Serum antibody responses to bovine retinal S-antigen and rod outer segments in proliferative diabetic retinopathy before and after argon laser photocoagulation.
Using the enzyme-linked immunosorbent assay, the serum antibody titers to bovine retinal S-antigen and rod outer segments in pre- and post-argon laser treated diabetic retinopathy patients were compared to each other and to the titers of age- and sex-matched normal controls. The increase in anti-S titer following the initial laser treatment gave a P less than 0.01 using the two-tailed paired Student's t-analysis as compared to the prelaser anti-S titer. Both pre- and post-laser anti-S titers were elevated over normal controls with P values of less than 0.02 and less than 0.001, respectively. Eight weeks after the initial laser treatment, anti-S titers began to decline approaching control levels 12 weeks later. No significant change was found between pre- and post-laser titers when rod outer segments were used as antigen although the pre- and post-laser titers were increased over normal controls with P values of less than 0.05 and less than 0.001, respectively. The release and possible alteration of retinal components following photocoagulation may account for the rise in anti-S titers, while the prephotocoagulation titers may be due to retinopathy-related photoreceptor cell alteration.


Sporotrichosis in a father and son.
A 41-year-old man developed classic lymphocutaneous sporotrichosis on the left arm; his 2-year-old son developed a single lesion of the "fixed" type on the right leg. Both patients responded rapidly to therapy with oral potassium iodide. Seven previous reports of familial sporotrichosis are listed, and therapy is reviewed briefly.


Cyclic electrodeposition of PtCu alloy: facile fabrication of highly porous platinum electrodes.
Cyclic electrodeposition of platinum and copper enables the fabrication of high surface area electrodes (roughness factors of >3000) by multiple alternation of alloy co-deposition and dealloying of copper from the just-fabricated alloy layers. The underlying processes, resulting electrode structures, and their applicability to potentially implantable glucose fuel cells are discussed.


Treating the emotional aspects of infertility: counseling services in an infertility clinic.
The physician treating the infertile couple, while attempting to diagnose and treat the cause of that problem, all too frequently overlooks the emotional aspects of involuntary sterility. Infertility can cause tremendous strains on the patients, either individually or as a couple. An approach to meeting these needs can be achieved through a program of counseling, provided as a service in an infertility center.


Ontogeny of functional innervation of bulbocavernosus muscles in male and female rats.
Electrical stimulation of the sixth lumbar ventral root reliably elicited contractions of the bulbocavernosus muscle (BC) in untreated female rats on the day before birth. This functional contact indicates that testosterone probably does not act to save the spinal nucleus of the bulbocavernosus (SNB) and its BC target muscles through the establishment of an active neuromuscular synapse, since this is already present in animals with an SNB system which is fated to die.


Peripunctal melanocytic nevi. Distinctive clinical findings and differential diagnosis.
A peripunctal nevus is a rare lesion of the eyelid margin, six examples of which are included in this report. The lesions all involved the lower punctum and had been present for many years without producing epiphora. In addition to their variable clinical pigmentation and translucent appearance on biomicroscopy, all shared several other diagnostically useful clinical features: an overall dome-shape with a fine micronodularity; a prominent ramifying vascularity; and, most importantly, circumferentially swollen punctal lips that created a slit-like punctal orifice. Histopathologically, the lesions were predominantly or exclusively subepithelial melanocytic nevi and were demonstrated not to compress the punctum or canaliculus. Infiltration of the nevus cells within the orbicularis striated muscle fibers was a common finding owing to the latter's superficial location in the eyelids. If patients request excision for cosmetic reasons, these lesions are best managed by a horizontal circular shave excision with the temporary placement of a silicon punctual plug. The differential diagnosis includes cyst, papilloma, melanoma, and basal cell carcinoma.


Epidemiological assessment of distress during chemotherapy: who is affected?
Following the rise in the incidence of cancer, the need for chemotherapy has escalated, as have its side effects. Psychological distress is one of the known side effects of chemotherapy; however, it has not received adequate attention. The purpose of this study was to measure psychological distress in patients receiving chemotherapy, making comparisons on the basis of age, gender, marital status, and chemotherapy dose, and to assess the patients' willingness to continue with treatment. A descriptive cross-sectional study was performed on outpatients receiving chemotherapy beyond the first dose at the Radiation & Isotopes Centre Khartoum (Rick). Data were collected via a face-to-face interview with the patients using the Hospital Anxiety and Depression Scale. Among patients undergoing chemotherapy, 55 (25.5%) experienced anxiety and depression. Of the 216 patients recruited, the majority were middle-aged (30-50 years old) married women. Development of psychological distress followed a U-shaped curve in relation to the number of chemotherapy doses received. Patients who received 1-5 and >10 doses experienced more psychological distress than those who received 6-10 chemotherapy doses. As many as 212 (98%) patients were willing to continue with chemotherapy. In our study, psychological distress burdened a quarter of the patients receiving chemotherapy. Psychological distress plays a role in cancer recurrence and recovery; thus, there is a need for a holistic approach to the management of patients with cancer, including psychological evaluation to identify those at risk.


Ensuring an exit strategy: RTEL1 restricts rogue recombination.
Success of homologous recombination-based DNA repair depends not only on recombinases, which promote invasion of the homologous DNA duplex that serves as a template for repair, but also on antirecombinases, which dismantle recombination intermediates to allow completion of repair. In this issue, Barber et al. (2008) identify a previously elusive antirecombinase activity important for maintaining genome stability in animals.


Serum lipids and lipoproteins after myocardial infarction: associations with cardiovascular mortality and experience in the Aspirin Myocardial Infarction Study.
Serum cholesterol and triglyceride levels were measured at baseline in 4021 men and 503 women (myocardial infarction survivors) participating in the Aspirin Myocardial Infarction Study (AMIS). A cohort of participants (1824 men and 226 women) had, in addition, a determination of high-density lipoprotein (HDL) cholesterol and an estimate of low-density lipoprotein (LDL) cholesterol. In comparison with values obtained for normal Americans by the Lipid Research Clinics Prevalence Study Group, AMIS participants had higher serum cholesterol, higher serum triglyceride, higher LDL cholesterol, and lower HDL cholesterol levels. These values were the most disparate in the women and younger men. The serum total cholesterol, the ratio of LDL to HDL cholesterol, and the serum triglyceride level were significantly related (p less than 0.05) to the 3-year cardiovascular mortality rate for men less than 55 years of age (univariate relationships). For men older than 55 years, these relationships were not statistically significant. After adjustment for multiple risk factors, serum cholesterol and the ratio of LDL to HDL cholesterol remained significant risk factors for cardiovascular death and the combined incidence of cardiovascular death or nonfatal myocardial infarction in men less than age 55 years.


Spectroscopic determination of the photodegradation of monovarietal extra virgin olive oils and their binary mixtures through intelligent systems.
A common phenomenon that takes place in bottled extra virgin olive oil (EVOO) is the photooxidation of its pigments, especially chlorophyll, which acts as a singlet-oxygen sensitizer. This translates into a severe decrease of quality, potentially leading to oxidized and rancid olive oils by the time they reach to the consumers. In this current research, the photochemical degradation has been monitored for 45 days in binary mixtures of four monovarietal EVOOs (Arbequina, Hojiblanca, Cornicabra, and Picual) through UV-Visible spectroscopy. A multilayer perceptron-based model was optimized to estimate the photodegradation suffered by the samples, in terms of photodegradation time, relying on the spectroscopic information gathered and attaining an error rate of 2.43 days (5.3%) in the determination of this parameter.


Retracted: Analysis of Rotator Cuff Muscle Injury on the Drawing Side of the Recurve Bow: A Finite Element Method.
[This retracts the article DOI: 10.1155/2022/8572311.].


Comparative Study of the Effect of Oral Chloral Hydrate and Intranasal Fentanyl on Sedation in Children for Electroencephalography.
Sedation and stability during electroencephalography (EEG) in pediatrics have high clinical importance. This study compares the sedative properties of oral chloral hydrate (OCH) and intranasal fentanyl (INF). This study was a randomized clinical trial conducted in 2020 in Isfahan City on sixty-two pediatric candidates for EEG. Patients were randomized into two groups receiving 50 mg/kg OCH and 2 μg/kg INF thirty minutes before the process. The heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), and oxygen saturation (O2 sat) of patients, sedation, and physician's satisfaction were measured and compared between groups. The HR of patients decreased significantly in both groups (P< 0.001), and the patients that received INF had significantly lower HR 15, 30, 45, and 60 minutes after drug administrations (P< 0.05). RR evaluation indicated significantly decreased RR in both groups (P< 0.001), and patients receiving INF had lower RR 30, 45, and 60 per minutes after drug administrations (P< 0.001). Both groups showed significantly increased sedation levels during the study (P< 0.001), and patients treated with INF had higher sedation levels 15, 30, and 45 minutes after drug administration. Satisfaction rates were higher among the group that received INF (P= 0.020). The use of INF had significant analgesic and sedative effects on pediatrics undergoing EEG.


Characterizing organic mood syndrome, depressed type.
In this report, a first comprehensive description of the clinical features of patients with organic mood syndrome, depressed type (OMS-D), in a psychiatric hospital population is presented. This description is based on information from 130 OMS-D patients among 14,889 patients who presented for initial evaluation over a 5-year period. This description includes an enumeration of the common clinical symptoms of this syndrome. Following this, the severity of the symptoms of OMS-D are compared with those of its crude "functional" equivalent of major depressive disorder, single episode (MDD-SE). In addition, associated factors are presented concerning demographics, level of functioning, comorbidity, electroencephalographic and computed tomographic abnormalities, and current physical problems. These findings provide preliminary support for the validity of this diagnostic category, and provide relevant information concerning proposed changes in this category as listed in the DSM-IV Options Book.


Reversal of impaired hippocampal long-term potentiation and contextual fear memory deficits in Angelman syndrome model mice by ErbB inhibitors.
Angelman syndrome (AS) is a human neuropsychiatric disorder associated with autism, mental retardation, motor abnormalities, and epilepsy. In most cases, AS is caused by the deletion of the maternal copy of UBE3A gene, which encodes the enzyme ubiquitin ligase E3A, also termed E6-AP. A mouse model of AS has been generated and these mice exhibit many of the observed neurological alterations in humans. Because of clinical and neuroanatomical similarities between AS and schizophrenia, we examined AS model mice for alterations in the neuregulin-ErbB4 pathway, which has been implicated in the pathophysiology of schizophrenia. We focused our studies on the hippocampus, one of the major brain loci impaired in AS mice. We determined the expression of neuregulin 1 and ErbB4 receptors in AS mice and wild-type littermates (ages 10-16 weeks) and studied the effects of ErbB inhibition on long-term potentiation in hippocampal area cornu ammonis 1 and on hippocampus-dependent contextual fear memory. We observed enhanced neuregulin-ErbB4 signaling in the hippocampus of AS model mice and found that ErbB inhibitors could reverse deficits in long-term potentiation, a cellular substrate for learning and memory. In addition, we found that an ErbB inhibitor enhanced long-term contextual fear memory in AS model mice. Our findings suggest that neuregulin-ErbB4 signaling is involved in synaptic plasticity and memory impairments in AS model mice, suggesting that ErbB inhibitors have therapeutic potential for the treatment of AS.


