Cardiovascular physical examination as a screening tool for congenital heart disease in newborns at a teaching hospital in Ghana.

Objectives: To determine the usefulness of cardiovascular physical examination (CPE) as a screening tool in a low-resource setting for detecting congenital heart disease (CHD) in newborns delivered at the Maternity Unit of Korle Bu Teaching Hospital (KBTH), Accra, Ghana. Design: A hospital-based cross-sectional study with a comparison group component. Setting: Maternity Unit of the KBTH, Accra, Ghana. Participants: Over eight months, newborns aged 1-14 days delivered at ≥ 34 weeks' gestation at the Maternity Unit, KBTH, were recruited into the study. Intervention: Each newborn was examined using a set of CPE parameters for the presence of congenital heart disease. Those with suggestive features of CHD had a confirmatory echocardiogram test. Main Outcome Measure: Abnormal CPE features and their corresponding echocardiogram findings. Results: A total of 1607 were screened, with 52 newborns showing signs of CHD on CPE, of which 20 newborns were proven on echocardiogram to have congenital heart disease. Abnormal CPE parameter that was associated with CHD was murmur (P=0.001), dysmorphism (p=0.01), newborns with chest recessions (p=0.01) and lethargy (p=0.02). CPE's sensitivity, specificity, and positive and negative predictive values were 95%, 60.7%, 36.5% and 98,1%, respectively. The most common acyanotic CHD found was isolated atrial septal defect (ASD), followed by patent ductus arteriosus (PDA). The only cyanotic CHD found was a case of tricuspid atresia. Conclusion: Cardiovascular physical examination at birth is an effective and inexpensive screening tool for detecting CHD in newborns, which can easily be utilised in low-resource settings. Funding: None declared.

Cardiovascular physical examination as a screening tool for congenital heart disease in newborns at a teaching hospital in Ghana

Objectives: To determine the usefulness of cardiovascular physical examination (CPE) as a screening tool in a lowresource setting for detecting congenital heart disease (CHD) in newborns delivered at the Maternity Unit of Korle Bu Teaching Hospital (KBTH), Accra, Ghana. Design: A hospital-based cross-sectional study with a comparison group component. Setting: Maternity Unit of the KBTH, Accra, Ghana. Participants: Over eight months, newborns aged 1-14 days delivered at ≥ 34 weeks' gestation at the Maternity Unit, KBTH, were recruited into the study. Intervention: Each newborn was examined using a set of CPE parameters for the presence of congenital heart disease. Those with suggestive features of CHD had a confirmatory echocardiogram test. Main Outcome Measure: Abnormal CPE features and their corresponding echocardiogram findings. Results: A total of 1607 were screened, with 52 newborns showing signs of CHD on CPE, of which 20 newborns were proven on echocardiogram to have congenital heart disease. Abnormal CPE parameter that was associated with CHD was murmur (P=0.001), dysmorphism (p=0.01), newborns with chest recessions (p=0.01) and lethargy (p=0.02). CPE's sensitivity, specificity, and positive and negative predictive values were 95%, 60.7%, 36.5% and 98,1%, respectively. The most common acyanotic CHD found was isolated atrial septal defect (ASD), followed by patent ductus arteriosus (PDA). The only cyanotic CHD found was a case of tricuspid atresia. Conclusion: Cardiovascular physical examination at birth is an effective and inexpensive screening tool for detecting CHD in newborns, which can easily be utilised in low-resource settings.

Rubella virus IgM and IgG antibodies with avidity in pregnant women and outcomes at a tertiary facility in Ghana.

