Mathematical modeling of ABE fermentation on glucose substrate with Zn supplementation for enhanced butanol production.

Supplementation or limitation of some micronutrients during acetone-butanol-ethanol (ABE) fermentation has led to improvement in butanol yield and productivity. A mechanistic model of ABE fermentation offers insights in understanding these complex interactions and improving productivity through optimal culture conditions. This study proposes a mechanistic kinetic model of ABE fermentation by two Clostridium Acetobutylicum strains, L7 and ATCC 824 using glucose as sole carbon source without zinc and with various zinc doses. The model incorporates enzyme regulation by zinc on several glycolytic, acidogenesis and solventogenesis enzymes. The model was fitted and validated to experimental data collected from the published literature. The simulated results were in compliance with the experimental data, most importantly indicating higher glucose consumption and butanol productivity when supplemented with zinc compared to the control culture. The average squared correlation factor (R2) between the experimental and the simulated results, without and with zinc, were 0.99 and 0.96 for glucose, and 0.89 and 0.95 for butanol, respectively. A sensitivity analysis performed on the fitted and validated model indicated that the glucose consumption and growth parameters most influenced the model outputs. The developed model can be used as a template for modeling ABE fermentation under different combinations of micronutrients that may offer improved butanol yield and productivity.

The understanding of Parkinson's disease through genetics and new therapies.

INTRODUCTION: Parkinson's disease is one of the progressive neurodegenerative diseases from which people suffer for years. The mechanism of this disease is associated with a decrease in the number of dopaminergic neurons in the substantia nigra (SN) while Lewy bodies are still present. As a result, both motor-ridity, tremor, and bradykinesia-and non-motor symptoms such as anxiety and depression. Nowadays, it is well known that the cause behind Parkinson's disease is mainly environmental changes, genetic susceptibility, and toxins. Unfortunately, there is no cure for the disease but treatments. The replacement of lost neurons, α-synuclein and apomorphine, is currently being studied for new therapies. This article focuses on history, mechanism, factors causing Parkinson's disease as well as future therapies for the cure of the diseases. METHODOLOGY: Data were collected from medical journals published on PubMed, The Lancet, Cells, and Nature Reviews Neurology databases with a predefined search strategy. All articles considering new therapies for Parkinson's disease were considered. RESULTS: The pathophysiology of Parkinson's disease is currently reasonably understood. However, there is no definitive cure so all the treatments focus mainly on reducing or limiting the symptoms. Current treatment studies focus on genetics, replacing lost neurons, α-synuclein and apomorphine. CONCLUSION: Parkinson's disease is the most common movement disorder worldwide because of the loss of dopaminergic neurons in the substantia nigra. Its symptoms include motor dysfunctions such as rigidity, tremor, and bradykinesia and non-motor dysfunctions such as anxiety and depression. Through genetics, environmental changes and toxins analysis, it is now known that future new therapies are working on replacing lost neurons, α-synuclein and apomorphine.

Neurological disorders in HIV: Hope despite challenges.

INTRODUCTION: Human Immunodeficiency virus (HIV) is a virus that causes several diseases by attacking the human immune system. It is transmitted by contact with certain bodily fluids of an infected person, most commonly during unprotected sex, through sharing needles, or from mother to baby during pregnancy, birth or breastfeeding. The central nervous system is not spared from this virus, as HIV has been shown to induce several neurological disorders. However most neurological pathologies (such as dementia, infections, meningitis, and neuropathy) rarely show until late stages, in this case, after the patients develop acquired immunodeficiency syndrome (AIDS). This article aims to review the neurological disorders in the HIV population and the attempts initiated to limit the disease. METHODOLOGY: Data were collected from medical journals published on PubMed, Ovid MEDLINE, Science Direct and Embase bibliographical databases with a predefined search strategy. All articles considering neurological disorders associated with HIV were considered. RESULTS: To date, the pathogenesis of HIV-associated neurological complications remains poorly elucidated; thus, imposing a hindrance and limitations on the treatment options. Nevertheless, some studies have reported alterations in dendritic spine as the causative agent for developing brain damage. CONCLUSION: HIV remains one of the most serious global health challenges, with neurological manifestations imposing a major concern among patients with HIV. Despite the availability and efficacy of antiretroviral therapies, yet, the risk of developing neurological complications remains relatively high among patients with HIV. Thus, the 2030 HIV vision must focus on further preventive measures to protect HIV patients from developing such neurological complications.

Quantitative analysis of the interaction of ethanol metabolism with gluconeogenesis and fatty acid oxidation in the perfused liver of fasted rats.