Development and Validation of a Prediction Model for Mortality and Adverse Outcomes Among Patients With Peripheral Eosinopenia on Admission for Clostridium difficile Infection.
Recent evidence from an animal model suggests that peripheral loss of eosinophils in Clostridium difficile infection (CDI) is associated with severe disease. The ability to identify high-risk patients with CDI as early as the time of admission could improve outcomes by guiding management decisions. To construct a model using clinical indices readily available at the time of hospital admission, including peripheral eosinophil counts, to predict inpatient mortality in patients with CDI. In a cohort study, a total of 2065 patients admitted for CDI through the emergency department of 2 tertiary referral centers from January 1, 2005, to December 31, 2015, formed a training and a validation cohort. The sample was stratified by admission eosinophil count (0.0 cells/μL or >0.0 cells/μL), and multivariable logistic regression was used to construct a predictive model for inpatient mortality as well as other disease-related outcomes. Inpatient mortality was the primary outcome. Secondary outcomes included the need for a monitored care setting, need for vasopressors, and rates of inpatient colectomy. Of the 2065 patients in the study, 1092 (52.9%) were women and patients had a mean (SD) age of 63.4 (18.4) years. Those with an undetectable eosinophil count at admission had increased in-hospital mortality in both the training (odds ratio [OR], 2.01; 95% CI, 1.08-3.73; P = .03) and validation (OR, 2.26; 95% CI, 1.33-3.83; P = .002) cohorts in both univariable and multivariable analysis. Undetectable eosinophil counts were also associated with indicators of severe sepsis, such as admission to monitored care settings (OR, 1.40; 95% CI, 1.06-1.86), the need for vasopressors (OR, 2.08; 95% CI, 1.32-3.28), and emergency total colectomy (OR, 2.56; 95% CI, 1.12-5.87). Other significant predictors of mortality at admission included increasing comorbidity burden (for each 1-unit increase: OR, 1.13; 95% CI, 1.05-1.22) and lower systolic blood pressures (for each 1-mm Hg increase: OR, 0.99; 95% CI, 0.98-1.00). In a subgroup analysis of patients presenting without initial tachycardia or hypotension, only patients with undetectable admission eosinophil counts, but not those with an elevated white blood cell count, had significantly increased odds of inpatient mortality (OR, 5.76; 95% CI, 1.99-16.64). This study describes a simple, widely available, inexpensive model predicting CDI severity and mortality to identify at-risk patients at the time of admission.


Activation of transient receptor potential vanilloid 1 ameliorates tau accumulation-induced synaptic damage and cognitive dysfunction via autophagy enhancement.
The autophagy-lysosomal pathway is important for maintaining cellular proteostasis, while dysfunction of this pathway has been suggested to drive the aberrant intraneuronal accumulation of tau protein, leading to synaptic damage and cognitive impairment. Previous studies have demonstrated that the activation of transient receptor potential vanilloid 1 (TRPV1) by capsaicin has a positive impact on cognition and AD-related biomarkers. However, the effect and mechanism of TPRV1 activation on neuronal tau homeostasis remain elusive. A mouse model of tauopathy was established by overexpressing full-length human tau in the CA3 area. Mice were fed capsaicin diet (0.0125%) or normal diet for 9 weeks. The cognitive ability, synaptic function, tau phosphorylation levels, and autophagy markers were detected. In vitro, capsaicin-induced alterations in cellular autophagy and tau degradation were characterized using two cell models. Besides, various inhibitors were applied to validate the role of TRPV1-mediated autophagy enhancement in tau clearance. We observed that TRPV1 activation by capsaicin effectively mitigates hippocampal tau accumulation-induced synaptic damages, gliosis, and cognitive impairment in vivo. Capsaicin promotes the degradation of abnormally accumulated tau through enhancing autophagic function in neurons, which is dependent on TRPV1-mediated activation of AMP-activated protein kinase (AMPK) and subsequent inhibition of the mammalian target of rapamycin (mTOR). Blocking AMPK activation abolishes capsaicin-induced autophagy enhancement and tau degradation in neurons. Our findings reveal that capsaicin-induced TRPV1 activation confers neuroprotection by restoring neuronal tau homeostasis via modulating cellular autophagy and provides additional evidence to support the potential of TRPV1 as a therapeutic target for tauopathies.


Outcomes Following Percutaneous Coronary Intervention in Renal Transplant Recipients: A Binational Collaborative Analysis.
To investigate the clinical and procedural characteristics in patients with a history of renal transplant (RT) and compare the outcomes with patients without RT in 2 national cohorts of patients undergoing percutaneous coronary intervention (PCI). Data from the National Inpatient Sample (NIS) and British Cardiovascular Intervention Society (BCIS) were used to compare the clinical and procedural characteristics and outcomes of patients undergoing PCI who had RT with those who did not have RT. The primary outcome of interest was in-hospital mortality. Of the PCI procedures performed in 2004-2014 (NIS) and 2007-2014 (BCIS), 12,529 of 6,601,526 (0.2%) and 1521 of 512,356 (0.3%), respectively, were undertaken in patients with a history of RT. Patients with RT were younger and had a higher prevalence of congestive cardiac failure, hypertension, and diabetes but similar use of drug-eluting stents, intracoronary imaging, and pressure wire studies compared with patients who did not have RT. In the adjusted analysis, patients with RT had increased odds of in-hospital mortality (NIS: odds ratio [OR], 1.90; 95% CI, 1.41-2.57; BCIS: OR, 1.60; 95% CI, 1.05-2.46) compared with patients who did not have RT but no difference in vascular or bleeding events. Meta-analysis of the 2 data sets suggested an increase in in-hospital mortality (OR, 1.79; 95% CI, 1.40-2.29) but no difference in vascular (OR, 1.24; 95% CI, 0.77-2.00) or bleeding (OR, 1.21; 95% CI, 0.86-1.68) events. This large collaborative analysis of 2 national databases revealed that patients with RT undergoing PCI are younger, have more comorbidities, and have increased mortality risk compared with the general population undergoing PCI.


Cytoplasmic expression of mature glycylglycine endopeptidase lysostaphin with an amino terminal hexa-histidine in a soluble and catalytically active form in Escherichia coli.
Methicillin-resistant Staphylococcus aureus is a major problem in the world, causing hospital acquired infections and the infections/pathogenesis in community. Lysostaphin is a novel therapeutic molecule to kill the multidrug-resistant S. aureus. Mature lysostaphin is a single polypeptide (approximately 27 kDa) chain metalloprotease glycylglycine endopeptidase, capable of specifically hydrolyzing penta-glycine crosslinks present in the peptidoglycan of the S. aureus cell wall. The mature lysostaphin gene of Staphylococcus simulans has been cloned and overexpressed in the cytoplasm of E. coli with amino terminal hexa-histidine as a fusion partner under the transcriptional control of bacteriophage T7 phi 10 promoter/lac operator and ribosome binding site. The transformed E. coli BL21 (lambdaDE3) cells produced catalytically active soluble (His)6-lysostaphin fusion protein in the cytoplasm representing approximately 20% of the total cellular proteins. The fusion protein was purified to homogeneity using a single chromatographic step of IMAC on Ni-NTA agarose. The present cloning, expression, and purification procedure of recombinant lysostaphin from a non-pathogenic organism E. coli enables preparation of large quantity of r-lysostaphin for structure function studies and evaluation of its clinical potential in therapy and prophylaxis of staphylococcal infections.


Interleukin-10-1082G/A polymorphism and acute liver graft rejection: a meta-analysis.
To investigate the association between interleukin (IL)-10-1082 (G/A) promoter polymorphism and acute rejection (AR) in liver transplant (LT) recipients. Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% CIs for IL-10-1082 G/A polymorphism and AR were calculated in a fixed- and a random-effects model as appropriate. This meta-analysis included seven case-control studies, which comprised 652 cases of LT recipients in which 241 cases developed AR and 411 cases did not develop AR. Overall, the variant A allele was not associated with AR risk when compared with the wild-type G allele (OR = 0.94, 95% CI: 0.64-1.39). Moreover, similar results were observed when the AA genotype was compared with the AG/GG genotype (OR = 1.05, 95% CI: 0.55-2.02). When stratifying for ethnicity, no significant association was observed among either Caucasians or Asians. Because only one study was performed in Asian patients, the result of subgroup analysis by ethnicity would not be reliable for Asians. Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. This meta-analysis suggests that IL-10-1082 G/A polymorphism may be not associated with AR risk in LT recipients among Caucasians.


Stability of a flavored formulation of acetylcysteine for oral administration.
The chemical and physical stability of a flavored solution of acetylcysteine stored at room temperature or under refrigeration for up to 35 days in amber plastic prescription bottles were studied. The flavored acetylcysteine solution was prepared by adding a sweetener and a strawberry creamsicle flavoring to acetylcysteine solution 10% to a final nominal acetylcysteine concentration of 86.5 mg/mL. Six identical samples of the formulation were prepared in amber plastic prescription bottles. Three bottles were stored at room temperature (23-25 degrees C) and the other three were stored in the refrigerator (3-5 degrees C). Immediately after preparation and at 7, 14, 21, 28, and 35 days, each sample was assayed in duplicate by high- performance liquid chromatography. Stability was defined as the retention of at least 90% of the initial drug concentration. On day 35, the refrigerated acetylcysteine samples retained 96.7% of their initial concentration. The samples stored at room temperature retained 92.5% of their initial concentration. A flavored oral formulation of acetylcysteine 86.5 mg/mL was stable for at least 35 days when stored at room temperature and in the refrigerator in amber plastic bottles.


Clinical relevance of various microscopical features of the second-look specimen in advanced ovarian cancer.
The second-look specimens of 70 patients with advanced ovarian cancer (FIGO 2B, 3, and 4) were reviewed and classified according to four categories: no response to chemotherapy (category a), predominantly histologically viable tumor with some necrotic and/or fibrotic tissue (category b), predominance of fibrosis and recrosis (category c), and no evidence of tumor, i.e., pathologically proven complete response (PCR) (category d). All of the patients in categories a and b had died because of ovarian cancer at the end of the observation period. In category c, 17/25 patients eventually achieved a PCR as established at a third-look procedure. The median survival of 56 months in this group was lower than that of the patients in category d (64 months), although this difference was without statistical significance. These observations underscore the importance of the microscopical features of the second-look specimen for the treatment of advanced ovarian cancer.