BACKGROUND: Congenital rubella syndrome (CRS) is a recognised cause of childhood deafness and blindness caused by the transplacental transmission of rubella virus during pregnancy. Women in the reproductive age group, and by extension their unborn babies may therefore be at increased risk. The prevalence of Rubella virus specific IgM and IgG antibodies, including IgG avidity, was determined in pregnant women attending the antenatal clinic at a Teaching Hospital in Ghana. METHODS: One hundred and forty-five women in their second and third trimesters of pregnancy from the outpatient clinic were recruited over a period of 2 months after written informed consent was obtained. Study participants completed a questionnaire and venous blood drawn for IgM, IgG, and avidity testing using SERION ELISA (SERION® Immunologics, Würzburg, Germany). Babies of mothers with positive or indeterminate IgM and low avidity IgG antibodies were offered specialist cardiological, ophthalmological or hearing assessment during follow up. RESULTS: One hundred and twenty-eight (88.3%) had only IgG antibodies, 5 (3.4%) had IgM and IgG antibodies, while 12 (8.3%) had no antibodies. No patient had IgM antibodies alone. Ten women (6.9%) had indeterminate levels of IgM antibodies. Majority of the women had high avidity IgG antibodies, while 5 (3.4%) had low avidity antibodies. No patient had IgM with low avidity antibodies. There was no statistical association between socio-demographic factors and the presence of IgM, IgG (low or high avidity) antibodies. Of all the children followed, none had the clinical definition of CRS. CONCLUSIONS: Consistent with the World Health Organization elimination strategy for measles and rubella viruses, non-immune women in the reproductive age group should be vaccinated. The immunization programme should be expanded to include teenagers and adults. Though Congenital Rubella Syndrome was not detected, the risk still remains.

Management of Hypoplastic Left Heart Syndrome in Low-Resource Settings and the Ethics of Decision-Making.

Hypoplastic left heart syndrome (HLHS) is possibly the most challenging congenital heart defect to confront in any setting. The highly specialized infrastructure and resources needed to treat HLHS is not available in many low-resource settings. However, low-resource settings must not be assumed to be synonymous with low- and middle-income countries as national income is not necessarily indicative of a country's prioritization of healthcare resources. Besides, a low-resource setting may be institution-specific as well as country-specific. We have stratified institutional capabilities for addressing the requirements of treatment for HLHS into five levels based on the capacity for diagnosis, intervention, and post-discharge monitoring. Depending on institutional capabilities, children born with HLHS in low-resource settings experience a spectrum of outcomes ranging from death without diagnosis to the hybrid or Norwood stage 1 palliation. The decision-making is ethically challenging when resources are scarce and economic efficiency must be considered in the context of distributive justice. Even in settings that would be classified as resource-rich where survival after surgery and quality of life afterward keep improving, not every parent would choose surgical intervention for their hypothetical child with HLHS.

Synchronous Signal Transmission Method of Minimally Invasive Renal Failure Surgery Based on Nano Molecular Image Probe.

The synchronous signal transmission can promote the successful completion of minimally invasive renal failure surgery, so the synchronous signal transmission method of minimally invasive renal failure surgery based on nano molecular image probe is studied. The nanoprobe is constructed by loading different signal molecules, photosensitizers, acoustic sensitizers and thermosensitives through the method of double emulsion or film hydration; the near-infrared confocal endoscope molecular image diagnosis and treatment equipment is designed based on the nanoprobe, and the intraoperative highfrequency image is obtained through the diagnosis and treatment equipment; the high-frequency injection energy and signal synchronous transmission method is adopted, and the signal is added to the primary and secondary resonance circuit. In the coupling module, a higher frequency alternating signal is added into the resonant coupling voltage to modulate the signal into the transmission resonance system, which is transmitted from the energy transmission coupling coil to the secondary end, and the injected signal part of the coupling coil is demodulated at the other end to complete the transmission of the signal coupling transmission loop, so as to realize the high-frequency image energy and index data signal of minimally invasive renal failure surgery. The experimental results show that the designed nano molecular image probe has good stability, and the simulated signal transmission waveform is consistent with the transmission waveform of the principle analysis. Applying the proposed method to the minimally invasive surgery of renal failure, it is found that the success rate and image signal transmission efficiency of the minimally invasive surgery of patients 1-5 are higher than 99.5%, and the operation image transmission accuracy is high and the operation effect is excellent.

Circ_0005875 sponges miR-502-5p to promote renal cell carcinoma progression through upregulating E26 transformation specific-1.

