Extrinsic versus intrinsic cues in avian paraxial mesoderm patterning and differentiation.

Somitic and head mesoderm contribute to cartilage and bone and deliver the entire skeletal musculature. Studies on avian somite patterning and cell differentiation led to the view that these processes depend solely on cues from surrounding tissues. However, evidence is accumulating that some developmental decisions depend on information within the somitic tissue itself. Moreover, recent studies established that head and somitic mesoderm, though delivering the same tissue types, are set up to follow their own, distinct developmental programmes. With a particular focus on the chicken embryo, we review the current understanding of how extrinsic signalling, operating in a framework of intrinsically regulated constraints, controls paraxial mesoderm patterning and cell differentiation.     

Is it a safe practice to administer oxygen during uncomplicated delivery: A randomized controlled trial?

Background

Newborns exposed to oxygen suffer from an oxidative stress with significant alterations in the concentrations of superoxide dismutase (SOD) and glutathione (GSSG).

Objective

To investigate the biological and clinical effects of oxygen administration to delivering mothers.

Methods

We conducted a randomized, double-blinded, controlled trial on a cohort of delivering women (n = 56) with an uncomplicated term pregnancy. Women were randomly assigned to one of two groups: Oxygen group or Room Air group. The Oxygen group received 100% oxygen (2 l/min) via nasal cannula for at least 30 min before delivery. Subjects in the Room Air group were connected to a nasal cannula while on room air. Concentrations of SOD (μg/g of Hb) and GSSG (μM/ml) were measured in maternal and umbilical cord blood. Bivariate and multivariate analyses were used to compare the two groups using the SAS system.

Results

Maternal SOD and GSSG did not differ between the two groups at baseline or after delivery. Concentrations of SOD and GSSG in umbilical cord blood did not differ between groups. More infants in Oxygen Group required delivery room resuscitation (20% vs. 0%, P = 0.03). This difference could not be explained by mode of delivery, infant sex, or other confounders.

Conclusions

Maternal exposure to oxygen during delivery is not associated with changes in umbilical cord SOD or GSSG. Further studies are needed to explore mechanisms responsible for the need of resuscitation in the oxygen group.     

Phenotypic delineation of the retinal arterial macroaneurysms with supravalvular pulmonic stenosis syndrome

Retinal arterial macroaneurysms with supravalvular pulmonic stenosis (RAMSVPS), also known as Familial Retinal Arterial Macroaneurysms (FRAM) syndrome, is a very rare multisystem disorder. Here, we present a case series comprising ophthalmologic and systemic evaluation of patients homozygous for RAMSVPS syndrome causative IGFBP7 variant. New clinical details on 22 previously published and 8 previously unpublished patients are described. Age at first presentation ranged from 1 to 34 years. The classical feature of macroaneurysms and vascular beading involving the retinal arteries was universal. Follow up extending up to 14 years after initial diagnosis revealed recurrent episodes of bleeding and leakage from macroaneurysms in 55% and 59% of patients, respectively. The majority of patients who underwent echocardiography (18/23) showed evidence of heart involvement, most characteristically pulmonary (valvular or supravalvular) stenosis, often requiring surgical correction (12/18). Four patients died in the course of the study from complications of pulmonary stenosis, cerebral hemorrhage, and cardiac complications. Liver involvement (usually cirrhosis) was observed in eight patients. Cerebral vascular involvement was observed in one patient, and stroke was observed in two. We conclude that RAMSVPS is a recognizable syndrome characterized by a high burden of ocular and systemic morbidity, and risk of premature death. Recommendations are proposed for early detection and management of these complications.     

Effect of piracetam,vincamine, vinpocetine,and donepezil on oxidative stress and neurodegeneration induced by aluminum chloride in rats