Autism-associated mutations in KV7 channels induce gating pore current.
Autism spectrum disorder (ASD) adversely impacts >1% of children in the United States, causing social interaction deficits, repetitive behaviors, and communication disorders. Genetic analysis of ASD has advanced dramatically through genome sequencing, which has identified >500 genes with mutations in ASD. Mutations that alter arginine gating charges in the voltage sensor of the voltage-gated potassium (KV) channel KV7 (KCNQ) are among those frequently associated with ASD. We hypothesized that these gating charge mutations would induce gating pore current (also termed ω-current) by causing an ionic leak through the mutant voltage sensor. Unexpectedly, we found that wild-type KV7 conducts outward gating pore current through its native voltage sensor at positive membrane potentials, owing to a glutamine in the third gating charge position. In bacterial and human KV7 channels, gating charge mutations at the R1 and R2 positions cause inward gating pore current through the resting voltage sensor at negative membrane potentials, whereas mutation at R4 causes outward gating pore current through the activated voltage sensor at positive potentials. Remarkably, expression of the KV7.3/R2C ASD-associated mutation in vivo in midbrain dopamine neurons of mice disrupts action potential generation and repetitive firing. Overall, our results reveal native and mutant gating pore current in KV7 channels and implicate altered control of action potential generation by gating pore current through mutant KV7 channels as a potential pathogenic mechanism in autism.


Fractional dependence of the free energy of activation on the driving force of charge transfer in the quenching of the excited states of substituted phenanthroline homoleptic ruthenium(ii) complexes in aqueous medium.
The photophysical characteristics of some homoleptic ruthenium(ii) phenanthroline derivatives are investigated in aqueous medium. The lifetimes of the excited 3MLCT state of the studied complexes were found to be very sensitive to the type of the substituents on the phenanthroline ligand and were found to increase from about 0.96 μs in case of the parent [Ru(Phen)3]2+ complex to 2.97 μs in case of [Ru(DPPhen)3]2+. The transient absorption spectra of the current set of complexes were studied also in aqueous medium. Quenching of the excited 3MLCT states of the studied complexes by molecular oxygen were studied and quenching rate constants were found to be in the range 1.02-4.83 × 109 M-1 s-1. Values of singlet oxygen quantum yields were found to be in the range 0.01 to 0.25, and the corresponding efficiencies of singlet oxygen thereby produced, f T Δ, were in the range 0.03-0.52. The mechanism by which the excited 3MLCT state is quenched by oxygen is discussed in light of the spin statistical factor rate constants and the competition between charge transfer and non-charge transfer quenching pathways. The partial charge transfer parameters, p CT, were obtained and found to be about 0.88 for all complexes except for complexes with f T Δ values lower than 0.25. The correlation of the activation free energies ΔG ≠ of the exciplexes formation with the driving force for charge transfer, ΔG CET, gives a charge transfer character of the exciplexes of about 35.0%.


Differentiation between active and chronic Crohn's disease using MRI small-bowel motility examinations - initial experience.
To evaluate the influence of locally active Crohn's disease on systemic small-bowel motility in patients with chronic Crohn's disease compared to healthy individuals. Fifteen healthy individuals (11 men, four women; mean age 37 years) and 20 patients with histopathologically proven active (n = 15; 10 women, 5 men; mean age 45 years) or chronic (n = 5; four women, one man; mean age 48 years) Crohn's disease were included in this institutional review board-approved, retrospective study. Magnetic resonance imaging (MRI; 1.5 T) was performed after standardized preparation. Two-dimensional (2D) cine sequences for motility acquisition were performed in apnoea (27 s). Motility assessment was performed using dedicated software in three randomly chosen areas of the small-bowel outside known Crohn's disease-affected hotspots. The main quantitative characteristics (frequency, amplitude, occlusion rate) were compared using Student's t-test and one-way analysis of variance (ANOVA). Three randomly chosen segments were analysed in each participant. Patients with active Crohn's disease had significantly (p < 0.05) reduced contraction frequencies (active Crohn's disease: 2.86/min; chronic: 4.14/min; healthy: 4.53/min) and luminal occlusion rates (active: 0.43; chronic: 0.70; healthy: 0.73) compared to healthy individuals and patients with chronic Crohn's disease. Contraction amplitudes were significantly reduced during active Crohn's disease (6.71 mm) compared to healthy participants (10.14 mm), but this only reached borderline significance in comparison to chronic Crohn's disease (8.87 mm). Mean bowel lumen diameter was significantly (p = 0.04) higher in patients with active Crohn's disease (16.91 mm) compared to healthy participants (14.79 mm) but not in comparison to patients with chronic Crohn's disease (13.68). The findings of the present study suggest that local inflammatory activity of small-bowel segments in patients with active Crohn's disease alters small-bowel motility in distant, non-affected segments. The motility patterns revealed reduced contraction-wave frequencies, amplitudes, and decreased luminal occlusion rates. Thus evaluation of these characteristics potentially helps to differentiate between chronic and active Crohn's disease.


Magnesium-dependent attachment and neurite outgrowth by PC12 cells on collagen and laminin substrata.
We report a study of the substratum and medium requirements for attachment and neurite outgrowth by cells of the pheochromocytoma-derived PC12 line. In attachment medium containing both Ca2+ and Mg2+, more than 50% of cells attached within 1 hr to petri dishes coated with native collagen Types I/III or II, native or denatured collagen Type IV, laminin, wheat germ agglutinin (WGA), or poly-L-lysine; attachment to dishes coated with nerve growth factor (NGF) was only about 20% and attachment to uncoated dishes or to dishes coated with fibronectin or gelatin was almost nil. Neither prior culturing in the presence of NGF nor addition of NGF to the attachment medium significantly affected the extent of attachment to collagen or laminin. With Ca2+ (1 mM) as the sole divalent cation, cells attached normally to WGA, polylysine, and NGF, but failed to attach to collagen or laminin. With Mg2+ (1 mM) as the only divalent cation, attachment to all substrata was about the same as in medium with both Ca2+ and Mg2+. Like the ionic requirements, the kinetics of attachment, insensitivity to protease treatment of the cells, and inhibition by low temperature and sodium azide were similar for PC12 attachment to collagen and laminin, suggesting that a common molecular mechanism may underlie attachment to these substrata. The only significant difference observed was that addition of WGA (30 micrograms/ml) to the attachment medium inhibited attachment to collagen but promoted attachment to laminin. Finally, PC12 cells extended neurites on laminin, on native collagens I/III, II, and IV, and on denatured collagen IV; they did not extend neurites on denatured collagens I/III or II, NGF, or WGA. Neurite outgrowth on collagen and laminin occurred with Mg2+ as the sole divalent cation. These results suggest that the same Mg2+-dependent adhesion mechanism operates at the cell body and at the growth cone.


Macrophytes are highly sensitive to the herbicide diquat dibromide in test systems of varying complexity.
The herbicide diquat dibromide is used in North America to manage nuisance macrophytes. However, its effect on native macrophytes is less clear and it could cause indirect effects on other aquatic biota. This study determined the sensitivity of both native and non-native macrophytes grown in test systems with varying complexity to diquat dibromide applied directly to water following label directions. In an outdoor mesocosm experiment and single species greenhouse concentration-response tests, Elodea canadensis Michx., Myriophyllum spicatum L., Ceratophyllum demersum L. and Hydrocharis morsus-ranae L. were exposed to a range of diquat dibromide concentrations (4.7 - 1153 µg/L), corresponding to 0.4 - 100% of the recommended label rate of the formulated product. The mesocosm experiment contained all four plant taxa in the same system along with caged amphipods (Hyalella azteca Saus.), tadpoles (Lithobates pipiens Schreber), phytoplankton and periphyton; however, this study focuses on the macrophytes only. In both test systems, severe direct effects of diquat dibromide on macrophytes were detected, with almost 100% mortality of all macrophytes in both test systems at 74 µg/L. The most sensitive species in the single species tests, E. canadensis, showed almost 100% mortality at concentrations below the HPLC-based method detection limit of 5 µg/L. Effects occurred very rapidly and showed no difference in severity between native and non-native macrophytes or complexity of test systems. These results suggest that diquat dibromide could be applied at a considerably lower label rate, depending on the characteristics of the waterbody, while still achieving effective control of nuisance macrophytes.


Radial vibration and ultrasonic field of a long tubular ultrasonic radiator.
The radial vibration of a metal long circular tube is studied analytically and its electro-mechanical equivalent circuit is obtained. Based on the equivalent circuit, the radial resonance frequency equation is derived. The theoretical relationship between the radial resonance frequency and the geometrical dimensions is studied. Finite element method is used to simulate the radial vibration and the radiated ultrasonic field and the results are compared with those from the analytical method. It is concluded that the radial resonance frequency for a solid metal rod is larger than that for a metal tube with the same outer radius. The radial resonance frequencies from the analytical method are in good agreement with those from the numerical method. Based on the acoustic field analysis, it is concluded that the long metal tube with small wall thickness is superior to that with large wall thickness in producing radial vibration and ultrasonic radiation. Therefore, it is expected to be used as an effective radial ultrasonic radiator in ultrasonic sewage treatment, ultrasonic antiscale and descaling and other ultrasonic liquid handling applications.


Uptake of [3H]L-serine in rat brain synaptosomal fractions.
Accumulation of [3H]L-serine in crude synaptosomal fractions freshly prepared from rat brain has been found to be temperature-sensitive and to consist of both Na(+)-dependent and Na(+)-independent components. The accumulation of [3H]L-serine measured at submicromolar concentrations had a distinct substrate selectivity, different from the uptake of [3H]L-proline, [3H]L-glutamate and [3H]GABA. It was fully inhibited by L-glutamine, L-asparagine, L-cysteine, L-alanine, L-leucine, L-isoleucine, L-tyrosine, L-phenylalanine, L-threonine and by the synthetic marker for the large neutral amino acid transport systems 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid, but not influenced by beta-alanine, taurine, glycine nor was it inhibited by the marker for the A system, L-2-methylamino isobutyric acid. D-Serine at 1 mM concentration produced no significant inhibition of the accumulation of 10 nM [3H]L-serine. We conclude that L-serine uptake observed in the present study is mediated by at least two distinct transport systems: a Na(+)-dependent one of lower affinity (K(m) in mM range) and a Na(+)-independent system of higher affinity (K(m) approximately 20-100 micro M). Characteristics of [3H]L-serine accumulation displayed at low substrate concentrations suggest that it was mediated neither by the typical 'A', nor by the 'large neutral', amino acid transport systems but predominantly by transporters belonging to the recently identified LAT (L-amino acid transporter) family.


