Sensitivity, specificity, and accuracy of molecular profiling on circulating cell-free DNA in refractory or relapsed multiple myeloma patients, results of MM-EP1 study.

As a promising alternative to bone marrow aspiration (BMA), mutational profiling on blood-derived circulating cell-free tumor DNA (cfDNA) is a harmless and simple technique to monitor molecular response and treatment resistance of patients with refractory/relapsed multiple myeloma (R/R MM). We evaluated the sensitivity and specificity of cfDNA compared to BMA CD138 positive myeloma plasma cells (PCs) in a series of 45 R/R MM patients using the 29-gene targeted panel (AmpliSeq) NGS. KRAS, NRAS, FAM46C, DIS3, and TP53 were the most frequently mutated genes. The average sensitivity and specificity of cfDNA detection were 65% and 97%, respectively. The concordance per gene between the two samples was good to excellent according to Cohen's κ coefficients interpretation. An increased number of mutations detected in cfDNA were associated with a decreased overall survival. In conclusion, we demonstrated cfDNA NGS analysis feasibility and accuracy in R/R MM patients who may benefit from early phase clinical trial.

An efficient method for screening rice breeding lines against races of Magnaporthe oryzae.

Rice blast, caused by Magnaporthe oryzae, is the most destructive rice disease worldwide. The disease symptoms are usually expressed on the leaf and panicle. The leaf disease intensity in controlled environmental conditions is frequently quantified using a 0-5 scale, where 0 represents the absence of symptoms and 5 represents large eyespot lesions. However, this scale restricts the qualitative classification of the varieties into intermediate resistant and susceptible categories. Here we develop a 0-6 scale for blast disease that allows proper assignment of rice breeding lines and varieties into six resistance levels (highly resistant, resistant, moderate resistant, moderate susceptible, susceptible, and highly susceptible). We evaluated 41 common rice varieties against four major blast races (IB1, IB17, IB49, and IE1-K). Varieties carrying the Pi-ta gene were either highly resistant, resistant, or moderate resistant to IB17. The IE1-K race was able to break Pi-ta-mediate resistance of the rice varieties. The Pi-z gene conferred resistance to the IB17 and IE1-K races. The varieties M201, Cheniere, and Frontier were highly susceptible (score 6; 100% disease) to the race IE1-K. Moreover, varieties that were resistant or susceptible to all four blast races also showed similar levels of resistance/susceptibility to blast disease in the field. Taken together, our data proved that the 0-6 blast scale can efficiently determine the resistance levels of rice varieties against major blast races. This robust method will assist rice breeding programs to incorporate durable resistance against major and emerging blast races.

Comparative study of piroxicam and nitroglycerin on prostaglandin-modulated blood and electrolyte indices during di-estrous in female Wistar Rats.

OBJECTIVE: Endogenous prostaglandins are involved in hemostasis, renal excretion of electrolytes, and implicated in dysmenorrhea. Piroxicam and Nitroglycerin are common drugs used in treating dysmenorrhea by inhibiting the cyclooxygenase pathway involved in prostaglandin production. However, studies comparing the effects of these drugs on prostaglandin-modulated hemostasis and renal function are lacking. METHODS: Fifteen female rats (120-160g) were divided into 3 groups (20 per group), namely Control (distilled water, 0.3 mL), Piroxicam treated (3mg/kg) and Nitroglycerin treated (1 mg/kg). Di-estrous phase was confirmed in animals in each group using the Pipette smear method. Treatment was administered for 4 days covering the estrous cycle. Bleeding and clotting time were assessed and blood concentrations of sodium, potassium, urea and platelet counts were evaluated in all phases. Data were analyzed using one-way ANOVA and Newman-Keuls post-hoc test. Statistical significance was considered at p<0.0. RESULTS: The nitroglycerin-treated group showed significant increases in blood potassium during di-estrous while the piroxicam-treated group showed significant increases in blood potassium, urea and clotting time with a significant decrease in sodium levels during di-estrous compared to controls. Results obtained in other phases were not significant compared to controls. CONCLUSIONS: The study showed that Nitroglycerin produces minimum alteration of blood and electrolyte indices compared to piroxicam during di-estrous.

Exposure to ultraviolet radiation during pregnancy influences offspring immune and inflammatory responses in Wistar-strain rats.

