Sepsis-Related Lung Injury and the Complication of Extrapulmonary Pneumococcal Pneumonia.

Globally, sepsis and pneumonia account for significant mortality and morbidity. A complex interplay of immune-molecular pathways underlies both sepsis and pneumonia, resulting in similar and overlapping disease characteristics. Sepsis could result from unmanaged pneumonia. Similarly, sepsis patients have pneumonia as a common complication in the intensive care unit. A significant percentage of pneumonia is misdiagnosed as septic shock. Therefore, our knowledge of the clinical relationship between pneumonia and sepsis is imperative to the proper management of these syndromes. Regarding pathogenesis and etiology, pneumococcus is one of the leading pathogens implicated in both pneumonia and sepsis syndromes. Growing evidence suggests that pneumococcal pneumonia can potentially disseminate and consequently induce systemic inflammation and severe sepsis. Streptococcus pneumoniae could potentially exploit the function of dendritic cells (DCs) to facilitate bacterial dissemination. This highlights the importance of pathogen-immune cell crosstalk in the pathophysiology of sepsis and pneumonia. The role of DCs in pneumococcal infections and sepsis is not well understood. Therefore, studying the immunologic crosstalk between pneumococcus and host immune mediators is crucial to elucidating the pathophysiology of pneumonia-induced lung injury and sepsis. This knowledge would help mitigate clinical diagnosis and management challenges.

Increased Brain-Derived Neurotrophic Factor and Hippocampal Dendritic Spine Density Are Associated with the Rapid Antidepressant-like Effect of Iron-citalopram and Iron-Imipramine Combinations in Mice.

Iron supplementation previously demonstrated antidepressant-like effects in post-partum rats. The present study evaluates the possible synergistic antidepressant effect of sub-therapeutic dose of iron co-administered with citalopram or imipramine in female Institute of Cancer Research mice. Depression-like symptoms were induced in the forced swim (FST), tail suspension (TST), and open space swim (OSST) tests while open field test (OFT) was used to assess locomotor activity. Mice (n = 8) received iron (0.8-7.2 mg/kg), citalopram (3-30 mg/kg), imipramine (3-30 mg/kg), desferrioxamine (50 mg/kg) or saline in the single treatment phase of each model and subsequently a sub-therapeutic dose of iron co-administered with citalopram or imipramine. Assessment of serum brain derived neurotrophic factor (BDNF) and dendritic spine density was done using ELISA and Golgi staining techniques respectively. Iron, citalopram and imipramine, unlike desferrioxamine, reduced immobility score in the TST, FST and OSST without affecting locomotor activity, suggesting antidepressant-like effect. Sub-therapeutic dose of iron in combination with citalopram or imipramine further enhanced the antidepressant-like effect, producing a more rapid effect when compared to the iron, citalopram or imipramine alone. Iron, citalopram and imipramine or their combinations increased serum BDNF concentration, hippocampal neuronal count and dendritic spine densities. Our study provides experimental evidence that iron has antidepressant-like effect and sub-therapeutic dose of iron combined with citalopram or imipramine produces more rapid antidepressant-like effect. We further show that iron alone or its combination with citalopram or imipramine attenuates the neuronal loss associated with depressive conditions, increases dendritic spines density and BDNF levels. These finding suggest iron-induced neuronal plasticity in the mice brain.

Gestational iron supplementation reverses depressive-like behavior in post-partum Sprague Dawley rats: Evidence from behavioral and neurohistological studies.

Background: Postpartum depression is a mood disorder that affects about 9-20% of women after child birth. Reports suggest that gestational iron deficiency can cause a deficit in behavioral, cognitive and affective functions and can precipitate depressive symptoms in mothers during the postpartum period. The present study examined the effect of iron supplementation on depressive behavior during postpartum period in a rat model. Method: Female Sprague-Dawley rats were crossed. Pregnant rats received iron, fluoxetine, desferrioxamine or vehicle throughout the period of gestation. During the postpartum period, mothers from all groups were taken through the open field test (OFT), forced swim test (FST), novelty-induced hypophagia (NIH) and sacrificed for histological examination of the brains. Results: Results showed that rats treated with iron-chelating agent, desferrioxamine, and vehicle during gestation exhibited increased immobility scores in the FST, increased latency to feed and reduced feeding in the NIH with corresponding decreased number of neurons and dendritic branches in the cortex of the brain. These depression-related effects were attenuated by perinatal iron supplementation which showed decreased immobility scores in the FST comparable to rats treated with fluoxetine, a clinically effective antidepressant. Iron treatment also decreased latency to feeding while increasing feeding behavior in the NIH. Iron-treated dams had a higher number of neurons with dendritic connections in the frontal cortex compared to vehicle- and desferrioxamine-treated groups. Conclusion: The results suggest that, iron supplementation during gestation exerts an antidepressant-like effect in postpartum Sprague-Dawley rats, attenuates neuronal loss associated with depression and increases dendritic spine density.

