Altered large-scale internetwork functional connectivity in patients with vestibular migraine and migraine without aura.
To investigate large-scale internetwork functional connectivity in patients with vestibular migraine (VM) and migraine without aura (MwoA). Resting-state functional magnetic resonance imaging data from 34 VM patients, 34 MwoA patients, and 33 healthy controls (HCs) were collected and the results were analyzed using independent component analysis (ICA). We also analyzed the correlations between clinical data and internetwork functional connectivity. In contrast to HCs, MwoA patients showed decreased functional connectivity between the left frontoparietal network (lFPN) and right frontoparietal network (rFPN), with increased functional connectivity between the sensorimotor network (SMN) and lateral visual network (lVN). When compared to MwoA patients, VM patients demonstrated decreased functional network connectivity between the dorsal attention network (DAN) and posterior medial visual network (pmVN), between the SMN and pmVN, and between the SMN and lVN. Meanwhile, increased functional network connectivity was found between the lFPN and rFPN; however, there was no significant difference in functional network connectivity between VM patients and HCs. In addition, associations were found between clinical data and internetwork functional connectivity. Functional connectivity between the lFPN and rFPN was reduced in patients with MwoA compared with HCs, which may indicate functional impairment in cognitive control, attention, somatosensory perception, and emotion regulation in patients with MwoA. VM patients showed decreased functional connectivity between the DAN, SMN, pmVN and lVN compared to patients with MwoA, which could account for the multisensory integration abnormalities and be the cause of vestibular symptoms in VM patients. These findings offer fresh perspectives on the pathophysiology of VM and MwoA.


Novel PGD strategy based on single sperm linkage analysis for carriers of single gene pathogenic variant and chromosome reciprocal translocation.
Preimplantation genetic diagnosis (PGD) analysis can be challenging for couples who carry more than one genetic condition. In this study, we describe a new PGD strategy to select which embryo(s) to transfer for two clinically challenging cases. Both cases lack essential family members for linkage analysis including de novo mutation combined with reciprocal translocation. Diverging from conventional method, we performed direct point mutation detection, quantitative analysis of gene copy number, combined with linkage analysis assisted by SNP information from single sperm (or polar bodies), thus establishing an all-in-one protocol for single embryonic cell preimplantation diagnosis for two co-existing genetic conditions (monogenic disease and chromosomal abnormality) on the NGS-based platform. Using this newly developed method, 15 embryos from two cases were screened, and two embryos were determined as free of the monogenic disease and specific chromosomal abnormalities created by the prospective father's reciprocal translocations. This novel PGD strategy could effectively select unaffected embryo(s) for couples affected with or carrying a monogenetic disease and a reciprocal chromosome translocation concurrently.


Long-term follow-up of children with testicular tumours: surgical issues.
Testicular tumours are rare in childhood. The clinical, pathological and follow-up details of 48 children are presented. The combined approach of surgery, chemotherapy and radiotherapy is confirmed as being extremely effective. Transcrotal orchiectomy is not an appropriate surgical procedure. Testicular biopsy is detrimental to prognosis.


The new T3b category has clinical significance? SEER-based study.
As per the eighth edition of the American Joint Committee on Cancer (AJCC) staging system for differentiated thyroid carcinoma (DTC), minimal extrathyroidal extension (mETE) has been removed. Instead, gross ETE (gETE) invading only strap muscles has been designated as a new T3b category. Our objective was to investigate the impact of the T3b category on survival in order to establish its prognostic value in DTC. In this retrospective study, we included patients who had undergone thyroidectomy between 2004 and 2012. Data from the Surveillance, Epidemiology and End Results (SEER) database were examined. We used the Kaplan-Meier method and log-rank test to analyse overall survival (OS) and cancer-specific survival (CSS). The effect of potential predictors associated with survival were estimated using the Cox regression model. To minimize selection bias, propensity-score matching (PSM) was performed. A total of 63 315 patients were included in our study. During the average follow-up duration of nearly 78 months, significant differences were observed in cancer-specific survival among patients with no ETE, mETE, gETE invading only strap muscles (T3b) and gETE invading perithyroidal structures other than strap muscles (T4) (P < .05). In univariable and multivariate analysis, both mETE and T3b exhibited significant poorer CSS compared with no ETE. After adjusting for patient features with PSM, it was confirmed that T3b was associated with worse CSS compared with no ETE and mETE. Both mETE and gETE are independent factors for DTC, implying that the new T3b category is worthy of reference for medical workers. Furthermore, mETE was significantly associated with poorer outcome. Our conclusion may provide support for the modification of the TNM staging system in the future.


Exogenous estrogens attenuate dietary hypercholesterolemia and atherosclerosis in the rabbit.
The effect of exogenous estrogens upon the response to dietary cholesterol was tested in New Zealand White rabbits. Cholesterol-fed, untreated rabbits had a 10-fold increase in plasma cholesterol in 12 wk. The major increase of cholesterol occurred in very low density lipoproteins (VLDL, 43.5-fold) followed by intermediate density lipoproteins (IDL, 26-fold) and low density lipoproteins (LDL, 6-fold) with no change in high density lipoproteins (HDL). These diet induced changes were markedly attenuated in the estrogen treated animals, in whom plasma cholesterol increased only 5-fold. This increase was distributed among LDL (6-fold), IDL (7.5-fold), and VLDL (9-fold), similarly with no change in HDL. All the lipoproteins in both groups of animals were considerably enriched in cholesterol during cholesterol feeding as indicated by a high cholesterol/protein and cholesterol/triglyceride ration. However, these ratios were lower in estrogen treated animals. There were no differences in the feed consumption, body weight or cholesterol absorption between the two groups of animals. Rabbits fed a cholesterol-rich diet but not treated with estrogen had well developed lesions in all parts of the aorta with higher content of cholesterol and phospholipids as compared to those injected with estrogen, whose aortas were completely clear of visible atherosclerosis. Equivalent total hypercholesterolemia was induced in other estrogen-treated rabbits by feeding twice the cholesterol dietary content (0.2%) as in nonestrogen-treated animals. Aortic atherosclerosis was far more evident in the latter, which had higher proportions of cholesterol-rich lipoproteins of d less than 1.006 g/ml.


Contribution to therapeutic decisions of ratios, absolute values and other measures of calcium, magnesium, urate or oxalate balance in stone formers.
Investigation of multiple serum and urinary factors in 44 patients with calcium urinary stone disease confirmed a number of defects that have been described previously: elevation of mean serum calcium and uric acid above normal, and depression of mean serum magnesium. Urinary excretion of calcium and uric acid was increased and was increased and was probably related to food ingestion. Urinary magnesium also increased after eating but less than calcium, with the result that for most patients the magnesium to calcium x 100 ratio approached levels observed in stone formation. Urinary oxalate excretion was constant during the entire observation period and apparently was not affected by ingestion of a defined diet. Nine additional patients had persistent hypercalcemia owing to hyperparathyroidism (5 confirmed, 1 suspected), malignancy (2) and drug ingestion (1). Metabolic evaluation of patients with calcium urinary calculi continues to contribute to decisions regarding their best therapeutic regimen.


A West Nile Virus infection expressed as unilateral limb paralysis and complicated by Parsonage-Turner syndrome: a case report.
West Nile Virus is a single-stranded Ribonucleic Acid arbovirus of the Flaviviridae family that is transmitted to humans by Culex species mosquitoes. West Nile Virus infection is asymptomatic in the majority of affected people. Of those who develop symptoms, the usual manifestation is a febrile syndrome, while only 1% develop neurological symptoms due to a neuroinvasive form of infection, including encephalitis, meningitis, asymmetrical flaccid paralysis, or a combination of all these features. Parsonage-Turner syndrome is a rare disorder characterized by sudden painful symptoms and subsequent paralysis, involving a shoulder or one of the upper limbs due to post-infective brachial plexopathy. The etiology is unknown, although it can be considered a multifactorial process: a predisposing factor, such as viral infection or strenuous upper-extremity exercise, can trigger an immune-mediated process localized in the brachial plexus. In late summer, a 79-year-old male Italian patient was admitted to the emergency department for acute right upper limb weakness and high fever, without any mental status impairment, pain, sensory alterations, or signs of meningeal irritation. Laboratory tests confirmed acute West Nile Virus infection, expressed as a unilateral upper limb flaccid paralysis. After a few days, the patient reported an acute pain in the right upper limb scarcely responsive to nonsteroidal anti-inflammatory drug therapy and a subsequent wider distribution of flaccid paralysis. After multiple examinations, Parsonage-Turner syndrome could be suspected. Patient was treated with steroids and reported an improvement of clinical condition after 2 months, with complete pain remission but partial strength recovery in the affected limb. West Nile Virus disease has a broad spectrum of neurological manifestations, among which the most common are signs of meningeal irritation or cognitive impairment. We report an unusual presentation of neuroinvasive West Nile Virus infection with arm weakness as expression of unilateral viral neuritis, followed by a post-infective brachial plexopathy consistent with Parsonage-Turner syndrome diagnosis. We diagnosed Parsonage-Turner syndrome after excluding the most common causes of atraumatic acute upper limb pain, through a challenging differential diagnosis in a patient with several comorbidities.


Post-hepatectomy liver failure prediction and prevention: Development of a nomogram containing postoperative anticoagulants as a risk factor.
Posthepatectomy liver failure (PHLF) is a serious complication after hepatectomy, and its effective methods for preoperative prediction are lacking. Here, we aim to identify predictive factors and build a nomogram to evaluate patients' risk of developing PHLF. A retrospective review of a training cohort, including 199 patients who underwent hepatectomy at the Shanghai Eastern Hepatobiliary Surgery Hospital, was conducted. Independent risk variables for PHLF were identified using multivariate analysis of perioperative variables, and a nomogram was used to build a predictive model. To test the predictive power, a prospective study in which a validation cohort of 71 patients was evaluated using the nomogram. The prognostic value of this nomogram was evaluated by the C-index. Independent risk variables for PHLF were identified from perioperative variables. In multivariate analysis of the training cohort, tumor number, Pringle maneuver, blood loss, preoperative platelet count, postoperative ascites and use of anticoagulant medications were determined to be key risk factors for the development of PHLF, and they were selected for inclusion in our nomogram. The nomogram showed a 0.911 C-index for the training cohort. In the validation cohort, the nomogram also showed good prognostic value for predicting PHLF. The validation cohort was used with similarly successful results to evaluate risk in two previously published study models with calculated C-indexes of 0.718 and 0.711. Our study establishes for the first time a novel nomogram that can be used to identify patients at risk of developing PHLF.