OBJECTIVE: During pregnancy, maternal exposure to ultraviolet radiation (UVR) has been linked to altered offspring immune and health status. This study was therefore designed to investigate some markers of immune response in the offspring of pregnant Wistar rats exposed to UVR at various points of gestation. METHODS: Thirty pregnant rats were divided into 6 groups (n=5) as follows; group I, control, consisting of pregnant rats unexposed to UVR. Animals in groups II, III, IV, V and VI were exposed to UVR for one hour daily, on gestational days 1-7,8-14,15-21,1-14 and 1-21, respectively. Animals were allowed to come to term and offspring birth weight was taken. On postnatal Day 10, weight of each offspring was taken again. Thereafter, blood samples were collected from each offspring per group and evaluated for total protein, albumin, globulin, C-reactive protein, interleukin-1ß, and complement component protein-3 (C3). Offspring hepatic samples were evaluated using standard histological techniques. RESULTS: Offspring birthweight increased (p<0.05), while weight gain on postnatal day 10 reduced in all experimental groups compared to controls. No significant differences were observed for offspring total protein, albumin, and C3 levels across all groups. Globulin increased (p<0.05) only in group VI, while C-reactive protein increased (p<0.05) in all experimental groups, except group III, compared to controls. Interleukin-1ß in groups II, III, V and VI increased significantly compared to controls. Offspring hepatic samples exhibited hepatocellular degeneration and necrosis that was independent of gestational stage of maternal exposure to UVR. CONCLUSIONS: Maternal exposure to ultraviolet radiation during gestation in Wistar rats activates offspring immune and inflammatory responses.

Regulation of effector and memory CD8 + T cell differentiation: a focus on orphan nuclear receptor NR4A family, transcription factor, and metabolism.

CD8 + T cells undergo rapid expansion followed by contraction and the development of memory cells after their receptors are activated. The development of immunological memory following acute infection is a complex phenomenon that involves several molecular, transcriptional, and metabolic mechanisms. As memory cells confer long-term protection and respond to secondary stimulation with strong effector function, understanding the mechanisms that influence their development is of great importance. Orphan nuclear receptors, NR4As, are immediate early genes that function as transcription factors and bind with the NBRE region of chromatin. Interestingly, the NBRE region of activated CD8 + T cells is highly accessible at the same time the expression of NR4As is induced. This suggests a potential role of NR4As in the early events post T cell activation that determines cell fate decisions. In this review, we will discuss the influence of NR4As on the differentiation of CD8 + T cells during the immune response to acute infection and the development of immunological memory. We will also discuss the signals, transcription factors, and metabolic mechanisms that control cell fate decisions. HIGHLIGHTS: Memory CD8 + T cells are an essential subset that mediates long-term protection after pathogen encounters. Some specific environmental cues, transcriptional factors, and metabolic pathways regulate the differentiation of CD8 + T cells and the development of memory cells. Orphan nuclear receptor NR4As are early genes that act as transcription factors and are highly expressed post-T cell receptor activation. NR4As influence the effector function and differentiation of CD8 + T cells and also control the development of immunological memory following acute infection.

Elastomeric seal stress analysis using photoelastic experimental hybrid method.

Stress freezing is an important and powerful procedure in 3-dimensional experimental stress analysis using photoelasticity. The application of the stress freezing technique to extract stress components from loaded engineering structures has, however, declined over the years even though its principles are well established. This is attributed to huge costs arising from energy consumption during the process. In addition, significant time is needed to generate the desired information from isoclinic and isochromatic fringes. To overcome the limitations of stress freezing in photoelasticity and transform it into an economical device for stress analysis in an engineering environment, a new stress freezing cycle that lasts 5 h is proposed. The proposed technique is used in several applications of elastomeric seals with different cross-sectional profiles to assess their suitability. It was found that reducing the cycle time can lead to huge energy savings without compromising the quality of the fringes. Moreover, the use of isochromatic only to extract stress components leads to a shorter processing time to achieve desirable information since the process of obtaining isoclinic data is involving. In this paper, results of stress analysis from stress-frozen elastomeric seals with various cross-sections using the new stress freezing cycle are presented.

Informative prior on structural equation modelling with non-homogenous error structure.

