Quality improvement of frozen cooked noodles by protein addition.

This study investigated the impact of protein enrichment on the physicochemical, cooking, textural, and color properties of frozen cooked noodles (FCN) stored for 0-3 weeks at -18 °C. Incorporating casein, egg white protein, and soy protein into the noodles significantly increased moisture content, with casein-enriched noodles showing the highest initial moisture levels. The addition of proteins also led to increased ash content, indicating improved nutritional quality. Protein enrichment resulted in reduced cooking loss and enhanced water retention during cooking and frozen storage. Casein-enriched noodles exhibited the highest water absorption capacity and the most substantial enhancement in textural properties, maintaining cohesiveness, gumminess, and elasticity better than egg white protein and soy protein during storage. The results indicated that egg white protein promotes intermolecular interactions, leading to enhanced color stability over time. These findings suggest that enriching with the protein could be a viable approach to elevate the overall quality of FCN.

Extracellular matrix modulates depot-specific adipogenic capacity in adipose tissue of dairy cattle.

Adipose tissue (AT) expands through both hyperplasia and hypertrophy. During adipogenesis, adipose stromal and progenitor cells (ASPCs) proliferate and then accumulate lipids, influenced by the local AT microenvironment. Increased adipogenic capacity is desirable as it relates to metabolic health, especially in transition dairy cows where excess free fatty acids in circulation can compromise metabolic and immune health. Our aim was to elucidate the depot-specific adipogenic capacity and ECM properties of subcutaneous (SAT) and visceral (VAT) AT of dairy cows and define how the ECM affects adipogenesis. Flank SAT and omental VAT samples were collected from dairy cows in a local abattoir. Tissue samples were utilized for transcriptome analysis, targeted RT-qPCR for adipogenic markers, adipocyte sizing, assessment of viscoelastic properties and collagen accumulation, and then decellularized for native ECM isolation. For in vitro analyses, SAT and VAT samples were digested via collagenase, and ASPCs cultured for metabolic analysis. Adipogenic capacity was assessed by adipocyte size, quantification of ASPCs in stromal vascular fraction (SVF) via flow cytometry, and gene expression of adipogenic markers. In addition, functional assays including lipolysis and glucose uptake were performed to further characterize SAT and VAT adipocyte metabolic function. Data were analyzed using SAS (version 9.4; SAS institute Inc., Cary, NC) and GraphPad Prism 9. Subcutaneous AT adipogenic capacity was greater than VAT's, as indicated by increased ASPCs abundance, increased magnitude of adipocyte ADIPOQ and FASN expression during differentiation, and higher adipocyte lipid accumulation as shown by an increased proportion of larger adipocytes and abundance of lipid droplets. Rheologic analysis revealed that VAT is stiffer than SAT, which led us to hypothesize that differences between SAT and VAT adipogenic capacity were partly mediated by depot-specific ECM microenvironment. Thus, we studied depot-specific ECM-adipocyte crosstalk using a 3D model with native ECM (decellularized AT). Subcutaneous AT and VAT ASPCs were cultured and differentiated into adipocytes within depot-matched and mis-matched ECM for 14d, followed by ADIPOQ expression analysis. Visceral AT ECM impaired ADIPOQ expression in SAT cells. Our results demonstrate that SAT is more adipogenic than VAT and suggest that divergences between SAT and VAT adipogenesis are partially mediated by the depot-specific ECM microenvironment.

Soil bacteriome diversity and composition of rooftop and surface gardens in urban and peri-urban areas of Bangladesh.

