopericarditis: Successful treatment and re-exposure with colchicine.
Vaccine-induced myocarditis is a rare complication of messenger RNA (mRNA) COVID-19 vaccines. We report a case of acute myopericarditis in a recipient of allogeneic hematopoietic cells following the first dose of the mRNA-1273 vaccine and the successful administration of a second and third dose while on prophylactic treatment with colchicine to successfully complete the vaccination. Treatment and prevention of mRNA-vaccine-induced myopericarditis represent a clinical challenge. The use of colchicine is feasible and safe to potentially reduce the risk of this rare but severe complication and allows re-exposure to an mRNA vaccine.


Subunit interactions and physical properties of bovine gallbladder mucin.
In this study the interaction of gallbladder mucin subunits was examined by gel permeation chromatography, quasielastic laser light scattering, and viscometry. Purified mucin eluted primarily in the void volume of a Sepharose 2B-Cl column, indicating a molecular weight above 2 x 10(6). Disaggregation of the mucin polymer resulted in the elution of glycoprotein in the included volume of the Sepharose 2B-Cl column. Gallbladder mucin had a hydrodynamic radius of 630 A that was independent of mucin concentration below 2 mg/ml. At mucin concentrations above 2 mg/ml, a concentration-dependent increase in both hydrodynamic radius and apparent viscosity of gallbladder mucin was observed. Mucin demonstrated a strong pH dependence in hydrodynamic radius and viscosity with the maximum occurring at approximately pH 5.5. These findings suggest that noncovalent interactions participate in bovine gallbladder mucin subunit associations. Furthermore, changes that occur in the physicochemical environment of the gallbladder during periods of stasis may enhance the viscoelastic properties of mucin and promote the accumulation of biliary sludge in the gallbladder.


Neuropeptide Y injected into the supraoptic nucleus causes secretion of vasopressin in the unanesthetized rat.
Injection of neuropeptide Y (NPY, 0.01-1.0 nmol in 0.25 microliter vehicle) into the supraoptic nucleus of unanesthetized rats increased plasma vasopressin, measured by radioimmunoassay, to a maximum of 90 +/- 18 ng/liter. Injections of vehicle or somatostatin did not increase plasma vasopressin, nor did injections of NPY into the amygdala. Double-labelling immunohistochemical studies demonstrated that fibers containing NPY-like immunoreactivity form a close association with vasopressin immunoreactive perikarya in the supraoptic nucleus. It appears that NPY may directly excite vasopressin-containing neurons causing secretion of vasopressin.


Assessment of the parallelization approach of d2_cluster for high-performance sequence clustering.
The exponential increase in expressed sequence tag (EST) sequence data amplifies the computational cost of clustering sequences such that new algorithms are required to analyze data at a greater rate. We have parallelized d2_cluster on a SGI Origin 2000 multiprocessor and observed a speedup of approximately 100x on 126 processors when processing a 15,876 EST dataset. The parallelized d2_cluster code is obtainable from the SANBI website (http://www.sanbi.ac.za/CODES).


An emergency physician's guide to prosthetic heart valves: valve-related complications.
Serious valve-related complications that occur in patients with prosthetic valves have been discussed. The emergency physician's role primarily is to recognize the high probability that one of these serious complications exists and hospitalize the patient so that rapid definitive diagnoses and therapeutic decisions are not delayed.