Interview-based ratings of DSM-IV Axis II/DSM-5 Section II Personality Disorder symptoms in consecutively admitted insomnia patients: A comparison study with consecutively admitted psychotherapy patients matched on age and gender.
Selected personality features may represent important predisposing as well as perpetuating factors for insomnia, and previous studies stressed the importance to assess personality disorders in insomnia patients. In order to evaluate the relationships between DSM-IV Axis II/DSM-5 Section II Personality Disorders (PDs) and insomnia, a sample of 171 consecutively admitted insomnia patients and a sample of 171 psychotherapy patients, matched on age and gender were administered the Italian translation of the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, Version 2.0 (SCID-II). Among insomnia patients, 52.0% (n = 89) received at least one DSM-IV Axis II/DSM-5 Section II PD diagnosis according to SCID-II assessment. Any PD base rate estimate in our insomnia patient sample was significantly and markedly higher than the median and mean base rate estimates for any PD in the general population. Within-group analyses showed that Narcissistic, Not otherwise specified PD, Histrionic PD, and Borderline PD represented the most frequently diagnosed-both dimensionally and categorically-DSM-IV Axis II/DSM-5 Section II PD features in our insomnia patient sample. When continuously-scored PDs were considered, insomnia patients showed a significantly lower number of Paranoid and Borderline PD features than psychotherapy patients; however, the corresponding effect size estimates suggested that these differences were modest. None of the categorically-scored PDs significantly differentiated insomnia patients from psychotherapy patients. As a whole, our findings seemed to suggest that personality dysfunction may play a role in insomnia, while stressing the need for a dimensional approach to the assessment of maladaptive personality traits even in insomnia patients.


Microtubule dynamics in mitosis in Aspergillus nidulans.
Mitosis in Aspergillus nidulans is very rapid, requiring less than 5 min at 37 °C in germlings (Bergen and Morris, 1983). In this time the cytoplasmic microtubules (MTs) must disassemble, the mitotic spindle assemble, function and disassemble, and cytoplasmic MTs reassemble. It follows that cytoplasmic MTs must be extremely dynamic in this period and we were interested, in particular, in examining the processes of MT disassembly in prophase and reassembly in anaphase and telophase. We observed a diploid strain that expressed GFP-α-tubulin. We used a spinning disk confocal microscope that allowed rapid image capture, which proved necessary because microtubule dynamics were extremely rapid. We found, for the first time, that microtubule severing occurs in prophase in a filamentous fungus and that catastrophe rather than nucleation limits astral microtubule growth.


Effect of phytogenic supplements on the reproductive physiology and metabolic hormones of rabbits exposed to heat stress conditions.
This study investigated the role of phytogenic supplements on the reproductive physiology and metabolic hormones of rabbits exposed to heat stress conditions. Fresh Moringa oleifera, Phyllanthus amarus and Viscum album leaves were obtained and processed into a leaf meal using standard procedure and served as a phytogenic supplements. Eighty rabbit bucks of 6 weeks old (514.84 ± 14.10 g) were randomly assigned to the four dietary groups consisting of Diet 1 without the leaf meal (control diet) and Diets 2 (D2); 3 (D3) and 4 (D4) contained 10% Moringa, 10% Phyllanthus and 10% Mistletoe, respectively, in an 84-day feed trial at the peak of thermal discomfort. Semen kinetics and seminal oxidative status, reproductive and metabolic hormones were assessed using standard procedure. Results reveal that sperm concentration and motility traits of bucks on D2, D3 and D4 were significantly (p < 0.05) higher than bucks on D1. Spermatozoa speed traits of bucks on D4 were significantly (p < 0.05) higher than bucks on other treatments. Seminal lipid peroxidation of bucks in D2-D4 was significantly (p < 0.05) lower than bucks on D1. Corticosterone of bucks on D1 was significantly higher than bucks on other treatments (D2-D4). Lutenizing hormone of bucks on D2 and testosterone of bucks on D3 was higher (p < 0.05) than in other groups, while follicle stimulating hormone of bucks on D2 and D3 were higher (p < 0.05) than bucks on D1 and D4. In conclusion, the three phytogenic supplements improved sex hormones, enhanced spermatozoa kinetics, viability and seminal oxidative stability of bucks during heat stress condition.


Ecological succession: out of the ash.
A new study of plants recolonising the land devasted when Mount St. Helens erupted in 1980 is providing important new insights into the interactions with herbivores that determine the pattern and outcome of ecological succession.


SARS-CoV-2 spike N-terminal domain modulates TMPRSS2-dependent viral entry and fusogenicity.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike N-terminal domain (NTD) remains poorly characterized despite enrichment of mutations in this region across variants of concern (VOCs). Here, we examine the contribution of the NTD to infection and cell-cell fusion by constructing chimeric spikes bearing B.1.617 lineage (Delta and Kappa variants) NTDs and generating spike pseudotyped lentivirus. We find that the Delta NTD on a Kappa or wild-type (WT) background increases S1/S2 cleavage efficiency and virus entry, specifically in lung cells and airway organoids, through use of TMPRSS2. Delta exhibits increased cell-cell fusogenicity that could be conferred to WT and Kappa spikes by Delta NTD transfer. However, chimeras of Omicron BA.1 and BA.2 spikes with a Delta NTD do not show more efficient TMPRSS2 use or fusogenicity. We conclude that the NTD allosterically modulates S1/S2 cleavage and spike-mediated functions in a spike context-dependent manner, and allosteric interactions may be lost when combining regions from more distantly related VOCs.


Prosthodontic restoration with dental implants and an intraoral cranial bone onlay graft: a case report.
In 1988, a 54-year-old edentulous patient received a cranial bone onlay graft with the immediate placement of five dental implants. Treatment procedures and early results of restoration are described.


Cardioprotective effect of oleuropein in a cisplatin-induced cardiotoxicity model in rats.
This study investigated the cardioprotective effect of oleuropein against cisplatin-induced cardiac damage in terms of inflammatory, oxidative stress and cardiac parameters. In this study, 40 female Wistar albino rats were divided into four groups: control, cisplatin, oleuropein and cisplatin+oleuropein. To establish the experimental model, oleuropein (200 mg/kg) was administered for 14 days and cisplatin (7 mg/kg) was administered as a single dose on the seventh day. Cisplatin increased MDA cardiac parameters (CK, CK-MB and cTnI) and inflammatory cytokines (TNF-α, IL-1β and IL-6) in cardiac tissue and decreased GSH, GSH-Px and catalase levels. On the other hand, oleuropein improved cardiac parameters and decreased inflammatory cytokine and oxidative stress levels in cardiac tissue.


Blood pressure control in an African American sample with diabetes mellitus in an urban eye clinic.
The adequate control of blood pressure in patients with diabetes mellitus (DM) is important to limit the ocular and systemic complications of the disease. Hypertension in African Americans is among the highest in the world. This cross-sectional study reports the level of blood pressure control in a small sample of African American patients with DM at an urban eye care facility using the criteria defined by the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VII). Five attending faculty members of the Illinois College of Optometry identified 234 African American patients with a diagnosis of DM over a period of 16 months. Blood pressure readings were recorded once at the time of their visit and were classified as controlled or uncontrolled based on the JNC VII cutoff of blood pressure less than 130/80 mmHg. Among the 234 African American patients in this study, 174 (74.4%) reported having DM and hypertension, and 60 (25.6%) reported having DM without hypertension. Of the patients with DM and a self-reported diagnosis of hypertension, 13.2% were controlled. Of the patients with diabetes without a self-reported diagnosis of hypertension, 26.7% were found to be adequately controlled. For the pooled data of 234 patients with diabetes, 16.7% met the JNC VII guidelines. The inadequate control of blood pressure in the African American population with DM is associated with increased disability and death from cardiovascular and renal disease. The results of this small cross-sectional study are consistent with those of other studies that show poor control of blood pressure in African American patients who have DM. Preventable blindness secondary to accelerated diabetic retinopathy from uncontrolled hypertension is a concern to all eye care practitioners.


Aspergillus nidulans contains six possible fatty acyl-CoA synthetases with FaaB being the major synthetase for fatty acid degradation.
Aspergillus nidulans can use a variety of fatty acids as sole carbon and energy sources via its peroxisomal and mitochondrial beta-oxidation pathways. Prior to channelling the fatty acids into beta-oxidation, they need to be activated to their acyl-CoA derivates. Analysis of the genome sequence identified a number of possible fatty acyl-CoA synthetases (FatA, FatB, FatC, FatD, FaaA and FaaB). FaaB was found to be the major long-chain synthetase for fatty acid degradation. FaaB was shown to localise to the peroxisomes, and the corresponding gene was induced in the presence of short and long chain fatty acids. Deletion of the faaB gene leads to a reduced/abolished growth on a variety of fatty acids. However, at least one additional fatty acyl-CoA synthetase with a preference for short chain fatty acids and a potential mitochondrial candidate (AN4659.3) has been identified via genome analysis.


Characterization of a nontoxic pyomelanin pigment produced by the yeast Yarrowia lipolytica.
In this study, we report on the ability of the yeast Yarrowia lipolytica W29 to produce an extracellular melanin-like brown pigment at high yield (0.5 mg/ml) in culture medium supplemented with L-tyrosine. This pigment has been characterized as pyomelanin and its synthesis was found to occur by the so-called HGA-melanin pathway. The purified pyomelanin was found embedded with antioxidant properties as it exhibited a radical scavenging activity toward 1,1-diphenyl-2-picrylhydrazyl (DPPH) with IC50 of 230 μg/ml. It was also characterized as noncytotoxic toward two mammalian cell lines, namely the mouse fibroblast NIH3T3 and human keratinocytes HaCaT. When blended with different commercial sunscreens, the purified pyomelanin increased significantly the sun protection factor (SPF) value, highlighting its potential utilization as UV-filter in cosmetic preparations.


First cigarette on waking and time of day as predictors of puffing behaviour in UK adult smokers.
There is known inter- and intra-individual variation in how cigarettes are smoked. The aim of this study was to explore the influence of diurnal factors, particularly the first cigarette of the day, on puffing behaviour in a sample of adult smokers. We recruited 130 adults aged 18–60 years who were smoking one of seven cigarette brands popular in the UK. Puffing behaviour was measured using a portable smoking device (CReSSmicro) through which participants smoked their cigarettes over a 24 h study period. The primary outcome was total smoke volume per cigarette (obtained by summing the puff volumes for each cigarette). Secondary outcome measures were puffing frequency, average puff volume, average puff flow, average puff duration and inter-puff interval. Total smoke volume was found to be significantly associated with the time the cigarette was smoked (P < 0.001), with cigarettes smoked between 2 and 10 a.m. being smoked less intensively than other cigarettes. After adjusting for time of cigarette, the first cigarette on waking was smoked slightly less intensively than other cigarettes and significantly so if smoked within 5 min of waking (P = 0.004). This study suggests that cigarettes smoked during the night and early morning, including the first cigarette of the day, are puffed less intensively. This is a potentially important finding that merits more research given the importance of the first cigarette of the day and diurnal smoking patterns for determining dependence, cessation and relapse.


