Performance of testers with contrasting provitamin A content to evaluate provitamin A maize for resistance to Aspergillus flavus infection and aflatoxin production.

In sub-Saharan Africa (SSA), millions of people depend on maize as a primary staple. However, maize consumers in SSA may be exposed to malnutrition due to vitamin A deficiency (VAD) and unsafe aflatoxin levels, which can lead to serious economic and public health problems. Provitamin A (PVA) biofortified maize has been developed to alleviate VAD and may have additional benefits such as reduced aflatoxin contamination. In this study, maize inbred testers with contrasting PVA content in grain were used to identify inbred lines with desirable combining ability for breeding to enhance their level of resistance to aflatoxin. Kernels of 120 PVA hybrids generated by crossing 60 PVA inbreds with varying levels of PVA (5.4 to 51.7 µg/g) and two testers (low and high PVA, 14.4 and 25.0 µg/g, respectively) were inoculated with a highly toxigenic strain of Aspergillus flavus. Aflatoxin had a negative genetic correlation with ß-carotene (r = -0.29, p < 0.0001) and PVA (r = -0.23, p < 0.0001), indicating that hybrids with high PVA content accumulated less aflatoxin than those with low to medium PVA. Both general combining ability (GCA) and specific combining ability (SCA) effects of lines and testers were significant for aflatoxin accumulation, number of spores, PVA, and other carotenoids, with additive gene actions playing a prominent role in regulating the mode of inheritance (GCA/SCA ratio >0.5). Eight inbreds had combined significant negative GCA effects for aflatoxin accumulation and spore count with significant positive GCA effects for PVA. Five testcrosses had combined significant negative SCA effects for aflatoxin with significant positive SCA effects for PVA. The high PVA tester had significant negative GCA effects for aflatoxin, lutein, ß-carotene, and PVA. The study identified lines that can be used as parents to develop superior hybrids with high PVA and reduced aflatoxin accumulation. Overall, the results point out the importance of testers in maize breeding programs to develop materials that can contribute to controlling aflatoxin contamination and reducing VAD.

Fetal glycated albumin levels in offspring of obese women.

OBJECTIVE: To determine the association between maternal obesity and fetal glycated albumin (GA) levels among pregnant women. METHODS: A comparative, cross-sectional study of 59 consenting, normoglycemic, pregnant women, who met the criteria for maternal obesity, attending the antenatal clinic of the University College Hospital, Nigeria, from June 2019 to December 2019. They were recruited at 36 weeks of gestation, followed up until delivery, and compared with 58 nonobese, normoglycemic pregnant controls. At delivery, blood samples were taken from the mothers and from the umbilical cords of their newborns for serum GA assay. Maternal and newborn variables were recorded, and comparisons were made using χ2 tests, independent t tests, odds ratios, analysis of variance, and Pearson correlates. Statistical significance was set at P < 0.05. RESULTS: The odds of elevated newborn GA were 3.21 times higher in obese women compared with nonobese women (P = 0.005) and 5-min APGAR scores were higher in the newborns of nonobese women (P = 0.039). There was a significant correlation between maternal and neonatal GA for all participants (r = 0.346, P = 0.000). CONCLUSION: These findings suggest that maternal obesity is associated with elevated fetal GA and low APGAR scores at 5 min in normoglycemic women.

Appropriate use of plasma glucose tests for diagnosis of diabetes mellitus in Ibadan, Nigeria.

Background: Diabetes mellitus is a growing epidemic in Africa. Its diagnosis relies exclusively on laboratory evidence, which differs based on clinical circumstances. Objective: The study described the appropriateness of plasma glucose test requests per the American Diabetes Association criteria. Methods: We reviewed the plasma glucose test requests received by the chemical pathology laboratory of the University College Hospital, Ibadan, Nigeria between June 2018 and November 2018. The American Diabetes Association diabetes diagnostic criteria were used to define the appropriateness of test requests and determine the potential for ill-informed clinical decisions. Results: Four hundred and twenty-three requisition forms were included, with the majority from the medical wards/clinics (72.3%); the most frequent reason for a plasma glucose test was systemic hypertension (28.6%). Fasting plasma glucose was most requested (254; 60.0%). One hundred and sixteen (27.4%) requests were potentially inappropriate, with the 2-h postprandial plasma glucose (2hPPG) test requests (83; 71.6%) being the most inappropriate. The difference in the proportion of inappropriate requests was not statistically significantly between medical or surgical wards/clinics (Odds ratio 1.131, 95% confidence interval 0.709-1.803, p = 0.605). Inappropriate requests in six cases may have triggered inappropriate action. Conclusion: A third of the glucose tests requested for querying diabetes mellitus may have been inappropriate. Results of such testing may trigger inappropriate clinical action. To improve the quality of care and for economic reasons, laboratories should have programmes to improve the appropriate use of their services.