Soil microbiome science, rapidly evolving, predominantly focuses on field crop soils. However, understanding garden soil microbiomes is essential for enhancing food production sustainability in garden environments. This study aimed to unveil the bacteriome diversity and composition in rooftop garden soils (RGS) and surface garden soils (SGS) across urban (Dhaka North and Dhaka South City Corporations) and peri-urban (Gazipur City Corporation) areas of Dhaka Division, Bangladesh. We analyzed 11 samples, including six RGS and five SGS samples from 11 individual gardens using 16S rRNA (V3-V4 region) gene-based amplicon sequencing. A total of 977 operational taxonomic units (OTUs), including 270 and 707 in RGS and SGS samples, respectively, were identified. The observed OTUs were represented by 21 phyla, 45 classes, 84 orders, 173 families, and 293 genera of bacteria. Alpha diversity indices revealed significantly higher bacterial diversity in SGS samples (p = 0.01), while beta diversity analyses indicated distinct bacteriome compositions between RGS and SGS samples (p = 0.028, PERMANOVA). Despite substantial taxonomic variability between sample categories, there was also a considerable presence of shared bacterial taxa. At the phylum level, Bacilliota (61.14%), Pseudomonadota (23.42%), Actinobacteria (6.33%), and Bacteroidota (3.32%) were the predominant bacterial phyla (comprising > 94.0% of the total abundances) in both types of garden soil samples. Of the identified genera, Bacillus (69.73%) and Brevibacillus (18.81%) in RGS and Bacillus (19.22%), Methylophaga (19.21%), Acinetobacter (6.27%), Corynebacterium (5.06%), Burkholderia (4.78%), Paracoccus (3.98%) and Lysobacter (2.07%) in SGS were the major bacterial genera. Importantly, we detected that 52.90% of genera were shared between RGS and SGS soil samples. Our data reveal unique and shared bacteriomes with probiotic potential in soil samples from both rooftop and surface gardens. Further studies should explore the functional roles of shared bacterial taxa in garden soils and how urban environmental factors affect microbiome composition to optimize soil health and sustainable food production.

Characterization of Shigella flexneri Serotype 6 Strains Isolated from Bangladesh and Identification of a New Phylogenetic Cluster.

A significant cause of shigellosis in Bangladesh and other developing countries is Shigella flexneri serotype 6. This serotype has been subtyped, on the basis of the absence or presence of a group-specific antigen, E1037, into S. flexneri 6a and 6b, respectively. Here, we provided rationales for the subclassification, using several phenotypic and molecular tools. A set of S. flexneri 6a and 6b strains isolated between 1997 and 2015 were characterized by analyzing their biochemical properties, plasmid profiles, virulence markers, pulsed-field gel electrophoresis (PFGE) results, and ribotype. Additionally, the genomic relatedness of these subserotypes was investigated with global isolates of serotype 6 using publicly available genomes. Both subserotypes of S. flexneri 6 agglutinated with monoclonal antiserum against S. flexneri (MASF) B and type VI-specific antiserum (MASF VI) and were PCR positive for O-antigen flippase-specific genes and virulence markers (ipaH, ial, sen, and sigA). Unlike S. flexneri 6a strains, S. flexneri 6b strains seroagglutinated with anti-E1037 antibodies, MASF IV-I. Notably, these two antigenically distinct subserotypes were clonally diverse, showing two distinct PFGE patterns following the digestion of chromosomal DNA with either XbaI or IceuI. In addition, hybridization of a 16S rRNA gene probe with HindIII-digested genomic DNA yielded two distinguishing ribotypes. Genomic comparison of S. flexneri subserotype 6a and 6b strains from Bangladesh indicated that, although these strains were in genomic synteny, the majority of them formed a unique phylogroup (PG-4) that was missing for the global isolates. This study supports the subserotyping and emphasizes the need for global monitoring of the S. flexneri subserotypes 6a and 6b. IMPORTANCE Shigella flexneri serotype 6 is one of the predominant serotypes among shigellosis cases in Bangladesh. Characterization of a novel subserotype of S. flexneri 6 (VI:E1037), agglutinated with type 6-specific antibody and anti-E1037, indicates a unique evolutionary ancestry. PFGE genotyping supports the finding that these two antigenically distinct subserotypes are clonally diverse. A phylogenetic study based on single-nucleotide polymorphism (SNP) data revealed that these two subserotypes were in genomic synteny, although their genomes were reduced. Interestingly, a majority of the S. flexneri 6 strains isolated from Bangladesh form a novel phylogenetic cluster. Therefore, this report underpins the global monitoring and tracking of the novel subserotype.