Insulin generates free radicals in human fibroblasts ex vivo by a protein kinase C-dependent mechanism, which is inhibited by pravastatin.
Insulin can generate oxygen free radicals. Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, exert a powerful antioxidant effect. The present study aimed to clarify the mechanisms through which insulin generates free radicals and to assess whether pravastatin modulates such effects. In cultured skin fibroblasts from human volunteers exposed to high insulin concentration, either in the presence or in the absence of pravastatin, insulin induced translocation of the p47(phox) subunit of NAD(P)H oxidase from the cytosol to the membrane and generation of radical oxygen species through a PKC delta-dependent mechanism. The insulin-induced translocation of p47(phox) was PKC delta dependent and attenuated by pravastatin, but independent of the activation of Akt and Rac1. Insulin-induced Akt phosphorylation was increased by pravastatin and ERK1/2 phosphorylation attenuated. The present study demonstrates a novel mechanism by which insulin stimulates the generation of free radicals in human fibroblasts, ex vivo. It involves phosphatidylinositol 3-kinase, PKC delta, and p47(phox) translocation and promotes ERK1/2 phosphorylation. Pravastatin inhibited radical oxygen species production by inhibiting PKC delta. These observations offer a robust explanation for the positive effects of pravastatin treatment in patients with insulin resistance syndrome.


Quality of life and functional status in patients with advanced cancer admitted to hospice home care in Malaysia: a cross-sectional study.
Cancer patients more than often experience poor quality of life after diagnosis and treatment of cancer. As the disease progresses quality of life issues become important. This cross-sectional study assessed various features of quality of life among 61 (33 women and 28 men) patients with advanced cancer cared by selected hospices in Peninsular Malaysia. The Hospice Quality of Life Index was used to assess quality of life. The mean total Hospice Quality of Life Index score for all subjects was 189.9 ± 51.7. The possible scores range from 0 to 280. The most problem areas in these patients were in the domain of functional well-being, followed by psychophysiological and social/spiritual domain. Patients with advanced cancer have a diminished quality of life. These findings suggest that there is a need for improving quality of life in terminally ill cancer patients in hospice care.


Human P450PCN1: sequence, chromosome localization, and direct evidence through cDNA expression that P450PCN1 is nifedipine oxidase.
P450PCN protein levels and nifedipine oxidase activities were quantitated in 12 human livers and were shown to be highly correlated. Antibody against rat P450PCN1 completely inhibited all nifedipine oxidase activity in three human liver samples. These results suggest that a human P450 related to rat P450PCN1 is the major form of P450 catalyzing nifedipine oxidation. The cDNA for a human P450, designated phPCN1, was isolated from a human liver lambda gt11 cDNA library, and sequenced completely. The deduced amino acid sequence is 77% similar to rat P450PCN1. By use of the adenovirus- and SV40-based expression vecotr p91023(B), the phP450PCN1 cDNA was expressed in COS cells and had high nifedipine oxidase activity, providing conclusive evidence that this P450 is the primary enzyme associated with metabolism and inactivation of this important drug. Using somatic cell hybrids, the P450PCN gene was localized to human chromosome 7.


Strain-specific differences in transcription of the gene for the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase.
Phenylethanolamine N-methyltransferase (PNMT), the enzyme which synthesizes the catecholamine epinephrine (adrenaline), may be regulated at many levels of expression. This study examines one level, the production of PNMT hnRNA, by measuring its rate of transcription in the rat adrenal gland and bovine adrenal medulla using an in vitro nuclear transcription run-on assay. Furthermore, when the transcriptional rate is compared in strains of rat known to possess distinctive levels of epinephrine and PNMT enzyme, the rate of PNMT transcription in Fischer rats is greater than in Buffalo or Sprague-Dawley rats: relative ratios are 0.54:1.00:1.6 for Buffalo:Sprague-Dawley:Fischer adrenal glands. As such, it appears that the rate of PNMT gene transcription is the major factor responsible for the strain-specific levels of PNMT mRNA among these rats. Therefore, in addition to regulation by neural and steroid influences, an intrinsic genetic component also governs the level of PNMT gene expression.