Ethanol is known to significantly affect gluconeogenesis and lipid metabolism in the liver, primarily by altering the redox ratio in both cytosol and mitochondria. The effect of ethanol was analyzed using a comprehensive, dynamic model of liver metabolism that takes into account sub-cellular compartmentation, detailed kinetics for the citric acid cycle, ethanol and acetaldehyde oxidation, and gluconeogenesis, and inter-compartmental transport of metabolites, including the malate-aspartate shuttle. The kinetic expression for alcohol dehydrogenase takes into account inhibition by ethanol and NADH. Simulations of perfusions of the rat liver were performed with various combinations of substrates (lactate, pyruvate, and fatty acids), with subsequent addition of ethanol to the perfusate. The model successfully predicts NADH/NAD+, in both cytosol and mitochondria, the expected directional flux of reducing equivalents between the two compartments during perfusion with different gluconeogenic precursors, and the effect of ethanol on glucose and ketone body production. This model can serve as a platform for in silico experiments investigating the effects of ethanol on the many dehydrogenases, and thus the major carbohydrate and lipid metabolic pathways in the liver, as well as potential effects of various drugs that may interact with ethanol.

Rift Valley fever during the COVID-19 pandemic in Africa: A double burden for Africa's healthcare system.

A new rising incidence of Rift Valley fever (RVF) among livestock and humans in the African continent during the COVID-19 pandemic has become of increasing concern. We analyzed the different ways COVID-19 has contributed to the increase in RVF cases and how it has impacted the interventions allocated to the disease by comparing it with the status of the disease before the pandemic. There is enough evidence to conclude that the COVID-19 pandemic has impacted the efforts being taken to prevent outbreaks of RVF. Therefore, with no definitive treatment in place and inadequate preventive measures and disease control, RVF may potentially lead to a future epidemic unless addressed urgently.

The syndemic burden of HIV/AIDS in Africa amidst the COVID-19 pandemic.

INTRODUCTION: The human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) has long affected millions of individuals across the globe. Historically, the prevalence of this disease is particularly noted within the African continent. Before the coronavirus disease 2019 (COVID-19) pandemic, many African countries struggled to effectively manage the increasing burden associated with HIV/AIDS. There is now a need to reassess this in a COVID-19 pandemic context so that the impact of COVID-19 on HIV/AIDS healthcare within Africa can be adequately evaluated. METHODS: Data collection was performed on the PubMed, Ovid MEDLINE and Embase bibliographical databases with a predefined search strategy. Searches were performed in blind duplicate and all articles considering COVID-19 and HIV/AIDS within African healthcare were considered. RESULTS: The COVID-19 pandemic has severely exacerbated the many issues surrounding HIV/AIDS care within many African countries. These impacts are noticeable in medical, psychological, and socio-political contexts. CONCLUSIONS: Before efforts are made to improve the provision of HIV/AIDS and COVID-19 care within Africa, it is important that this issue is brought to the attention of the scientific and clinical community so that the continent can receive the necessary support and aid.

YouTube as a source of information on breast cancer in the Arab world.

BACKGROUND: The general population is increasingly using YouTube as a source of information on breast cancer, the most frequent cancer among women. Arabs are the most interested population in breast cancer on YouTube. The transmission of accurate information is important to reduce mortality rates. This cross-sectional study aims to evaluate breast cancer videos on YouTube in the Arab world. METHODS: A YouTube search for "breast cancer" in Arabic was performed. The most viewed 60 videos included were evaluated for global quality (GQS score), reliability (modified DISCERN score), content (content score), and misleading claims. Recorded and calculated data included views, duration, videos power index, and viewers' interaction. Sources from legal persons (governments, universities, TV channels, physicians' groups), and blogs (online health channels, individuals) were categorized. RESULTS: The median global quality (3/5), reliability (2/5), and content scores (4/11) were overall low. Misleading information was found in 42% of the videos. Although videos uploaded by legal persons were less popular (163,454 vs 327,488 views), they hosted more physicians (52% vs 15%), were less misleading (15% vs 64%), covered more content, and were of higher global quality and reliability than videos uploaded by blogs [p < 0.05]. While the topic of symptoms (55%) was discussed the most, genetic counseling (13%) and prevention (20%) were the least mentioned. CONCLUSIONS: YouTube is poorly informational and inaccurate on breast cancer in the Arab World where it is highly used. Although videos uploaded by legal persons tend to be more adequate, they are of lower popularity. Governments and physicians are encouraged to upload more intelligibly informational videos, guide the population to reliable sources, and support regulations.