Increasing evidence has shown that circular RNAs (circRNAs) play critical roles in various cancers, including renal cell carcinoma (RCC). We aimed to explore the role and underlying mechanism of circ_0005875 in RCC. The expression levels of circ_0005875, microRNA-502-5p (miR-502-5p) and E26 transformation specific-1 (ETS1) mRNA were determined by quantitative real-time PCR. Cell proliferation was assessed by Cell Counting Kit-8, colony formation, and 5-Ethynyl-2'-deoxyuridine (EdU) assays. Cell migration and invasion were monitored by wound healing assay and transwell assay, respectively. Flow cytometry analysis was applied to determine cell apoptosis and cell cycle distribution. Western blot assay was performed to measure the protein expression of CyclinD1 and ETS1. The interaction between miR-502-5p and circ_0005875 or ETS1 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. A xenograft tumor model was established to confirm the role of circ_0005875 in vivo. Circ_0005875 and ETS1 were upregulated and miR-502-5p was downregulated in RCC tissues and cells. Knockdown of circ_0005875 suppressed RCC cell proliferation, migration and invasion, and induced apoptosis and cell cycle arrest. MiR-502-5p was a target of circ_0005875, and miR-502-5p inhibition reversed the inhibitory effects of circ_0005875 knockdown on the malignant behaviors of RCC cells. ETS1 was a direct target of miR-502-5p, and miR-502-5p exerted its anti-tumor role in RCC cells by targeting ETS1. Moreover, circ_0005875 knockdown decreased ETS1 expression by sponging miR-502-5p. Additionally, circ_0005875 depletion suppressed tumor growth in vivo. Circ_0005875 knockdown suppressed RCC progression by regulating miR-502-5p/ETS1 axis, which might provide a promising therapeutic target for RCC.

Delivering pediatric cardiac care in sub-Saharan Africa: a model for the developing countries.

PURPOSE OF REVIEW: It is projected that by 2050, around 40% of all births, and about 40% of all children, will be in Africa, up from about 10% in 1950. Consequently, this trend will cause an increase in noncommunicable diseases in children, such as congenital and rheumatic heart diseases. The current state of pediatric cardiac care in sub-Saharan Africa is dire with some countries without cardiac surgical services at all. The purpose of this review is to highlight those components needed to build a sustainable model for a pediatric cardiac care center in sub-Saharan Africa. RECENT FINDINGS: Review of the literature reveals that capacity-building for pediatric cardiac care in sub-Saharan Africa can be a challenging entity. Several factors must come into play to lay the foundation for a successful cardiac program. Key among them are early diagnosis of heart disease, human resources, financing cardiac care, and political commitment. SUMMARY: The burgeoning pediatric population in sub-Saharan African lends itself to an increase in the incidence of pediatric heart disease. The need for sustainable, patient-centered cardiac centers is pressing. Establishing such pediatric cardiac care models will require the essential components of early diagnosis, increasing human resources, financing cardiac care, and political commitment. VIDEO ABSTRACT: http://links.lww.com/HCO/A59.

Morphine Stimulates Migration and Growth and Alleviates the Effects of Chemo Drugs via AMPK-Dependent Induction of Epithelial-Mesenchymal Transition in Esophageal Carcinoma Cells.

The role of morphine, an opioid analgesic drug, in cancer biology has increasingly garnered attention due to its frequent usage in postoperative period for pain management in cancer patients. In this work, we demonstrated that morphine, at clinically relevant concentrations, stimulated migration and growth, and alleviated chemo drugs' efficacy in esophageal carcinoma cells. Although morphine did not affect survival, it protected esophageal carcinoma cells from chemo drugs-induced apoptosis. Mechanistical studies showed that morphine increased RhoA but not Rac1 activity. In addition, morphine activated AMP-activated protein kinase (AMPK) pathway, induced epithelial-mesenchymal transition (EMT) via upregulating Snail and Slug levels, and increased oxidative stress in esophageal carcinoma cells. Rescue studies further demonstrated that the stimulatory effects of morphine in esophageal carcinoma cells are through activation of AMPK pathway but not RhoA or opioid receptor. In addition, morphine induced EMT in an AMPK-dependent manner whereas increased RhoA activity in an AMPK-independent manner. Our work demonstrates the protective role of morphine on esophageal carcinoma cells via AMPK activation, which may provide a new guide in clinical use of morphine for patients with esophageal carcinoma.

Challenges of Caring for Functionally Single Ventricle Patients in Africa.

Surgical palliation has remarkably improved survival of functionally single ventricle (FSV) patients born in developed nations but such outcomes have not occurred in Africa. The poor care coverage for FSV patients in Africa exists within the larger sphere of deficient health care for children born with congenital heart defects (CHDs) in Africa generally. This review takes the position that to improve health-care coverage for CHD patients on the continent, political priority is paramount. This can be attained with cohesive leadership for the CHD agenda, a guiding institution, and the mobilization of civil society to drive advocacy at national and international levels.

Genomics and Epigenomics of Congenital Heart Defects: Expert Review and Lessons Learned in Africa.