In this study, we investigated the effects of the memory-enhancing drugs piracetam, vincamine, and vinpocetine or the cholinesterase inhibitor donepezil on the development of oxidative stress, inflammation, and brain damage induced in rat brain by aluminum chloride (AlCl₃). Saline (control), piracetam (100 or 300 mg/kg), vincamine (10 or 20 mg/kg), vinpocetine (10 or 20 mg/kg), piracetam 100 mg/kg plus vincamine 10 mg/kg, piracetam 100 mg/kg plus vinpocetine 10 mg/kg, or donepezil 5 mg/kg were administered once daily intraperitoneally for 45 days along with AlCl₃ (10 mg/kg, intraperitoneally). Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, acetylcholinesterase (AChE), butrylcholinesterase (BChE), paraoxonase (PON1) activities, and prostaglandin E₂ (PGE₂) concentrations were measured in brain. Histopathology and caspase-3 immunohistochemistry (an apoptotic marker) were also performed. Results indicated that (1) compared to controls, injection of AlCl₃ significantly increased brain lipid peroxidation (MDA) and nitric oxide concentrations together with decreased GSH concentrations. PON1 activity in brain was significantly decreased, while AChE and BChE activities were significantly increased compared to control animals. Cortical atrophy, neuronal shrinkage, red neurons, surrounded by vacuolations with cytoplasmic neurofibrillary tangles, intense caspase-3 expression in degenerated neurons, and amyloid deposition were observed; (2) in AlCl₃-treated rats, (i) lipid peroxidation was significantly decreased by the lower doses of piracetam, vincamine, and vinpocetine as well as by piracetam plus either vincamine or vinpocetine; (ii) nitric oxide was significantly decreased by the lower doses of piracetam, and vinpocetine, by both doses of vincamine, and by piracetam plus either vincamine or vinpocetine; (iii) nitric oxide also showed significant decrease after treatment with donepezil; (iv) both GSH and PON1 activity showed significant increase following the administration of the test drugs; (v) PGE₂ significantly increased by the higher dose of piracetam, vincamine, vinpocetine, and piracetam plus either vincamine or vinpocetine; (vi) AChE and BChE activities decreased after treatment with the lower dose of piracetam, vinpocetine, and piracetam plus either vincamine or vinpocetine; (vii) AChE activity decreased following 20 mg/kg vincamine, and BChE activity decreased following 10 mg/kg vincamine; (viii) AChE but not BChE activity decreased after donepezil; (ix) on histopathology, the low dose of singly used drugs and donepezil had the best improvement in neuronal look, cortical thickness, and degree of vascular congestion. Rats treated with 10 mg/kg vinpocetine showed decreased capsase-3 immunoreactivity in brain and regenerating neurons. These results suggest that while the low therapeutic doses of the nootropic drugs piracetam, vincamine, and vinpocetine display anti-oxidant and neuroptotective effects, their high doses are likely to have prooxidant and proinflammatory properties.     

Induced Microphase Separation in Hybrid Composite Polymer Electrolytes Based on Poly(acrylonitrile‐r‐butadienes) and Ionic Liquids

Novel hybrid, composite polymer electrolytes (HCPEs) based on poly(acrylonitrile‐r‐butadiene) (PAN‐r‐PB), CN‐modified silica nanoparticles (CN‐MSNs), Li triflate, and ionic liquids (ILs) are synthesized. Using a combination of methods, it is demonstrated that these materials segregate into PAN‐rich and PB‐rich phases, the behavior of which changes depending on the IL type. The incorporation of ILs containing hexyl and octyl substituents at the imidazolium rings leads to a higher mobility of the PB‐rich phase and a decrease of the density of the neighboring PAN‐rich phase, allowing an improvement of the Li ion conductivity. However, with an increase of the substituent length from decyl to dodecyl, ordering of the hydrophobic tails in the PB‐rich phase leads to both stiffening of the latter and corresponding ordering of the ionic pairs of ILs, resulting in a decreased conductivity. The results of this work are broadly applicable for controlling the structure and properties of polymeric materials exhibiting microphase segregation.

     

Infection of Immunodeficient Horses with Sarcocystis neurona Does Not Result in Neurologic Disease

Equine protozoal myeloencephalitis is a progressive neurologic disease of horses most commonly caused by infection with the apicomplexan parasite Sarcocystis neurona. Factors affecting neuroinvasion and neurovirulence have not been determined. We investigated the pathogenesis of infection with S. neurona in horses with severe combined immune deficiency (SCID). Two immunocompetent (IC) Arabian horses and two Arabian horses with SCID were infected orally with 5 × 10⁵ sporocysts of S. neurona. Four IC horses and one SCID horse were infected intravenously (i.v.) with 5 × 10⁸ merozoites of the WSU-1 isolate of S. neurona. Despite prolonged parasitemia and persistent infection of visceral tissues (skeletal muscle, cardiac muscle, lung, liver, and spleen) as demonstrated by PCR and culture, SCID horses did not develop neurologic signs after oral or i.v. infection. S. neurona was undetectable in the neuronal tissues of SCID horses by either PCR, immunohistochemistry, or culture. In contrast, although parasitemia was undetectable in orally infected IC horses and of only short duration in i.v. infected IC horses, four of six IC horses developed neurologic signs. S. neurona was detectable by PCR and/or culture of neural tissue but not visceral tissue of IC horses with neurologic disease. Infected SCID horses are unable to clear S. neurona from visceral tissues, but the infection does not result in neurologic signs; in contrast, IC horses rapidly control parasitemia and infection of visceral tissues but frequently experience neuroinvasion and exhibit clinical signs of neurologic disease.     