Beyond motor hyperactivity: Racing thoughts are an integral symptom of adult attention deficit hyperactivity disorder.
Adults with ADHD experience mental restlessness, akin to racing thoughts, but data on this symptom in ADHD remain scarce. Our study aims at investigating self-reported racing thoughts in adults with ADHD, and its relationship with affective dysregulation and insomnia. We were also interested in whether racing thoughts may aid differential diagnosis with bipolar disorder (BD). 182 adults with ADHD, 30 ADHD+BD, 31 hypomanic BD, and 20 euthymic BD patients completed the Racing and Crowded Thoughts Questionnaire (RCTQ). ADHD, anxiety, insomnia and depression symptoms, as well as affective temperament were also assessed in ADHD and ADHD+BD subjects. Results show that RCTQ scores were higher in ADHD compared to hypomania and euthymia and were associated with cyclothymic traits and anxiety. Moreover, in ADHD and ADHD+BD, racing thoughts increased in the evening and at bedtime and were associated with insomnia severity. In conclusion, self-reported racing thoughts are a neglected but an intrinsic feature of adult ADHD that is particularly related to cyclothymia and anxiety, but cannot differentiate ADHD and BD.


Is There an Association Between Diet, Physical Activity and Depressive Symptoms in the Perinatal Period? An Analysis of the UPBEAT Cohort of Obese Pregnant Women.
Depression is a common morbidity of the perinatal period (during pregnancy and up to one year postpartum). There is evidence for an association between diet and physical activity, and depression in the non-pregnant population but this association has been relatively less explored during the perinatal period; particularly poorly understood is the relationship between specific dietary components and depression. The aim of this study was to explore the association between glycaemic load, saturated fat intake and physical activity and depressive symptoms in a high-risk population of obese pregnant women. In a cohort of 1522 women participating in the UPBEAT trial, physical activity, glycaemic load and saturated fat intake were used as predictors of depressive symptoms measured using the Edinburgh Postnatal Depression Scale (EPDS). Measures taken in early pregnancy were used in linear and logistic regression models. Repeated measures at three points during pregnancy and at six months postpartum were utilised in multilevel mixed effects models. Multiple imputation was used to account for missing data. Increased glycaemic load was associated with small increases in levels of depressive symptoms across the perinatal period (adjusted beta coefficient 0.01; 95% CI 0.01,0.02). There was no evidence for an association between reduced physical activity and increased saturated fat intake and increased levels of depressive symptoms. Glycaemic load may be a useful focus for interventions aiming to optimise the mental health of obese women in the perinatal period.


Early Predictors of Adolescent Irritability.
Limited research has examined precursors/risk factors for adolescent irritability. This study examines continuity of irritability from early childhood to adolescence and identifies antecedents of adolescent irritability. Across self-reports and mother-reports, evidence was found for continuity of irritability. A range of variables assessed at age 3 predicted irritability at age 15. These findings suggest that adolescent irritability is characterized by distinct developmental pathways from age 3 that have potential to result in an irritable phenotype at age 15. Adolescent-reported and mother-reported irritability may be capturing distinct underlying constructs of irritability; both should be considered in assessments of adolescent irritability.


Major Streptomyces species associated with fissure scab of potato in South Africa including description of Streptomyces solaniscabiei sp. nov.
Streptomyces species are the causal agents of several scab diseases on potato tubers. A new type of scab symptom, caused by Streptomyces species, was observed in South Africa from 2010 onwards. The disease was initially thought to be caused by a single Streptomyces species, however, subsequent isolations from similar symptoms on other potato tubers revealed diversity of the Streptomyces isolates. The objective of this study was to characterise these isolates in order to determine what are the major species involved in the disease. This was done by sequencing and phylogenetic analyses of the 16S rDNA as well as five housekeeping genes, investigation of growth on different culture media, standard phenotypic tests and scanning electron microscopy of culture morphology. The presence of the pathogenicity island (PAI) present in plant pathogenic Streptomyces species was also investigated. The genomes of eight isolates, selected from the three main clades identified, were sequenced and annotated to further clarify species boundaries. Three isolates of each of the three main clades were also inoculated onto susceptible potato cultivars in order to establish the pathogenicity of the species. The results of the phylogenetic and genome analyses revealed that there are three main species involved, namely, Streptomyces werraensis, Streptomyces pseudogriseolus and a novel Streptomyces species that is described here as Streptomyces solaniscabiei sp. nov., with strain FS70T (= PPPPB BD 2226T = LMG 32103T) as the type strain. The glasshouse trial results showed that all three of the Streptomyces species are capable of producing fissure scab symptoms. None of the Streptomyces isolates from fissure scab contained the full PAI and the mechanism of disease initiation still needs to be determined. Genomic comparisons also indicated that S. gancidicus Suzuki 1957 (Approved Lists 1980) is a later heterotypic synonym of S. pseudogriseolus Okami and Umezawa 1955 (Approved Lists 1980).


Effect of storage on the rheological and viscoelastic properties of mayonnaise emulsions of different oil droplet size.
The rheological and viscoelastic properties of mayonnaise emulsions with different size of oil droplets were investigated. Α programmable rotational rheometer was used for the measurements and flow curves were determined at constant and variable shear rate. Mayonnaise exhibited a non-Newtonian, shear-thinning flow with yield stress and time-dependent features. The data from rotational tests were modeled by the Herschel-Bulkley equation. The temperature-dependence of η a was modelled using the Arrhenius equation. Activation energy, E a ranged from 15 to 20 kJ/mol. Viscoelastic properties were characterized using small amplitude oscillatory shear. Mayonnaise exhibited weak gel-like properties. The values of apparent and complex viscosity were correlated using the generalised Cox-Merz rule. According to the obtained values of parameter α, this rule could not be cut-down to one-parameter linear function. The rheological characteristics of mayonnaise were well correlated to the size of oil droplets.


[Enzymes protecting the erythrocyte membrane during the combined exposure to an antioxidant complex and acute irradiation].
The data are presented concerning the effect of ionizing radiation on the hemolytic process and the influence of an antioxidant vitamin complex on the pentosephosphate metabolism and glutathione reductase activity after gamma-irradiation. The antioxidant vitamin complex has been shown to produce a favourable effect on the erythrocyte membrane stability in correcting the radiation-induced changes.


Heme oxygenase: a novel target for the modulation of the inflammatory response.
Chronic inflammatory diseases place a heavy social and economic burden on the resources of many nations, but the number of safe and effective treatments is limited. To date, the major research effort has concentrated on those mediators responsible for the initiation and maintenance of the pathological process. In contrast, little attention has been focused on endogenous factors responsible for the resolution of the inflammation. Heme oxygenase ((HO); EC 188.8.131.52) is the rate-limiting enzyme in the catabolism of heme to biliverdin (which is converted to bilirubin by biliverdin reductase), free iron and carbon monoxide (CO). Two isoforms of HO have been characterized, the constitutive isoform, HO-2, which is the major isoform present under physiological conditions, and the stress-induced isoform, HO-1, which has also been classified as heat-shock protein 32K (ref. 1). Increases in HO activity have been implicated in tissue protection against oxidative stress. In this communication, we describe the effects of modulating HO during an acute complement-dependent inflammatory response. Elevation of this enzyme resulted in a striking suppression, whereas inhibition of the enzyme led to a potentiation of the inflammatory response. Such novel enzyme modulation has application on the one hand to the treatment of inflammatory diseases and on the other hand to immnosuppressed states in which the impaired ability to mount an adequate inflammatory response may result in death from opportunistic infections.


3'-Azido-3'-deoxythymidine (AZT) is a competitive inhibitor of thymidine phosphorylation in isolated rat heart and liver mitochondria.
Long-term use of 3'-azido-3'-deoxythymidine (AZT) is associated with various tissue toxicities, including hepatotoxicity and cardiomyopathy, and with mitochondrial DNA depletion. AZT-5'-triphosphate (AZTTP) is a known inhibitor of the mitochondrial DNA polymerase gamma and has been targeted as the source of the mitochondrial DNA depletion. However, in previous work from this laboratory with isolated rat heart and liver mitochondria, AZT itself was shown to be a more potent inhibitor of thymidine phosphorylation (IC50 of 7.0+/-1.0 microM AZT in heart mitochondria and of 14.4+/-2.6 microM AZT in liver mitochondria) than AZTTP is of polymerase gamma (IC50 of >100 microM AZTTP), suggesting that depletion of mitochondrial stores of TTP may limit replication and could be the cause of the mitochondrial DNA depletion observed in tissues affected by AZT toxicity. The purpose of this work is to characterize the nature of AZT inhibition of thymidine phosphorylation in isolated rat heart and rat liver mitochondria. In both of these tissues, AZT was found to be a competitive inhibitor of the phosphorylation of thymidine to TMP, catalyzed by thymidine kinase 2. The inhibition constant (Ki) for heart mitochondria is 10.6+/-4.5 microM AZT, and for liver mitochondria Ki is 14.0+/-2.5 microM AZT. Since AZT is functioning as a competitive inhibitor, increasing thymidine concentrations may be one mechanism to overcome the inhibition and decrease AZT-related toxicity in these tissues.


Electrophoretic separations in poly(dimethylsiloxane) microchips using mixtures of ionic, nonionic and zwitterionic surfactants.
The use of surfactant mixtures to affect both EOF and separation selectivity in electrophoresis with PDMS substrates is reported, and capacitively coupled contactless conductivity detection is introduced for EOF measurement on PDMS microchips. First, the EOF was measured for two nonionic surfactants (Tween 20 and Triton X-100), mixed ionic/nonionic surfactant systems (SDS/Tween 20 and SDS/Triton X-100), and finally for the first time, mixed zwitterionic/nonionic surfactant systems (TDAPS/Tween 20 and TDAPS/Triton X-100). EOF for the nonionic surfactants decreased with increasing surfactant concentration. The addition of SDS or TDAPS to a nonionic surfactant increased EOF. After establishing the EOF behavior, the separation of model catecholamines was explored to show the impact on separations. Similar analyte resolution with greater peak heights was achieved with mixed surfactant systems containing Tween 20 and TDAPS relative to the single surfactant system. Finally, the detection of catecholamine release from PC12 cells by stimulation with 80 mM K(+) was performed to demonstrate the usefulness of mixed surfactant systems to provide resolution of biological compounds in complex samples.