Microtubules in early development of the megagametophyte of Ginkgo biloba.
Food storage tissue in the seeds of gymnosperms is female gametophyte (megagametophyte) that develops before fertilization, whereas, in seeds of angiosperms, food is stored as endosperm initiated by double fertilization. The megagametophyte is haploid, and endosperm is usually triploid, at least initially. Despite differences in origin, ploidy level, and developmental trigger, the early events of female gametophyte development in ginkgo are very similar to nuclear endosperm development in the seeds of angiosperms. In both, development begins as a single cell that undergoes multiple mitoses without cytokinesis, to produce a large syncytium. This study provided evidence that microtubule involvement in organization of the syncytium into nuclear cytoplasmic domains (NCDs) via nuclear-based radial microtubule systems is a critical developmental feature in the ginkgo megagametophyte, as it is in endosperm. Once the initial anticlinal walls have been deposited at the boundaries of NCDs, cellularization proceeds by the process of alveolation. Continued unidirectional growth of the alveolar walls is an outstanding example of polar cytokinesis. Ginkgo megagametophyte development appears to occur uniformly throughout the entire chamber, whereas nuclear type endosperm usually exhibits distinct developmental domains. These observations suggest that there is a fundamental pathway for the development and cellularization of syncytia in seed development.


Clinical and genetic heterogeneity in Melkersson-Rosenthal Syndrome.
Melkersson Rosenthal syndromes (MRS) is a rare autosomal dominantly inherited neurocutaneous syndrome characterised by a triad of facial (seventh cranial) nerve palsy, recurrent orofacial swelling and fissuring of the tongue. A recent report implicated a heterozygous missense variant in SLC27A1 (FATP1) as the cause of this condition in members of an affected Chinese family. We undertook Sanger sequencing of this gene in 14 affected unrelated individuals affected by MRS. We did not detect any putative pathogenic variants. Our data indicates that there is both clinical and genetic heterogeneity in this condition and that the causative gene remains to be identified for the majority of cases.


Inhibition of 5,9-dimethyldibenzo[c,g]carbazole-DNA adduct formation in mouse liver by pretreatment with cytochrome P4501A inducers in vivo.
Mice of the XVIInc/Z and DBA/2N strains, which are responsive and nonresponsive, respectively, to the aryl hydrocarbon (Ah) receptor, were treated with the hepatocarcinogen 5,9-dimethyldibenzo[c,g]carbazole and their livers were examined by nuclease P1-enhanced 32P-postlabeling for the levels of DNA adducts formed. Pretreatment at the doses usually reported in the literature with the cytochrome P4501A (CYP1A) inducers 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), beta-naphthoflavone (BNF), and isosafrole modulated DNA adduction. In XVIInc/Z mice, DNA adduction was totally inhibited by TCDD (a CYP1A1/1A2 inducer), BNF (a CYP1A1/1A2 inducer), and isosafrole (a CYP1A2 inducer). In DBA/2N mice, in which DNA adduction was also inhibited by TCDD, about 25% of the DNA adduct levels persisted after pretreatment with BNF (not a CYP1A1/1A2 inducer in this strain) or isosafrole (a CYP1A2 inducer in this strain). The increase (in all cases less than twofold) in the levels of the phase-II drug-metabolizing enzymes glutathione S-transferase and uridine diphospho-glucuronyltransferase after treatment with inducers cannot explain the total disappearance of DNA adducts. Assays of 5-bromo-2'-deoxyuridine incorporation did not show any induction of DNA synthesis which could explain the decrease in adducts. These results suggest that in vivo 1) increases in CYP1A enzymes by inducers are not correlated with enhanced levels of certain DNA adducts; and 2) phase-II drug metabolizing enzymes are not the main cellular protection pathway for detoxification. An additional mechanism, perhaps also induced by the Ah receptor but highly dependent on the dose of inducer, could be involved in parallel to multidrug resistance (mdr); further experiments are needed to identify this process used by the cell to enhance its protection against toxic or genotoxic effects.


Chlamydia trachomatis IgG3 seropositivity is associated with gastroschisis.
To investigate the association between Chlamydia trachomatis (CT) infection seropositivity and gastroschisis. In this case-control study we enrolled pregnant women either prenatally diagnosed with gastroschisis (cases, n=33) or with a normal ultrasound (controls, n=66). Both groups attended the University of Utah's Maternal Fetal Medicine Diagnostic Center for their diagnostic ultrasound or because of a community obstetrician referral. Participants completed a structured interview on potential risk factors. Anti-CT immunoglobulin (IgG)1 and IgG3 were measured by a CT elementary body enzyme-linked immunosorbent assay. Median age at sexual debut was lower and reported sexual partner number higher in cases compared with controls. Risk factors for gastroschisis included having ⩾ 3 sexual partners (odds ratio (OR)=3.3, 95% CI 1.2, 9.4), change in partner from the previous pregnancy (OR=3.6, 95% CI 0.9, 13.9) and anti-CT IgG3 seropositivity (age-adjusted OR=3.9, 95% CI: 1.1, 13.2). Anti-CT IgG3 seropositivity was associated with greater than a threefold risk for gastroschisis.


Cognitive functions before and 1 year after surgical and endovascular treatment in patients with unruptured intracranial aneurysms.
This prospective study investigated whether surgery or endovascular treatment for unruptured intracranial aneurysms (UIAs) affects cognitive functions. Four neuropsychological variables from an Auditory Verbal Learning Test (overall capacity of verbal memory and delayed recall) and a Trail Making Test (psychomotor speed and cognitive flexibility) were investigated before and 1 year after treatment for UIAs in 65 patients < 61 years of age. This cohort consists of 15 men and 50 women aged 15-60 (mean age 44.9) years. Group-rate analysis showed a non-significant increase in post-treatment scores in the four neuropsychological variables. In addition, no significant differences were found between the surgical clipping (SC) and endovascular coiling (EC) group. Event-rate analysis demonstrated that two patients from the EC and one from the SC group developed cognitive impairment after treatment. Surgical and endovascular repair for UIAs do not impair cognition in patients without postoperative restrictions in lifestyle.


Atrioventricular node ablation and permanent ventricular pacemaker implantation without fluoroscopy: use of an electroanatomic navigation system.
Non-fluoroscopy AV ablation and pacemaker implantation. Fluoroscopic guidance is the standard tool used for transvenous pacemaker implantations and for electrophysiological and ablation procedures. It implies X-ray exposure, occasionally with high dose of radiation for the patient and operator. We describe the case of a 47-year-old man with uncontrollable permanent atrial fibrillation to whom ablation of the AV conduction and a permanent ventricular pacemaker implantation were successfully performed under the guidance of an electroanatomic navigation EnSite NavX system and with no use of fluoroscopy. This case illustrates the stand-alone use of one of the new non-fluoroscopic navigation systems for a complete procedure such as AV ablation and pacemaker implantation.


Logistic regression and CART in the analysis of multimarker studies.
The rapid development of new biomarkers increasingly motivates multimarker studies to assess/compare the value of different markers for risk stratification or diagnostic prediction. Analysis of these studies is usually governed by logistic regression (LR) which is however often applied quite uncritically resulting in unclear or even deceptive results. This methodological review is intended for the practical medical researcher and critically discusses in non-technical terms where possible LR models and CART (classification and regression trees) as analytical approaches for multimarker studies. Some in practice often neglected but vital aspects for a valid application and interpretation of LR models are presented and the basic principles of building and interpreting a CART tree are demonstrated. All approaches are applied to original data of a multimarker study which aimed to assess and compare the value of different laboratory parameters to predict the need for intensive care treatment in unselected emergency room patients. When applied prudently, both LR and CART are suitable for the analysis of multimarker studies. For a valid interpretation of LR it is especially important that the format of the model fits the study design. In general LR and CART will identify very similar sets of significant markers. While LR models generally focus more on the relative statistical significance of the assessed markers, CART results emphasise the absolute effects; results come as observed risk groups. Thus the complementary use of both techniques seems to be a promising approach to perform the difficult task of analysing and interpreting the results of multimarker studies.


How to obtain industrial waste data at the county scale: Two downscaling models and their application in Dongguan, China.
The availability of environmental emission data is critical in evaluation of countries' ecological security and the implementation of environmental management. However, access to environmental emission data at the county level is not provided by statistical publications and bulletins. Therefore, in this paper, we develop two novel data downscaling models, an environmental Kuznets curve downscaling model (EKCDM) and a scale model (SM), to obtain county-level environmental emission data. The EKCDM relies on the EKC hypothesis and the assumption that the same model applies across scales, whereas the SM depends on the assumption that the share of a region's environmental pollution is equivalent to its share of economic output. Subsequently, environmental emission data above the county scale can be obtained through model transformation and simple calculations. By verifying and analyzing the official data with the one obtained through downscaling at municipal level and above, we verify the feasibility of the models, after which we apply the models to extrapolate information on the industrial waste of the counties of Dongguan city in Guangdong Province, China. We find that the EKCDM should be given priority in most cases, especially for the quadratic parameter model, and that the SM can be adopted when per capita gross domestic product differs greatly between adjacent levels of administrative units. In general, scholars can synthesize the characteristics of these two models, and obtain more accurate data by supplementing and verifying one with the other. Compared with other downscaling methods, our methods require far less data and the concepts are easily understood, which makes them more feasible and increases applicability. This study provides scholars with powerful tools to explore the relationship between industrial pollution and economic development in depth by obtaining industrial waste data at the county scale, thereby supporting scientific research and policy design.


9,10-Dioxo-9,10-di-hydro-anthracene-1,4-diyl di-acetate.
In the title compound, C18H12O6, the anthra-quinone ring system is nearly planar [maximum deviation = 0.161 (3) Å] and both acetate groups are located on the same side of the ring plane. A supra-molecular architecture arises in the crystal owing to π-π stacking between parallel benzene rings of adjacent mol-ecules [centroid-centroid distance = 3.883 (4) Å] and weak inter-molecular C-H⋯O hydrogen bonding.


[Mammary carcinoma in Switzerland (author's transl)].
Combined surgical, radiotherapeutic, and sometimes chemotherapeutic treatment of early stages of operable mammary cancer results in 5-year survival without recurrence in a similar percentage of cases as modified radical mastectomy does. This is demonstrated with 1296 patients of two French and one American groups using comparable indication and therapeutic principles. No controlled studies of long-term results using these principles are thus far available. Preliminary results of a Swiss adjuvant polychemotherapy study after mastectomy show a significant favorable effect only in patients with negative axillary lymph nodes.


