Intrauterine cytomegalovirus infection and glycoprotein B genotypes

Cytomegalovirus (CMV) strains display polymorphisms for the gene encoding glycoprotein B (gB; gpUL55). Recent data suggest that the gB genotype may influence the outcome of acquired CMV infections. To determine whether the gB genotype also contributes to the outcome of intrauterine infection, CMV strains were studied from 56 infants with culture-confirmed intrauterine CMV infections who were born in Iowa or Texas. CMV gB genotypes were compared with the neonatal clinical features and neurodevelopmental outcomes. Fifty-three strains (95%) could be assigned a gB genotype. The overall distribution of genotypes was as follows: type 1, 50%; type 2, 18%; type 3, 23%; and type 4, 4%. Strains with the gB 3 genotype were more common among the Iowa infants (P=.082). The gB 3 genotype was more common among infants with asymptomatic infections (P=.004), but geographic location and ascertainment biases may have accounted for these differences. The gB genotypes did not correlate with the neurodevelopmental outcome of intrauterine infection.     

Development of an instrument for the identification of frail older people as a target population for integrated care

Background

Primary care is increasingly interested in the identification of frailty, as it selects the target population for integrated care. However, instruments for the identification of frailty specifically validated for use in primary care are scarce. This study developed the Easycare Two-step Older persons Screening (Easycare-TOS), which provides a valid, efficient, and pragmatic screening procedure to identify frail older people.

Aim

This paper aims to describe the development of the Easycare-TOS and the data from the pilot studies.

Design and setting

Observational pilot study in seven academic GP practices in and around Nijmegen, The Netherlands.

Method

The Easycare-TOS was developed in a cyclic process with the input of stakeholders. In every cycle, the requirements were first defined, then translated into a prototype that was tested in a pilot study. The Easycare-TOS makes optimal use of prior knowledge of the GP, and the professionals’ appraisal is decisive in the frailty decision, instead of a cut-off score. Further, it considers aspects of frailty, as well as aspects of the care context of the patient.

Results

The pilot data have shown that after step 1, two-thirds of the patients do not need further assessment, because they are judged as not frail, based on prior knowledge of the GP. The overall prevalence of frailty in this pilot study is 24%. Most professionals who participated in the pilot studies considered the time investment acceptable and the method to be of added value.

Conclusion

The Easycare-TOS instrument meets the predefined efficiency, flexibility, and acceptability requirements for use as an identification instrument for frailty in primary care.     

Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.     

Involvement of guanine nucleotide binding proteins in neutrophil activation and priming by GM-CSF

Pre-incubation of human neutrophils with pertussis toxin significantly inhibited the neutrophil-directed biologic actions of granulocyte- macrophage colony-stimulating factor (GM-CSF) in three separate assays: the induction of c-fos mRNA, the enhancement of both platelet- activating factor-induced mobilization of intracellular calcium, and stimulation of leukotriene synthesis by the calcium ionophore A23187. Cholera toxin did not have an effect on the latter two assays. Pre- treatment of human neutrophils with pertussis toxin did not affect the binding of GM-CSF to its surface receptor. These results provide the first evidence that a pertussis toxin substrate plays an important mediatory role in the mechanism of action of GM-CSF.     

Aggregation of mammalian cells expressing the platelet glycoprotein (GP) Ib-IX complex and the requirement for tyrosine sulfation of GP Ib alpha

The glycoprotein (GP) Ib-IX complex mediates platelet aggregation in response to high shear forces by binding von Willebrand factor (vWF) in the plasma. We investigated the possibility that the complex could mediate a similar phenomenon if expressed in nonhematopoietic cells. When agitated on a tabletop shaker, CHO and L cells expressing the full complex formed large aggregates in the presence of vWF and the modulator ristocetin. When the rate of agitation was increased, aggregation occurred without added ristocetin and appeared to require only the application of a physical force. The aggregation was homophilic and temperature-dependent and required a functional ligand- binding subunit of the GP Ib-IX complex, GP Ib alpha. Posttranslational tyrosine sulfation of GP Ib alpha was required for aggregate formation and stability. Thus, aggregation of cells expressing the GP Ib-IX complex is a unique example of a ligand-receptor interaction induced by mechanical forces and demonstrates an important biological role for sulfation of tyrosine residues.     

Ultrasound-guided versus computed tomography-controlled periradicular injections in the middle and lower cervical spine: a prospective randomized clinical trial

Purpose

We conducted this study to evaluate accuracy, time saving, radiation doses, safety, and pain relief of ultrasound (US)-guided periradicular injections versus computed tomography (CT)-controlled interventions in the cervical spine in a prospective randomized clinical trial.