Three months of abstinence from alcohol normalizes energy expenditure and substrate oxidation in alcoholics: a longitudinal study.
The aim of this study was to evaluate the energy expenditure, substrate oxidation, and body composition in alcoholics during addiction and after several months of abstinence. A total of 32 alcoholics without liver cirrhosis and malabsorption were consecutively recruited. A total of 55 social drinkers, matched for gender and height, were studied as a control group. Anthropometry and bioimpedance analysis were performed to assess body composition, and indirect calorimetry was used to measure basal metabolic rate (BMR) and substrate oxidation. Total abstinence was then achieved in 15 subjects. At 1, 2, 3, and 6 months of abstinence, the metabolic variables and the energy intake were re-examined. At enrollment (T0) alcoholics compared to controls showed a significant decrease in body mass index (22.2+/-2.71 vs 23.6+/-1.3 kg/m2; p < 0.05), fat mass (14.1+/-4.5 vs 16.7+/-3.3 kg; p < 0.01), an increased BMR normalized by fat-free mass (34.5+/-3.7 vs 32.1+/-2.01 kcal/kg/day; p < 0.01), a lower nonprotein respiratory quotient (npRQ: 0.76+/-0.03 vs 0.83+/-0.03; p < 0.001), with a consequently higher lipid oxidation (0.08+/-0.02 vs 0.04+/-0.02 g/min; p < 0.01), and a lower carbohydrate oxidation (0.05+/-0.02 vs 0.10+/-0.03 g/min; p < 0.01). Although at 1 and 2 months of abstinence the metabolic parameters had improved, only after 3 months of abstinence did alcoholics show values of body mass index (23.2+/-2.6 kg/ m2), fat mass (17.0+/-5.34 kg), BMR/fat-free mass (33.1+/-2.78 kcal/kg/day), npRQ (0.82+/-0.02), lipid oxidation (0.05+/-0.03 g/min) and carbohydrate oxidation (0.11+/-0.04 g/min) comparable to those of controls; these values remained constant at 6 months. Three months of abstinence from alcohol could represent the minimum time necessary to obtain a normalization of the metabolic variables considered and of the nutritional status for these patients, probably related to a regression of the functional alterations of the microsomal ethanol oxidizing system and of mitochondria secondary to chronic ethanol abuse.


Vibrational deactivation of singlet oxygen: does it play a role in stereoselectivity during photooxygenation?
Oxazolidinone-substituted enecarbamates offer a system to explore vibrational quenching and the strategic placement of CH bonds as a method for manipulating the stereoselectivity of photoreactions.


PIK3R3 is a candidate regulator of platelet count in people of Bangladeshi ancestry.
Blood platelets are mediators of atherothrombotic disease and are regulated by complex sets of genes. Association studies in European ancestry populations have already detected informative platelet regulatory loci. Studies in other ancestries can potentially reveal new associations because of different allele frequencies, linkage structures, and variant effects. To reveal new regulatory genes for platelet count (PLT). Genome-wide association studies (GWAS) were performed in 20,218 Bangladeshi and 9198 Pakistani individuals from the Genes & Health study. Loci significantly associated with PLT underwent fine-mapping to identify candidate genes. Of 1588 significantly associated variants (P < 5 × 10-8) at 20 loci in the Bangladeshi analysis, most replicated findings in prior transancestry GWAS and in the Pakistani analysis. However, the Bangladeshi locus defined by rs946528 (chr1:46019890) did not associate with PLT in the Pakistani analysis but was in the same linkage disequilibrium block (r2 ≥ 0.5) as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning 8 coding genes. Functional annotation, mapping to megakaryocyte regulatory regions, and colocalization with blood expression quantitative trait loci identified the likely mediator of the PLT phenotype to be PIK3R3 encoding a regulator of phosphoinositol 3-kinase (PI3K). Abnormal PI3K activity in the vessel wall is already implicated in the pathogenesis of atherothrombosis. Our identification of a new association between PIK3R3 and PLT provides further mechanistic insights into the contribution of the PI3K pathway to platelet biology.