Effect of microplastics on greenhouse gas and ammonia emissions during aerobic composting.
The aim of this study was to investigate the effect of polyethylene (PE), polyvinyl chloride (PVC) and polyhydroxyalkanoate (PHA) microplastics on greenhouse gas and ammonia emissions during 60 days composting. PE, PVC and PHA microplastics were respectively mixed with the cow manure; and a treatment without microplastics was used as the control. Compared to the control, PE and PVC inhibited organic matter degradation. Conversely, PHA accelerated temperature increases and organic matter degradation. Meanwhile, PE and PHA aggravated CH4 and NH3 emissions by 7.9-9.1% and 20.9-33.9%, respectively. PVC decreased CH4 and NH3 emissions by 6.6% and 30.4%, respectively. Additionally, the N2O emissions of the PE and PVC treatments were higher than those of the control while PHA decreased N2O emissions by 11.8%. Furthermore, PE, PVC and PHA microplastics reduced the NO3--N contents and compost maturity. The results indicated that microplastics reduced compost quality while the effects of microplastics on greenhouse gases and ammonia emissions were related to their sources.


Measuring Oxygenation in Newborn Infants with Targeted Oxygen Ranges (MONITOR): a randomised crossover pilot study.
The Neonatal Oxygenation Prospective Meta-analysis (NeOProM) Collaboration showed that high (91-95%) versus low (85-89%) SpO2 targets reduced mortality. Trials of higher targets are needed to determine whether any more survival advantage may be gained. This pilot study explored the achieved oxygenation patterns observed when targeting SpO2 92-97% to facilitate the design of future trials. Single-centre prospective randomised crossover pilot study. Manual FiO2 adjustment. Study time 12 hours per infant. 6 hours targeting SpO2 90-95% and 6 hours targeting SpO2 92-97%. Twenty preterm infants born <29 weeks' gestation, greater than 48 hours old, receiving supplemental oxygen. Primary outcome was percentage time with SpO2 above 97% and below 90%. Pre-defined secondary outcomes included percentage time spent within, above or below transcutaneous PO2 (TcPO2) 6.7-10.7 kPa (50-80 mm Hg). Comparisons were made using paired-samples t-test (2-tailed). With SpO2 target 92-97% versus 90-95%, the mean (IQR) percentage time above SpO2 97% was 11.3% (2.7-20.9) versus 7.8% (1.7-13.9), p=0.02. Percentage time with SpO2 <90% was 13.1% (6.7-19.1) versus 17.9% (11.1-22.4), p=0.003. Percentage time with SpO2 <80% was 1% (0.1-1.4) versus 1.6% (0.4-2.6), p=0.119. Percentage time with TcPO2 <6.7 kPa (50 mm Hg) was 49.6% (30.2-66.0) versus 55% (34.3-73.5), p=0.63. Percentage time above TcPO2 10.7 kPa (80 mm Hg) was 1.4% (0-1.4) versus 1.8% (0-0), p=0.746. Targeting SpO2 92-97% produced a right shift in SpO2 and TcPO2 distribution, with reduced time at SpO2 <90% and increased time at SpO2 >97%, without increasing time with TcPO2 >10.7 kPa (80 mm Hg). Clinical trials targeting this higher SpO2 range could be conducted without significant hyperoxic exposure. NCT03360292.


Interactions of atrazine with transition metal ions in aqueous media: experimental and computational approach.
Transition metal ions have their own significances and utility. Externally applied pesticides may alter the bioavailability of these metal ions to plants through the coordinating ability of these pesticides with metal ions. In current study a series of metal complexes containing atrazine (Atr) group(s) attached to metal(II) (M) frame, with the formula; [M(Atr)n.xH2O.yCl] (where M = Mn, Fe, Co, Ni, Cu or Zn; n = 1 or 2; x = 1-4; y = 1-2), have been synthesized for the first time to check the interactions of atrazine with transition metal ions. More importantly, all the complexes were synthesized at neutral pH in aqueous medium. The major differences among the FTIR spectra were observed between 3,700-2,800 and 1,800-1,350 cm-1. On the basis of FTIR, CHN and computational study, it was observed that Mn, Ni and Cu formed complexes in 1:2 and Fe, Co and Zn in 1:1. The obtained results were supported by 3D molecular modeling using GAMESS computations as a package of ChemBio3D Ultra14 program. The FTIR spectral analysis and 3D molecular modeling suggests that the Atr can show coordination through the nitrogen (in between two side chains) of ring as well as nitrogen (non steric amine) of side chain with different metal ions.


The correlation between automated hematology and manually read smears for the determination of nucleated red blood cells in umbilical cord blood.
To determine the correlation between automated hematology nucleated red blood cell counts and manual counts in umbilical cord blood. Umbilical cord venous blood was obtained after cord clamping at the time of delivery. The number of nucleated red blood cells per one hundred white blood cells was measured using an automated hematology analyzer and compared with direct microscopic visualization of prepared slides by experienced hematology technicians. The umbilical cord blood from 128 women was studied. The mean, median and standard deviations of nucleated red blood cell counts were not significantly different between the automated reading and the manual reading (mean 9.3+/-11.2 versus 9.1+/-13.1, respectively, P=0.76; median 5.9 versus 5.0, P=0.95; range 0-77, 0-105). Automated derived nucleated red blood cell counts and manual numbers were highly correlated with a correlation coefficient of 0.794. The automated hematology analyzer readings of nucleated red blood cell counts correlate well with readings by laboratory hematologists.


Aging in movement representations for sequential finger movements: a comparison between young-, middle-aged, and older adults.
Studies show that as we enter older adulthood (>64years), our ability to mentally represent action in the form of using motor imagery declines. Using a chronometry paradigm to compare the movement duration of imagined and executed movements, we tested young-, middle-aged, and older adults on their ability to perform sequential finger (fine-motor) movements. The task required number recognition and ordering and was presented in three levels of complexity. Results for movement duration indicated no differences between young- and middle-aged adults, however both performed faster than the older group. In regard to the association between imagined and executed actions, correlation analyses indicated that values for all groups were positive and moderate (r's .80,.76,.70). In summary, whereas the older adults were significantly slower in processing actions than their younger counterparts, the ability to mentally represent their actions was similar.


When is supervised exercise therapy considered useful in peripheral arterial occlusive disease? A nationwide survey among vascular surgeons.
Although international guidelines state that supervised exercise therapy (SET) should be offered to all patients with intermittent claudication (IC), SET appears to be underutilised in clinical practice. The aim of this study was to document current opinions of Dutch vascular surgeons on SET as treatment option for peripheral arterial occlusive disease (PAOD). Vascular surgeons and fellows in vascular surgery were asked to complete a 24-question survey either at the 2011 Annual Meeting of the Dutch Society for Vascular Surgery or online. Ninety-one participants, including 83 vascular surgeons (51% of all Dutch vascular surgeons), completed the survey. The respondents would refer 75.4% of newly diagnosed patients with IC for SET. SET was considered less useful in patients with IC and major (cardiopulmonary) co-morbidity or a significant iliac artery stenosis. In critical limb ischaemia, the combination of SET and angioplasty was considered useful in 71.9%. Respondents regarded patient satisfaction (63.3%) and improvement in pain-free or maximal walking ability (26.6%) as clinically most relevant goals of SET. Most (84.4%) agreed that SET should also include lifestyle management. Although the vast majority of Dutch vascular surgeons consider SET as an important treatment option for PAOD, SET should receive more emphasis in clinical practice since arguments not to refer for SET are outdated. Furthermore, vascular surgeons agree that lifestyle management should be integrated in SET.


Cytotoxic effects of toximul MP8 in human lymphocytes in culture: a preliminary investigation.
Toximul MP8, a commercial emulsifier formulation, has been used for a number of years to spray forest trees infested with spruce budworm with the organophosphate insecticides, Fenitrothion and Phosphamidon. To assess its cytotoxic effects on human lymphocytes varying amounts of Toximul MP8 were added to human whole blood (0--50 ppm) and cultured along with phytohaemagglutinin for 52h. At the end of the culture period cytotoxicity to human lymphocytes was assessed by (1) mitotic index, (2) DNA labelling index and (3) the frequency of chromatid breaks. The cytotoxic effects were apparent even at the lowest concentration tested, i.e., 10 ppm. A significant dose-dependent decrease in the mitotic and DNA-labelling indicies was observed. Toximul MP8 also produced a significant level of chromatid breaks even at 10 ppm.


Association Between Systemic Immune-Inflammation Index and Symptomatic Intracranial Hemorrhage in Acute Ischemic Stroke Patients Undergoing Endovascular Treatment.
Systemic immune-inflammation index (SII) is a novel inflammatory factor, which may be involved in the destruction of the blood-brain barrier (BBB) after acute ischemic stroke (AIS); however, the association between SII and symptomatic intracranial hemorrhage (sICH) in AIS patients undergoing endovascular treatment (EVT) remains unclear. Patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) who underwent EVT were consecutively enrolled. Blood samples were collected in the emergency room and SII was calculated by neutrophils × platelets/lymphocytes. Participants were categorized into tertiles according to admission SII. The main outcome was defined as the occurrence of sICH, following the European Cooperative Acute Stroke Study III (ECASS-III) criteria. A total of 379 AIS-LVO patients with EVT were enrolled (median age = 71 years, 52.5% males). The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 15 (IQR, 12-18). The median of SII was 820.9 × 109/L (IQR, 473.1-1345.2). Forty-three (11.3%) patients developed sICH. SII was found to be independently associated with sICH after EVT (adjusted odd ratio (OR) = 1.005 (per 10 units increase); 95% confidence interval (CI): 1.002-1.008; p = 0.002). Compared to patients in the lowest SII tertile, patients in the highest tertile had a higher risk of sICH (adj-OR 3.379; 95% CI 1.302-8.768; p = 0.012). The risk of sICH increased with the increase of SII in a dose-dependent manner (p for trend = 0.004). There was no interaction between potential modifiers and SII on sICH. Admission SII is positively associated with sICH in AIS-LVO patients treated with EVT. These results need to be confirmed in future studies.