Increased iron utilization and oxidative stress tolerance in a Vibrio cholerae flrA mutant confers resistance to amoeba predation.

IMPORTANCE: Persistence of V. cholerae in the aquatic environment contributes to the fatal diarrheal disease cholera, which remains a global health burden. In the environment, bacteria face predation pressure by heterotrophic protists such as the free-living amoeba A. castellanii. This study explores how a mutant of V. cholerae adapts to acquire essential nutrients and survive predation. Here, we observed that up-regulation of iron acquisition genes and genes regulating resistance to oxidative stress enhances pathogen fitness. Our data show that V. cholerae can defend predation to overcome nutrient limitation and oxidative stress, resulting in an enhanced survival inside the protozoan hosts.

Metagenomic and culture-dependent approaches unveil active microbial community and novel functional genes involved in arsenic mobilization and detoxification in groundwater.

BACKGROUND: Arsenic (As) and its species are major pollutants in ecological bodied including groundwater in Bangladesh rendering serious public health concern. Bacteria with arsenotrophic genes have been found in the aquifer, converting toxic arsenite [As (III)] to less toxic arsenate [As (V)] that is easily removed using chemical and biological trappers. In this study, genomic and metagenomic approaches parallel to culture-based assay (Graphical abstract) have made it possible to decipher phylogenetic diversity of groundwater arsenotrophic microbiomes along with elucidation of their genetic determinants. RESULTS: Seventy-two isolates were retrieved from six As-contaminated (average As concentration of 0.23 mg/L) groundwater samples from Munshiganj and Chandpur districts of Bangladesh. Twenty-three isolates harbored arsenite efflux pump (arsB) gene with high abundance, and ten isolates possessing arsenite oxidase (aioA) gene, with a wide range of minimum inhibitory concentration, MICAs (2 to 32 mM), confirming their role in arsenite metabolism. There was considerable heterogeneity in species richness and microbial community structure. Microbial taxa from Proteobacteria, Firmicutes and Acidobacteria dominated these diversities. Through these combinatorial approaches, we have identified potential candidates such as, Pseudomonas, Acinetobacter, Stenotrophomonas, Achromobacter, Paraburkholderia, Comamonas and Klebsiella and associated functional genes (arsB, acr3, arsD, arsH, arsR) that could significantly contribute to arsenite detoxification, accumulation, and immobilization. CONCLUSIONS: Culture-dependent and -independent shotgun metagenomic investigation elucidated arsenotrophic microbiomes and their functions in As biogeochemical transformation. These findings laid a foundation for further large-scale researches on the arsenotrophic microbiomes and their concurrent functions in As biogeochemical transformation in As-contaminated areas of Bangladesh and beyond.

SARS-CoV-2 infection alters the gut microbiome in diabetes patients: A cross-sectional study from Bangladesh.

Populations of different South Asian nations including Bangladesh reportedly have a high risk of developing diabetes in recent years. This study aimed to investigate the differences in the gut microbiome of COVID-19-positive participants with or without type 2 diabetes mellitus (T2DM) compared with healthy control subjects. Microbiome data of 30 participants with T2DM were compared with 22 age-, sex-, and body mass index (BMI)-matched individuals. Clinical features were recorded while fecal samples were collected aseptically from the participants. Amplicon-based (16S rRNA) metagenome analyses were employed to explore the dysbiosis of gut microbiota and its correlation with genomic and functional features in COVID-19 patients with or without T2DM. Comparing the detected bacterial genera across the sample groups, 98 unique genera were identified, of which 9 genera had unique association with COVID-19 T2DM patients. Among different bacterial groups, Shigella (25%), Bacteroides (23.45%), and Megamonas (15.90%) had higher mean relative abundances in COVID-19 patients with T2DM. An elevated gut microbiota dysbiosis in T2DM patients with COVID-19 was observed while some metabolic functional changes correlated with bidirectional microbiome dysbiosis between diabetes and non-diabetes humans gut were also found. These results further highlight the possible association of COVID-19 infection that might be linked with alteration of gut microbiome among T2DM patients.