[CHILD syndrome--a case report for understanding this rare genetic dermatosis].
CHILD syndrome in a 4 6/12 years old girl with manifestation of the typical unilateral ichthyosiform erythroderma and hypoplasia of the left arm and leg after birth is reported. The symptoms are listed in a table for comparison to other publications. The moderate shortening of the mother's left arm has significance to the unclear mode of heredity. Local therapy with vitamin A acid brought a satisfactory result. Finally, a short reference is given to a new case from another kindred.


Ultrastructure of neurons in the auditory cortex of ageing rats: a morphometric study.
The cell bodies of pyramidal cells in layers II and V of rat auditory cortex were quantitatively examined in groups of rats 3, 6, 15, 23, 27 and 34-36 months of age. The mean diameters of cell bodies of both layer II and layer V neurons, as measured in 1 micron plastic sections, increased between 3 and 15 months of age, then decreased to a diameter that was less in the 36-month-old than in the 3-month-old rats. Morphometry of the nuclei of the cells was done by measuring nuclear area and nuclear envelope length directly on electron micrographs. In the layer II cells, neither parameter changed with advancing age. In the layer V cells, the mean nuclear area decreased significantly in the old animals and the mean envelope length increased. Point-counting techniques were applied to electron micrographs of cell bodies to determine the relative volume of selected organelles, inclusions and ground substance in the perikaryal cytoplasm. In this part of the study the chronological pattern of change in layer II and layer V pyramidal cells was similar. The relative volume of dense bodies increased linearly with advancing age, with a slightly more accelerated rate in layer II cells. The relative volume of ground substance remained essentially constant through 27 months, and then at 34-36 months decreased to 83% and 89% of the three-month level in layer V and layer II, respectively. The relative volume of the rough endoplasmic reticulum (RER) did not change significantly until after 15 months, at which time it began to occupy increasingly a larger fraction of the perikaryal cytoplasm. Finally, the relative volumes of mitochondria, multivesicular bodies and Golgi apparatus did not show clear trends of change during the 33-month period.


Molecular epidemiological surveillance to assess emergence and re-emergence of tick-borne infections in tick samples from China evaluated by nested PCRs.
An investigation was performed to detect eight pathogens in ticks collected from grass tips or animals in the southern, central and northeast regions of China. DNA samples extracted from ticks were collected from ten different locations in eight provinces of China and subjected to screening for tick-borne pathogens, including Borrelia burgdorferi sensu lato, Ehrlichia spp., Rickettsia spp., Babesia/Theileria spp., Ehrlichia ruminantium, Coxiella burnetii, and Francisella tularensis, using nested PCR assays and sequencing analysis. The results indicated that Borrelia spp., Rickettsia spp., and Babesia/Theileria spp. were detected in all of the investigated provinces. Ehrlichia spp. was also found in all of the surveyed areas, except Guangxi, Luobei and Tonghe counties in Heilongjiang province. The average prevalence of these pathogens was 18.4% (95% CI=12.8-42.5), 60.3% (95% CI=18.2-65.3), 26.0% (95% CI=25.8-65.1), and 28.7% (95% CI=5.6-35.2), respectively. A sequencing analysis of the pCS20 gene of E. ruminantium revealed an E. ruminantium-like organism (1/849, 0.1%, 95% CI=0-0.3) in one tick DNA sample extracted from Rhipicephalus (Boophilus) microplus in Hunan. In addition, Borrelia americana in Ixodes persulcatus, Babesia occultans in Haemaphysalis qinghaiensis and both Rhipicephalus sanguineus and an Ehrlichia muris-like organism in R. (B.) microplus was detected, possibly for the first time in China. Four DNA sequences closely related to Borrelia carolinensis and/or Borrelia bissettii from Haemaphysalis longicornis, Candidatus Rickettsia principis from H. qinghaiensis, and I. persulcatus and Ehrlichia canis (named E. canis-like) from Haemaphysalis bispinosa were also detected in this work.