Oxygen free radicals: in search of a unifying theory of disease.
The purpose of this paper is to examine the subject of oxygen free radicals and the damage they do in the human body, providing understanding of the basic principles involved, while at the same time highlighting areas of debate relevant to nurses working in critical care areas. Links to various areas of disease are explored, including coronary artery disease, cancer and reperfusion injuries. Ageing is also discussed. The role of antioxidant therapy is examined, as is the need for further research of the subject in general.


Influence of size of neodymium:yttrium-aluminium-garnet laser posterior capsulotomy on visual function.
The aim of this study was to examine the influence that the size of a neodymium:yttrium-aluminium-garnet (Nd:YAG) laser capsulotomy performed for posterior capsule opacification (PCO) has on visual acuity (VA), and on contrast VA and that in the presence of glare (glare VA). A total of 41 consecutive eyes with PCO first underwent Nd:YAG laser capsulotomy of smaller than pupillary size, after which the capsulotomy was secondarily enlarged, 2 weeks later, to greater than pupillary size. Best-corrected VA, and contrast VA and glare VA under photopic and mesopic conditions were measured after the small and large capsulotomies were made. After enlargement, the mean capsulotomy area increased significantly from 4.8 to 15.3 mm(2) (P<0.0001). Best-corrected VA did not improve significantly after enlargement (P=0.1282). However, photopic contrast VA and glare VA at moderate to low contrast visual target before enlargement were significantly worse than those after enlargement (P<or=0.0242); furthermore, mesopic contrast VA and glare VA improved significantly after enlargement (P<or=0.0431). Contrast VA and glare VA with a small capsulotomy were significantly worse than those with a large capsulotomy, which suggests that a capsulotomy larger than the pupillary size is necessary to restore contrast sensitivity and glare disability.


Hitchhiking into a cell: flavonoids may produce complexes with transition metals for transmembrane translocation.
Flavonoids are a group of food polyphenols that are delivered to the human body with plant foods. In recent years, these substances have attracted the attention of researchers due to their effectiveness in preventing a wide variety of diseases, including neurodegenerative, oncological, autoimmune, and cardiovascular. Similar pathologies may also occur with a lack of some first-row transition metals, including Cu(II), Zn(II), Mn(II), Fe(II/III). It is noteworthy that flavonoids are known as transition metal chelators. When a complex with these metals is formed, the therapeutic effect of flavonoids can be enhanced, assuming the possibility of synergy. Molecular models have shown that the lipophilicity of flavonoid-metal complexes can vary significantly depending on their binding stoichiometry. Therefore, a unique process of translocation of flavonoid-metal complexes of various lipophilicity through cell membranes is assumed, based on the possibility of their sequential association and dissociation, called "hitchhiking". It is expected that studies of the interaction of flavonoids with metals will improve the effectiveness of drugs based on flavonoids.


Hypophysitis induced by ipilimumab and nivolumab combination therapy for advanced renal cell carcinoma: A case report.
Ipilimumab and nivolumab combination therapy is effective against unresectable or metastatic renal cell carcinoma. However, it is associated with many immune-related adverse events, including hypophysitis that is difficult to diagnose early because of non-specific initial symptoms. Herein, we report the case of a 54-year-old man with metastatic renal cell carcinoma who developed hypophysitis after receiving ipilimumab and nivolumab combination therapy. The initial symptom was headache. However, endocrine tests showed decreased levels of cortisol, free thyroxine and thyroid-stimulating hormone. Moreover, magnetic resonance imaging revealed pituitary enlargement. Accordingly, we diagnosed hypophysitis and immediately started hydrocortisone replacement therapy, which improved the symptoms.


A Multi-User Collaborative AR System for Industrial Applications.
Augmented reality (AR) applications are increasingly being used in various fields (e.g., design, maintenance, assembly, repair, training, etc.), as AR techniques help improve efficiency and reduce costs. Moreover, collaborative AR systems extend applicability, allowing for collaborative environments for different roles. In this paper, we propose a multi-user collaborative AR system (aptly called the "multi-user collaborative system", or MUCSys); it is composed of three ends-MUCStudio, MUCView, and MUCServer. MUCStudio aims to construct industrial content with CAD model transformation, simplification, database update, marker design, scene editing, and exportation, while MUCView contains sensor data analysis, real-time localization, scene loading, annotation editing, and virtual-real rendering. MUCServer-as the bridge between MUCStudio and MUCView-presents collaborative and database services. To achieve this, we implemented the algorithms of local map establishment, global map registration, optimization, and network synchronization. The system provides AR services for diverse industrial processes via three collaborative ways-remote support, collaborative annotation, and editing. According to the system, applications for cutting machines were presented to improve efficiency and reduce costs, covering cutting head designs, production line sales, and cutting machine inspections. Finally, a user study was performed to prove the usage experience of the system.


Home-based exercise training influences gut bacterial levels in multiple sclerosis.
Multiple sclerosis is associated with gut microbiome alterations. The current study aimed to investigate the effect of home-based exercise on gut bacteria in people with multiple sclerosis (MS). We also examined the association of exercise-induced gut bacterial modulation with circulating levels of inflammatory and anti-inflammatory cytokines. Forty-two people with MS (female/male: 31/11, expanded disability scale status <5) participated in this study and were divided into two groups: 6 months of home-based exercise (5 sessions per week) and controls. Before and after the intervention, the following parameters were assessed: gut microbiota, including faecalibacterium prausnitzii, akkermansia muciniphila, prevotella and bacteroides counts; cytokine levels including interleukin (IL)-10 and tumor necrosis factor-alpha (TNF-α); and psychosocial factors including anxiety, depression, and fatigue. Home-based exercise significantly increased prevotella counts, and decreased akkermansia muciniphila counts (p < 0.05); however, there were no significant effects on faecalibacterium prausnitzii and bacteroides counts (p > 0.05). There were no significant effects of home-based exercise on circulating cytokine levels (p > 0.05). Moreover, home-based exercise was associated with significant improvements in anxiety and depression (p < 0.05); however, fatigue revealed no significant change (p > 0.05). Akkermansia muciniphila, prevotella and bacteroides count changes in response to the intervention were correlated with changes in IL-10 (r = -0.052, r = 0.67, and r = -0.55, respectively). In general, our data revealed the effect of exercise on gut bacteria, especially prevotella, and akkermansia muciniphila counts, which can probably have a beneficial effect on MS disease pathology and course; however, the lack of changes in cytokines following exercise suggests the possible role of mechanisms other than modulation of circulating IL-10 and TNF- α levels.


Inhibition of Tumor VEGFR2 Induces Serine 897 EphA2-Dependent Tumor Cell Invasion and Metastasis in NSCLC.
Anti-angiogenic treatment targeting vascular endothelial growth factor (VEGF)-VEGFR2 signaling has shown limited efficacy in lung cancer patients. Here, we demonstrate that inhibition of VEGFR2 in tumor cells, expressed in ∼20% of non-squamous non-small cell lung cancer (NSCLC) patients, leads to a pro-invasive phenotype. Drug-induced inhibition of tumor VEGFR2 interferes with the formation of the EphA2/VEGFR2 heterocomplex, thereby allowing RSK to interact with Serine 897 of EphA2. Inhibition of RSK decreases phosphorylation of Serine 897 EphA2. Selective genetic modeling of Serine 897 of EphA2 or inhibition of EphA2 abrogates the formation of metastases in vivo upon VEGFR2 inhibition. In summary, these findings demonstrate that VEGFR2-targeted therapy conditions VEGFR2-positive NSCLC to Serine 897 EphA2-dependent aggressive tumor growth and metastasis. These data shed light on the molecular mechanisms explaining the limited efficacy of VEGFR2-targeted anti-angiogenic treatment in lung cancer patients.


A new masticatory performance scale to integrate food biting, comminution and mixing ability in removable partial denture wearers.
The existing masticatory performance (MP) tests cannot comprehensively evaluate objective masticatory function. We aimed to examine the construct validity and responsiveness and determine the clinically minimum important difference (MID) and related factors of a newly developed MP scale to integrate food biting, comminution and mixing ability in patients with removable partial dentures (RPDs). Masticatory performance tests using gummy jelly, peanuts and colour-changeable gum were performed before and 3 months after RPD treatment in 248 partially dentate patients. A 10-point ordinal subscale was created for each MP test based on the distributions of MP values, and the three subscales were integrated into a single scale (iMP scale). We analysed the correlations between MP values and iMP scores and determined the effect size for RPD treatments and the MID on the basis of patient perception of chewing ability. iMP scores exhibited moderate correlations with the three MP values (|ρ| = 0.73-0.79, p < .001) and with the change scores (|ρ| =0.61-0.64, p < .001). The mean iMP score significantly increased after RPD treatment (p < .001), and the effect size was 0.35. Of the 248 patients, 55 (22%) reported a slight improvement in chewing ability with a mean iMP score change of 2.1 points. Sex and the number of missing teeth were significantly associated with iMP scores (p < .05). The iMP scale comprehensively evaluated objective masticatory function, including food biting, comminution and mixing ability in RPD wearers, and an increase of two points on the iMP scale was considered to be the MID in RPD treatments.


Mechanochromic Delayed Fluorescence Switching in Propeller-Shaped Carbazole-Isophthalonitrile Luminogens with Stimuli-Responsive Intramolecular Charge-Transfer Excited States.
Herein, the universal design of high-efficiency stimuli-responsive luminous materials endowed with mechanochromic luminescence (MCL) and thermally activated delayed fluorescence (TADF) functions is reported. The origin of the unique stimuli-triggered TADF switching for a series of carbazole-isophthalonitrile-based donor-acceptor (D-A) luminogens is demonstrated based on systematic photophysical and X-ray analysis, coupled with theoretical calculations. It was revealed that a tiny alteration of the intramolecular D-A twisting in the excited-state structures governed by the solid morphologies is responsible for this dynamic TADF switching behavior. This concept is applicable to the fabrication of bicolor emissive organic light-emitting diodes using a single TADF emitter.