Dengue fever outbreak in Cook Island: A rising concern, efforts, challenges, and future recommendations.

The Cook Island government has made several efforts to ensure zero confirmed cases and transmission of COVID-19, especially among visiting travelers. However, the Cook Island ministry of health has to deal with the new strain of dengue fever outbreak, known as dengue fever type 2 (DEN-2), by adopting several measures to control its spread, especially in the affected parts of the subtropical country. This paper aims to describe the dengue fever response taken in Cook Island and suggest recommendations to control the risk of transmission in endemic parts of the world.

Bird flu outbreak amidst COVID-19 pandemic in South Africa: Efforts and challenges at hand.

Over the months of April and May 2021, South Africa has witnessed several outbreaks of highly infective avian influenza (H5N1) in different poultry farms. This came as a shock to a country that was already battling with the deadly COVID-19 pandemic. The emergence of the virus has spurred import bans and massive culls in the poultry business. Local experts have also called for a restriction on the movement of people and cars in and out of their chicken farms. Employees have also been encouraged to shower in the mornings when they arrive at the farms and wear fresh clothes, as the flu spreads very quickly. In a country that is already facing the economic implications of the COVID-19, this has the potential to cause a significant dent in the economy, as well as severely impact people's day-to-day life. Bird flu-also called avian influenza-is a viral infection that can infect not only birds but also humans and other animals. The threat of a new influenza pandemic has prompted countries to draft national strategic preparedness plans to prevent, contain and mitigate the next human influenza pandemic. This paper describes the South African burden, current efforts, and preparedness against the avian influenza virus.

Data on clinical significance of second trimester inflammatory biomarkers in the amniotic fluid in predicting preterm delivery.

In this article second trimester amniotic fluid biomarkers are measured for correlation with preterm delivery. One additional milliliter of amniotic fluid is collected during amniocentesis for dosages of IL-6, MMP-9, CRP and glucose levels, along with maternal serum CRP and glucose. MMP-9 and Il-6 levels were measured with the corresponding Human Quantikine(R) ELISA Kit (R&D systems) according to the instructions provided by the manufacturer. Cut-off values for AF MMP-9 and IL-6 were fixed by the kit sensitivity thresholds. Data includes ROC curves for glucose (Fig. 1), IL-6 (Fig. 2) and MMP-9 (Fig. 3), aiming to search for sensitivity and specificity in the prediction of premature delivery. Statistical analyses are performed with SPSS v20.0 software. Statistical significance is determined using the Mann-Whitney and one way ANOVA test. The association with preterm delivery is performed using a two proportions test. Correlations are measured using the Pearson׳'s coefficient. A p value<0.05 is considered statistically significant. The data is presented in the figures provided. Data relied on a previous publication "Prediction of preterm delivery by second trimester inflammatory biomarkers in the amniotic fluid" (A. Kesrouani, E. Chalhoub, E. El Rassy, M. Germanos, A. Khazzaka, J. Rizkallah, E. Attieh, N. Aouad, 2016) [1].

Prediction of preterm delivery by second trimester inflammatory biomarkers in the amniotic fluid.

OBJECTIVE: To search for a correlation between mid-pregnancy altered levels of inflammatory markers and preterm delivery. METHODS: A prospective cohort series included 39 patients undergoing amniocentesis one additional milliliter of amniotic fluid (AF) was stored for later dosage of interleukin-6 (Il-6), matrix metalloproteinase-9 (MMP-9), glucose and C-reactive protein (CRP). Maternal serum CRP and glucose levels were also obtained. Exclusion criteria were multiple pregnancies, chorioamnionitis, group B streptococcus colonization, bacterial vaginosis and cases with proven aneuploidy. We searched for correlation between AF and plasmatic markers and also for a difference between patients with term and preterm delivery. RESULTS: 33 participants were eligible and one third had preterm delivery. Levels of the plasmatic biomarkers did not correlate with the AF biomarkers except for plasmatic glucose and AF IL-6 levels (r=0.350; p=0.016). The levels of all AF biomarkers did not differ significantly between the pre-term and the term groups (p>0.05). The optimal screening cutoffs for identifying pregnancies at risk were different than the ones initially indicated. CONCLUSION: Mid-pregnancy amniotic fluid biomarker levels do not correlate with preterm delivery. Plasma CRP is not correlated with these markers. Cutoff levels suggested are sparse and heterogeneous. Larger studies are needed before advising routine measurement of these markers.

