Maternal plasma level of antimicrobial peptide LL37 is a major determinant factor of neonatal plasma LL37 level

Aim: To determine cathelicidin antimicrobial peptide LL37subcellular distribution in cord neutrophils and normal plasma LL37 levels in mothers and neonates, relate them to delivery mode and relevant biochemical markers, including 25‐OHvitamin D [25(OH)D] as this molecules increases cathelicidin gene expression. Methods: A total of 115 infants were included, n = 68 with normal delivery and n = 47 with elective Caesarean section (C‐section), a subset of these being 50 mother–infant pairs. Biomarkers were determined in maternal and cord blood. Subcellular peptide LL37 distribution was analysed with immunoelectron microscopy. Results: Cord plasma LL37 levels were three‐times higher after normal delivery compared with C‐section. A highly significant correlation was observed between maternal and cord plasma LL37 levels, regardless of delivery mode. No relationship was found between LL37 and 25(OH)D levels. Neutrophils from cord blood after normal delivery contained 10‐times more cytoplasmatic cathelicidin peptide compared with corresponding cells after C‐section where a strict granular localization was found. Conclusion: These data are consistent with a placental transfer of LL37 and identifies maternal stores as the critical factor determining neonatal plasma LL37 level. An additional enhancement of neonatal cathelicidin mobilization and release is connected to normal delivery stress.     

A comparative laboratory diagnosis of malaria: microscopy versus rapid diagnostic test kits

Objective

To compare the two methods of rapid diagnostic tests (RDTs) and microscopy in the diagnosis of malaria.

Methods

RDTs and microscopy were carried out to diagnose malaria. Percentage malaria parasitaemia was calculated on thin films and all non-acute cases of plasmodiasis with less than 0.001% malaria parasitaemia were regarded as negative. Results were simply presented as percentage positive of the total number of patients under study. The results of RDTs were compared to those of microscopy while those of RDTs based on antigen were compared to those of RDTs based on antibody. Patients'' follow-up was made for all cases.

Results

All the 200 patients under present study tested positive to RDTs based on malaria antibodies (serum) method (100%). 128 out of 200 tested positive to RDTs based on malaria antigen (whole blood) method (64%), while 118 out of 200 patients under present study tested positive to visual microscopy of Lieshman and diluted Giemsa (59%). All patients that tested positive to microscopy also tested positive to RDTs based on antigen. All patients on the second day of follow-up were non-febrile and had antimalaria drugs.

Conclusions

We conclude based on the present study that the RDTs based on malaria antigen (whole blood) method is as specific as the traditional microscopy and even appears more sensitive than microscopy. The RDTs based on antibody (serum) method is unspecific thus it should not be encouraged. It is most likely that Africa being an endemic region, formation of certain levels of malaria antibody may not be uncommon. The present study also supports the opinion that a good number of febrile cases is not due to malaria. We support WHO''s report on cost effectiveness of RDTs but, recommend that only the antigen based method should possibly, be adopted in Africa and other malaria endemic regions of the world.     

Predictors of maternal mortality in institutional deliveries in Nigeria

Background

Maternal mortality in poor countries reflects the under-development in these societies. Global recognition of the burden of maternal mortality and the urgency for a reversal of the trend underpin the Millenium Development Goals (MDGs).

Objective

To determine risk factors for maternal mortality in institutional births in Nigeria.

Method

Twenty one health facilities in three states were selected using stratified multi-stage cluster sampling strategy. Information on all delivered mothers and their newborn infants within a three-month period was culled from medical records.

Results

A total of 9 208 deliveries were recorded. About one-fifth (20.5%) of women had no antenatal care while 79.5% had at least one antenatal visit during pregnancy. Four-fifths (80.5%) of all deliveries were normal deliveries. Elective and emergency caesarean section rates were 3.1% and 11.5% respectively. There were 79 maternal deaths and 8 526 live births, giving a maternal mortality ratio of 927 maternal deaths per 100 000 live births. No antenatal care, parity, level of education, and mode of delivery were significantly associated with maternal mortality. Low maternal education, high parity, emergency caesarean delivery, and high risk patients risk independently predicted maternal mortality.