The urokinase plasminogen activator (u-PA) and its inhibitor (PAI-1) in embryo-fetal bone formation in the human: an immunohistochemical study.
The role of urokinase plasminogen activator and plasminogen activator inhibitor-1 in human embryo-fetal bone formation between the 9th and the 20th week of gestation has been studied immunohistochemically. While mature osteocytes of the secondary spongiosa and resting chondrocytes of the bone epiphyses were negative for both antigens in each developmental stage, metabolically active parts of the osseocartilaginous system showed a strong immunoreactivity. Until the end of the 10th week of gestation urokinase plasminogen activator and plasminogen activator inhibitor-1 could not be demonstrated in the shaft of the preexisting cartilaginous models of bones, which correlates with the morphological developmental stage of the embryos. Later, osteoblasts and chondrocytes in the areas of enchondral ossification, and the perivascular chondrocytes of the epiphyseal secondary ossification centres, showed similarly high concentrations of urokinase plasminogen activator and plasminogen activator inhibitor-1. Moreover, the individual ossification stages of the different bones in embryo-fetal development could be demonstrated immunohistochemically. While humeri and femora showed diaphyseal immunoreactivities at an early stage, positive reactions in the phalanges were found only much later. Thus, the enzymes of the fibrinolytic system studied are clearly involved in the desmal and enchondral ossification process in the osseocartilaginous compartment.


Biopurification of dairy farm wastewater through hybrid constructed wetland system: Groundwater quality and health implications.
Groundwater is under heavily threat owing to enormous infilteration of dairy farm originated wastewater into it. The anoxic environment in the groundwater due to mixing of organic rich wastewater can produce significant alterations in the groundwater quality. It is therefore necessary to treat such wastewaters before discharging to surrounding areas. Therefore, in this study we evaluated a hybrid constructed wetland (CW) system(40 m2 area) consisting of three beds, i.e. Vertical (16 m2) - Horizontal (18 m2) - Vertical (6 m2) connected in series for the treatment of dairy farm wastewater under typical high humid climate in northern India. Tropical perennial plant such as Arundo donax L. was grown on both vertical beds, whereas Hibiscus esculentus L. and Solanum melongena L. were grown on the horizontal bed of the system.The average purification of TSS, BOD3, total N, and P was significant (p < 0.05) in HF bed and recorded as 92.2 ± 6.1, 95 ± 3.8, 83.6 ± 9.0 and 86.1 ± 10.0% respectively.The average load of BOD3, total N, and P in the influent and effluent was recorded (with no significant differences, p > 0.05) as 7.0 ± 7.17, 1.9 ± 0.7, 0.72 ± 0.5 g m-2 day-1and 0.3 ± 0.2, 0.3 ± 0.2 and 0.04 ± 0.01 g m-2 day-1 respectively.The average values of total biomass content of Arundo donax L. were differed significantly and recorded as 0.31 ± 0.06, 0.43 ± 0.17, and 0.43 ± 0.16 g g-1 fresh wt. in control, VF-1, and VF-2 respectively. Therefore, the hybrid CW system can be efficiently used for the treatment of dairy farm wastewater with implications on groundwater and health. Future research may focus on performance analysis of upgraded combined anaerobic reactor and hybrid CW system planted with series of macrophytes for on-site treatment of high strength dairy farm wastewater in tropical regions.


Linking phytoplankton community composition to seasonal changes in f-ratio.
Seasonal changes in nitrogen assimilation have been studied in the western English Channel by sampling at approximately weekly intervals for 12 months. Nitrate concentrations showed strong seasonal variations. Available nitrogen in the winter was dominated by nitrate but this was close to limit of detection from May to September, after the spring phytoplankton bloom. The (15)N uptake experiments showed that nitrate was the nitrogen source for the spring phytoplankton bloom but regenerated nitrogen supported phytoplankton productivity throughout the summer. The average annual f-ratio was 0.35, which demonstrated the importance of ammonia regeneration in this dynamic temperate region. Nitrogen uptake rate measurements were related to the phytoplankton responsible by assessing the relative abundance of nitrate reductase (NR) genes and the expression of NR among eukaryotic phytoplankton. Strong signals were detected from NR sequences that are not associated with known phylotypes or cultures. NR sequences from the diatom Phaeodactylum tricornutum were highly represented in gene abundance and expression, and were significantly correlated with f-ratio. The results demonstrate that analysis of functional genes provides additional information, and may be able to give better indications of which phytoplankton species are responsible for the observed seasonal changes in f-ratio than microscopic phytoplankton identification.


Emergencies in motoneuron disease.
Genetic and acquired motor-neuron-disorders (MNDs) may undergo acute deterioration resulting in various emergency situations. This literature review aims at summarising and discussing current knowledge about emergencies in MNDs. Emergencies that have been reported in MND patients include: respiratory, bulbar, cardiac, septic, epileptic, psychiatric, pain-related, and traumatic emergencies. Emergencies due to respiratory insufficiency have the strongest impact on morbidity and mortality in MNDs. To optimise the management of emergencies in MNDs, it is recommended to discuss these topics with the patient prior to their occurrence. After informed consent, patients may indicate their decision by signing an advance directive as to how such emergencies should be managed in case they arise. Generally, treatment of emergencies in MNDs is not at variance from treatment of similar emergencies due to other causes, but some peculiarities need to be pointed out. It is concluded that patients with MNDs may experience various emergencies during the disease course. Management of these conditions should be discussed with the patient prior to their appearance. Management of these emergencies follows general guidelines, which widely vary between countries, and depend on the availability of a patient's advance directive.


Early auditory processing dysfunction in schizophrenia: Mechanisms and implications.
Schizophrenia is a major mental disorder that affects approximately 1% of the population worldwide. Cognitive deficits are a key feature of the disorder and a primary cause of long-term disability. Over the past decades, significant literature has accumulated demonstrating impairments in early auditory perceptual processes in schizophrenia. In this review, we first describe early auditory dysfunction in schizophrenia from both a behavioral and neurophysiological perspective and examine their interrelationship with both higher order cognitive constructs and social cognitive processes. Then, we provide insights into underlying pathological processes, especially in relationship to glutamatergic and N-methyl-D-aspartate receptor (NMDAR) dysfunction models. Finally, we discuss the utility of early auditory measures as both treatment targets for precision intervention and as translational biomarkers for etiological investigation. Altogether, this review points out the crucial role of early auditory deficits in the pathophysiology of schizophrenia, in addition to major implications for early intervention and auditory-targeted approaches.


Inhibition of Pseudomonas aeruginosa alginate expression by subinhibitory concentrations of antibiotics.
The effects of subinhibitory concentrations (1/4, 1/8, 1/16 of the MIC) of quinolones (ciprofloxacin, enoxacin, nalidixic acid, norfloxacin, ofloxacin, pefloxacin), aminoglycosides (amikacin, gentamicin, netilmicin, streptomycin, tobramycin), beta-lactams (aztreonam, ceftazidime, imipenem, ticarcilin) and macrolides (erythromycin, roxitromycin) on the excretion of alginate by a P. aeruginosa strain were studied. Both beta-lactam and macrolide antibiotics were found ineffective at the concentrations tested, except erythromycin and imipenem at 1/4 MIC. Aminoglycosides at a concentration of 1/4 MIC reduced most effectively the excretion of alginate. Quinolones were also effective at this sub-MIC; 1/16 MIC was ineffective with all antibiotics or stimulated the production of alginate.


Histochemical, cytochemical and autoradiographic studies on the rostellum of Hymenolepis diminuta.
Histochemical studies on the rostellum of Hymenolepis diminuta revealed diastase-stable, protein/neutral carbohydrate-rich material localized in the rostellum tegument. The remainder of the rostellum, primarily composed of the glycogen-rich myocytons of the rostellum musculature, is protein-poor, but rich in diastase-labile, neutral and acidic carbohydrates. Ultrastructural cytochemical studies, using the periodic acid-thiocarbohydrazide osmium (PATCO) technique, indicated that the granules of the rostellar tegumental cytons and distal cytoplasm are carbohydrate-rich. Lipids are present in the rostellar myocytons but not in the tegumental cytons. Autoradiography using a pulse-labeling with [3H]leucine revealed an apical translocation of tegumental granules, but at a slower rat than had been reported for the strobilar tegument of the same organism. Neither [3H]galactose nor [3H]glucose were incorporated into the rostellar tegumental granules. The function of the secretory glycoprotein(s) produced in the rostellar tegument and its (their) possible role in the regulation of maturation and/or strobilization remain enigmatic.


Little known and less understood: the benefits of a lower hematocrit (~40%) in reconstituted blood for double volume exchange transfusion.
A double volume exchange transfusion (DVET) is an important, if infrequently performed, intervention to acutely lessen the total serum bilirubin (TSB) and reduce the extravascular CNS bilirubin exposure when neonatal hyperbilirubinemia poses a neurotoxicity risk. The current analysis based on the seminal works of Valaes, and Sproul and Smith, predicts that a DVET blood product of lower hematocrit (~40%) via its greater plasma volume and corresponding higher albumin content optimizes the benefits of an DVET in several ways. First, by augmenting bilirubin clearance from the extravascular space and thereby further reducing the CNS bilirubin exposure, second, by favorably positioning the intravascular albumin-bilirubin binding capacity at DVET completion to accommodate additional bilirubin equilibration and rebound hyperbilirubinemia post-exchange, and third by correcting anemia if present.


Stability evaluation and validation of appropriate reference genes for real-time PCR expression analysis of immune genes in the rohu (Labeo rohita) skin following argulosis.
Argulosis is one of the most unrestrained economically significant freshwater fish ectoparasitic diseases. Proper selection or normalization of the best reference gene governs the accuracy of results of gene expression studies using real-time PCR. Earlier studies in rohu carp (Labeo rohita) have used reference genes without proper validation. Here, seven candidate reference genes viz., acidic ribosomal protein (ARP0), glyceraldehyde 3-phosphate dehydrogenase, RNA polymerase II (RPo), elongation factor1α (EF1α), α- tubulin (AT), ribosomal protein L 10, and β-actin were evaluated using four algorithms (geNorm, BestKeeper, NormFinder and ∆Ct) followed by a comprehensive gene expression analysis using skin tissue of rohu at varied time points of experimental Argulus siamensis infection. ARP0 and EF1α were found to be the most stable whereas RPo and AT were considered as least stable genes based on basal expression level and variation in expression levels. Validation of candidate reference genes was undertaken by looking into the expression of six immune-related genes using the two most stable and two least stable genes as housekeeping genes in Argulus-infected rohu skin at different time points of infection. An increased expression of immune genes indicated the role of inflammation and the immune modulation process at the site of attachment of parasites in governing infection.