Introduction: This study investigates the impact of informative prior on Bayesian structural equation model (BSEM) with heteroscedastic error structure. A major drawback of homogeneous error structure is that, in most studies the underlying assumption of equal variance across observation is often unrealistic, hence the need to consider the non-homogenous error structure. Methods: Updating appropriate informative prior, four different forms of heteroscedastic error structures were considered at sample sizes 50, 100, 200 and 500. Results: The results show that both posterior predictive probability (PPP) and log likelihood are influenced by the sample size and the prior information, hence the model with the linear form of error structure is the best. Conclusions: The study has been able to address sufficiently the problem of heteroscedasticity of known form using four different heteroscedastic conditions, the linear form outperformed other forms of heteroscedastic error structure thus can accommodate any form of data that violates the homogenous variance assumption by updating appropriate informative prior. Thus, this approach provides an alternative approach to the existing classical method which depends solely on the sample information.

Irvingia gabonensis (O'Rorke) Bail polymer matrix system for controlled drug delivery.

BACKGROUND: Irvingia gabonensis kernel polymer has gained attention in drug delivery systems because of its compatibility and degradation under natural and physiological conditions. OBJECTIVES: This study aimed to evaluate Irvingia gabonensis polymer as a matrix system for the controlled delivery of ibuprofen in comparison to xanthan gum and hydroxypropylmethylcellulose (HPMC). MATERIAL AND METHODS: Irvingia gabonensis polymer was extracted using established methods and dried using the ovenand freeze-drying methods. Ibuprofen tablets were prepared by direct compression and the effects of polymer concentration (10-50%), excipients (lactose, microcrystalline cellulose and dicalcium phosphate dihydrate) and polymers (xanthan gum and HPMC) on the mechanical and drug release properties of the tablets were evaluated. Density measurements and the Heckel and Kawakita equations were used to determine the compression properties of the tablets. Friability, crushing strength and the crushing strength-friability ratio (CSFR) were used to evaluate the mechanical properties of the tablets, while dissolution times were used to evaluate drug release from the matrices. The drug release mechanisms were determined by fitting the dissolution data into classic kinetic equations. RESULTS: Irvingia gabonensis polymer deformed plastically with a fast onset and a high amount of plastic deformation compared with xanthan gum and HPMC. This polymer was directly compressible and formed intact non-disintegrating tablets; the mechanical and dissolution properties of Irvingia gabonensis polymer tablets generally decreased with increasing concentration of ibuprofen. The ranking of dissolution times was xanthan gum > freeze-dried Irvingia gabonensis > HPMC > oven-dried Irvingia gabonensis. The addition of the excipients improved the mechanical properties of the tablets, aided ibuprofen release, and altered the release kinetics, which was largely defined by the Korsmeyer-Peppas model. Increasing the proportion of xanthan gum and HPMC in the matrices resulted in a decreased amount of ibuprofen released after 9 h, with xanthan gum having a greater effect. CONCLUSIONS: Irvingia gabonensis polymer matrices may be effective in the preparation of controlled release tablets, and their right combination with xanthan gum or HPMC could provide a time-independent release for longer durations.

Biogenic amine production from processed animal and plant protein-based foods contaminated with Escherichia coli and Enterococcus feacalis.

The aim of the study was to investigate biogenic amine production in different types of cooked protein foods. The food samples were incubated at varying temperatures (4, 37 and 55 °C) on different microbiological media for 48, 72 and 180 h. Resulting bacteria were isolated and characterized using cultural, biochemical and molecular methods, further screened for production of biogenic amines in decarboxylase broth media supplemented with 0.4% of histidine, tyrosine, lysine and ornithine. The samples were incubated at 25 °C for 48 h and the biogenic amine concentration in each food sample determined by means of HPLC. There was a high prevalence of the isolates among the food samples. All the isolates except Klebsiella sp. and Pseudomonas sp. were positive for decarboxylase activity indicating 84.6% of the isolates capable of biogenic amine production. The amine concentration varied among the types of food and methods of cooking. Histamine was detected in 41.67% of the inoculated food samples (9.2 ± 1.2-100.95 ± 0.1 µg/g) while putrescine was the least detected (41.67%) in the inoculated food sample (7.7 ± 0.1-8.8 ± 0.2 µg/g). Cadaverine and histamine were detected in 16.4% (2.6 ± 0.2-49.9 ± 0.9 µg/g) and 7.5% (1.4 ± 0.1-20.4 ± 0.3 µg/g) of the foods, respectively. Microbial contamination of the cooked protein foods led to high levels of biogenic amines irrespective of the cooking methodology adopted and type of foods investigated. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05576-0.