Environmental Reservoirs of Pathogenic Vibrio spp. and Their Role in Disease: The List Keeps Expanding.

Vibrio species are natural inhabitants of aquatic environments and have complex interactions with the environment that drive the evolution of traits contributing to their survival. These traits may also contribute to their ability to invade or colonize animal and human hosts. In this review, we attempt to summarize the relationships of Vibrio spp. with other organisms in the aquatic environment and discuss how these interactions could potentially impact colonization of animal and human hosts.

Adaptation to an Amoeba Host Leads to Pseudomonas aeruginosa Isolates with Attenuated Virulence.

The opportunistic pathogen Pseudomonas aeruginosa is ubiquitous in the environment, and in humans, it is capable of causing acute or chronic infections. In the natural environment, predation by bacterivorous protozoa represents a primary threat to bacteria. Here, we determined the impact of long-term exposure of P. aeruginosa to predation pressure. P. aeruginosa persisted when coincubated with the bacterivorous Acanthamoeba castellanii for extended periods and produced genetic and phenotypic variants. Sequencing of late-stage amoeba-adapted P. aeruginosa isolates demonstrated single nucleotide polymorphisms within genes that encode known virulence factors, and this correlated with a reduction in expression of virulence traits. Virulence for the nematode Caenorhabditis elegans was attenuated in late-stage amoeba-adapted P. aeruginosa compared to early-stage amoeba-adapted and nonadapted counterparts. Further, late-stage amoeba-adapted P. aeruginosa showed increased competitive fitness and enhanced survival in amoebae as well as in macrophage and neutrophils. Interestingly, our findings indicate that the selection imposed by amoebae resulted in P. aeruginosa isolates with reduced virulence and enhanced fitness, similar to those recovered from chronic cystic fibrosis infections. Thus, predation by protozoa and long-term colonization of the human host may represent similar environments that select for similar losses of gene function. IMPORTANCE Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute infections in plants and animals, including humans, and chronic infections in immunocompromised and cystic fibrosis patients. This bacterium is commonly found in soils and water, where bacteria are constantly under threat of being consumed by bacterial predators, e.g., protozoa. To escape being killed, bacteria have evolved a suite of mechanisms that protect them from being consumed or digested. Here, we examined the effect of long-term predation on the genotypes and phenotypes expressed by P. aeruginosa. We show that long-term coincubation with protozoa gave rise to mutations that resulted in P. aeruginosa becoming less pathogenic. This is particularly interesting as similar mutations arise in bacteria associated with chronic infections. Importantly, the genetic and phenotypic traits possessed by late-stage amoeba-adapted P. aeruginosa are similar to those observed in isolates obtained from chronic cystic fibrosis infections. This notable overlap in adaptation to different host types suggests similar selection pressures among host cell types as well as similar adaptation strategies.

Evolutionary dynamics of SARS-CoV-2 nucleocapsid protein and its consequences.