The influence of anchoring on pain judgment.
Research on decision making suggests that a wide range of spontaneous processes may influence medical judgment. We considered an easily accessible strategy, anchoring and insufficient adjustment, which might contribute to health care professionals' miscalibration of patients' pain. A sample (n=423) of physicians, nurses, medical students, and nursing students participated in a computerized task that showed 16 vignettes featuring fictitious patients reporting headache. In the experimental condition, participants were asked to evaluate the severity of the patient's pain before and after knowing the patient's rating. In the control condition, participants were shown all information about the patient at the same time and were required to make judgments in a single stage. When participants could express an initial impression before knowing the patient's rating, they fully anchored to their initial impressions in almost half of the responses. Moreover, even among those who revised their initial impression, the extent of the revision was often insufficient. Greater anchoring was associated with patients' ratings that were higher than the participants' initial impression. Finally, we provided evidence that anchoring increased pain miscalibration. We discuss our findings in terms of their contribution to the understanding of the cognitive processes involved in pain assessment. When estimating patients' pain intensity, observers are driven by anchoring, a rule of thumb that might have pernicious consequences in terms of unwarranted overreliance on initial impressions and insufficient revision in light of relevant disconfirming evidence. Taking this heuristic into account might foster accurate pain assessment and treatment.


Association of local anesthesia versus conscious sedation with functional outcome of acute ischemic stroke patients undergoing embolectomy.
Compare functional outcomes of acute ischemic stroke patients undergoing embolectomy with either local anesthesia or conscious sedation. Secondarily, identify differences in hemodynamic parameters and complication rates between groups. Single institution, retrospective review of all acute ischemic stroke patients undergoing embolectomy between January 2014 and July 2018 (n = 185). Patients receiving general anesthesia (n = 27) were excluded. One-hundred and eleven of 158 (70.3%) composed the local anesthesia group, and 47 (29.7%) composed the conscious sedation group. Median age was 71 years (interquartile range 59-79). Seventy-eight (49.4%) were male. The median National Institute of Health stroke scale score was 17.5 (interquartile range 11-21). Hemodynamic, medication, complication, and functional outcome data were collected from the anesthesia protocol and medical records. Good functional outcome was defined as a three-month modified Rankin Scale < 2. A multivariate analysis was performed to estimate the association of anesthesia type on three-month modified Rankin Scale score. Three-month modified Rankin Scale score <2 was similar between groups (p = 0.5). Patients receiving conscious sedation were on average younger than patients receiving local anesthesia (p = 0.01). Conscious sedation patients were more likely to receive intravenous thrombolytic prior to embolectomy (p = 0.025). The complication rate and hemodynamic parameters were similar between groups. Functional outcome of acute ischemic stroke patients undergoing embolectomy appears to be similar for patients receiving local anesthesia and conscious sedation. This similarity may be beneficial to a future study comparing general anesthesia to local anesthesia and conscious sedation. The use of local anesthesia or conscious sedation does not significantly impact hemodynamic status.


Ultrastructural aspects of corneal fibrous tissue in the Scheie syndrome.
An ultrastructural study of the corneal fibrous tissue was performed in a case of Scheie's syndrome. Mucopolysaccharidosis deposits in keratocytes were observed as electron-clear and electron-dense inclusions. Modifications of the extracellular space included modifications of lamellar collagen organization and local hypertrophy of collagen bundles; presence of microfibrillar dense material isolating large irregular collagen fibers; and presence of fibrous long spacing type collagen fibers. The significance of these changes is discussed. This special form of collagen organization is supposed to appear in a modified microenvironment, that is the presence of an abnormal concentration of proteoglycans.


Detection of human Dicer and Argonaute 2 catalytic activity.
The microRNA (miRNA)-guided RNA silencing pathway is a central and well-defined cellular process involved in messenger RNA (mRNA) translational control. This complex regulatory process is achieved by a well orchestrated machinery composed of a relatively few protein components, among which the ribonuclease III (RNase III) Dicer and Argonaute 2 (Ago2) play a central role. These two proteins are essential and it is of particular interest to measure and detect their catalytic activity under various situations and/or conditions. In this chapter, we describe different protocols that aim to study and determine the catalytic activity of Dicer and Ago2 in cell extracts, immune complexes, and size-fractionated cell extracts. Another protocol aimed at assessing miRNA binding to Ago2 is also described. These experimental approaches are likely to be useful to researchers investigating the main steps of miRNA biogenesis and function in human health and diseases.


Chuanzhitongluo regulates microglia polarization and inflammatory response in acute ischemic stroke.
Chuanzhitongluo (CZTL), a traditional Chinese medicine mixture, is used in the recovery period of acute ischemic stroke (AIS), and effectively improves the prognosis of AIS patients. This study aims to evaluate whether CZTL regulates microglia polarization and inflammatory response to reduce brain damage in the acute phase of AIS. A mouse model of AIS was prepared by the photochemical method. Cerebral infarct volume was detected by 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to assess neuronal apoptosis. Gene expression profile change was explored by Gene chip. Inflammatory factors were analyzed by Protein microarray. The Immunofluorescence double-labeling assay was executed to elucidate the effects of CD16+ / Iba-1+ and CD206+ / Iba-1+ in the peripheral area of cerebral ischemia. Results revealed that CZTL treatment alleviated the neurological impairment, reduced cerebral infarct volume, and inhibited neuronal apoptosis. CZTL altered gene expression profiles, which indicate that CZTL may be involved in regulating neuroinflammation. CZTL restrained inflammatory responses by down-regulated pro-inflammatory cytokines expression and enhanced anti-inflammatory cytokines level. Further experiments demonstrated that CZTL inhibited the activation of NLRP3 inflammasome, which decreasing the inflammatory response. In addition, CZTL promoted the transformation of microglia from M1 to M2 phenotype. These results indicate that CZTL alleviates neuroinflammation and brain damage after AIS in mice, which may be mediated by modulating microglia polarization.


Nirmatrelvir/ritonavir treatment in SARS-CoV-2 positive kidney transplant recipients - a case series with four patients.
Despite vaccination coronavirus disease 2019 (COVID-19)-associated mortality caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains high in kidney transplant recipients. Nirmatrelvir is a protease inhibitor with activity against SARS-CoV-2. Nirmatrelvir reduces the risk for mortality and hospitalization, which is approved for treating adults at risk for severe disease. Nirmatrelvir is metabolized by the cytochrome P-450 (CYP) 3A4 isozyme CYP3A4 and is therefore co-administered with the irreversible CYP3A4 inhibitor ritonavir, which results in a drug interaction with tacrolimus. A limited number of patients with nirmatrelvir/ritonavir and tacrolimus therapy after kidney transplantation have been reported to date. It has been reported that tacrolimus was paused during the five-day nirmatrelvir/ritonavir therapy and subtherapeutic tacrolimus levels were observed after finishing nirmatrelvir/ritonavir in two patients. Therefore, optimization of tacrolimus dosing is urgently needed in transplant recipients receiving nirmatrelvir/ritonavir treatment. Here, we present our first-hand experience with four patients receiving tacrolimus therapy following kidney transplantation and nirmatrelvir/ritonavir therapy due to COVID-19. Tacrolimus was paused during nirmatrelvir/ritonavir therapy in all patients, which resulted in stable therapeutic tacrolimus levels. Tacrolimus was continued directly after finishing nirmatrelvir/ritonavir to avoid subtherapeutic levels in the first patient treated. This patient received his usual tacrolimus maintenance dose, which resulted in toxic levels. Based on this observation, tacrolimus therapy was continued 24 h after finishing nirmatrelvir/ritonavir treatment at a reduced dose in the subsequent patients. In these patients, therapeutic to supratherapeutic tacrolimus levels were observed despite the therapeutic break and dose reduction. Based on altered CYP3A4 metabolism, tacrolimus levels have to be closely monitored after treatment with nirmatrelvir/ritonavir. Our study suggests that tacrolimus treatment should be paused during nirmatrelvir/ritonavir medication and be continued 24 h after completing nirmatrelvir/ritonavir therapy at a reduced dose and under close monitoring. Based on the limited number of patients in this study, results must be interpreted with caution.


Applications of brain organoids in neurodevelopment and neurological diseases.
A brain organoid is a self-organizing three-dimensional tissue derived from human embryonic stem cells or pluripotent stem cells and is able to simulate the architecture and functionality of the human brain. Brain organoid generation methods are abundant and continue to improve, and now, an in vivo vascularized brain organoid has been encouragingly reported. The combination of brain organoids with immune-staining and single-cell sequencing technology facilitates our understanding of brain organoids, including the structural organization and the diversity of cell types. Recent publications have reported that brain organoids can mimic the dynamic spatiotemporal process of early brain development, model various human brain disorders, and serve as an effective preclinical platform to test and guide personalized treatment. In this review, we introduce the current state of brain organoid differentiation strategies, summarize current progress and applications in the medical domain, and discuss the challenges and prospects of this promising technology.


Erratum to: A Review of the Long-Term Oncologic Outcomes of Robotic Surgery Versus Laparoscopic Surgery for Colorectal Cancer.
[This corrects the article DOI: 10.1007/s12262-015-1375-8.].


Endostar, a recombined humanized endostatin, inhibits lymphangiogenesis and lymphatic metastasis of Lewis lung carcinoma xenograft in mice.
The aim of this study was to investigate the effects of Endostar, a recombined humanized endostatin, on lymphatic tumor growth, lymphangiogenesis and lymphatic metastasis of Lewis lung carcinoma (LLC) xenograft in mice. Lewis lung carcinoma xenografts were established in C57BL/6 mice by intravenous injection of 1 × 10(6) cells. Then the mice were assigned to two groups: the control group received caudal vein injections of 0.2 ml of 0.9% sodium chloride for 15 days, and the treatment group received 500 µg Endostar daily. Six weeks after LLC cell injection, the mice were sacrificed, and tumor multiplicity and tumor sizes were recorded. The expression of vascular endothelial growth factor C (VEGF-C) and podoplanin were observed by immunohistochemical staining. Tumor numbers and sizes in the control group were significantly higher than those of the treatment group. The microlymphatic vessel density (MLVD) was 5.67 ± 1.57 in the treatment group, which was markedly lower than in the control mice (7.78 ± 1.56). Two lymph node metastases were observed in the treatment group, and eight in the control group. Lymphatic metastases were more frequent in the control group than in the treatment group. Expression of VEGF-C in the control group was significantly higher than that in the treatment group. Endostar significantly inhibits the lymphatic tumor growth, lymphangiogenesis and lymphatic metastasis of Lewis lung carcinoma xenografts, and its inhibitory effect is due to its ability to partially regulate the tumor expression of VEGF-C.


