BACKGROUND
Annually 125 million pregnancies are at risk of malaria infection. However, the impact of exposure to malaria in pregnancy on neurodevelopment in children is not well understood. We hypothesized that malaria in pregnancy and associated maternal immune activation result in neurodevelopmental delay in exposed offspring.

METHODS AND FINDINGS
Between April 2014 and April 2015, we followed 421 Malawian mother-baby dyads (median [IQR] maternal age: 21 [19, 28] years) who were previously enrolled (median [IQR] gestational age at enrollment: 19.7 [17.9, 22.1] weeks) in a randomized controlled malaria prevention trial with 5 or 6 scheduled assessments of antenatal malaria infection by PCR. Children were evaluated at 12, 18, and/or 24 months of age with cognitive tests previously validated in Malawi: the Malawi Developmental Assessment Tool (MDAT) and the MacArthur-Bates Communicative Development Inventories (MCAB-CDI). We assessed the impact of antenatal malaria (n [%] positive: 240 [57.3]), placental malaria (n [%] positive: 112 [29.6]), and maternal immune activation on neurocognitive development in children. Linear mixed-effects analysis showed that children exposed to antenatal malaria between 33 and 37 weeks gestation had delayed language development across the 2-year follow-up, as measured by MCAB-CDI (adjusted beta estimate [95% CI], -7.53 [-13.04, -2.02], p = 0.008). Maternal immune activation, characterized by increased maternal sTNFRII concentration, between 33 and 37 weeks was associated with lower MCAB-CDI language score (adjusted beta estimate [95% CI], -8.57 [-13.09, -4.06], p < 0.001). Main limitations of this study include a relatively short length of follow-up and a potential for residual confounding that is characteristic of observational studies.

CONCLUSIONS
This mother-baby cohort presents evidence of a relationship between malaria in pregnancy and neurodevelopmental delay in offspring. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental injury independent of birth weight or prematurity. Successful interventions to prevent malaria during pregnancy may reduce the risk of neurocognitive delay in children.

/pdf/neurocognitive-outcomes-in-malawian-children-exposed-to-cl3mm524fk.pdf

Neurocognitive outcomes in Malawian children exposed to malaria during pregnancy: An observational birth cohort study.

Pancreatic cancer remains the third leading cause of death amongst men and women in the United States. Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer maintains its reputation of being the most aggressive with a poor prognosis. One of the contributing factors to the high mortality of PDAC is the absence of biomarkers for early detection of disease and the complexity of tumor biology and genomics. In this review, we explored the current understanding of epigenetics and diagnostic biomarkers in PDAC and summarized recent advances in molecular biology. We discussed current guidelines on diagnosis, prognosis, and treatment, especially in high-risk individuals. We also reviewed studies that have touched on identifying biomarkers and the role they play in making early diagnosis although there are currently no screening tools for PDAC. We explored the recent understanding of epigenetic alterations of PDAC and the future implications for early detection and prognosis. In conclusion, the new and emerging advances in the detection and treatment of PDAC can lead to an improvement in the current outcome of PDAC.

/pdf/molecular-markers-of-pancreatic-cancer-a-10-year-3m6elki7.pdf

Molecular Markers of Pancreatic Cancer: A 10-Year Retrospective Review of Molecular Advances