Effects of anthracycline derivatives on human leukemia K562 cell growth and differentiation.
New derivatives of daunorubicin (DRB), doxorubicin (DOX), and epidoxorubicin (EDOX) with an amidine group bonded to C-3' of daunosamine moiety with either morpholine or hexamethyleneimine ring attached to the amidine group are studied in this paper. We have shown that all of these newly synthesized anthracycline derivatives inhibit human leukemia K562 cell line proliferation but only some of them induce erythroid differentiation when used at subtoxic concentrations. Morpholine derivative of DOX has the greatest potential to inhibit proliferation and to induce differentiation in vitro. The correlation between these two cellular processes was also significant for other tested compounds. In cell cycle analysis, we have demonstrated that those anthracycline derivatives that exert the greatest cytostatic potential caused G(2)/M arrest, which in turn, might contribute to the development of a differentiating phenotype. The concentrations of the compounds used in the study are pharmacologically relevant. These new potent inducers of differentiation might be exploited as anticancer drugs for treatment of leukemia by differentiation therapy.


Stunting and associated factors among children aged 6-59 months from productive safety net program beneficiary and non-beneficiary households in Meta District, East Hararghe zone, Eastern Ethiopia: a comparative cross-sectional study.
Undernutrition is one of the major public health problems affecting children in developing settings. Despite impressive interventions like productive safety net program (PSNP), there is limited information on the association between stunting and PSNP implementation in Ethiopia. Community-based comparative cross-sectional study design was used among systematically selected 1555 children and their mothers/caregivers from households enrolled in PSNP and not, respectively, in Meta District east Ethiopia from 5th-20th of March 2017. Data were collected using pretested structured questionnaire. Measuring board was used to measure length/height of children. Length/height for age Z-score was generated using World Health Organization (WHO) Anthro version 3.2.2. Descriptive statistics was used to describe all relevant variables. Bivariable and multivariable logistic regression analyses were used to identify predictors of stunting. Odds ratio along with 95% confidence intervals were estimated to measure the strength of association. The statistical significance was declared at p value less than 0.05. The prevalence of stunting was 47.7%, 95% CI (44.1%, 51.5%) and 33.5%, 95% CI (29.9%, 36.9%) among children from households enrolled in PSNP and non-PSNP ones, respectively. Lack of maternal education [AOR = 3.39; 95% CI (1.12, 5.11)], women's empowerment [AOR = 3.48; 95% CI (2.36, 5.12)] and fourth antenatal care visit [AOR = 4.2, 95% CI (2.5, 6.8)], practicing hand washing [AOR = 0.46; 95% CI (0.28, 0.76)], living in mid-land [AOR = 1.94, 95% CI (1.12, 3.35)] and low-land[AOR = 0.27: 95% CI (0.16, 0.45)] agro-ecological zones, PSNP membership [AOR = 1.82, 95% CI (1.14, 2.89)], childhood illness [AOR = 8.41; 95% CI (4.58, 12.76)], non-exclusive breastfeeding [AOR = 3.6; 95% CI (2.30, 4.80)], inadequate minimum dietary diversity [AOR = 4.7; 95% CI (3.0, 7.40)], child's sex [AOR = 1.73, 95% CI (1.18, 2.53)] and age (24-59 months) [AOR = 3.2; 95% CI (1.6, 6.3)] were independent predictors of stunting. The prevalence of stunting was high among children from households enrolled in PSNP. Stunting was significantly associated with maternal- and child-related factors. Therefore, women empowerment on household's issues and improving infant and young child feeding practices could reduce the prevalence of stunting and its adverse consequences.


Technical Note: Deep Learning approach for automatic detection and identification of patient positioning devices for radiation therapy.
Automatic detection and identification of setup devices, using a deep convolutional neural network (CNN) for real-time multiclass object detection, has the potential to reduce errors in the treatment delivery process by avoiding documentation errors. A database of the setup device photos from the most recent 1200 patients treated at our institution was downloaded from the record and verify (R&V) system along with the corresponding setup notes. Images were manually labeled with bounding boxes of each device. A real-time object detection CNN using the "you only look once" (YOLOv2) architecture was trained using transfer learning of a pretrained CNN (ResNet50). The CNN was trained to detect and identify 11 of the most common treatment accessories used at our institution. Using transfer learning of a CNN for multiclass object detection, we are able to automatically detect and identify setup devices in photographs with an accuracy of 96%. Automation in radiation oncology has the potential to reduce risk. Automatic detection of setup devices is possible using a CNN and transfer learning. This work shows both the value of incident learning systems (ILS) in practice knowledge dissemination, and shows how automation of clinical processes and less reliance on manual documentation has the potential for risk reduction in radiation oncology treatments.


The interaction of 3,3',4',5-tetrachlorosalicylanilide with phosphatidylcholine bilayers.
1. The interaction of the germicide 3,3',4',5-tetrachlorosalicylanilide (T4CS) with vesicles and dispersions of egg phosphatidylcholine has been studied by gel permeation chromatography, electron microscopy, electron spin resonance spin labelling and ion permeability measurements. 2. Incorporation of T4CS into vesicles of egg phosphatidylcholine gives rise to a large increase in the permeability rate of the paramagnetic cation N,N-dimethyl-N-(1'-oxyl-2',2',6',6'-tetramethyl-4'-piperidyl)-2-hydroxyethylammonium chloride through the lipid bilayer but has no significant effect on the vesicle sizes as measured by gel permeation chromatography or electron microscopy. 3. ESR studies using a spin-labelled fatty acid have demonstrated the presence of two different environments for the spin label when T4CS is incorporated into phosphatidylcholine bilayers. These two environments are identified as (a) highly ordered areas of the bilayer, rich in T4CS and (b) areas with very similar ordering to that in pure egg phosphatidylcholine. 4. The effectiveness of very low concentrations of the germicide in increasing vesicle permeability is explained in terms of its clustering to give rigid patches, rich in T4CS, rather than being evenly distributed throughout the bilayer. It is proposed that the increased ion permeability arises from leakage at the interfaces between the rigid and flexible regions of the lipid bilayer. 5. Comparisons between the effective levels of T4CS in phosphatidylcholine vesicles and its minimum inhibitory concentration with a Gram-positive bacterium confirm the validity of phospholipid vesicles as a model for studies of germicidal activity.


Rapid induction of the expression of proto-oncogene fos during human monocytic differentiation.
The differentiation into macrophages of the monocytic cell line U-937 or the monomyelocytic cell line HL-60 induced by phorbol esters is accompanied by a rapid induction of the expression of the proto-oncogene c-fos. Maximal levels of c-fos gene transcripts accumulate within 20-30 min following induction. By 2 hr, the c-fos-specific mRNA level drops 5 to 10 fold below that detected at 30 min after induction. The concentration of c-fos mRNA remains unchanged for the next 5 days, at which time over 99% of the viable precursor cells are converted to adherent macrophages. c-fos protein can be detected within 20 min of induction, reaching maximal levels by 40-60 min. Little or no c-fos protein is detected by 120-150 min after induction, even though c-fos mRNA remains detectable. Presence of cycloheximide leads to superinduction of c-fos mRNA transcripts. No c-fos gene transcripts are detected when the HL-60 cell line is induced with Me2SO to differentiate to granulocytes. A role for the c-fos protein is envisaged in the monocyte differentiation pathway.


Standardization of beta-thromboglobulin and platelet factor 4: a collaborative study to investigate the sources and extent of variation in the measurement of platelet specific proteins.
A collaborative study involving seven laboratories has been carried out to investigate the sources and extent of variation in the measurement by radioimmunoassay of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4). Three plasma samples, one purified beta-TG sample and two purified PF4 samples were assayed against house standards for the respective antigens by each laboratory. The main source of variation of both beta-TG and PF4 measurements was inter-assay (particularly for PF4). It was found that a significant component of this variation was due to the participants' use of different preparations as house standards for beta-TG and for PF4. This indicates that the first step in the standardization of beta-TG and PF4 measurement should be the introduction of a reference for each.


Novel adopted immunotherapy for mixed chimerism after unrelated cord blood transplantation in Omenn syndrome.
Omenn syndrome is a variant form of severe combined immunodeficiency. It is fatal unless treated by allogeneic stem cell transplantation (SCT), which is the only curative approach. However, both treatment-related complications and graft rejection are major obstacles to treatment success. This report describes a case with Omenn syndrome who developed mixed chimerism after unrelated cord blood transplantation (UCBT). This case was successfully treated by altering the patient's immunosuppression and donor lymphocyte infusion (DLI) with donor cord blood-derived activated CD4+ T cells ex vivo expanded from the cord blood cell residues in an infused bag. This novel development to expand CD4+ T-lymphocytes from the donor cord blood unit for the use of DLI would serve as a useful method to overcome the risk of graft rejection in SCT for primary immunodeficiency disorders with residual cell-mediated immunity without compounding graft-vs.-host disease, especially in the UCBT setting.


Cloning of Campylobacter jejuni genes required for leucine biosynthesis, and construction of leu-negative mutant of C. jejuni by shuttle transposon mutagenesis.
Campylobacter jejuni is a Gram-negative pathogen responsible for diarrhoeal diseases in humans. To date, very little is known about the genetic organization and molecular biology of this microorganism. The cosmid vector pHC79 was used to construct a genomic library from the total genomic DNA of C. jejuni strain C31 in Escherichia coli and recombinant cosmids capable of complementing the auxotrophic defect in leucine biosynthesis of E. coli HB101 were identified. Three of 400 clones tested were found to be capable of complementing the nutritional defect of E. coli HB101 as well as those of independent leuB mutants of E. coli strains. These results indicated that the cloned genes responsible for leucine complementation encoded an enzyme analogous to the beta-isopropylmalate dehydrogenase specified by the leuB gene in E. coli strains. The sizes of the recombinant cosmids which became stabilized in E. coli cells ranged from 12.9 to 15.4 kb compared to the expected, originally packaged, 45- to 50-kb molecules, attesting to major rearrangements occurring in this background. The recombinant plasmid pILL547 was shown to carry genes that were analogous to the leuB gene and also to the leuC and leuD genes of E. coli. The gene required for leuB complementation was subcloned on a 1.6-kb restriction fragment and was mapped more precisely by insertional mutagenesis using as transposon a newly constructed (MiniTn3-Km) element engineered to mutagenize Campylobacter genes. The leuB gene of C. jejuni was shown to be expressed from its own promoter in E. coli cells. In E. coli minicells, the cloned insert encoded a polypeptide with an apparent molecular weight of 40 kDa. A leucine auxotrophic mutant of C. jejuni strain C31 was constructed in vitro by allelic exchange, replacing the original copy of the leucine gene by an allele mutated by the insertion of the kanamycin transposable element.