The emerged novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global health crisis that warrants an accurate and detailed characterization of the rapidly evolving viral genome for understanding its epidemiology, pathogenesis, and containment. Here, we explored 61,485 sequences of the nucleocapsid (N) protein, a potent diagnostic and prophylactic target, for identifying the mutations to review their roles in real-time polymerase chain reaction based diagnosis and observe consequent impacts. Compared to the Wuhan reference strain, a total of 1034 unique nucleotide mutations were identified in the mutant strains (49.15%, n = 30,221) globally. Of these mutations, 367 occupy primer binding sites including the 3'-end mismatch to the primer-pair of 11 well-characterized primer sets. Noteworthily, CDC (USA) recommended the N2 primer set contained a lower mismatch than the other primer sets. Moreover, 684 amino acid (aa) substitutions were located across 317 (75.66% of total aa) unique positions including 82, 21, and 83 of those in the RNA binding N-terminal domain (NTD), SR-rich region, and C-terminal dimerization domain, respectively. Moreover, 11 in-frame deletions, mostly (n = 10) within the highly flexible linker region, were revealed, and the rest was within the NTD region. Furthermore, we predicted the possible consequence of high-frequency mutations (≥20) and deletions on the tertiary structure of the N protein. Remarkably, we observed that a high frequency (67.94% of mutated sequences) co-occuring mutations (R203K and G204R) destabilized and decreased overall structural flexibility. The N protein of SARS-CoV-2 comprises an average of 1.2 mutations per strain compared to 4.4 and 0.4 in Middle East respiratory syndrome-related coronavirus and SARS-CoV, respectively. Despite being proposed as the alternative target to spike protein for vaccine and therapeutics, the ongoing evolution of the N protein may challenge these endeavors, thus needing further immunoinformatics analyses. Therefore, continuous monitoring is required for tracing the ongoing evolution of the SARS-CoV-2 N protein in prophylactic and diagnostic interventions.

Microbial co-infections in COVID-19: Associated microbiota and underlying mechanisms of pathogenesis.

The novel coronavirus infectious disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has traumatized the whole world with the ongoing devastating pandemic. A plethora of microbial domains including viruses (other than SARS-CoV-2), bacteria, archaea and fungi have evolved together, and interact in complex molecular pathogenesis along with SARS-CoV-2. However, the involvement of other microbial co-pathogens and underlying molecular mechanisms leading to extortionate ailment in critically ill COVID-19 patients has yet not been extensively reviewed. Although, the incidence of co-infections could be up to 94.2% in laboratory-confirmed COVID-19 cases, the fate of co-infections among SARS-CoV-2 infected hosts often depends on the balance between the host's protective immunity and immunopathology. Predominantly identified co-pathogens of SARS-CoV-2 are bacteria such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Acinetobacter baumannii, Legionella pneumophila and Clamydia pneumoniae followed by viruses including influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. The cross-talk between co-pathogens (especially lung microbiomes), SARS-CoV-2 and host is an important factor that ultimately increases the difficulty of diagnosis, treatment, and prognosis of COVID-19. Simultaneously, co-infecting microbiotas may use new strategies to escape host defense mechanisms by altering both innate and adaptive immune responses to further aggravate SARS-CoV-2 pathogenesis. Better understanding of co-infections in COVID-19 is critical for the effective patient management, treatment and containment of SARS-CoV-2. This review therefore necessitates the comprehensive investigation of commonly reported microbial co-pathogens amid COVID-19, their transmission pattern along with the possible mechanism of co-infections and outcomes. Thus, identifying the possible co-pathogens and their underlying molecular mechanisms during SARS-CoV-2 pathogenesis may shed light in developing diagnostics, appropriate curative and preventive interventions for suspected SARS-CoV-2 respiratory infections in the current pandemic.

Microbiome dynamics and genomic determinants of bovine mastitis.

The milk of lactating cows presents a complex ecosystem of interconnected microbial communities which can influence the pathophysiology of mastitis. We hypothesized possible dynamic shifts of microbiome composition and genomic features with different pathological conditions of mastitis (Clinical Mastitis; CM, Recurrent CM; RCM, Subclinical Mastitis; SCM). To evaluate this hypothesis, we employed whole metagenome sequencing (WMS) in 20 milk samples (CM, 5; RCM, 6; SCM, 4; H, 5) to unravel the microbiome dynamics, interrelation, and relevant metabolic functions. The WMS data mapped to 442 bacterial, 58 archaeal and 48 viral genomes with distinct variation in microbiome composition (CM > H > RCM > SCM). Furthermore, we identified a number of microbial genomic features, including 333, 304, 183 and 50 virulence factors-associated genes (VFGs) and 48, 31, 11 and 6 antibiotic resistance genes (ARGs) in CM, RCM, SCM, and H-microbiomes, respectively. We also detected different metabolic pathway and functional genes associated with mastitis pathogenesis. Therefore, profiling microbiome dynamics in different conditions of mastitis and associated microbial genomic features contributes to developing microbiome-based diagnostics and therapeutics for bovine mastitis.