Prevalence of overweight, obesity, and early adiposity rebound in nursery school children in southeastern France.

BACKGROUND: The aim of the present study was to assess the prevalence of overweight, obesity, and early adiposity rebound in nursery school children aged 3.5-4.5 years and to evaluate associations with deprivation. METHODS: A cross-sectional study was conducted in the Bouches-du-Rhône department in southeastern France. Data for all nursery school children aged 3.5-4.5 years were collected during systematic medical examinations. The prevalence of overweight and obesity was determined using French, International Obesity Task Force (IOTF), and World Health Organization reference values. A French ecological deprivation index was used to assess associations with deprivation. RESULTS: Among 19,295 children included in the study, the prevalence of overweight (IOTF-25 < BMI < IOTF-30) was 9.1% and the prevalence of obesity (BMI > IOTF-30) was 2.6%. Children attending nursery schools in the most disadvantaged areas were 4.3 times more likely to be affected by obesity than those from schools in the most advantaged areas (OR: 4.32; 95% CI: 2.98-6.25, p < 0.001), after adjusting for gender, age group, and school status. Early adiposity rebound was observed in 2131 of 9872 children (21.6%). CONCLUSION: Programs to prevent childhood overweight and obesity in France should be intensified and take account of major persistent social inequalities. Medical practitioners should learn to systematically assess BMI curve dynamics and early adiposity rebound.

Neurobiology of Schizophrenia: A Comprehensive Review.

Schizophrenia is a debilitating disease that presents with both positive and negative symptoms affecting cognition and emotions. Extensive studies have analyzed the different factors that contribute to the disorder. There is evidence of significant genetic etiology involving multiple genes such as dystrobrevin binding protein 1 (DTNBP1) and neuregulin 1 (NRG1). There is no clear link between neurotransmitter changes and the pathophysiology of schizophrenia; however, studies have shown that subcortical dopamine dysfunction is the key mechanism. Specific regions of gray and white matter changes are observed in patients with schizophrenia; gray matter changes being more significant after the onset of psychosis. These pathological changes may be implicated in the impairment of executive functioning, attention, and working memory. The disease can be managed with pharmacological treatments based on individual patient profile, patient compliance, and disease severity. The challenge of disease management sometimes persists due to the side effects. A better understanding of the pathological processes in schizophrenia may lead to more specific and effective therapies.

Comparative prospective study of early outcomes after osteosynthesis with locked intramedullary nailing or plating for closed femoral shaft fractures at the National Orthopaedic Hospital Enugu, Nigeria.

AIM OF THE STUDY: This was to compare the early outcome of closed femoral shaft fractures treated with locked intramedullary nailing and plating at the National Orthopaedic Hospital Enugu. METHODS: The study was a prospective study over 12-month period at the National Orthopaedic Hospital Enugu. Ethical clearance was obtained from the hospital ethical committee. Written informed consent was obtained from all prospectively recruited participants. Patients who met the inclusion criteria were randomly selected by simple balloting into either intramedullary nailing group or plating group. The patients were evaluated at presentation and postoperatively within 48 hours, then at two weeks, six weeks, 12 weeks and 18 weeks, respectively. Participants were evaluated using Thoresen criteria. RESULTS: A total of 52 femoral shaft fractures in 50 patients were included and analysed using SPSS version 20.0. Bone union was obtained in all the patients in the intramedullary nailing group at 12 weeks and in 84.6% patients in the plating group between 12 and 18 weeks. The overall wound infection rate was 11.5% in the locked intramedullary group and 7.7% in the plating group. Similarly, the overall limb length discrepancy was 11.5% in the locked intramedullary nailing group and 19.2% in the plating group. Based on the Thoresen criteria, good to excellent outcome was achieved in 65.4% of patients in the locked intramedullary nailing group. DISCUSSION: The patients in both groups were evaluated clinically, radiologically and functionally based on the Thoresen criteria and significantly higher number of patients in the intramedullary nailing group (17; 65.4%) than the plating group had good to excellent outcome (x2 = 9.734; p = 0.020). CONCLUSION: The early outcome of treatment of closed femoral shaft fractures in adults is significantly better following locked intramedullary nailing than plating.