[A dynamic study of the impulse processes in human cerebral neurons by using the principal-component method].
Evoked activity (EA) of single neurons to verbal (or sensory) stimuli was recorded by microelectrodes in the nucleus reticularis and some other thalamic nuclei of the human brain during stereotaxic operations. An approach is considered which results from the assumptions of the cumulativeness and variability of the EA pattern and is based on the principal component analysis and peristimulus covariation matrices. Application of these methods for estimating unitary responses showed their efficiency for the quantitative analysis of the dynamic structure and interneuronal relations within the EA patterns during the performance of voluntary motor acts.


Hostplant, larval age, and feeding behavior influence midgut pH in the gypsy moth (Lymantria dispar).
The midgut pH of late instar gypsy moth (Lymantria dispar L.) larvae is strongly alkaline, and varies with diet, larval stadium, and time since feeding. Midgut pH rises with time since feeding, and does so more quickly, reaching greater maximum values, on some diets than others. Leaf tissues of 23 tree species resist increases in alkalinity differentially; this trait and differing initial leaf pH may explain the impact of diet on gut pH. Third instar larvae may have gut conditions favorable for tannin-protein binding shortly after ingesting certain foods, but with time midgut alkalinity becomes great enough to dissociate tannin-protein complexes. Older instars rarely exhibit gut pHs low enough to permit tannin activity. Alkaline gut conditions may explain the gypsy moth's ability to feed on many tanniniferous plant species, especially in later instars. Consequences for pathogen effectiveness are discussed.


Novel Bio-Based Materials: From Castor Oil to Epoxy Resins for Engineering Applications.
The paper presents the synthesis and thermal behavior of novel epoxy resins prepared from epoxidized castor oil in the presence of or without trimethylolpropane triglycidyl ether (TMP) crosslinked with 3-hexahydro-4-methylphtalic anhydride (MHHPA) and their comparison with a petroleum-based epoxy resin (MHHPA and TMP). Epoxidized castor oil (ECO) was obtained via in situ epoxidation of castor oil with peroxyacetic acid. The chemical structures of castor oil (CO), ECO, and epoxy matrix were confirmed using FT-IR and 1H-NMR spectroscopy. The morphological and thermal behavior of the resulting products have been investigated. Compared to petroleum-based resins, castor oil-based ones have a lower Tg. Anyway, the introduction of TMP increases the Tg of the resins containing ECO. The morphological behavior is not significantly influenced by using ECO or by adding TMP in the synthesis of resins. The dielectric properties of epoxy resins have been analyzed as a function of frequency (1 kHz-1 MHz) and temperature (-50 to 200 °C). The water absorption test showed that as Tg increased, the percent mass of water ingress decreased.


EFFECT of nicotine on hippocampal nicotinic acetylcholine alpha7 receptor and NMDA receptor subunits 2A and 2B expression in young and old rats.
Nicotinic acetylcholine (nAChR) and N-methyl-D-aspartate receptors (NMDARs) play critical roles in memory function. This study administered chronic nicotine to determine the alterations of N-methyl-D-aspartate receptor subunit 2A and 2B (NR2A, NR2B) and the alterations of alpha7nAChR receptor. It was determined that the effectivity of nicotine and the data support that nicotine increases hippocampal NR2A and B expression. Additionally, the role of nicotine in the cognitive improvement was not supported by the antioxidative mechanisms or the authors observed no effect of nicotine on lipid peroxidation at the hippocampus.


Enhancement of vascular contractility by plasma substances obtained from pregnancy-induced hypertension.
1. Augmentation of norepinephrine (NE)-induced contraction of isolated dog mesenteric arteries by ouabain was significantly enhanced under 4 mM potassium ([K+]) medium condition compared with usual medium condition at 6 mM [K+]. 2. Vascular contractility to NE was significantly enhanced by plasma substances obtained from pregnancy-induced hypertension (PIH) patients compared with that from normotensive pregnant women under 4 mM [K+] medium condition despite of no difference between them under 6 mM [K+] medium condition. 3. These results suggest the possible involvement of the ouabain-like substance in development of hypertension in PIH patients.