Isotopic data for bioarchaeological samples from Polynesia (pre-Contact and modern periods).
Two datasets are presented in this paper, one from archaeologically-derived human remains and one from modern plants and animals. First, isotopic data (δ13C, δ15N, δ34S, and 87Sr/86Sr) along with some radiocarbon dates from archaeologically-derived bone and teeth from individuals buried in pre-Contact Tonga and Fiji are provided. The second dataset is comprised of modern plant and animal samples (n = 27) collected from the island of Atiu (Cook Islands). δ13C and δ15N data from these samples are presented, and this data is integrated with other datasets to provide an aggregated tropical Pacific dietary baseline for paleodietary studies in this region. First collected to explore the interactions between diet, mobility, social status, and the physical environment, the archaeologically-derived samples are from two Polynesian islands. From the Tongan island of Tongatapu, two burial mounds designated To-At-1 and To-At-2 and collectively called 'Atele, are radiocarbon dated to the Complex Centralized Chiefdom period (c. 500-150 BP). The second collection is from the coastal site of Bourewa in the Republic of Fiji, dated to the Vuda Phase (c. 750-150 BP). From these human remains the following tissues and isotopes were analyzed: bone and dentine collagen analysis of δ15N and δ13C (n = 81) as well as δ34S where collagen yield was large enough (n = 37), tooth enamel 87Sr/86Sr (n = 47), and radiocarbon dates to supplement the relative dating of the burial sites (n = 16). The human data provides a relatively large dataset (for the region) to compare to other contemporaneous sites to consider intra- and inter-island dietary practices and consider movement in the wider region (while being mindful of issues with interpretation). The amalgamated dietary baseline has utility for placing archaeological and ecological samples within the tropic Pacific foodweb.


From molecular imaging to systems diagnostics: time for another paradigm shift?
The term "Molecular Imaging" has hit the consciousness of radiologists only in the past decade although many of the concepts that molecular imaging encompasses has been practiced in biomedical imaging, especially in nuclear medicine, for many decades. Many new imaging techniques have allowed us to interrogate biologic events at the cellular and molecular level in vivo in four dimensions but the challenge now is to translate these techniques into clinical practice in a way that will enable us to revolutionize healthcare delivery. The purpose of this article is to introduce the term "Systems Diagnostics" and examine how radiologists can become translators of disparate sources of information into medical decisions and therapeutic actions.


Tachycardia in spontaneously hypertensive and normotensive rats after fusaric acid and bupicamide.
1. The effects of the dopamine-beta-hydroxylase inhibitors bupicamide, fusaric acid, FLA-63 and U-14,624 on blood pressure and heart rate of spontaneously hypertensive rats were examined. 2. Bupicamide and fusaric acid caused marked tachycardia whereas FLA-63 and U-14,624 caused modest bradycardia; all drugs decreased blood pressure. 3. In normotensive rats, fusaric acid caused the same degree of tachycardia as in spontaneously hypertensive rats, but blood pressure was only slightly reduced. 4. Tachycardia after fusaric acid was not due to increased sympathetic activity or decreased parasympathetic activity but required intact catecholamine stores. 5. It is concluded that fusaric acid causes tachycardia by releasing catecholamines indirectly and that a metabolite of fusaric acid is also involved.


Pathologic primary tumor factors associated with risk of lymph node involvement in patients with non-endometrioid endometrial cancer.
Lymph node (LN) involvement is an important factor in guiding adjuvant treatment for patients with endometrial cancer. Risk factors for LN involvement are fairly well-established for endometrial adenocarcinoma, but it is not as well defined whether these factors similarly predict LN positivity in less common histologies. Patients diagnosed with pathologic T1-T2 carcinosarcoma, clear cell, uterine papillary serous carcinoma (UPSC), and mixed histologic type endometrial cancer between 2004 and 2016 undergoing primary surgery with at least 1 lymph node sampled in the National Cancer Data Base were identified. Logistic regression was performed to identify primary pathologic tumor predictors of LN positivity. Nomograms were created to predict overall, pelvic only, and paraaortic with or without pelvic LN involvement. Among 11,390 patients included, 1950 (18%) were node positive. On multivariable analysis, increasing pathologic tumor stage (pT2 versus pT1a, odds ratio [OR] 3.63, 95% confidence interval [CI] 3.15-4.18, p < 0.001), increase in tumor size per centimeter (OR 1.08, 95% CI 1.06-1.10, p < 0.001), and the presence of lymphovascular invasion (LVI) (OR 4.97, 95% CI 4.43-5.57, p < 0.001) were predictive of overall LN positivity. Relative to carcinosarcoma, both clear cell (OR 1.54, 95% CI 1.22-1.95, p < 0.001) and UPSC (OR 1.73, 95% CI 1.48-2.02, p < 0.001) histology were significantly associated with a higher risk of LN positivity while mixed histology was not (OR 1.07, 95% CI 0.92-1.24, p = 0.42). Among patients with non-endometrioid endometrial cancer, predictors of LN positivity are similar to endometrial adenocarcinoma. The nomograms provided could be helpful in making adjuvant treatment decisions for these less common histologies.


Qualitative and quantitative determination of nitrite and nitrate with ion chromatography.
Reactions of nitrogen monoxide and peroxynitrite often yield nitrite and nitrate as stable end products. The simultaneous detection of these two ions by anion chromatography with conductivity detection is described. The chromatographic system used is similar to conventional isocratic or gradient high-performance liquid chromatography equipment. The columns are packed with ion-exchanging resins instead of silica-derived adsorbents. Conductivity, though inherently nonspecific, has the advantage of covering a linear dynamic signal range of five orders of magnitude, which is far better than spectroscopic techniques; these are generally limited to two orders of magnitude. Typical run times per chromatogram are 15-30 min, and sample and standard concentrations can be between 100 nM and 10 mM. Injection volumes vary from 5 to 200 microl. Unlike with the Griess method, which determines only nitrite, a true mass balance from independent signals can be obtained if nitrate and nitrite are the only products.


Voluntary wheel running during adolescence distinctly alters running output in adulthood in male and female rats.
Adult female rats show greater running output compared with age-matched male rats, and the midbrain dopaminergic system may account for behavioral differences in running output. However, it is unknown if the lower running output in adult males can be regulated by wheel running experience during adolescence, and whether wheel running experience during adolescence will diminish the sex differences in running output during adulthood. We therefore determined and compared the exercise output in adult male and female rats that either had initiated voluntary wheel running only during adulthood or during adolescence. Our results demonstrate that running output in adult males were significantly higher when running was initiated during adolescence, and this higher running output was not significantly different from females. Running output did not differ during adulthood in females when wheel running was initiated during adolescence or during adulthood. Higher running output in females was associated with reduced expression of tyrosine hydroxylase and hyperactivation of calcium/calmodulin-dependent protein kinase II (CaMKII) in the dorsal striatum. Notably, running during adolescence-induced higher exercise output in adult males was associated with hyperactivation of CaMKII in the dorsal striatum, indicating a mechanistic role for CaMKII in running output. Together, the present results indicate sexually dimorphic adaptive biochemical changes in the dorsal striatum in rats that had escalated running activity, and highlight the importance of including sex as a biological variable in exploring neuroplasticity changes that predict enhanced exercise output in a voluntary physical activity paradigm.


Cholesterol and cholesterol bilayer domains inhibit binding of alpha-crystallin to the membranes made of the major phospholipids of eye lens fiber cell plasma membranes.
The concentration of α-crystallin decreases in the eye lens cytoplasm, with a corresponding increase in membrane-bound α-crystallin during cataract formation. The eye lens's fiber cell plasma membrane consists of extremely high cholesterol (Chol) content, forming cholesterol bilayer domains (CBDs) within the membrane. The role of high Chol content in the lens membrane is unclear. Here, we applied the continuous-wave electron paramagnetic resonance spin-labeling method to probe the role of Chol and CBDs on α-crystallin binding to membranes made of four major phospholipids (PLs) of the eye lens, i.e., phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylserine (PS), and phosphatidylethanolamine (PE). Small unilamellar vesicles (SUVs) of PC, SM*, and PS with 0, 23, 33, 50, and 60 mol% Chol and PE* with 0, 9, and 33 mol% Chol were prepared using the rapid solvent exchange method followed by probe-tip sonication. The 1 mol% CSL spin-labels used during SUVs preparation distribute uniformly within the Chol/PL membrane, enabling the investigation of Chol and CBDs' role on α-crystallin binding to the membrane. For PC, SM*, and PS membranes, the binding affinity (Ka) and the maximum percentage of membrane surface occupied (MMSO) by α-crystallin decreased with an increase in Chol concentration. The Ka and MMSO became zero at 50 mol% Chol for PC and 60 mol% Chol for SM* membranes, representing that complete inhibition of α-crystallin binding was possible before the formation of CBDs within the PC membrane but only after the formation of CBDs within the SM* membrane. The Ka and MMSO did not reach zero even at 60 mol% Chol in the PS membrane, representing CBDs at this Chol concentration were not sufficient for complete inhibition of α-crystallin binding to the PS membrane. Both the Ka and MMSO were zero at 0, 9, and 33 mol% Chol in the PE* membrane, representing no binding of α-crystallin to the PE* membrane with and without Chol. The mobility parameter profiles decreased with an increase in α-crystallin binding to the membranes; however, the decrease was more pronounced for the membrane with lower Chol concentration. These results imply that the membranes become more immobilized near the headgroup regions with an increase in α-crystallin binding; however, the Chol antagonizes the capacity of α-crystallin to decrease the mobility near the headgroup regions of the membranes. The maximum splitting profiles remained the same with an increase in α-crystallin concentration, but there was an increase in the maximum splitting with an increase in the Chol concentration in the membranes. It implies that membrane order near the headgroup regions does not change with an increase in α-crystallin concentration but increases with an increase in Chol concentration in the membrane. Based on our data, we hypothesize that the Chol and CBDs decrease hydrophobicity (increase polarity) near the membrane surface, inhibiting the hydrophobic binding of α-crystallin to the membranes. Thus, our data suggest that Chol and CBDs play a positive physiological role by preventing α-crystallin binding to lens membranes and possibly protecting against cataract formation and progression.