Toward Smaller Aqueous-Phase Plasmonic Gold Nanoparticles: High-Stability Thiolate-Protected ∼4.5 nm Cores.

Most applications of aqueous plasmonic gold nanoparticles benefit from control of the core size and shape, control of the nature of the ligand shell, and a simple and widely applicable preparation method. Surface functionalization of such nanoparticles is readily achievable but is restricted to water-soluble ligands. Here we have obtained highly monodisperse and stable smaller aqueous gold nanoparticles (core diameter ∼4.5 nm), prepared from citrate-tannate precursors via ligand exchange with each of three distinct thiolates: 11-mercaptoundecanoic acid, α-R-lipoic acid, and para-mercaptobenzoic acid. These are characterized by UV-vis spectroscopy for plasmonic properties; Fourier transform infrared (FTIR) spectroscopy for ligand-exchange confirmation; X-ray diffractometry for structural analysis; and high-resolution transmission electron microscopy for structure and size determination. Chemical reduction induces a blueshift, maximally +0.02 eV, in the localized surface plasmon resonance band; this is interpreted as an electronic (-) charging of the monolayer-protected cluster (MPC) gold core, corresponding to a -0.5 V change in electrochemical potential.

Impact of Climate Change and Land Use on Groundwater Salinization in Southern Bangladesh-Implications for Other Asian Deltas.

Pervasive salinity in soil and water is affecting agricultural yield and the health of millions of delta dwellers in Asia. This is also being exacerbated by climate change through increases in sea level and tropical storm surges. One consequence of this has been a widespread introduction of salt water shrimp farming. Here, we show, using field data and modeling, how changes in climate and land use are likely to result in increased salinization of shallow groundwater in SE Asian mega-deltas. We also explore possible adaptation options. We find that possible future increase of episodic inundation events, combined with salt water shrimp farming, will cause rapid salinization of groundwater in the region making it less suitable for drinking water and irrigation. However, modified land use and water management practices can mitigate the impacts on groundwater, as well as the overlying soil, from future salinization. The study therefore provides guidance for adaptation planning to reduce future salinization in Asian deltas.

Differential Hepatotoxic Effects of Sodium Valproate at Different Doses in Albino Rats.

Background Liver plays an essential role for transforming and clearing chemicals that may cause harmful effects to it. Sodium Valproate, renowned to be a potent antiepileptic drug, when taken in overdose may cause toxic effects to liver and other organs as well. Liver damage can be assessed with histological changes and measurement of enzymes produced by it. Objective To investigate the histological changes induced by different doses of Sodium Valproate ranging from 100-500 mg/kg/day and observe its correlation with liver enzymes level in serum. Method Three-months old albino rats were divided into six groups, five in each. Control group was treated with normal saline and rest five groups with Sodium Valproate in different doses 100, 200, 300, 400 and 500 mg/kg/day respectively. Then, liver of those experimented rats were examined histologically under the light microscope. Furthermore, Liver enzymes; Alanine Transaminase and Aspartate transaminase were measured to assess the micro-anatomical changes in liver. Result Distorted hepatic lobular architecture with aggregations of nuclei at certain interval was observed in the groups of higher doses; 300 mg/kg/day and above. However, accumulation of adipocytes was observed in all the Sodium Valproate treated rats unlike the control group. When compared the enzyme levels among the groups, it was found to be significantly increased in dose dependent manner. Besides, it also showed skin lesions in all rats treated with the dose 400 mg/kg/day and above. Conclusion Higher doses of Sodium Valproate; 300 mg/kg/day and above induces hepatotoxicity and skin lesions in adult albino rats.