The incidence of childhood obesity has received a lot of attention lately, especially in the United States. The increased prevalence of pediatric obesity and its association with comorbidities has piqued the attention of more scientists in the epidemic's patterns. Our research examined the National (Nationwide) Inpatient Sample (NIS) data set for hospitalized persons aged 18 years or younger with primary or secondary obesity between 2016 and 2019 to investigate the prevalence, risk factors, and related diseases.We retrospectively examined individuals with primary or secondary obesity from 2016 to 2019 using the NIS database. To extract the weighted samples, we utilized the International Classification of Diseases (ICD)-10 diagnostic codes E66, E660, E6601, E6609, E662, E668, and E669. Individuals with drug-related obesity or obesity caused by a recognized pathologic disease unrelated to high-calorie intake were excluded. First, we queried the total population, then separated them by age category and picked our population of interest, i.e., those aged 18 and under. The NIS is a deidentified database available to the public. It collects data on around 8 million hospitalizations annually, accounting for roughly 20% of all admissions in the United States. Results: The findings show that between 2016 and 2019, prevalence rates of childhood obesity were still on the rise and plateaued in 2019. There were 28,484,087 study subjects in this weighted sample between 2016 and 2019. Of these, 13.9% (3,946,889) were diagnosed with obesity. The sample population for those 18 years of age or under was 62,669 (1.5%) children with obesity with a mean age of 14 (SD = 4). Also, there was a 64.2% female preponderance. The obtained yearly showed a steady and significant rise from 2016 to 2018 (24% vs. 26%), with a slight decline in 2019 (25%; p < 0.001). Even though the white population had the highest overall prevalence of childhood obesity (40.9%), the Hispanic and black people had a higher prevalence per population, with a 0.5% and 0.33% prevalence, respectively, compared to 0.14% in the white population (p < 0.0001). When geographical regions were considered, south had the highest rate (36.40%), followed by the west (24.71%) and the midwest (23.56%). The analysis also showed that people with lower median household income (0-25th percentile) had the highest rate of childhood obesity (38.17%) compared to higher-income earners (13.19%).In our finding, obesity in the pediatric population is still increasing, continuing on its previously recorded trajectory. Various recommendations from health policymakers have bolstered efforts to tackle this escalating pandemic. However, additional information on the compliance, use, and adherence to these policies by healthcare professionals and members of the public, as well as the consequence of utilization or compliance to these guidelines, is needed. Nevertheless, given the continuous growth of childhood obesity, despite the avalanche of these recommendations, the issue of compliance arises, or other essential risk factors might have been overlooked. Additional studies may be needed to unmask this looming phenomenon. 

Obesity in the Pediatric Population of the National (Nationwide) Inpatient Sample (NIS), USA

Abstract Introduction Pancreatic adenocarcinoma (PDAC) has a poor prognosis since often diagnosed too late. Dyslipidemia and hyperglycemia are considered risk factors, but the presence of the tumor itself can determine the onset of these disorders. Therefore, it is not easy to predict which subjects with diabetes or dyslipidemia will develop or have already developed PDAC. Over the past decade, tests based on the use of nanotechnology, alone or coupled with common laboratory tests (e.g., hemoglobin levels), have proven useful in aiding the diagnosis of PDAC. Tests based on magnetic levitation (MagLev) have demonstrated high diagnostic accuracy in compliance with the REASSURED criteria. Here, we aimed to assess the ability of the MagLev test in detecting PDAC when coupled with the blood levels of glycemia, cholesterol, and triglycerides. Methods Blood samples from 24 PDAC patients and 22 healthy controls were collected. Human plasma was let to interact with graphene oxide (GO) nanosheets and the emerging coronated systems were put in the MagLev device. Outcomes from Maglev experiments were coupled to glycemia, cholesterol, and triglycerides levels. Linear discriminant analysis (LDA) was carried out to evaluate the classification ability of the test in terms of specificity, sensitivity, and global accuracy. Statistical analysis was performed with Matlab (MathWorks, Natick, MA, USA, Version R2022a) software. Results The positions of the levitating bands were measured at the starting point (i.e., as soon as the cuvette containing the sample was subjected to the magnetic field). Significant variations in the starting position of levitating nanosystems in controls and PDACs were detected. The combination of the MagLev outcomes with the blood glycemic levels returned the best value of global accuracy (91%) if compared to the coupling with those of cholesterol and triglycerides (global accuracy of ~ 77% and 84%, respectively). Conclusion If confirmed by further studies on larger cohorts, a multiplexed Maglev-based nanotechnology-enabled blood test could be employed as a screening tool for PDAC in populations with hyperglycemia. 

/pdf/coupling-magnetic-levitation-of-graphene-oxide-protein-3kbwxta0.pdf

Coupling magnetic levitation of graphene oxide–protein complexes with blood levels of glucose for early detection of pancreatic adenocarcinoma