Preliminary Investigation into Plasmodium-like Piroplasms (Babesia/Theileria) among Cattle, Dogs and Humans in A Malaria-Endemic, Resource-Limited Sub-Saharan African City.

Babesia and Theileria are protozoan parasites belonging to the order piroplasmida, transmitted by hard ticks, and can cause diseases known as piroplasmosis. Human infections are usually asymptomatic, except in immuno-compromised persons who present malaria-like symptoms. Moreover, microscopically, the morphologies of Babesia and Theileria can resemble that of the malaria parasite, Plasmodium. In malaria-endemic areas with limited resources, these similarities can increase the possibility of misdiagnosing a patient as having malaria instead of piroplasmosis, which may further lead to inappropriate choice of disease management. This preliminary investigation aimed at detecting Babesia/Theileria in cattle, dogs and humans in some parts of Accra. Whole blood samples were taken from febrile cattle (n = 30) and dogs (n = 33), as well as humans diagnosed with malaria (n = 150). Blood samples of all study subjects were microscopically screened for possible presence of haemoparasites. Samples whose smears had features suggestive of possible piroplasmic infection were all given the label "suspected Babesia/Theileria-infected" samples. Nested polymerase chain reaction (PCR) was performed on extracted deoxyribonucelic acid (DNA) from all the "suspected" samples of cattle, dogs and humans, with primer sets that can detect 18S rRNA genes of Babesia/Theileria spp. In addition to this, amplification was performed on the "suspected" dog samples using the BcW-A/BcW-B primer set which detects the 18S rRNA genes of B. canis, while the BoF/BoR primer set which targets the rap-1 region of B. bovis and another primer set which detects the 18S rRNA genes of most bovine Babesia spp. (including B. divergens) were used on the suspected cattle samples. For the human samples, however, additional amplification was done on the extracted DNA using primers for the three other Babesia targeted (B. divergens, B. bovis and B. canis). Microscopy showed possible Babesia/Theileria infection suspected in all three groups of subjects in the following proportions: cattle (10/30; 33%), dogs (3/33; 9%) and humans (6/150; 4%). DNA from one-third of the "suspected" dog samples yielded amplification with Babesia canis primers. Moreover, a broad-detecting set of primers (that can amplify some Babesia and Theileria species) amplified DNA from nine (9/30; 30%) of the "suspected" cattle samples, but none from those of the humans. Although for this study conducted in the city, the Babesia/Theileria primers used did not amplify DNA from the six "suspected" human samples; the possibility of Babesia/Theileria infection in humans in other parts of the country cannot be overruled. There is therefore a need for further studies on possible emergence of human babesiosis/theileriosis in other parts of Ghana and sequencing for specific identification of any circulating strain.

Nasopharyngeal Carriage of Methicillin-Resistant Staphylococcus aureus (MRSA) among Sickle Cell Disease (SCD) Children in the Pneumococcal Conjugate Vaccine Era.