Central Nervous System Toxoplasmosis and Cytomegalovirus Colitis in an Asymptomatic HIV Positive Patient.

Human immunodeficiency virus (HIV) associated opportunistic infections are complications of patients with advanced HIV infection who are unaware of their disease or non-compliant with antiretroviral therapy. HIV patients with low CD4 count, generally less than 200 cells/µL, are at risk of developing opportunistic infections. We report a case of a 53-year-old male diagnosed with opportunistic infections, Toxoplasma gondii and cytomegalovirus (CMV). His initial presentation was central nervous system Toxoplasmosis and he later developed CMV colitis. Both are consequences of his undiagnosed advanced HIV status. The patient was promptly treated with appropriate medications for both conditions. The patient's HIV status is well controlled with highly active antiretroviral therapy (HAART) and his CD4 count is improving. It further exhibits the significance of adequate screening protocols and the importance of early treatment for HIV patients.

The Influence of Pineapple Leaf Fiber Orientation and Volume Fraction on Methyl Methacrylate-Based Polymer Matrix for Prosthetic Socket Application.

This work reports on the use of low-cost pineapple leaf fiber (PALF) as an alternative reinforcing material to the established, commonly used material for prosthetic socket fabrication which is carbon-fiber-reinforced composite (CFRC) due to the high strength and stiffness of carbon fiber. However, the low range of loads exerted on a typical prosthetic socket (PS) in practice suggests that the use of CFRC may not be appropriate because of the high material stiffness which can be detrimental to socket-limb load transfer. Additionally, the high cost of carbon fiber avails opportunities to look for an alternative material as a reinforcement for composite PS development. PALF/Methyl Methacrylate-based (MMA) composites with 0°, 45° and 90° fiber orientations were made with 5-50 v/v fiber volume fractions. The PALF/MMA composites were subjected to a three-point flexural test to determine the effect of fiber volume fraction and fiber orientation on the flexural properties of the composite. The results showed that 40% v/v PALF/MMA composite with 0° fiber orientation recorded the highest flexural strength (50 MPa) and stiffness (1692 MPa). Considering the average load range exerted on PS, the flexural performance of the novel composite characterized in this work could be suitable for socket-limb load transfer for PS fabrication.

Chitosan-Coated Halloysite Nanotubes As Vehicle for Controlled Drug Delivery to MCF-7 Cancer Cells In Vitro.

The aim of the work is to improve the release properties of curcumin onto human breast cancer cell lines using coated halloysite nanotubes (HNTs) with chitosan as a polycation. A loading efficiency of 70.2% (w/w) was attained for loading 4.9 mg of the drug into 0.204 g bed volume of HNTs using the vacuum suction method. Results acquired from Brunauer-Emmett-Teller (BET), Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), scanning electron spectroscopy (SEM), zeta potential, and thermogravimetric analysis (TGA) indicated the presence of the drug and the biopolymer in and around the nanotubes. The release properties of drug-loaded HNTs (DLHNTs) and chitosan-coated drug-loaded HNTs (DLHNTs-CH) were evaluated. The release percentages of DLHNTs and DLHNTs-CH after 6 h were 50.7 and 37%, respectively. Based on the correlation coefficients obtained by fitting the release nature of curcumin from the two samples, the Korsmeyer-Peppas model was found to be the best-fitted model. In vitro cell viability studies were carried out on the human breast cancer cell line MCF-7, using the MTT and trypan blue exclusion assays. Prior to the Trypan blue assay, the IC50 of curcumin was determined to be ~30 µM. After 24 h of incubation, the recorded cell viability values were 94, 68, 57, and 51% for HNTs, DLHNTs-CH, DLHNTs, and curcumin, respectively. In comparison to the release studies, it could be deducted that sustained lethal doses of curcumin were released from the DLHNTs-CH within the same time. It is concluded from this work that the "burst release" of naked drugs could be slowly administered using chitosan-coated HNTs as potential drug carriers.

Revision Laparoscopic Adjustable Gastric Band as a Successful Alternative Over Sleeve Gastrectomy After Failed Initial Weight Loss Therapies.