Congenital heart defects (CHD) are structural malformations found at birth with a prevalence of 1%. The clinical trajectory of CHD is highly variable and thus in need of robust diagnostics and therapeutics. Major surgical interventions are often required for most CHDs. In Africa, despite advances in life sciences infrastructure and improving education of medical scholars, the limited clinical data suggest that CHD detection and correction are still not at par with the rest of the world. But the toll and genetics of CHDs in Africa has seldom been systematically investigated. We present an expert review on CHD with lessons learned on Africa. We found variable CHD phenotype prevalence in Africa across countries and populations. There are important gaps and paucity in genomic studies of CHD in African populations. Among the available genomic studies, the key findings in Africa were variants in GATA4 (P193H), MTHFR 677TT, and MTHFR 1298CC that were associated with atrial septal defect, ventricular septal defect (VSD), Tetralogy of Fallot (TOF), and patent ductus arteriosus phenotypes and 22q.11 deletion, which is associated with TOF. There were no data on epigenomic association of CHD in Africa, however, other studies have shown an altered expression of miR-421 and miR-1233-3p to be associated with TOF and hypermethylation of CpG islands in the promoter of SCO2 gene also been associated with TOF and VSD in children with non-syndromic CHD. These findings signal the urgent need to develop and implement genetic and genomic research on CHD to identify the hereditary and genome-environment interactions contributing to CHD. These projected studies would also offer comparisons on CHD pathophysiology between African and other populations worldwide. Genomic research on CHD in Africa should be developed in parallel with next generation technology policy research and responsible innovation frameworks that examine the social and political factors that shape the emergence and societal embedding of new technologies.

Conotruncal Heart Defect Repair in Sub-Saharan Africa: Remarkable Outcomes Despite Poor Access to Treatment.

BACKGROUND: The outcome of children born with conotruncal heart defects may serve as an indication of the status of pediatric cardiac care in sub-Saharan Africa (SSA). This study was undertaken to determine the outcome of children born with conotruncal anomalies in SSA, regarding access to treatment and outcomes of surgical intervention. METHODS: From our institution in Ghana, we retrospectively analyzed the outcomes of surgery, in the two-year period from June 2013 to May 2015. The birth prevalence of congenital heart defects (CHDs) in SSA countries was derived by extrapolation using an incidence of 8 per 1,000 live births for CHDs. RESULTS: The birth prevalence of CHDs for the 48 countries in SSA using 2013 country data was 258,875; 10% of these are presumed to be conotruncal anomalies. Six countries (Nigeria, Democratic Republic of the Congo, Ethiopia, Tanzania, Uganda, and Kenya) accounted for 53.5% of the birth prevalence. In Ghana, 20 patients (tetralogy of Fallot [TOF], 17; pulmonary atresia, 3) underwent palliation and 50 (TOF, 36; double-outlet right ventricle, 14) underwent repair. Hospital mortality was 0% for palliation and 4% for repair. Only 6 (0.5%) of the expected 1,234 cases of conotruncal defects underwent palliation or repair within two years of birth. CONCLUSION: Six countries in SSA account for more than 50% of the CHD burden. Access to treatment within two years of birth is probably <1%. The experience from Ghana demonstrates that remarkable surgical outcomes are achievable in low- to middle-income countries of SSA.

Enzymatic production of HMO mimics by the sialylation of galacto-oligosaccharides.

Human milk oligosaccharides (HMOs) are a family of structurally diverse unconjugated glycans that exhibit a wide range of biological activities. In this report, we describe an efficient, Multi-Enzyme One-Pot strategy to produce HMO mimics by the sialylation of galacto-oligosaccharides (GOSs), which are often added to infant formula as an inexpensive alternative to HMOs. In this system, the sialyltransferase donor, cytidine-5'-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac), was generated in situ using a CMP-sialic acid synthetase. The sialylated GOSs were obtained by one-step purification after digesting CMP using the alkaline phosphatase PhoA to cytidine and inorganic phosphate. Although the synthesized α2,3-, α2,6- and α2,3/8-sialyl-GOSs exhibit different sialylation levels and patterns, all of these mixtures can be fermented by Bifidobacterium longum subsp. infantis ATCC 15697 but not by Bifidobacterium adolescentis ATCC 15703. The sialidase NanH2, which is unique to the former strain, hydrolyzed all of the synthesized HMO mimics.