The aim of this cross-sectional study was to investigate Staphylococcus aureus nasopharyngeal carriage epidemiology in relation to other nasopharyngeal bacterial colonizers among sickle cell disease (SCD) children about five years into pneumococcal conjugate vaccine 13 (PCV-13) introduction in Ghana. The study involved bacteriological culture of nasopharyngeal swabs obtained from 202 SCD children recruited from the Princess Marie Louise Children's Hospital. S. aureus isolates were identified using standard methods and subjected to antimicrobial susceptibility testing using the Kirby-Bauer disc diffusion method. Cefoxitin-resistant S. aureus isolates were screened for carriage of the mecA, pvl, and tsst-1 genes using multiplex polymerase chain reaction. The carriage prevalence of S. aureus was 57.9% (n = 117), and that of methicillin-resistant S. aureus (MRSA) was 3.5% (n = 7). Carriage of the mecA, pvl, and tsst-1 genes were respectively demonstrated in 20.0% (n = 7), 85.7% (n = 30), and 11.4% (n = 4) of the cefoxitin-resistant S. aureus isolates. PCV-13 vaccination (OR = 0.356, p = 0.004) and colonization with coagulase-negative staphylococci (CoNS) (OR = 0.044, p < 0.0001) each protected against S. aureus carriage. However, none of these and other features of the participants emerged as a determinant of MRSA carriage. The following antimicrobial resistance rates were observed in MRSA compared to methicillin-sensitive S. aureus: clindamycin (28.6% vs. 4.3%), erythromycin (42.9% vs. 19.1%), tetracycline (100% vs. 42.6%), teicoplanin (14.3% vs. 2.6%), penicillin (100% vs. 99.1%), amoxiclav (28.6% vs. 3.5%), linezolid (14.3% vs. 0.0%), ciprofloxacin (42.9% vs. 13.9%), and gentamicin (42.9% vs. 13.0%). The proportion of S. aureus isolates that were multidrug resistant was 37.7% (n = 46). We conclude that S. aureus was the predominant colonizer of the nasopharynx of the SCD children, warranting the continuous monitoring of this risk group for invasive S. aureus infections.

Nasopharyngeal Carriage and Antimicrobial Susceptibility Profile of Staphylococcus aureus among Children under Five Years in Accra.

This cross-sectional study investigated the Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) nasopharyngeal carriage epidemiology in Accra approximately five years post-pneumococcal conjugate vaccines introduction in the country. Archived nasopharyngeal swabs collected from 410 children aged under five years old were bacteriologically cultured. The resultant S. aureus isolates were subjected to antimicrobial susceptibility testing and screening for carriage of the mecA and LukF-PV (pvl) genes, following standard procedures. The data obtained were analyzed with Statistical Products and Services Solutions (SPSS) using descriptive statistics and Chi square tests of associations. The isolated bacteria decreased across coagulase-negative Staphylococci (47.3%, n = 194), S. aureus (23.2%, n = 95), Diphtheroids (5.4%, n = 22), Micrococcus species (3.7%, n = 15), Klebsiella pneumoniae (3.2%, n = 13), Moraxella species and Citrobacter species (1.5% each, n = 6), Escherichia coli, Enterobacter species, and Pseudomonas species (0.9% each, n = 2). The MRSA carriage prevalence was 0.49% (n = 2). Individuals aged 37-48 months recorded the highest proportion of S. aureus carriage (32.6%, 31/95). Resistance of S. aureus to the antibiotics tested were penicillin G (97.9%, n = 93), amoxiclav (20%, n = 19), tetracycline (18.9%, n = 18), erythromycin (5.3%, n = 5), ciprofloxacin (2.1%, n = 2), gentamicin (1.1%, n = 1), cotrimoxazole, clindamycin, linezolid, and teicoplanin (0% each). No inducible clindamycin resistance was observed for the erythromycin-resistant isolates. Three (3.2%) of the isolates were multidrug resistant, of which 66.7% (2/3) were MRSA. The pvl gene was associated with 59.14% (55/93) of the methicillin-sensitive S. aureus (MSSA) isolates, but was not detected among any of the MRSA isolates.

Reduced Serum Circulation of Cell-Free DNA Following Chemotherapy in Breast Cancer Patients.

Breast cancer is the most common malignancy in women, with alarming mortalities. Neoadjuvant treatments employ chemotherapy to shrink tumours to a well-defined size for a better surgical outcome. The current means of assessing effectiveness of chemotherapy management are imprecise. We previously showed that breast cancer patients have higher serum circulating cell-free DNA concentrations. cfDNA is degraded cellular DNA fragments released into the bloodstream. We further report on the utility of cfDNA in assessing the response to chemotherapy and its potential as a monitoring biomarker. A total of 32 newly diagnosed and treatment-naive female breast cancer patients and 32 healthy females as controls were included. Anthropometric, demographic and clinicopathological information of participants were recorded. Each participant donated 5 mL of venous blood from which sera were separated. Blood sampling was carried out before the commencement of chemotherapy (timepoint 1) and after the third cycle of chemotherapy (timepoint 2). qPCR was performed on the sera to quantify ALU 115 and 247 levels, and DNA integrity (ALU247/ALU115) was determined. ALU 115 and 247 levels were elevated in cancer patients but were significantly decreased after the third cycle of chemotherapy (T2) compared to T1. DNA integrity increased after the third cycle. Serum cfDNA may provide a relatively inexpensive and minimally invasive procedure to evaluate the response to chemotherapy in breast cancer.