Patient-derived xenografts effectively capture responses to oncology therapy in a heterogeneous cohort of patients with solid tumors.

BACKGROUND: While patient-derived xenografts (PDXs) offer a powerful modality for translational cancer research, a precise evaluation of how accurately patient responses correlate with matching PDXs in a large, heterogeneous population is needed for assessing the utility of this platform for preclinical drug-testing and personalized patient cancer treatment. PATIENTS AND METHODS: Tumors obtained from surgical or biopsy procedures from 237 cancer patients with a variety of solid tumors were implanted into immunodeficient mice and whole-exome sequencing was carried out. For 92 patients, responses to anticancer therapies were compared with that of their corresponding PDX models. RESULTS: We compared whole-exome sequencing of 237 PDX models with equivalent information in The Cancer Genome Atlas database, demonstrating that tumorgrafts faithfully conserve genetic patterns of the primary tumors. We next screened PDXs established for 92 patients with various solid cancers against the same 129 treatments that were administered clinically and correlated patient outcomes with the responses in corresponding models. Our analysis demonstrates that PDXs accurately replicate patients' clinical outcomes, even as patients undergo several additional cycles of therapy over time, indicating the capacity of these models to correctly guide an oncologist to treatments that are most likely to be of clinical benefit. CONCLUSIONS: Integration of PDX models as a preclinical platform for assessment of drug efficacy may allow a higher success-rate in critical end points of clinical benefit.

HIV-1 Alters Intestinal Expression of Drug Transporters and Metabolic Enzymes: Implications for Antiretroviral Drug Disposition.

This study investigated the effects of HIV-1 infection and antiretroviral therapy (ART) on the expression of intestinal drug efflux transporters, i.e., P-glycoprotein (Pgp), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP), and metabolic enzymes, such as cytochrome P450s (CYPs), in the human upper intestinal tract. Intestinal biopsy specimens were obtained from HIV-negative healthy volunteers, ART-naive HIV-positive (HIV(+)) subjects, and HIV(+) subjects receiving ART (10 in each group). Intestinal tissue expression of drug transporters and metabolic enzymes was examined by microarray, real-time quantitative reverse transcription-PCR (qPCR), and immunohistochemistry analyses. Microarray analysis demonstrated significantly lower expression of CYP3A4 and ABCC2/MRP2 in the HIV(+) ART-naive group than in uninfected subjects. qPCR analysis confirmed significantly lower expression of ABCC2/MRP2 in ART-naive subjects than in the control group, while CYP3A4 and ABCG2/BCRP showed a trend toward decreased expression. Protein expression of MRP2 and BCRP was also significantly lower in the HIV(+) naive group than in the control group and was partially restored to baseline levels in HIV(+) subjects receiving ART. In contrast, gene and protein expression of ABCB1/Pgp was significantly increased in HIV(+) subjects on ART relative to HIV(+) ART-naive subjects. These data demonstrate that the expression of drug-metabolizing enzymes and efflux transporters is significantly altered in therapy-naive HIV(+) subjects and in those receiving ART. Since CYP3A4, Pgp, MRPs, and BCRP metabolize or transport many antiretroviral drugs, their altered expression with HIV infection may negatively impact drug pharmacokinetics in HIV(+) subjects. This has clinical implications when using data from healthy volunteers to guide ART.

Monitoring contaminants of emerging concern from tertiary wastewater treatment plants using passive sampling modelled with performance reference compounds.