Methods

Forty adult patients were consecutively enrolled and randomly assigned to either a US or a CT group. US-guided periradicular injections were performed on a standard ultrasound device using a broadband linear array transducer. By basically following the osseous landmarks for level definition in “in-plane techniques”, a spinal needle was advanced as near as possible to the intended, US-depicted nerve root. The respective needle tip positioning was then verified by CT. The control group underwent CT-guided injections, which were performed under standardized procedures using the CT-positioning laser function.

Results

The accuracy of US-guided interventions was 100 %. The mean time to final needle placement in the US group was 02:21 ± 01:43 min:s versus 10:33 ± 02:30 min:s in the CT group. The mean dose-length product radiation dose, including CT confirmation for study purposes only, was 25.1 ± 16.8 mGy cm for the US group and 132.5 ± 78.4 mGy cm for the CT group. Both groups showed the same significant visual analog scale decay (p < 0.05) without “inter-methodic” differences of pain relief (p > 0.05).

Conclusions

US-guided periradicular injections are accurate, result in a significant reduction of procedure expenditure under the avoidance of radiation and show the same therapeutic effect as CT-guided periradicular injections.     

Early prenatal stress impact on coping strategies and learning performance is sex dependent

Diseases involving cognitive disorders and maladaptive stress-coping behaviors including autism and schizophrenia are present in children born to mothers exposed to stress during pregnancy. To determine the gestational time window when stress exposure produces the greatest impact on cognition, dams were exposed to chronic variable stress (CVS) early, mid-, or late in gestation and offspring learning performance and navigation strategies assessed. These studies utilized a modified version of the Barnes maze to allow investigation of coping responses to stress stimuli. In our study, males exposed to early gestational stress showed significantly impaired learning performance, requiring twice as long to locate the target following training. In stark contrast, early prenatal stress enhanced female performance, where these females located the target in a quarter of the time required by controls. Differences in search strategies whether cued, random, or serial accounted for divergent performances between sex and CVS groups. While control males' behavior expectedly evolved to a cued strategy, the early stressed offspring continued to rely on serial and random searching. Surprisingly, in a long-term memory recall test 6 weeks following previous maze exposure, these early stressed offspring now located the target significantly faster than controls suggesting gestational effects of stress on memory retention that were specific to prenatal time window of stress exposure. Overall, these results provide important insight into the temporal specificity of the effects of prenatal CVS revealing a remarkable vulnerability during early development and a sexually dichotomous influence on cognitive abilities and stress-coping strategies.     

Role of precise spike timing in coding of dynamic vibrissa stimuli in somatosensory thalamus

Rats discriminate texture by whisking their vibrissae across the surfaces of objects. This process induces corresponding vibrissa vibrations, which must be accurately represented by neurons in the somatosensory pathway. In this study, we investigated the neural code for vibrissa motion in the ventroposterior medial (VPm) nucleus of the thalamus by single-unit recording. We found that neurons conveyed a great deal of information (up to 77.9 bits/s) about vibrissa dynamics. The key was precise spike timing, which typically varied by less than a millisecond from trial to trial. The neural code was sparse, the average spike being remarkably informative (5.8 bits/spike). This implies that as few as four VPm spikes, coding independent information, might reliably differentiate between 10⁶ textures. To probe the mechanism of information transmission, we compared the role of time-varying firing rate to that of temporally correlated spike patterns in two ways: 93.9% of the information encoded by a neuron could be accounted for by a hypothetical neuron with the same time-dependent firing rate but no correlations between spikes; moreover, 93.4% of the information in the spike trains could be decoded even if temporal correlations were ignored. Taken together, these results suggest that the essence of the VPm code for vibrissa motion is firing rate modulation on a submillisecond timescale. The significance of such a code may be that it enables a small number of neurons, firing only few spikes, to convey distinctions between very many different textures to the barrel cortex.     

The free healthcare initiative in Sierra Leone: Evaluating a health system reform, 2010‐2015

This article presents the findings of a theory‐based evaluation of the Sierra Leone Free Health Care Initiative (FHCI), using mixed methods. Analytical approaches included time‐series analysis of national survey data to examine mortality and morbidity trends, as well as modelling of impact using the Lives Saved Tool and expenditure trend analysis. We find that the FHCI responded to a clear need in Sierra Leone, was well designed to bring about needed changes in the health system to deliver services to the target beneficiaries, and did indeed bring funds and momentum to produce important systemic reforms. However, its ambition was also a risk, and weaknesses in implementation have been evident in a number of core areas, such as drugs supply. We conclude that the FHCI was one important factor contributing to improvements in coverage and equity of coverage of essential services for mothers and children. Modelled cost‐effectiveness is high—in the region of US$ 420 to US$ 444 per life year saved. The findings suggest that even—or perhaps especially—in a weak health system, a reform‐like fee removal, if tackled in a systematic way, can bring about important health system gains that benefit vulnerable groups in particular.