A novel mechanism of protein thermostability: a unique N-terminal domain confers heat resistance to Fe/Mn-SODs.

Superoxide dismutases (SODs), especially thermostable SODs, are widely applied in medical treatments, cosmetics, food, agriculture, and other industries given their excellent antioxidant properties. A novel thermostable cambialistic SOD from Geobacillus thermodenitrificans NG80-2 exhibits maximum activity at 70 °C and high thermostability over a broad range of temperatures (20-80 °C). Unlike other reported SODs, this enzyme contains an extra repeat-containing N-terminal domain (NTD) of 244 residues adjacent to the conserved functional SODA domain. Deletion of the NTD dramatically decreased its optimum active temperature (OAT) to 30 °C and also impaired its thermostability. Conversely, appending the NTD to a mesophilic counterpart from Bacillus subtilis led to a moderately thermophilic enzyme (OAT changed from 30 to 55 °C) with improved heat resistance. Temperature-dependant circular dichroism analysis revealed the enhanced conformational stability of SODs fused with this NTD. Furthermore, the NTD also contributes to the stress resistance of host proteins without altering their metal ion specificity or oligomerisation form except for a slight effect on their pH profile. We therefore demonstrate that the NTD confers outstanding thermostability to the host protein. To our knowledge, this is the first discovery of a peptide capable of remarkably improving protein thermostability and provides a novel strategy for bioengineering thermostable SODs.

Strictly-posterior thoracotomy: a minimal-access approach for construction of the modified Blalock-Taussig shunt in West African children.

INTRODUCTION: In resource-poor settings, the modified Blalock-Taussig shunt (MBTS) is often performed for symptomatic relief of Fallot's tetralogy. From September 2011, we adopted the strictly posterior thoracotomy (SPOT), a minimal-access technique for the MBTS and report the cosmetic advantages in this communication. METHODS: We retrospectively analyzed the records of consecutive patients in whom the SPOT approach was used to construct the MBTS. Study end-points were early mortality, improvement in peripheral oxygenation, morbidity, and the cosmetic appeal. RESULTS: Between September 2011 and January 2013, 15 males and 8 females, median age 4 years (1.3 - 17 years) and weight 13 kg (11 - 54 kg) underwent the MBTS through the SPOT approach. The polytetrafluoroethylene grafts used ranged from sizes 4 - 6mm (median 5mm). The median preoperative SpO2 was 74% (55% - 78%), increasing to a postoperative median value of 84% (80% - 92%). Shunts were right-sided in 22 patients and left-sided in one. There were no shunt failures. Hospital stay ranged from 7 - 10 days. There was one early death (4.3%), and two postoperative complications (re-exploration for bleeding and readmission for drainage of pleural effusion). The surgical scars had excellent cosmetic appeal: they ranged from 5-10 cm in length; all were entirely posterior and imperceptible to the patient. CONCLUSION: The SPOT approach represents a safe and cosmetically superior alternative to the standard posterolateral thoracotomy, the scar being imperceptible to the patient. The excellent cosmetic appeal and preservation of body image makes this approach particularly attractive in children and young adults.

Genome Sequence of a Thermophilic Bacillus, Geobacillus thermodenitrificans DSM465.

Geobacillus thermodenitrificans NG80-2 encodes a LadA-mediated alkane degradation pathway, while G. thermodenitrificans DSM465 cannot utilize alkanes. Here, we report the draft genome sequence of G. thermodenitrificans DSM465, which may help reveal the genomic differences between these two strains in regards to the biodegradation of alkanes.

Mediastinal and neck kaposiform hemangioendothelioma: report of three cases.

Kaposiform hemangioendothelioma is an aggressive vascular tumor, named for its striking histologic resemblance to Kaposi sarcoma and locally invasive growth. Mortality is high, and ranges from 10% to 24% for all kaposiform hemangioendothelioma lesions, with a significantly higher mortality for deep soft-tissue or visceral lesions occurring in infants less than 6 months. Mediastinal and neck kaposiform hemangioendothelioma in particular merit special discussion, as involvement of these critical anatomic locations results in significant site-specific therapeutic challenges due to invasion of vital structures, inherent delays in establishing histopathologic confirmation, and difficulties in monitoring disease status. We report our experience with three cases of mediastinal and neck kaposiform hemangioendothelioma, emphasizing the unique diagnostic and management challenges, variable response to treatment and outcome of this anatomic variant of kaposiform hemangioendothelioma.