Ménière's disease: effects of glycerol on tasks involving temporal processing.
The present study examined the effect of glycerol ingestion on aspects of auditory performance in subjects having Ménière's disease. It was hypothesized that Ménière's disease may be associated with abnormal firing in the auditory nerve and that this should result in a decreased ability to code the auditory temporal fine structure. Psychoacoustical measures of interaural time discrimination and quasi frequency modulation rate discrimination were used as measures of temporal coding, and performance on these tasks was examined both before and after glycerol ingestion. Pre- and postglycerol measures of speech recognition and audiometric thresholds were also obtained. In agreement with previous results, glycerol-related changes in audiometric thresholds were modest or absent, but improvements in speech recognition were relatively reliable. Improvements in interaural time discrimination and quasi frequency modulation rate discrimination were also observed. The results provide limited support for the hypothesis that Ménière's disease may be associated with a reduced ability to code the temporal fine structure of sound.


Stress and obesity as risk factors in cardiovascular diseases: a neuroimmune perspective.
Obesity is now growing at an alarming rate reaching epidemic proportions worldwide thus increasing morbidity and mortality rates for chronic disease. But although we have ample information on the complications associated with obesity, precisely what causes obesity remains poorly understood. Some evidence attributes a major role to a low-grade chronic inflammatory state (neurogenic inflammation) induced in obesity by inflammatory mediators produced and secreted within the expanded activated adipocyte pool. Adipose tissue is an endocrine organ that secretes numerous adipose tissue-specific or enriched hormones, known as adipokines, cytokine-like molecules thought to play a pathogenic role in cardiovascular diseases. The imbalance between increased inflammatory stimuli and decreased anti-inflammatory mechanisms may depend on chronic stress. Hence the positive correlation found between stress, obesity and cardiovascular diseases. The chronic inflammatory state associated with insulin resistance and endothelial dysfunction is highly deleterious for vascular function. This review focuses on the proposed neuroimmunodulatory mechanisms linking chronic (psychological) stress, obesity and cardiovascular diseases.


Antibodies to tissue-type plasminogen activator (t-PA) in patients with inflammatory bowel disease: high prevalence, interactions with functional domains of t-PA and possible implications in thrombosis.
Patients with inflammatory bowel disease (IBD) have an increased prevalence of thromboembolic events. The pathogenetic mechanisms of these events include reduced fibrinolysis, which may be caused by antibodies to tissue-type plasminogen activator (t-PA). To evaluate anti-t-PA antibodies in patients with IBD, considering clinical, biochemical and functional characteristics. We immunoenzymatically measured anti-t-PA antibodies in plasma from 97 consecutive IBD patients and 97 age- and sex-matched healthy controls. We also assessed the antibody interactions with different epitopes of t-PA, the antibody inhibition on t-PA activity and the correlations with clinical features and other serum antibodies. IBD patients had higher median anti-t-PA antibody levels (5.4 U mL(-1) vs. 4.0 U mL(-1); P < 0.0001): 18 patients were above the 95th percentile of the controls (OR 5.3; 95% CI 1.7-16.3; P < 0.003), and the six with a history of thrombosis tended to have high levels (6.9 U mL(-1)). Anti-t-PA antibody levels did not correlate with IBD type, activity, location or treatment, or with age, sex, acute-phase reactants or other antibodies. The anti-t-PA antibodies were frequently IgG1 and bound t-PA in fluid phase; they recognized the catalytic domain in 10 patients and the kringle-2 domain in six. The IgG fraction from the three patients with the highest anti-t-PA levels slightly reduced t-PA activity in vitro. The prevalence of anti-t-PA antibodies is high in IBD patients. By binding the catalytic or kringle-2 domains of t-PA, these antibodies could lead to hypofibrinolysis and contribute to the prothrombotic state of IBD.


A once-weekly R207910-containing regimen exceeds activity of the standard daily regimen in murine tuberculosis.
R207910 (TMC207 or J) is a member of the diarylquinolines, a new family of antituberculous drugs with high bactericidal activity when given daily in the murine model of tuberculosis. R207910 exhibits a long half-life and thus is a good candidate for once-weekly therapy of tuberculosis. To study the activity of once-weekly R207910 monotherapy and combinations of R207910 with other antituberculous agents (isoniazid, rifapentine, moxifloxacin, and pyrazinamide). The established infection model of murine tuberculosis was used. Colony counts were determined in the lungs. Eight weeks of monotherapy reduced the bacillary load by 3 to 4 log(10) for rifapentine and by 5 to 6 log(10) for R207910 (P < 0.05). The addition of rifapentine and isoniazid or moxifloxacin did not improve the bactericidal activity of R207910 monotherapy. In contrast, the triple combination of R207910 plus rifapentine plus pyrazinamide given once weekly for 2 months (i.e., a total of only eight administrations), was significantly (P < 0.05) more active than R207910 monotherapy or other R207910 combinations, and led to lung culture negativity in 9 of 10 mice, whereas all lungs were culture positive in the groups treated with other drug combinations. Moreover, R207910 plus rifapentine plus pyrazinamide given once weekly was more active than the current standard regimen of rifampin plus isoniazid plus pyrazinamide given five times per week. The unprecedented activity of the triple combination of R207910 plus rifapentine plus pyrazinamide suggests that it may be feasible to develop a fully intermittent once-weekly regimen.


The sputum microbiome associated with different sub-types of AECOPD in a Chinese cohort.
Chronic obstructive pulmonary disease (COPD) is one of the most prevalent diseases worldwide. Episodes of acute exacerbations of COPD (AECOPD) are associated with disease severity and progression. Although substantial progress has been made in understanding the dynamics of AECOPD, little is known about the sputum microbiome of AECOPD in the Chinese population. In this study, we characterized the sputum microbiomes from sputum specimens collected from healthy controls (n = 10), stable (n = 4), AECOPD (n = 36), and recovery (n = 18) stages by sequencing the V3-V4 region of the 16S rRNA gene with a HiSeq sequencer. Streptococcus was the most dominant genus among all the different types of sputum. A random forest model was developed to identify bacterial taxa that differentiate AECOPD samples from others. Most of the top predictors, except Pseudomonas, were less abundant in AECOPD samples. We also developed random forest models to differentiate subtypes of AECOPD based on blood eosinophil counts, the frequency of AECOPD, and sputum eosinophils. Bacterial taxa associated with Pasteurellaceae, Fusobacterium, Solobacterium, Haemophilus, Atopobium, Corynebacterium and Streptococcus, were enriched in the sputum microbiomes of eosinophilic AECOPD. Random forest models also demonstrate that a total of 2 bacterial OTUs were needed to differentiate frequent from non-frequent AECOPDs, and 23 OTUs were enough to accurately predict sputum-eosinophilic (sputum eosinophilic concentration ≥ 3%) AECOPD. This study expanded our understanding of the sputum microbiome associated with different subtypes and clinical status of patients with AECOPD in a Chinese cohort, which provides insights into novel and more targeted management of the different subtypes of AECOPD.


Dilated cardiomyopathy in infants and children.
The outcome of medical treatment of dilated cardiomyopathy in infants and children was reviewed to develop a predictive index for selection of patients likely to benefit from cardiac transplantation. The clinical findings, laboratory investigations, treatment and outcome of 20 patients (Group 1) less than 2 years of age at presentation and 12 patients (Group 2) greater than 2 years of age at onset were compared. Of 20 Group 1 patients, 5 (25%) died. Available autopsies (four patients) showed endocardial fibroelastosis. Of 15 survivors, 10 showed improvement in cardiac status and 5 remained unchanged. Ninety-three percent of survivors had dilated cardiomyopathy consistent with endocardial fibroelastosis by angiocardiography. All 12 Group 2 patients died. In addition to age at presentation and poor outcome, Group 2 differed from Group 1 in having a higher incidence of other family members with cardiomyopathy, more significant rhythm disturbances at presentation and a more rapid course to death. Risk factors of poor outcome in both groups included persistent cardiomegaly and the development of significant arrhythmias by Holter electrocardiographic monitoring. Cardiac transplantation is recommended for children with dilated cardiomyopathy presenting after age 2 years who survive 1 month. Those patients less than 2 years old at presentation whose condition has not improved after 1 year and who have persistent cardiomegaly or complex ventricular arrhythmias may also benefit from transplantation.


Intravaginal high-dose-rate brachytherapy for stage I endometrial cancer: a randomized study of two dose-per-fraction levels.
To compare two different fractionation schedules for postoperative vaginal high-dose-rate (HDR) irradiation in endometrial carcinomas. In a complete geographic series of 290 low-risk endometrial carcinomas, the efficacy and side effects of two different fractionation schedules for postoperative vaginal irradiation were evaluated. The patients were treated during the years 1989-2003. The tumors were in International Federation of Gynecology and Obstetrics Stages IA-IB and Grades 1-2. The HDR MicroSelectron afterloading equipment (iridium-192) was used. Perspex vaginal applicators with diameters of 20-30 mm were used, and the dose was specified at 5 mm from the surface of the applicator. Six fractions were given, and the overall treatment time was 8 days. The size of the dose per fraction was randomly set to 2.5 Gy (total dose of 15.0 Gy) or 5.0 Gy (total dose of 30.0 Gy). One hundred forty-four patients were treated with the 2.5-Gy fraction and 146 patients with the 5.0-Gy fraction. The overall locoregional recurrence rate of the complete series was 1.4% and the rate of vaginal recurrences 0.7%. There was no difference between the two randomized groups. The vaginal shortening measured by colpometry was not significant (p = 0.159) in the 2.5-Gy group (mean, 0.3 cm) but was highly significant (p < 0.000001) in the 5.0-Gy group (mean 2.1 cm) after 5 years. Mucosal atrophy and bleedings were significantly more frequent in the 5.0-Gy group. Symptoms noted in the 2.5-Gy group were not different from what could be expected in a normal group of postmenopausal women. The fractionation schedule recommended for postoperative vaginal irradiation in low-risk endometrial carcinoma is six fractions of 2.5 Gy when the HDR technique is used.


Prolactin secretion during sleep: a comparison between depressed patients and healthy control subjects.
Although several neuroendocrine abnormalities have been described in depressed patients, relatively little attention has been paid to the pattern of prolactin secretion during sleep. Sleep disturbances are frequently found in depressed patients, and the sleep electroencephalogram (EEG) typically shows significant changes in the first and last 100 min, when prolactin secretion frequently occurs. In this study, carefully defined inclusion criteria were used to ensure comparability in the quality of the sleep maintenance, so that the pattern of sleep-related prolactin secretion in a group of 26 depressed inpatients could be compared to that in a group of 20 healthy control subjects. Starting from sleep onset, the patients did not show any statistically significant difference in either the serum prolactin concentration or the pattern of integrated prolactin secretion relative to the control subjects. A statistically significant relationship between prolactin secretion and the REM-non-REM sleep cycle could not be demonstrated in these subjects.