Flexibility of in vitro cortical circuits influences resilience from microtrauma.

Background: Small clusters comprising hundreds to thousands of neurons are an important level of brain architecture that correlates single neuronal properties to fulfill brain function, but the specific mechanisms through which this scaling occurs are not well understood. In this study, we developed an in vitro experimental platform of small neuronal circuits (islands) to probe the importance of structural properties for their development, physiology, and response to microtrauma. Methods: Primary cortical neurons were plated on a substrate patterned to promote attachment in clusters of hundreds of cells (islands), transduced with GCaMP6f, allowed to mature until 10-13 days in vitro (DIV), and monitored with Ca2+ as a non-invasive proxy for electrical activity. We adjusted two structural factors-island size and cellular density-to evaluate their role in guiding spontaneous activity and network formation in neuronal islands. Results: We found cellular density, but not island size, regulates of circuit activity and network function in this system. Low cellular density islands can achieve many states of activity, while high cellular density biases islands towards a limited regime characterized by low rates of activity and high synchronization, a property we summarized as "flexibility." The injury severity required for an island to lose activity in 50% of its population was significantly higher in low-density, high flexibility islands. Conclusion: Together, these studies demonstrate flexible living cortical circuits are more resilient to microtrauma, providing the first evidence that initial circuit state may be a key factor to consider when evaluating the consequences of trauma to the cortex.

Access to pathology and laboratory medicine services: a crucial gap.

As global efforts accelerate to implement the Sustainable Development Goals and, in particular, universal health coverage, access to high-quality and timely pathology and laboratory medicine (PALM) services will be needed to support health-care systems that are tasked with achieving these goals. This access will be most challenging to achieve in low-income and middle-income countries (LMICs), which have a disproportionately large share of the global burden of disease but a disproportionately low share of global health-care resources, particularly PALM services. In this first in a Series of three papers on PALM in LMICs, we describe the crucial and central roles of PALM services in the accurate diagnosis and detection of disease, informing prognosis and guiding treatment, contributing to disease screening, public health surveillance and disease registries, and supporting medical-legal systems. We also describe how, even though data are sparse, these services are of both insufficient scope and inadequate quality to play their key role in health-care systems in LMICs. Lastly, we identify four key barriers to the provision of optimal PALM services in resource-limited settings: insufficient human resources or workforce capacity, inadequate education and training, inadequate infrastructure, and insufficient quality, standards, and accreditation.

Delivering modern, high-quality, affordable pathology and laboratory medicine to low-income and middle-income countries: a call to action.

Modern, affordable pathology and laboratory medicine (PALM) systems are essential to achieve the 2030 Sustainable Development Goals for health in low-income and middle-income countries (LMICs). In this last in a Series of three papers about PALM in LMICs, we discuss the policy environment and emphasise three crucial high-level actions that are needed to deliver universal health coverage. First, nations need national strategic laboratory plans; second, these plans require adequate financing for implementation; and last, pathologists themselves need to take on leadership roles to advocate for the centrality of PALM to achieve the Sustainable Development Goals for health. The national strategic laboratory plan should deliver a tiered, networked laboratory system as a central element. Appropriate financing should be provided, at a level of at least 4% of health expenditure. Financing of new technologies such as molecular diagnostics is challenging for LMICs, even though many of these tests are cost-effective. Point-of-care testing can substantially reduce test-reporting time, but this benefit must be balanced with higher costs. Our research analysis highlights a considerable deficiency in advocacy for PALM; pathologists have been invisible in national and international health discourse and leadership. Embedding PALM in LMICs can only be achieved if pathologists advocate for these services, and undertake leadership roles, both nationally and internationally. We articulate eight key recommendations to address the current barriers identified in this Series and issue a call to action for all stakeholders to come together in a global alliance to ensure the effective provision of PALM services in resource-limited settings.

Demographic and epidemiological characteristics of HIV opportunistic infections among older adults in Nigeria.