The pharmacist's role in managing chronic opioid therapy.
Chronic pain is a costly and prevalent problem. Pain, itself, is a symptom. Pain has received attention in the form of health care policy reform, development of assessment tools, and treatment protocols. Chronic pain is an ongoing problem that requires constant monitoring and can be challenging to health care providers and patients. Many barriers exist in treating chronic pain, especially when treating with opioid analgesics. Pharmacists can help in the assessment and treatment of chronic pain. This article discusses the impact of chronic pain, barriers to care, and the role of the pharmacist in managing chronic opioid therapy.


Factors Affecting Treatment Outcome of Graft Infection Following Penetrating Keratoplasty.
To evaluate the factors affecting treatment outcome of graft infection following penetrating keratoplasty (PKP). In this retrospective study, 28 patients who underwent PKP between January 2005 and January 2013 and who were diagnosed with graft infection were classified into a treatment success group or a treatment failure group. Demographic and clinical characteristics, as well as the results of the microbiologic investigation, were analyzed and compared. A subsequent binary logistic regression analysis was performed to identify the prognostic factors affecting treatment outcome. Graft infection occurred at a mean of 38.29 ± 36.16 months (range, 1 to 96 months) after PKP. Seventeen patients developed bacterial keratitis, and 11 patients developed fungal keratitis. Overall, of the 28 patients, nine (32.1%) were classified in the treatment failure group. Multivariate analysis identified pre-existing graft failure (p = 0.019), interval longer than 72 hours between donor death and PKP (p = 0.010), and fungal infection (p = 0.026) as significant risk factors for treatment failure. Pre-existing graft failure, extended interval between donor death and PKP, and fungal infection were important risk factors for treatment failure of graft infection following PKP.


Significance of respiratory artifact in the electrocardiogram.
Electrocardiographic artifact is generally considered to be a nuisance. Respiratory artifact, however, is a physiologic signal that may carry useful diagnostic information. Our goal was to evaluate the characteristics, prevalence, and clinical significance of respiratory artifact observed in electrocardiograms (ECGs). ECGs exhibiting repetitive microoscillations were systematically collected. The morphologic characteristics of the microoscillations were analyzed and their association with the respiratory cycle was evaluated using simultaneous respiratory waveform tracings. The presence and rate of respiratory artifact were correlated with the patient's clinical status, including medical diagnoses and the need for ventilatory support. During a 30-month period, respiratory artifact was detected in 320 12-lead ECGs. It was best seen in leads II, III, aVF, and V5. Respiratory artifact occurred during the inspiratory phase and its rate correlated precisely with objective measures of the respiratory rate. The majority of patients with respiratory artifact revealed diseases of the respiratory (26.6%) and circulatory systems (24.0%) and, of note, respiratory artifact was never detected in patients with normal cardiorespiratory function; 43.5% of patients with respiratory artifact required ventilatory support, including 28.2% requiring continuous mechanical ventilation. Successful treatment of the underlying condition resulted in a decrease in the rate or in complete disappearance of the respiratory artifact. In conclusion, respiratory artifact is commonly seen in routine 12-lead ECGs of hospitalized patients. It is associated with a high-risk state of increased work of breathing due to either compromised cardiac or pulmonary function. Additionally, the presence of respiratory artifact enables precise evaluation of the respiratory rate-a commonly miscalculated vital sign.


Cardiorespiratory Responses to Acoustic Noise in Belugas.
To date, most research on the adverse effects of anthropogenic noise on marine mammals has focused on auditory and behavioral responses. Other responses have received little attention and are often ignored. In this study, the effect of acoustic noise on heart rate was examined in captive belugas. The data suggest that (1) heart rate can be used as a measure of physiological response (including stress) to noise in belugas and other cetaceans, (2) cardiac response is influenced by parameters of noise and adaptation to repeated exposure, and (3) cetacean calves are more vulnerable to the adverse effect of noise than adults.