Increased levels of inflammatory mediators in children and adults infected with Vibrio cholerae O1 and O139

Investigations were carried out to study the production of factors associated with the innate immune response in the systemic and mucosal compartments in adults and children infected with Vibrio cholerae O1 and V. cholerae O139. The levels of nonspecific mediators of the innate defense system, i.e., prostaglandin E(2) (PGE(2)), leukotriene B(4) (LTB(4)), and lactoferrin (Lf), as well as myeloperoxidase (MPO), were elevated at the acute stage of the disease in stools obtained from both O1- and O139-infected adults and children. In the systemic compartment, the levels of Lf were increased after onset of disease, which in children remained elevated up to convalescence compared to the healthy controls. Increased concentrations of C-reactive protein were seen in the sera of adult cholera patients at the acute stage of infection. Elevated levels of the nitric oxide (NO*) metabolites (nitrite and nitrate [NO(2)(-) and NO(3)(-)]) were detected in plasma but not in urine. The activity of the scavenger of reactive oxygen species, superoxide dismutase, was higher in the plasma of adults immediately after the onset of disease, suggesting that an active scavenging of reactive oxygen species was taking place. The concentration of 8-iso-prostaglandin F(2 alpha) remained unchanged in the systemic and mucosal compartments in the study subjects. After the recovery of patients from cholera, the concentration of the majority of the metabolites decreased to baseline levels by day 30 after the onset of infection. Immunohistochemical staining showed increased tissue expression of MPO, Lf, and inducible nitric oxide synthase at the acute stage in the duodenal biopsies of adults and rectal biopsies obtained from children with cholera. Very little difference was seen in the levels of the different inflammatory mediators in patients infected with V. cholerae O1 or the encapsulated V. cholerae O139. In summary, these results suggest that elevated concentrations of Lf, MPO, PGE(2), LTB(4), and NO*, as well as other metabolites, during the acute stage of the disease indicate that the innate defense system, as well as the inflammatory process, is activated in both adults and pediatric patients infected with V. cholerae O1 and O139.     

Web-Based Virtual Microscopy of Digitized Blood Slides for Malaria Diagnosis: An Effective Tool for Skills Assessment in Different Countries and Environments

BackgroundMorphological examination of blood films remains the reference standard for malaria diagnosis. Supporting the skills required to make an accurate morphological diagnosis is therefore essential. However, providing support across different countries and environments is a substantial challenge.ObjectiveThis paper reports a scheme supplying digital slides of malaria-infected blood within an Internet-based virtual microscope environment to users with different access to training and computing facilities. The feasibility of the approach was established, allowing users to test, record, and compare their own performance with that of other users.MethodsFrom Giemsa stained thick and thin blood films, 56 large high-resolution digital slides were prepared, using high-quality image capture and 63x oil-immersion objective lens. The individual images were combined using the photomerge function of Adobe Photoshop and then adjusted to ensure resolution and reproduction of essential diagnostic features. Web delivery employed the Digital Slidebox platform allowing digital microscope viewing facilities and image annotation with data gathering from participants.ResultsEngagement was high with images viewed by 38 participants in five countries in a range of environments and a mean completion rate of 42/56 cases. The rate of parasite detection was 78% and accuracy of species identification was 53%, which was comparable with results of similar studies using glass slides. Data collection allowed users to compare performance with other users over time or for each individual case.ConclusionsOverall, these results demonstrate that users worldwide can effectively engage with the system in a range of environments, with the potential to enhance personal performance through education, external quality assessment, and personal professional development, especially in regions where educational resources are difficult to access.     

Are Pathogenic Leptospira Species Agents of Community-Acquired Pneumonia? Case Reports of Leptospirosis Presenting as Pneumonia

We report four Indonesian cases meeting the clinical and radiological criteria for community-acquired pneumonia and other findings suggestive of leptospirosis. Quantitative PCR (qPCR) analyses of serum and urine samples and serology confirmed the diagnosis of leptospirosis in each. Results of qPCR analysis of throat swabs were concordant with those obtained with acute-phase serum samples, which suggests its potential for use as a noninvasive diagnostic tool for leptospirosis.