BACKGROUND: In view of the maturing HIV epidemic in sub-Saharan Africa, better understanding of its epidemiology among older adults is necessary in order to design appropriate care and treatment programmes for them. OBJECTIVES: To describe the demographic and epidemiological characteristics of HIV opportunistic infections among newly enrolled patients aged 50 years and above in Ibadan, South-West Nigeria. METHODS: Analysis of data extracted from electronic records of 17, 312 subjects enrolled for HIV/AIDS care and treatment between January 2006 and December 2014 at the ART clinic, University College Hospital, Ibadan. RESULTS: Age of the patients ranged from 18 to 90 years with a mean of 36.4 years (SD= 10.3) with older adults constituting 12.0% (2075). Among older adults, about half (52.9%) were females. Majority (59.1%) were currently married while 25.9% were widowed. Prevalence of opportunistic infections was 46.6%. The commonest opportunistic infections (OIs) were: oral candidiasis (27.6%), chronic diarrhoea (23.5% and peripheral neuropathy (14.8%). Significant factors associated with opportunistic infections in older adults were: CD4 count less than 350 (OR=3.12, CI: 2.29-4.25) and hepatitis C virus co-infection (OR=2.17, CI: 1.14-4.13). CONCLUSION: There is need for prompt response to the peculiar challenges associated with the emerging shift in the epidemiology of HIV and associated infections in sub-Saharan Africa.

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant.

The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.

Analysis of human breath samples using a modified thermal desorption: gas chromatography electrospray ionization interface.

A two-stage thermal desorption/secondary electrospray ionization/time-of-flight mass spectrometry for faster targeted breath profiling has been studied. A new secondary electrospray ionization (SESI) source was devised to constrain the thermal desorption plume and promote efficient mixing in the ionization region. Further, a chromatographic pre-separation stage was introduced to suppress interferences from siloxanes associated with thermal desorption profiles of exhaled breath samples.In vitro tests with 5-nonanone indicated an increased sensitivity and a lowered limit-of-detection, both by a factor of ~4, the latter to an on-trap mass of 14.3 ng, equivalent to a sampled breath concentration of 967 pptv. Analysis of the mass spectrometric responses from 20 breath samples acquired sequentially from a single participant indicated enhanced reproducibility (reduced relative standard deviations (RSD) for 5-nonanone, benzaldehyde and 2-butanone were 28 %, 16% and 14% respectively. The corresponding values for an open SESI source were that 5-nonanone was not detected, with %RSD of 39% for benzaldehyde and 31% for 2-butanone).The constrained source with chromatographic pre-separation resulted in an increase in the number of detectable volatile organic compounds (VOCs) from 260 mass spectral peaks with an open SESI source to 541 peaks with the constrained source with pre-separation. Most of the observed VOCs were present at trace levels, at less than 2.5% of the intensity of the base peak.Seventeen 2.5 dm(3) distal breath samples were collected from asthma patients and healthy controls respectively, and subjected to comparative high-throughput screening using thermal desorption/SESI/time-of-flight mass spectrometry (TD-SESI-ToFMS). Breath metabolites were detected by using a background siloxane ion (hexamethylcyclotrisiloxane m/z 223.0642) as an internal lockmass. Eleven breath metabolites were selected from the breath research literature and successfully targeted. These data reinforce the proposition that TD-SESI-MS has potential for development as a rapid screening method for disease stratification and targeted metabolism profiling.

Physicians utilisation of internet medical databases at the tertiary health institutions in Osun State, south west, Nigeria.

OBJECTIVES: To determine the extent, purpose, determinants and the impact of the utilization of Internet medical databases among the respondents. METHODOLOGY: A descriptive cross sectional survey of 540 randomly selected physicians at the two tertiary health institutions in Osun State, south west, Nigeria. RESULT: A total of 444 (82.2%) physicians completed the questionnaires. All the respondents have used the internet medical databases within the last 4 weeks of the study. Majority, (53.8%) used the internet resources at least once in 2 weeks, while 12.2% used the resources every day. The online resources are mainly sought for Routine patient care and for Research purposes. pubmed (70.3%), hinari (69.0%), and Free medical journals (60.1%) are the frequently used online databases/digital archives. The internet resources has positively impacted the Clinical practice (40.0%) and Research output (65.5%) of the physicians. CONCLUSION: There had been considerable increase in the extent and quality of utilization of online medical databases which has positively impacted on the Clinical practice and Research output of the physicians. Ease of finding the needed information and the availability of evidence based resources are the major determinants of the databases utilized.