Association of perceived stress with memory decline in older Chinese: The Guangzhou Biobank Cohort Study.
Previous studies on associations of perceived stress with poor memory performance in older adults showed inconsistent results. We examined the prospective associations of perceived stress with memory decline using data from Guangzhou Biobank Cohort Study (GBCS). Perceived stress was measured by the Perceived Stress Scale (PSS) at baseline (2003-2006), with greater scores indicating greater stress. Memory function was measured by delayed 10-word recall test (DWRT) and immediate 10-word recall test (IWRT), with greater scores indicating better performance, at baseline and follow-up (2008-2012) examinations, analyzed as mean annual change in scores. 9656 participants (72 % women) with mean age 61.6 (standard deviation = 6.4) years were included. During an average of 4.4 years of follow-up, after adjusting for confounders, each one-point greater PSS score was associated with mean annual decline in DWRT scores (β (95 % CI) = -0.005 (-0.008 to -0.002)). Greater Perceived Helplessness (PH) scores, but not Perceived Self-efficacy scores, was associated with greater mean annual decline in DWRT and IWRT scores (β (95 % CI) = -0.005 (-0.009 to -0.001) and - 0.012 (-0.018 to -0.005), respectively), and similar patterns were observed in five out of seven PH items (βs from -0.02 to -0.07). Interaction analysis showed that the association of greater PSS with greater decline in DWRT scores was observed only in those with low family income (β (95 % CI) = -0.08 (-0.13 to -0.04), P for interaction = 0.03). Greater perceived stress was associated with a greater decline in delayed recall memory, especially in those with low family income.


The complete nucleotide sequence of chicken ribosomal protein L7a gene and the multiple factor binding sites in its 5'-flanking region.
The nucleotide sequence of the gene encoding chicken ribosomal protein L7a was determined. The gene contains eight exons and seven introns, which spread over 3613 nucleotides. The transcription initiation sites were located on four consecutive nucleotides GCCC, which are at the 5' terminus of a short polypyrimidine tract of eight base-pairs flanked by G + C-rich regions. Neither a canonical TATA nor a CAAT box was found in the 5'-flanking region. Instead, a short A + T-rich stretch was found at the position where the TATA box is expected to be. There is an intensive nuclear protein binding motif repeated four times in the region -134 to -50. This motif is common to many ribosomal protein genes and may play an important role in the control of ribosomal protein gene expression.


Evaluation of reactive Epstein-Barr Virus (EBV) in Iranian patient with different subtypes of multiple sclerosis (MS).
Epstein-Barr virus has been recently associated with the onset of multiple sclerosis, yet understanding how it elicits autoimmunity remains elusive. We investigated the relation between Epstein-Barr virus reactivation and disease development in different subtypes of multiple sclerosis. In the present research, we have determined the Epstein-Barr virus-DNA load by quantitative real-time polymerase chain reaction and Epstein-Barr virus antibody levels by EIA technique in both multiple sclerosis patients (n=78) and healthy controls (n=123). Our results demonstrated increased titer of both anti-Epstein-Barr virus-IgG and IgM antibodies in patients (91.02% vs 82.11% in controls, p<0.001 and 14.1% vs 4.06% in controls, p<0.001, respectively). Overall, Epstein-Barr virus reactivation was found in 68.75% of subtypes of multiple sclerosis, 4.54% of multiple sclerosis primary subtype, and in only 3.25% of healthy control subjects. Moreover, in samples of patients with disease relapse (exacerbation) cell free viral DNA was elevated in contrast to other patients (p<0.001). These findings provide further support for the detrimental effects of Epstein-Barr virus in the reactivation of multiple sclerosis attacks.