Radium-223 in Bone-Metastatic Prostate Cancer: Current Data and Future Prospects.

Ra-223 (radium-223) is an alpha particle-emitting radiopharmaceutical with targeted uptake in areas of osteoblastic lesions. The combination of targeted skeletal uptake, short tissue-penetration range, and high energy of alpha particles allows for targeted cell killing and a low toxicity profile. A phase III trial (ALSYMPCA) demonstrated improvements in overall survival and symptomatic skeletal events in patients with castration-resistant prostate cancer and multifocal symptomatic bone metastases. Adverse events were limited but included both gastrointestinal and hematologic effects. This article will describe the historic background of Ra-223; outline the clinical studies which led to phase III trials of this agent; highlight key results of these phase III studies; and explore possible future directions for use of Ra-223 and other alpha particles--both in prostate cancer and for management of other diseases.

Hypercalcemia in histoplasmosis aggravated with antifungal treatment.

INTRODUCTION: Hypercalcemia is a known, but rare complication of histoplasmosis, a granulomatous disease. We present a case of chronic disseminated histoplasmosis, complicated by hypercalcemia, transiently worsening after initiation of antifungal treatment. CASE PRESENTATION: A 61-year-old gentleman presented with shortness of breath, cough, weight loss, but no fever or hemoptysis. His physical exam was unremarkable except for decreased air entry on both lung fields, and axillary and inguinal lymphadenopathies. Computed tomography of the chest showed bilateral cavitary lung lesions, biopsy of which showed non caseating granulomas, and tissue culture showing Histoplasma capsulatum. Itraconazole was started. One month later, patient presented with transient acute renal failure and worsening hypercalcemia. His workup showed a non-PTH mediated hypercalcemia, with a normal PTH-rP, and low calcifediol, but high normal calcitriol level. Hypercalcemia secondary to histoplasmosis was reported in six cases, none of which worsened after antifungal treatment. Several mechanisms have been elucidated. CONCLUSION: We recommend monitoring of serum calcium after initiation of antifungal treatment, especially in patients with underlying hypercalcemia. More studies are needed to understand the pathophysiology.

Cardiac angiosarcoma presenting with tamponade.

Primary cardiac angiosarcoma is extremely rare, but it is the most common primary malignant cardiac tumor. We herein present the case of a 51-year-old man who presented with symptoms of acute right heart failure, secondary to pericardial tamponade. Pericardiocentesis showed bloody fluid with negative pathology. Repeat 2-D echocardiography and a trans-esophageal echocardiogram showed a right atrial mass. The patient underwent surgery and adjuvant chemotherapy, but died seven months after the diagnosis. Despite being rare, cardiac angiosarcoma should be included in the differential diagnosis of bloody pericardial effusions, even with negative early investigations. The prognosis of the disease is usually poor. Treatment is mainly surgical resection if the cancer is localized, and can include neadjuvant and adjuvant chemotherapy, radiation treatment, and immunotherapy.

A computer model of gluconeogenesis and lipid metabolism in the perfused liver.

A mathematical model of the perfused rat liver was developed to predict intermediate metabolite concentrations and fluxes in response to changes in various substrate concentrations in the perfusion medium. The model simulates gluconeogenesis in the liver perfused separately with lactate and pyruvate and the combination of these substrates with fatty acids (oleate). The model consists of key reactions representing gluconeogenesis, glycolysis, fatty acid metabolism, tricarboxylic acid cycle, oxidative phosphorylation, and ketogenesis. Michaelis-Menten-type kinetic expressions, with control by ATP/ADP, are used for many of the reactions. For key regulated reactions (fructose-1,6-bisphosphatase, phosphofructokinase, pyruvate carboxylase, pyruvate dehydrogenase complex, and pyruvate kinase), rate expressions were developed that incorporate allosteric effectors, specific substrate relationships (e.g., cooperative binding), and/or phosphorylation/dephosphorylation using in vitro enzyme activity data and knowledge of the specific mechanisms. The model was independently validated by comparing model predictions with 10 sets of experimental data from 7 different published works, with no parameter adjustments. The simulations predict the same trends, in terms of stimulation of substrate uptake by fatty acid addition, as observed experimentally. In general, the major metabolic indicators calculated by the model are in good agreement with experimental results. For example, the simulated glucose/pyruvate mass yield is 43% compared with the average of 45% reported in the literature. The model accurately predicts the specific time constants of the glucose response (2.5-4 min) and the dynamic behavior of substrate and product fluxes. It is expected that this model will be a useful tool for analyzing the complex relationships between carbohydrate and fat metabolism.