Unravelling the Perspectives of Day and Night Traders in Selected Markets within a Sub-Saharan African City with a Malaria Knowledge, Attitude and Practice Survey.

BACKGROUND: Malaria is still endemic in sub-Saharan Africa, with a high disease burden. Misconceptions about malaria contribute to poor attitudes and practices, further increasing the burden in endemic countries. Studies have examined the knowledge, attitudes, and practices (KAP) of malaria among different populations. However, there seems to be no available literature reporting on the perspectives of day and night market traders. To the best of our knowledge, this is the first report on malaria KAP with a focus on day and night market traders. METHODS: A descriptive cross-sectional study involving day and night market traders in 10 selected markets within the Greater Accra Region of Ghana was carried out. Data were collected from consenting respondents using a structured questionnaire. RESULTS: Of the 760 respondents (33.3% (n = 253) night and 66.7% (n = 507) day traders) interviewed, there was no significant difference between the day and night market traders in terms of malaria KAP. Although the market traders had an overall moderate knowledge (54.0% of the day traders and 56.5% of the night traders), misconceptions about malaria (especially that it could be caused by exposure to the sun) still existed among the traders. Moreover, the majority of the traders who demonstrated high knowledge (43.98%, n = 250) did not always take laboratory tests to confirm their suspicion, indicating poor attitude. Furthermore, the market traders' choice of drug for malaria treatment (p = 0.001) and preferred malaria treatment type (orthodox or herbal) (p = 0.005) were significantly associated with their knowledge level. CONCLUSIONS: Despite the observation that no significant difference in KAP exists between day and night market traders, appropriate health education programs and interventions still need to be directed at misconceptions, poor attitudes, and poor practices revealed by this study. This will ultimately help in the prevention and control of malaria in Ghana, and globally.

Light Microscopic Morphology of Indigenous Ghanaian African Hair from Scalp, Eyebrow, Axilla, and Pubic Regions.

CONTEXT: Relatively scanty literature on autochthonic African Negroid hair morphology provokes research interest for anthropological, forensic, and cosmetic purposes. AIMS: This study aimed to contribute basic morphological information on Ghanaian African hairs. SETTINGS AND DESIGN: The study was done in selected second-cycle schools in Accra, Ghana, using convenient sampling. SUBJECTS AND METHODS: Hairs were obtained by pluck method, from 30 males and 30 females aged 15-20 years. Ghanaian African autochthony was established if individuals had two generations of indigenous Ghanaian parentage. Scalp, eyebrow, axilla, and pubic hairs were image captured using a digital light microscope eyepiece connected to a computer. Diameters of hair strands were measured; types of the medulla and the form and shape of the hair roots were studied. STATISTICAL ANALYSIS USED: ANOVA test (SPSS Version 17.0) was used to compare the means of quantitative hair features among the sexes and the four regions of the body studied. RESULTS: Pubic hair shaft was thickest (respective male and female diameters were 100.21 µm, 88.40 µm) and eyebrow hair was thinnest (53.97 and 46.69-µm diameters in males and females, respectively). Axillary and scalp hairs were the closest in diameters with 76.21 and 72.02 µm, respectively, in males and 73.07 and 71.15 µm, respectively, in females. Continuous type medulla was predominant in all hairs, with a trend of percentage occurrence in descending order from the pubic, axilla, eyebrow, and scalp in both sexes. CONCLUSIONS: Bodily regional differences in diameter of hair shaft and medullary presence were affirmed.

Microscopic Characteristics Of Scalp Hair Subjected To Cultural Styling Methods In Ghanaian African Females.