Background: Literature documenting the in-hospital cardiovascular outcomes of sleep deprivation (SD) patients is scarce. We aimed to compare inpatient cardiovascular outcomes in patients with sleep deprivation and those without sleep deprivation. Method: We queried the National Inpatient Sample (NIS) database from 2016 to 2019 to conduct a retrospective observational study. Using the International Classification of Diseases, Tenth Revision (ICD-10) codes, we identified patients with sleep deprivation (SD) diagnosis and compared them to their counterparts without sleep deprivation (NSD). The cardiovascular outcomes of interest were hypertensive heart disease (HHD), atrial fibrillation (AF), and ST-segment and non-ST-segment elevation myocardial infarction (STEMI and NSTEMI, respectively). We used multivariable regression analysis to unearth the relationship between sleep deprivation and cardiovascular disease. Results: There were 28,484,087 patients admitted during the study period, among which 2.1% (6,08,059) with a mean age of 59 (sd=19) years had a sleep deprivation diagnosis unrelated to medical or psychiatric illness. Of these, 75.7% were Caucasians, 11.5% were Blacks, and 8% were Hispanics. Individuals with sleep deprivation had a higher odds ratio (OR) of HHD, i.e., OR=1.3 (1.29-1.31), p<0.0001. The odds of heart failure with reduced ejection fraction (HFrEF) was 0.9 (0.9-1.92), p=0.45; heart failure with preserved ejection fraction (HFpEF) was 0.98 (0.97-1.01), p=0.31; and the odds of the SD population for AF was 0.9 (0.89-1.03), p=0.11. Conclusion: Sleep deprivation seems to be more prevalent in the Caucasian population. Individuals with sleep deprivation have a higher risk of hypertensive heart disease but similar outcomes to the general population in terms of AF, HFrEF, and HFpEF.

/pdf/sleep-deprivation-is-associated-with-increased-risk-for-i1vm6mz0.pdf

Sleep Deprivation Is Associated With Increased Risk for Hypertensive Heart Disease: A Nationwide Population-Based Cohort Study

Hypertension is the most common modifiable risk factor for cardiovascular and cerebrovascular diseases. In the last two decades, the guidelines have evolved tremendously from areas with no recommendations for screening or treatment to targeted recommendations for some at-risk groups. We sought to go through the literature that provided guidelines for the management of hypertension at any point in time over the last 22 years from 2000 to 2022. We searched four databases: PubMed, Embase, Google Scholar, and Cochrane, using specified search terms. The keywords used were "hypertension" and "guidelines." We combined them using the Boolean operators (AND, OR) and searched for articles. A total of 2461 publications were initially identified; 348 publications were excluded after screening for full-text availability. The full-text articles were further filtered based on title and abstract screening. Following this, a total of 1443 articles were excluded. The remaining 670 full-text articles were assessed for eligibility. Of the 670 full-text articles, 480 were excluded based on exclusion criteria, and following the full-text article screening, 190 articles met the final inclusion criteria. Most of these guideline evolutions concerned establishing and adjusting thresholds for the subgroups of the elderly population and patients with diabetic kidney disease, chronic kidney disease, and stroke. Furthermore, the medications of choice are now guided by the stage of disease, presence or absence of comorbidities, and other relevant information, as opposed to ethnicity, which was previously a heavy yardstick for medication choice.

/pdf/the-evolution-of-hypertension-guidelines-over-the-last-20-hriow04s.pdf

The Evolution of Hypertension Guidelines Over the Last 20+ Years: A Comprehensive Review

In Africa, a large number of pregnancies are exposed to Plasmodium falciparum infection. The in-utero environment extremely influences childhood neurodevelopment and behaviour. The complement 5a receptor (C5aR) is linked to several disease conditions. However, the influence of Plasmodium berghei during pregnancy on maternal complement 5a receptor and subsequently on fetal behaviour is unknown. Pregnant mice were intra-peritoneally inoculated on gestational day 13 with 1.02x105 infected red blood cells (iRBCs). iRBCs used in this experiment were gotten by in vivo passage of P. berghei in mice when the level of iRBCs have gotten to about 10-20%. A section of pregnant mice (both test and control groups) were earmarked to give birth and their offspring monitored up to postnatal day 42 when depression-like behaviour was evaluated using tail suspension test model. The other pregnant mice were subjected to cardiac puncture on gestational day 19 for C5a receptor estimation using Elisa assay. Results showed that pregnant mice infected with P. berghei had elevated C5a receptor compared with uninfected pregnant females. It was also shown that P. berghei-exposed offspring presented a depressive-like behaviour compared to unexposed controls. It may be concluded from this study, that complement 5a receptor demonstrates a pathogenic role in signaling and its possible role in mediating depression linked to Plasmodium berghei exposure in utero.