Integral equations in the study of polar and ionic interaction site fluids.
In this review article we consider some of the current integral equation approaches and application to model polar liquid mixtures. We consider the use of multidimensional integral equations and in particular progress on the theory and applications of three dimensional integral equations. The IEs we consider may be derived from equilibrium statistical mechanical expressions incorporating a classical Hamiltonian description of the system. We give example including salt solutions, inhomogeneous solutions and systems including proteins and nucleic acids.


Non-MS autoimmune demyelination.
Connective tissue diseases can be characterised by central nervous system (CNS) involvement, in some patients manifested by demyelination areas in the white matter of the brain and spinal cord, which are difficult to differentiate from multiple sclerosis (MS) and other demyelinating processes, such as transverse myelitis and optic neuritis. Demyelinating process may be the feature of nervous impairment in systemic lupus erythematosus, Behcet's disease (BD), Sjoegren's syndrome (SS), systemic sclerosis (SSc) or very rarely other systemic autoimmune diseases. An acute isolated neurological syndrome, as the most common symptom of MS can sometimes be the only feature or even first manifestation of nervous impairment in connective tissue disease, hence presenting the diagnostic problem. Although the white matter abnormalities seen by magnetic resonance imaging may be similar in non-MS autoimmune demyelination and MS, it is the most important diagnostic tool in the differential diagnosis of the mentioned conditions. Investigating the presence of various autoantibodies potentially involved in the pathogenesis of demyelinating lesions as well as cerebrospinal fluid (CSF) analysis can be helpful.


Subunit-selective PI3-kinase control of action strategies in the medial prefrontal cortex.
PI3-kinase (PI3K) is an intracellular signaling complex that is stimulated upon cocaine exposure and linked with the behavioral consequences of cocaine. We recently genetically silenced the PI3K p110β subunit in the medial prefrontal cortex following repeated cocaine in mice, reinstating the capacity of these mice to engage in prospective goal-seeking behavior. In the present short report, we address two follow-up hypotheses: 1) The control of decision-making behavior by PI3K p110β is attributable to neuronal signaling, and 2) PI3K p110β in the healthy (i.e., drug-naïve) medial prefrontal cortex has functional consequences in the control of reward-related decision-making strategies. In Experiment 1, we found that silencing neuronal p110β improved action flexibility following cocaine. In Experiment 2, we reduced PI3K p110β in drug-naïve mice that were extensively trained to respond for food reinforcers. Gene silencing caused mice to abandon goal-seeking strategies, unmasking habit-based behaviors that were propelled by interactions with the nucleus accumbens. Thus, PI3K control of goal-directed action strategies appears to act in accordance with an inverted U-shaped function, with "too much" (following cocaine) or "too little" (following p110β subunit silencing) obstructing goal seeking and causing mice to defer to habit-like response sequences.


Super-factors associated with transmission of occupational COVID-19 infection among healthcare staff in Wuhan, China.
Globally, there have been many cases of coronavirus disease 2019 (COVID-19) among medical staff; however, the main factors associated with the infection are not well understood. To identify the super-factors causing COVID-19 infection in medical staff in China. A cross-sectional study was conducted between January 1st and February 30th, 2020, in which front-line members of medical staff who took part in the care and treatment of patients with COVID-19 were enrolled. Epidemiological and demographic data between infected and uninfected groups were collected and compared. Social network analysis (SNA) was used to establish socio-metric social links between influencing factors. A total of 92 medical staff were enrolled. In all participant groups, the super-factor identified by the network was wearing a medical protective mask or surgical mask correctly (degree: 572; closeness: 25; betweenness centrality: 3.23). Touching the cheek, nose, and mouth while working was the super-factor in the infected group. This was the biggest node in the network and had the strongest influence (degree: 370; closeness: 29; betweenness centrality: 0.37). Self-protection score was the super-factor in the uninfected group but was the isolated factor in the infected group (degree: 201; closeness: 28; betweenness centrality: 5.64). For family members, the exposure history to Huanan Seafood Wholesale Market and the contact history to wild animals were two isolated nodes. High self-protection score was the main factor that prevented medical staff from contracting COVID-19 infection. The main factor contributing to COVID-19 infections among medical staff was touching the cheek, nose, and mouth while working.


Anti-Tumour Activity of Glycodendrimer Nanoparticles in a Subcutaneous MEC-1 Xenograft Model of Human Chronic Lymphocytic Leukemia.
Chronic Lymphocytic Leukaemia (CLL) is an indolent disorder, which mainly affects older adults. Since the advent of chemoimmunotherapy, great progress has been made in its treatment. However, some patients develop a more aggressive form of the disease and are included in the group of high-risk CLL patients with a dismal prognosis and a need for new therapies. Maltotriose-modified poly(propylene imine) dendrimers were presented as potential agents in targeted therapy for CLL in the murine xenograft model. Tumour, brain and internal organs resected from NOD scid gamma mice were subjected to gross and histopathological evaluation. The results of ex vivo tissue examination indicated that open-shell glycodendrimers prevented/inhibited the spread of CLL into the brain and internal organs and its transformation into a more aggressive form. The results of the study have a potentially important impact on the design of future personalized therapies as well as clinical trials.


Fluctuations in Fe, Cu, Zn, Br, As, Se, and Rb concentrations in C57L/J mice bearing BW7756 murine hepatoma using radioisotope-induced X-ray fluorescence.
The effects of selenite or selenate supplementation on the concentration and distribution of Fe, Cu, Zn, As, Br, and Rb are investigated using the radioisotope-induced X-ray fluorescence, RIXRF. These effects are studied in the animals bearing BW7756 murine hepatoma and healthy animals for both of the oxidation states. Selenite and selenate induce different effects on the distribution of selenium, zinc, copper, bromine, and rubidium. The differences may be attributed to the differences in the inter element interaction after absorption into the bloodstream as well as to the mode of their intestinal absorption. Simultaneous supplementation of copper with selenite or selenate at the described levels has a profound influence on the concentration levels of other elements in the normal as well as in the diseased mice. The administration of selenium (0.67 micrograms/g body wt sodium selenite or sodium selenate, daily) and selenium and copper (0.67 and 1.35 micrograms/g body wt, respectively) has no effect on the incidence rate of hepatoma development.


A cell-based in vitro alternative to identify skin sensitizers by gene expression.
The ethical and economic burden associated with animal testing for assessment of skin sensitization has triggered intensive research effort towards development and validation of alternative methods. In addition, new legislation on the registration and use of cosmetics and chemicals promote the use of suitable alternatives for hazard assessment. Our previous studies demonstrated that human CD34(+) progenitor-derived dendritic cells from cord blood express specific gene profiles upon exposure to low molecular weight sensitizing chemicals. This paper presents a classification model based on this cell type which is successful in discriminating sensitizing chemicals from non-sensitizing chemicals based on transcriptome analysis of 13 genes. Expression profiles of a set of 10 sensitizers and 11 non-sensitizers were analyzed by RT-PCR using 9 different exposure conditions and a total of 73 donor samples. Based on these data a predictive dichotomous classifier for skin sensitizers has been constructed, which is referred to as VITOSENS. In a first step the dimensionality of the input data was reduced by selectively rejecting a number of exposure conditions and genes. Next, the generalization of a linear classifier was evaluated by a cross-validation which resulted in a prediction performance with a concordance of 89%, a specificity of 97% and a sensitivity of 82%. These results show that the present model may be a useful human in vitro alternative for further use in a test strategy towards the reduction of animal use for skin sensitization.


Validation of Cutaneous Dermatomyositis Disease Area and Severity Index Activity Score and Other Efficacy Outcomes as Measures of Skin Disease in Dermatomyositis in the Lenabasum Phase 3 Trial.
In the past decade, there have been six industry-sponsored phase 3 trials in adult patients with dermatomyositis (DM), primarily focusing on improving muscle weakness. However, skin disease is a cardinal manifestation of DM. This study evaluated the sensitivity of Cutaneous Dermatomyositis Disease Area and Severity Index Activity score, Cutaneous Dermatomyositis Activity Investigator Global Assessment, Total Improvement Score, and other outcome measures used in DM clinical trials to detect improvement in DM skin disease activity. Data analyzed from the lenabasum phase 3 trial in DM showed that improvement in Cutaneous Dermatomyositis Disease Area and Severity Index Activity score increased proportionately with the degree of patient- or physician-reported improvement in skin disease, consistently measuring improvement when clinically meaningful improvement was reported at weeks 16-52. In contrast, Cutaneous Dermatomyositis Activity Investigator Global Assessment measured little change from baseline with reported no improvement in skin disease but also a similar change from baseline with slight improvement. No Skindex-29+3 subscale performed well at reflecting increasing degrees of improvement in skin disease. Extramuscular Global Assessment and Total Improvement Score generally showed increasing levels of improvement as the degree of patient- and physician-reported improvement in skin disease increased, but these are composite measures and are not specific to improvement in DM skin disease. To measure clinically meaningful improvement in skin disease in a DM trial, Cutaneous Dermatomyositis Disease Area and Severity Index Activity score is the more sensitive outcome measure across time points.


The protective effects of hypoxia-induced hypometabolism in the Nautilus.
Specimens of Nautilus pompilius were trapped at depths of 225-300 m off the sunken barrier reef southeast of Port Moresby, Papua New Guinea. Animals transported to the Motupore Island laboratory were acclimated to normal habitat temperatures of 18 degrees C and then cannulated for arterial and venous blood sampling. When animals were forced to undergo a period of progressive hypoxia eventually to encounter ambient partial pressure of oxygen (PO2) levels of approximately 10 mmHg (and corresponding arterial PO2's of approximately 5 mmHg), they responded by lowering their aerobic metabolic rates to 5-10% of those seen in resting normoxic animals. Coincident with this profound metabolic suppression was an overall decrease in activity, with brief periods of jet propulsion punctuating long periods of rest. Below ambient PO2 levels of 30-40 mmHg, ventilatory movements became highly periodic and at the lowest PO2 levels encountered, ventilation occasionally ceased altogether. Cardiac output estimated by the Fick equation decreased during progressive hypoxia by as much as 75 80%, and in the deepest hypometabolic states heart rates slowed to one to two cycles of very low amplitude per minute. By the end of 500 min exposure to ambient PO2 levels of 10 mmHg or less, the anaerobic end products octopine and succinate had increased significantly in adductor muscle and heart, respectively. Increased concentrations of octopine in adductor muscle apparently contributed to a small intracellular acidosis and to the development of a combined respiratory and metabolic acidosis in the extracellular compartment. On the other hand, increases in succinate in heart muscle occurred in the absence of any change in cardiac pHi. Taken together, we estimate that these anaerobic end products would make up less than 2% of the energy deficit arising from the decrease in aerobic metabolism. Thus, metabolic suppression is combined with a massive downregulation of systemic O2 delivery to match metabolic supply to demand.