PURPOSE: To provide data for forensic use and provoke ideas to preserve shaft integrity, we studied microstructural alterations of female scalp hair subjected to Ghanaian cultural styling methods. Hence, topographical features of female hairs styled by braiding/weaving, and chemical relaxation sampled from five different scalp regions were assessed and compared with natural (Afro) hair. SUBJECTS AND METHODS: Ninety-six indigenous Ghanaian females volunteered 480 hairs, which were analyzed by light microscopy. Hairs were plucked using a pair of cosmetologist's tweezers from frontal, left temporal, right temporal, vertex, and occipital regions of the scalp. Hairs were categorized by their grooming styles as Afro (natural-unstyled), natural-styled (weaved/braided), and chemically relaxed. These were studied according to shaft/medulla dimensions and conventional cuticular scale features, and comparisons were made between styling procedures and scalp regions. RESULTS: Chemically styled hair had the widest shaft diameter, but the lowest incidence of continuous medullation. Medullary diameter and index increased from chemically relaxed, natural-styled, to Afro hair. A positive but modest correlation between shaft and medullary diameters existed for Afro (r = 0.320, p = 0.011) and natural-styled hairs (r = 0.235, p = 0.022) but not chemically relaxed hair (r = 0.122, p = 0.2). Scale margins were predominantly smooth in Afro hair, crenate in natural-styled hair, and rippled in chemically relaxed hair. With respect to scalp regions, hair shaft diameter was widest in vertex hair and smallest in right temporal hair in all styling methods. CONCLUSION: Medulla was thickest in Afro hair, which also exhibited a correlation with shaft diameter in conformity with the published data. Chemically relaxed hairs did not exhibit these characteristics, which affirm altered morphology. Research on how chemicals affect these changes should help find antidote. The dimensional variations of hairs from different scalp regions are instructive for both cosmetic and forensic examination of hairs.

Natural cocoa inhibits maternal hypercholesterolaemia-induced atherogenesis in rabbit pups.

Atherosclerosis begins during foetal development and is enhanced by maternal hypercholesterolaemia during pregnancy. This study assessed the effect of natural cocoa on atherosclerosis in offspring conceived in maternal hypercholesterolaemia. Female rabbits were fed a cholesterol-enriched diet for two weeks and hypercholesterolaemia was confirmed, after which they were crossed with normocholesterolaemic males. One group of hypercholesterolaemic mothers (HCC) received natural cocoa powder (NCP) in their drinking water, whereas the other group (HC) received only water. Histological analysis of three segments of the aorta (arch, thoracic and abdominal) from offspring of both groups was compared with a control group (NC). Intima-media thickness of the aortic arch in offspring born to hypercholesterolaemic rabbits (HC: 146 µm) was higher compared to HCC (99 µm) and control rabbits (58.5 µm). All the sections from the aortic arch of the HC group had atherosclerotic lesions while none of the sections of the aortic arch from the NC and HCC groups had lesions present. Inferentially, regular and voluntary consumption of NCP during pregnancy may inhibit aortic atherogenesis in offspring of hypercholesterolaemic mothers.

The molecular and cellular signatures of the mouse eminentia thalami support its role as a signalling centre in the developing forebrain.

The mammalian eminentia thalami (EmT) (or thalamic eminence) is an embryonic forebrain structure of unknown function. Here, we examined the molecular and cellular properties of the mouse EmT. We first studied mRNA expression of signalling molecules and found that the EmT is a structure, rich in expression of secreted factors, with Wnts being the most abundantly detected. We then examined whether EmT tissue could induce cell fate changes when grafted ectopically. For this, we transplanted EmT tissue from a tau-GFP mouse to the ventral telencephalon of a wild type host, a telencephalic region where Wnt signalling is not normally active but which we showed in culture experiments is competent to respond to Wnts. We observed that the EmT was able to induce in adjacent ventral telencephalic cells ectopic expression of Lef1, a transcriptional activator and a target gene of the Wnt/ß-catenin pathway. These Lef1-positive;GFP-negative cells expressed the telencephalic marker Foxg1 but not Ascl1, which is normally expressed by ventral telencephalic cells. These results suggest that the EmT has the capacity to activate Wnt/ß-catenin signalling in the ventral telencephalon and to suppress ventral telencephalic gene expression. Altogether, our data support a role of the EmT as a signalling centre in the developing mouse forebrain.