Potential link between Complement 5a Receptor and mood disorders in mouse exposed to experimental malaria in utero.

Introduction High consumption of alcohol has an enormous toll on the health status of individuals. A direct affectation of cardiac integrity concerns cardiologists, primary care physicians, and the healthcare system because this increases the disease burden. Alcoholic cardiomyopathy (ACM) results from the enormous consumption of alcohol over a long period of time. The prevalence varies between regions and sex and ranges between 4% and 40%. Viewing the entire spectrum of cardiomyopathies, ACM makes up about 4% of all cardiomyopathies. However, it causes dilated-type cardiomyopathy and is the second most common cause of dilated cardiomyopathy. We sought to explore the outcomes of percutaneous coronary intervention (PCI) among patients with ACM. Methods This was a retrospective, cross-sectional study of the National Inpatient Sample (NIS) for hospital discharges in the United States between 2012 and 2014. We identified the number of patients with a primary or secondary diagnosis of ACM using the International Classification of Diseases, Ninth Revision (ICD-9) code of 4.255. Using the ICD-9 codes for PCI (00.66, 36.01, 36.02, 36.05, 36.06, 36.07, and 17.55), we identified patients diagnosed with ACM who underwent a PCI (ACPCI). The racial and sexual prevalence, hospital length of stay (LOS), mortality, cost of hospitalization, and cardiovascular outcomes (ventricular fibrillation (VF) and atrial fibrillation (AF)) were compared between patients with and without ACM who underwent a PCI. Results A total of 2,488,293 PCIs were performed between 2012 and 2014. Of these, there were a total of 161 admissions for ACM. About 93% (151) of the ACM PCI group were men. Ethnic distribution revealed a majority of Caucasians with 69% (98), and blacks and Asians at 13.4% (19) and 11.3% (16), respectively. The mean age was 59.8 (SD = 9). The patients with ACPCI were likely to stay longer in the hospital, with an average stay of 6.6 days (SD = 6.2) compared to patients without ACM undergoing PCI (NOACPCI) (3.7 days; SD = 5.0) (p = 0.0001). The mean cost of hospital admission for patients with ACPCI was $120,225 (SD = 101,044), while that of those without ACM who underwent PCI (NOACPCI) was $87,936 (SD = 83,947) (p = 0.0001). A higher death rate during hospitalization (3.7%) was recorded in the ACPCI category vs. 2.3% in patients without ACM who underwent PCI (p = 0.0001). Patients with ACPCI had a higher prevalence of AF (30.4%) than VF (7.5%). Conclusion The ACPCI group had overall poorer hospital outcomes. The majority affected were older Caucasian men with an increased prevalence of AF, higher cost of hospitalization, and longer hospital stays. Further studies are needed to explore the burden of long-term alcohol consumption on cardiovascular disease treatment outcomes.

Percutaneous Coronary Intervention Outcomes Among Patients With Alcoholic Cardiomyopathy: An Analysis of the National Inpatient Sample

Wellens syndrome is a precursor of left anterior descending (LAD) coronary stenosis. It is characterized by biphasic T waves in V2-V3 (type A) or negative deep T waves in V2-V4 (type B). The ability of emergency physicians, hospitalists, or primary care providers to recognize these early ECG patterns is primordial because the definitive treatment is urgent cardiac catheterization with percutaneous coronary intervention. However, failure to identify a type A or type B Wellens syndrome may lead to devastating outcomes, such as myocardial infarction or even death. We presented a clinical case of Wellens’ syndrome with deep T waves in V2-V3 associated with COVID pneumonia, pleural effusions, and congestive heart failure that went to a rapid and massive myocardial infarction.

https://www.cureus.com/articles/123486-wellens-syndrome-a-possible-precursor.pdf

O E Okobi

Papers

The Evolution of Hypertension Guidelines Over the Last 20+ Years: A Comprehensive Review

Molecular Markers of Pancreatic Cancer: A 10-Year Retrospective Review of Molecular Advances

Potential link between Complement 5a Receptor and mood disorders in mouse exposed to experimental malaria in utero.

Percutaneous Coronary Intervention Outcomes Among Patients With Alcoholic Cardiomyopathy: An Analysis of the National Inpatient Sample

Wellens Syndrome: A Possible Precursor