The Lake Simcoe watershed in Ontario, Canada is an important recreational area and a recharge zone for groundwater resources. Lake Simcoe is a relatively shallow lotic system that has been impacted by urban development, recreation, industry and agriculture. As part of a watershed management plan, six wastewater treatment plants (WWTPs) located in this catchment basin were selected to measure the inputs of contaminants of emerging concern (CECs) of wastewater origin. These WWTPs were recently upgraded to tertiary treatment for phosphorus removal. Polar organic chemical integrative samplers (POCIS) and semipermeable membrane devices (SPMDs) were used to monitor for hydrophilic and hydrophobic CECs, respectively, in treated and untreated wastewater. The passive samplers were calibrated with performance reference compounds (PRCs) by measuring the loss of deuterated beta blocker drugs spiked into POCIS and the loss of PCB congeners spiked into SPMDs over the course of 14-day deployment periods. From the PRC data, field sampling rates of CECs were determined and applied to estimate time-weighted average (TWA) concentrations and mass loadings in mg/day/1000 members of the population serviced. In treated wastewater, TWA concentrations of an antibiotic, sulfamethoxazole, the prescription drugs, carbamazepine, naproxen and gemfibrozil, and the non-prescription drug, ibuprofen, were estimated to be in the low (<18 ng/L) range. The artificial sweeteners, sucralose and acesulfame, were particularly useful chemical tracers, with estimated TWA concentrations in treated wastewater ranging from 128 to 213 ng/L and 4 to 33 ng/L, respectively. The steroid hormones were detected only rarely in treated wastewater. Triclosan, triclocarban and the synthetic musks, HHCB and AHTN, were removed efficiently (>77 %), possibly because of the tertiary treatment technologies. Therefore, the mass loadings for these personal care products were all <5 mg/day/1000 people. Overall, this study indicates that tertiary treatment technologies designed for phosphorus removal do not entirely remove the target CECs.

Left Atrial Myxoma in a Late Case of Lung Carcinoma.

Concomitant occurrence of lung carcinoma and an atrial myxoma is rare. We are reporting such a case, a 55 year old male, farmer, smoker for 30 years was under evaluation for his recent episode of stroke with hemiparesis during which an echocardiography showed presence of a left atrial myxoma and chest x-ray showed a lesion in the midzone of right lung. Fine needle aspiration cytology (FNAC) from enlarged right supraclavicular lymphnode revealed metastatic adenocarcinoma. Patient was referred to a tertiary cancer care hospital thereafter.

Evaluation of Iron Store by Serum Ferritin in Healthy Blood Donors of Bangladesh.

Iron stores in the body exist primarily in the form of ferritin. Small amounts of ferritin secreted into the plasma and plasma ferritin is positively correlated with the size of the total body iron stores. The present study conducted to determine the iron status using the serum ferritin level among healthy Bangladeshi blood donors. The present cross sectional study was conducted in the Department of Transfusion Medicine, Dhaka Medical College, Dhaka, Bangladesh from July 2011 to June 2012. Blood donor signed informed consent and has satisfactory pre-donation health assessment and satisfactory post-donation blood test results were included in the study. Full blood counts were performed within 4 hours of collection using an automated haematology analyzer. Serum ferritin was measured using a validated enzyme immunoassay. Data were analyzed using SPSS version 16 (SPPS Incorporation, Chicago, IL, USA). P value <0.05 was considered as statistically significant. Total 100 blood donors were included in the study, among them 88 were male and 12 were female. Mean±SD of the age of the respondents was 26.8±5.9 years with a range of 19 to 45 years. Mean±SD of heamoglobin level (gm/dl) and total count of Red Blood Cell (million/cmm) were 14.1±1.4 and 5.1±0.4 respectively. Mean±SD of serum ferritin level (ng/ml) was 96.4±69.0ng/ml with a range of 4.1ng/ml to 298.7ng/ml. Among the respondents 9.0% had depleted iron store, 7.0 reduced iron store and 84.0% had normal iron store. Among the respondents 5.0% had iron deficiency anaemia in term of serum ferritin level. Statistically significant difference of serum ferritin level observed between male and female and donors with and without history of previous blood donation. Among the healthy blood donors of Bangladesh abnormal serum ferritin is highly prevalent among blood donors specially among female. Monitoring of iron stores by serum ferritin seems justified in order to identify those with depleted iron stores who will benefit from iron supplementation.