Conclusion

Meeting goal five of the MDGs remains a major challenge in Nigeria. Multi-sectoral approaches and focused political will are needed to revert the high maternal mortality.     

Exploiting the mutanome for tumor vaccination

Multiple genetic events and subsequent clonal evolution drive carcinogenesis, making disease elimination with single-targeted drugs difficult. The multiplicity of gene mutations derived from clonal heterogeneity therefore represents an ideal setting for multiepitope tumor vaccination. Here, we used next generation sequencing exome resequencing to identify 962 nonsynonymous somatic point mutations in B16F10 murine melanoma cells, with 563 of those mutations in expressed genes. Potential driver mutations occurred in classical tumor suppressor genes and genes involved in proto-oncogenic signaling pathways that control cell proliferation, adhesion, migration, and apoptosis. Aim1 and Trrap mutations known to be altered in human melanoma were included among those found. The immunogenicity and specificity of 50 validated mutations was determined by immunizing mice with long peptides encoding the mutated epitopes. One-third of these peptides were found to be immunogenic, with 60% in this group eliciting immune responses directed preferentially against the mutated sequence as compared with the wild-type sequence. In tumor transplant models, peptide immunization conferred in vivo tumor control in protective and therapeutic settings, thereby qualifying mutated epitopes that include single amino acid substitutions as effective vaccines. Together, our findings provide a comprehensive picture of the mutanome of B16F10 melanoma which is used widely in immunotherapy studies. In addition, they offer insight into the extent of the immunogenicity of nonsynonymous base substitution mutations. Lastly, they argue that the use of deep sequencing to systematically analyze immunogenicity mutations may pave the way for individualized immunotherapy of cancer patients.     

Ability of Activation Recovery Intervals to Assess Action Potential Duration During Acute No-Flow Ischemia in the In Situ Porcine Heart

Activation Recovery Intervals During No-Flow Ischemia . Introduction : The ability to assess transmural changes in action potential duration during acute no-flow ischemia is essential to an understanding of the tachyarrhythmias that occur in this setting. The purpose of this study was to determine if activation recovery intervals determined from unipolar electrograms would provide this information.
Methods and Results : We recorded simultaneously transmembrane action potentials and unipolar electrograms from sites located as closely together as possible in the center and at the lateral margin of the ischemic zone during acute no-flow ischemia and correlated the changes in activation recovery intervals obtained from the unipolar electrograms to the changes in action potential duration. We found that the activation recovery intervals provided an accurate measure of the changes in action potential duration during acute no-flow ischemia provided the electrograms had a well-defined, single negative component to the QRS complex with a maximum negative dV/dt > 10 V/sec and a single positive component to the T wave having a maximum positive dV/dt > 1.6 V/sec. Electrograms meeting these criteria comprised 90% of the electrograms recorded at the margin of the ischemic zone throughout 60 minutes of no-flow ischemia. In the center of the ischemic zone, 75% of the recorded electrograms met these criteria for the first 20 minutes of no-flow ischemia. Thereafter, the percentage declined and after 40 minutes of no-flow ischemia, none of the electrograms recorded in the center of the ischemic zone met these criteria.
Conclusion : Activation recovery intervals obtained from unipolar electrograms provide an accurate assessment of changes in action potential duration throughout the ischemic zone during acute no-flow ischemia, provided the characteristics of the electrograms meet specific predetermined criteria.     

Surgical removal of a knotted and entrapped subclavian hemodialysis catheter guidewire

Many mechanical complications associated with insertion, maintenance, and removal of the hemodialysis catheters have been reported in the literature. A 47-year-old man was consulted to our hospital because of an entrapped hemodialysis catheter guidewire. Computed tomographic scan revealed that the right subclavian vein was perforated by the guidewire and the wire was knotted over itself, one loop inside the vein and two loops in the extravascular site. Guidewire is pulled out from a 3-cm incision over the wire loops lateral to the right sternocleidomastoid muscle. He was discharged home on postoperative day 2 without any complication. Our suggestion is that any abnormal resistance should be immediately evaluated for the presence of any potential knots using the most appropriate imaging technique.