Open-label, ascending dose, prospective cohort study evaluating the antiviral efficacy of Rosuvastatin therapy in serum and lipid fractions in patients with chronic hepatitis C.
HMG CoA reductase inhibition suppresses in vitro HCV replication through depletion of cellular sterol proteins such as geranylgeraniol. Our aims were to prospectively evaluate the changes in serum and lipid fraction HCV RNA with Rosuvastatin in non-responder (NR) patients with CHC. A total of 11 patients with CHC genotype-1 received Rosuvastatin at 20 mg qd (weeks 0-4), 40 mg qd (weeks 5-12), with 4 week follow up. Lipid fractions were separated by a sucrose density gradient ultracentrifugation, HCV RNA determined at wks 0, 2, 4, 8, 12, 16 in serum, and in selected very low- (VLDF) to high-density (HDF) lipid fractions. A reduction in LDL and total cholesterol (TC) was not accompanied by significant decline in HCV RNA. At baseline, there was an inverse correlation between HDL and HCV RNA (ρ = -0.45, P = 0.036). At 20 mg, there was correlation between change (Δ) in TG and Δ HCV RNA (ρ = 0.75, P = 0.007), Δ ALT and Δ TC (ρ = -0.64, P = 0.03) and Δ LDL (ρ = -0.67, P = 0.02). At 40 mg, Δ TG maintained a positive correlation with Δ HCV RNA (ρ = 0.65, P = 0.03). There was a group difference for HCV RNA in relation to lipid fractions (P = 0.04) but not study time intervals (P = 0.17); mean log HCV RNA was greater in VLDF compared to HDF (5.81 ± 0.59 vs 5.06 ± 0.67, P = 0.0002) with no other differences to study time intervals (P = 0.099). Short-term Rosuvastatin monotherapy is not associated with significant changes in serum or lipid fraction HCV RNA in NR patients. HCV co-localizes with the lowest density lipid fractions in serum.


Bleeding complications in the patient with cardiac disease following thrombolytic and anticoagulant therapies.
Thrombolytic and anticoagulant therapies are used frequently in the cardiac patient. Bleeding complications and other coagulation defects, such as heparin-induced thrombocytopenia (HITP), can occur following the administration of these drugs. Nurses caring for the cardiac patient need to be aware of the potential for bleeding and know how to safely and effectively care for the patient who experiences a bleeding event.


Successful repair of double-outlet right ventricle by a modified Fontan operation.
Patients having a double-outlet right ventricle with an unfavorable anatomy for reparative conduit procedure present a formidable surgical challenge. Three such patients, aged 10, 13, and 14 years, with double-outlet right ventricle associated with atrioventricular discordance in 2 and atrioventricular concordance in 1, levotransposition of the great vessels and dextrocardia. A large-diameter direct anastomosis of the right atrium to the pulmonary artery was performed after the closure of the atrioventricular and pulmonary valves. All patients were operated on successfully with good clinical and hemodynamic results. Postoperatively, all 3 were acyanotic and had an improved physical activity compared with their preoperative status. Mean cardiac index at rest was 3.23 L/min/m2 and was increased to 5.04 L/min/m2 during exercise. These results indicate that this procedure can be of value for patients with double-outlet right ventricle in whom reparative surgery is technically difficult or infeasible.


Examining Associations Between Negative Affect and Substance Use in Treatment-Seeking Samples: A Review of Studies Using Intensive Longitudinal Methods.
Understanding dynamic relationships between negative affect and substance use disorder (SUD) outcomes, including craving, may help inform adaptive and personalized interventions. Recent studies using intensive longitudinal methods were reviewed to examine relationships between negative affect and the outcomes of either craving or substance use during and following SUD treatment. Results on associations between negative affect and craving/substance use were mixed and difficult to synthesize, given methodological differences across studies. The strength and direction of these relationships varied across outcomes, subgroups, contexts, and time course. The current literature is mixed concerning negative affect and craving/substance use associations during and following SUD treatment. Researchers should increasingly recruit diverse individuals, for example, samples of varying racial and ethnic backgrounds and those reporting co-occurring disorders and polysubstance use. Experimental, qualitative, and person-specific methods will improve our understanding of relationships between negative affect and substance-related outcomes during SUD treatment.


Safety and immunogenicity of an intranasal Shigella flexneri 2a Invaplex 50 vaccine.
Shigella flexneri 2a lipopolysaccharide 50 is a nasally delivered subunit vaccine consisting of a macromolecular complex composed of LPS, IpaB, IpaC and IpaD. The current study examined vaccine safety and immunogenicity across a dose range and the clinical performance of a new intranasal delivery device. Volunteers (N=36) were randomized to receive vaccine via the Dolphin™ (Valois of America, Congers, New York) intranasal spray device at one of three doses (240, 480, and 690 μg) on days 0, 14, and 28. Another group (N=8) received the 240 μg dose via pipette. Vaccine safety was actively monitored and antigen-specific humoral and mucosal immune responses were determined. There were no serious adverse events and the majority of adverse events (98%) were mild. Antibody secreting cells (ASC), plasma, and mucosal immune responses to Shigella antigens were detected at all three dose levels with the 690 μg dose inducing the highest magnitude and frequency of responses. Vaccination with comparable doses of Invaplex 50 via the Dolphin™ resulted in higher plasma and ASC immune responses as compared to pipette delivery. In this trial the S. flexneri 2a Invaplex 50 vaccine was safe, well-tolerated and induced robust levels of antigen-specific intestinal IgA and ASC responses. The spray device performed well and offered an advantage over pipette intranasal delivery.


New investigation on the tetragonal liquid-crystalline phase or SmQ.
Chiral liquid crystals, for which twist and smectic order strongly compete, can exhibit complex architectures. This is the case of the SmQ phase which shows a high degree of 3D order (tetragonal or hexagonal) as well as a liquid signature. We have combined X-ray scattering and optical observations on a new compound exhibiting a SmQ phase to discriminate between the two models proposed by A.M. Levelut et al. (J. Phys. II 7, 981 (1997)) at the molecular level for the phase with the I4(1)22 space group.


Treatment of ruptured fusiform aneurysm in the posterior cerebral artery with posterior cerebral artery-superior cerebellar artery anastomosis combined with parent artery occlusion: case report.
Surgical management of a fusiform aneurysm in the PCA sometimes requires occlusion of the parent artery. In such cases, reconstruction of the PCA may prevent the development of postoperative visual field defects. A 30-year-old woman with a fusiform aneurysm in the P2 of the left PCA presented with subarachnoid hemorrhage. The left superficial temporal artery and OA were hypoplastic. Left temporal craniotomy revealed that the lateromesencephalic ambient segment of the SCA and the posterior half portion of the P2 segment ran parallel and near each other, and that the calibers of both arteries were relatively consistent. Thus, the 2 arteries were anastomosed in a side-to-side fashion, and the anterior half of the left P2 segment was occluded by clipping proximal and distal to the aneurysm that was located at the left P2 segment just distal to the junction to the posterior communicating artery. The patient had an uneventful postoperative course, and postoperative cerebral angiography demonstrated resolution of the aneurysm, with perfusion of the left PCA from the left SCA via the anastomosis. Posterior cerebral artery-superior cerebellar artery anastomosis is a useful method of achieving PCA reconstruction in the context of a PCA aneurysm requiring occlusion of the parent vessel and when superficial temporal artery or OA-PCA anastomosis cannot be performed.


Biosensors for inflammation as a strategy to engineer regulatory T cells for cell therapy.
Engineered regulatory T cell (Treg cell) therapy is a promising strategy to treat patients suffering from inflammatory diseases, autoimmunity, and transplant rejection. However, in many cases, disease-related antigens that can be targeted by Treg cells are not available. In this study, we introduce a class of synthetic biosensors, named artificial immune receptors (AIRs), for murine and human Treg cells. AIRs consist of three domains: (a) extracellular binding domain of a tumor necrosis factor (TNF)-receptor superfamily member, (b) intracellular costimulatory signaling domain of CD28, and (c) T cell receptor signaling domain of CD3-ζ chain. These AIR receptors equip Treg cells with an inflammation-sensing machinery and translate this environmental information into a CD3-ζ chain-dependent TCR-activation program. Different AIRs were generated, recognizing the inflammatory ligands of the TNF-receptor superfamily, including LIGHT, TNFα, and TNF-like ligand 1A (TL1A), leading to activation, differentiation, and proliferation of AIR-Treg cells. In a graft-versus-host disease model, Treg cells expressing lymphotoxin β receptor-AIR, which can be activated by the ligand LIGHT, protect significantly better than control Treg cells. Expression and signaling of the corresponding human AIR in human Treg cells prove that this concept can be translated. Engineering Treg cells that target inflammatory ligands leading to TCR signaling and activation might be used as a Treg cell-based therapy approach for a broad range of inflammation-driven diseases.


Distinct effects of dual substitution on inductive and differentiative activities of C8-substituted guanine ribonucleosides.
The current studies compare the inductive and differentiative properties of 8-mercaptoguanosine with those of 7-methyl-8-oxoguanosine. 7-Methyl-8-oxoguanosine (7m8oGuo) is a new member of the family of C8-substituted guanine ribonucleosides, the first such biologically active compound described that differs from guanosine other than by the specific substituent at the 8 position. Like 8MGuo, 7m8oGuo stimulates proliferation selectively in B lymphocytes. However, 7m8oGuo possesses greater activity than 8MGuo as a mitogen and greater potency as an adjuvant for humoral immune responses. Thus, as a B-lymphocyte mitogen, 7m8oGuo induces quantitatively greater [3H]TdR uptake than does 8MGuo, but with the same concentration optimum. As an adjuvant for in vitro antibody responses, however, 7m8oGuo achieves the same degree of immunoenhancement as 8MGuo but at approximately 10-fold lower concentrations, that is, the dose-response profile has been shifted to the left. Moreover, whereas the mitogenic responses to 8MGuo and 7m8oGuo exhibit parallel kinetic profiles, the adjuvant activity of 7m8oGuo arises earlier and persists later than does that of 8MGuo. These results are interpreted in terms of two distinct intracellular pathways: one mediating mitogenesis and the other adjuvanticity.


Innumerable cerebral microbleeds in hepatitis B virus-related decompensated liver cirrhosis: a case report.
Cerebral microbleeds (CMBs) are small, rounded, dark-signal lesions on brain MRI that represent cerebral hemosiderin deposits resulting from prior microhemorrhages and are neuroimaging biomarkers of cerebral amyloid angiopathy (CAA). Here, we report a case of innumerable CMBs in a patient with hepatic encephalopathy underlying decompensated liver cirrhosis. An 83-year-old woman diagnosed with hepatitis B virus-related liver cirrhosis 40 years before was referred to our neurology clinic for progressive disorientation of time and place, personality changes, and confusion with somnolence over 2 weeks. Based on the laboratory, neuroimaging, and electrophysiological findings, we diagnosed the patient with hepatic encephalopathy, and her symptoms recovered within 12 h after proper medical management. Brain MRI showed innumerable CMBs in the bilateral frontal, parietal, temporal, and occipital lobes. Since the distribution of CMBs in the patient was mainly corticosubcortical and predominantly in the posterior cortical regions, and the apolipoprotein E genotype was ε4/ε4, we speculated that CAA and hepatic encephalopathy coexisted in this patient. We suggest that severe liver dysfunction associated with long-term decompensated liver cirrhosis may be related to an increased number of CMBs in the brain. Our findings indicate that decompensated liver cirrhosis may be a risk factor for the development of CMBs and corroborate a link between the liver and the brain.