Bariatric surgery is one of the most successful treatment options for morbid obesity and related comorbidities that is reserved for patients when lifestyle modifications and medical treatments fail. Bariatric surgeries are proven to result in weight reduction and improve obesity-related complications; however, there still are some reported failures. We report the case of a 35-year-old woman with morbid obesity and diabetes mellitus who had failed laparoscopic adjustable gastric band (LAGB) and laparoscopic sleeve gastrectomy (LSG) when done individually. The patient finally had a successful weight loss after undergoing revision LAGB over LSG. Although the present literature reports LAGB being an unsuccessful weight loss procedure, this case highlights the significance of LAGB as an effective bariatric surgery compared to other procedures. Our patient not only lost her weight successfully but also resolved her comorbid conditions and mental illness following the LAGB.

Euglycemic Diabetic Ketoacidosis and Sodium-Glucose Cotransporter-2 Inhibitors: A Focused Review of Pathophysiology, Risk Factors, and Triggers.

Diabetic ketoacidosis (DKA) is an acute and significant life-threatening complication of diabetes. The association of sodium-glucose cotransporter-2 inhibitors (SGLT2i) with euglycemic diabetic ketoacidosis (EDKA) has been well reported. This literature review was conducted to understand the mechanism of EDKA and identify the potential risk factors and precipitants for patients taking SGLT2i. After reviewing the published literature between 2010 and 2020, 32 articles are included in the final review. The underlying mechanism is mainly enhanced lipolysis and ketone body reabsorption. SGLT2i also stimulates pancreatic alpha cells and inhibits beta cells, causing an imbalance in glucagon/insulin levels, further contributing to lipolysis and ketogenesis. Most patients were diagnosed with blood glucose less than 200 mg/dL, blood pH <7.3, increased anion gap, increased blood, or urine ketones. Perioperative fasting, pancreatic etiology, low carbohydrate or ketogenic diet, obesity, and malignancy are identified precipitants in this review. As normoglycemia can conceal the underlying acidosis, physicians should be cognizant of the EDKA diagnosis and initiate prompt treatment. Patient education on risk factors and triggers is recommended to avoid future events.

Modeling flow in embryonic lymphatic vasculature: what is its role in valve development?

A majority of lymphatic valves tend to form in proximity to vessel junctions, and it is often proposed that disturbed flow at junctions creates oscillating shear stress that leads to accumulation of transcription factors which bring about valvogenesis at these sites. In images of networks of dorsal skin lymphatics from embryonic mice (day E16), we compared simulated fluid flow patterns and observed distributions of the transcription factor Prox1, which is implicated in valve formation. Because of creeping-flow conditions, flow across vessel junctions was not 'disturbed', and within a given vessel, shear stress varied inversely with local conduit width. Prox1 concentration was indeed localised to vessel end-regions, but over three networks was not consistently correlated with the vessel normalised-distance distribution of either fluid shear stress or shear-stress axial gradient. These findings do not support the presently accepted mechanism for the role of flow in valve localisation.

Shear stress affects the architecture and cohesion of Chlorella vulgaris biofilms.

The architecture of microalgae biofilms has been poorly investigated, in particular with respect to shear stress, which is a crucial factor in biofilm-based reactor design and operation. To investigate how microalgae biofilms respond to different hydrodynamic regimes, the architecture and cohesion of Chlorella vulgaris biofilms were studied in flow-cells at three shear stress: 1.0, 6.5 and 11.0 mPa. Biofilm physical properties and architecture dynamics were monitored using a set of microscopic techniques such as, fluorescence recovery after photobleaching (FRAP) and particle tracking. At low shear, biofilms cohesion was heterogeneous resulting in a strong basal (close to the substrate) layer and in more loose superficial ones. Higher shear (11.0 mPa) significantly increased the cohesion of the biofilms allowing them to grow thicker and to produce more biomass, likely due to a biological response to resist the shear stress. Interestingly, an acclimation strategy seemed also to occur which allowed the biofilms to preserve their growth rate at the different hydrodynamic regimes. Our results are in accordance with those previously reported for bacteria biofilms, revealing some general physical/mechanical rules that govern microalgae life on substrates. These results may bring new insights about how to improve productivity and stability of microalgae biofilm-based systems.