Carrier State Research Articles

Case-control study to identify management practices associated with morbidity or mortality due to bovine anaplasmosis in Mississippi cow-calf herds

Bovine anaplasmosis (BA) is a costly disease affecting the U.S. beef cattle industry. Chlortetracycline (CTC) in feed or mineral supplements is often used to control clinical signs of BA. The objective of this study was to determine if manage­ment practices, such as feeding CTC, are associated with ill­ness or death from BA in Mississippi cow-calf herds. Case and control herds were solicited from veterinary practices across Mississippi. Cases were herds with clinical BA diagnosed by a veterinarian within the previous calendar year. Controls were herds under the care of the same practice with no clini­cal BA diagnosed in the previous year. Blinded interviewers conducted telephone surveys of case and control herd owners. Management and biosecurity factors were tested for associa­tion with herd status using a logistic regression generalized linear mixed model with veterinary practice as a random vari­able. Twenty-two case and 25 control herds from 6 veterinary practices across Mississippi were interviewed, representing 22 counties. The average herd size was 132 for case herds, and 136 for control herds. Twenty case herds and 13 control herds fed CTC medicated mineral or feed. Providing CTC was associated with case herd status (OR = 9.2, 95% C.I. = 1.7-50.7). The association observed between case herds and feeding CTC might be because: 1) herds that had experienced previous BA morbidity and mor­tality subsequently began feeding CTC, or 2) some individual cattle consume enough CTC to achieve clearance of the per­sistent carrier state, thereby increasing risk of reinfection and clinical BA.

#2436 Genetic variability in rosuvastatin metabolism explains rhabdomyolysis and consequent acute renal failure

Abstract Background and Aims Low density lipoprotein cholesterol is an independent risk factor for atherosclerotic cardiovascular disease. Rosuvastatin is one of the most frequently prescribed statins and also one of the most frequent causes of rhabdomyolysis with consequent acute renal failure (ARF). Risk factors for statin induced rhabdomyolysis, i.e. the type of statin and its dose, patient's age, kidney and liver function, gender and concurrent treatment with cytochrome P450 (CYP) inhibitors, should be considered at the time of statin prescription. Single nucleotide polymorphisms (SNPs) in genes coding the transport proteins (SLCO1B1, ABCG2) and CYP2C9, catalysing rosuvastatin oxidation, may lead to decreased protein function leading to accumulation of plasma rosuvastatin which increases the risk of rhabdomyolysis. Herewith we present a case of a female patient admitted to our department due to rhabdomyolysis and ARF with the aim of alerting against uncritical high dose rosuvastatin prescribing and of pointing out the role of genetic variability in drug metabolizing enzymes and transporters (DMET) in rosuvastatin side effects. Method a 79-years old Caucasian woman admitted to our department due to rhabdomyolysis and ARF was genotyped for polymorphisms in DMET genes coding for CYP2C9 (rs1799853, rs1057910, rs28371686, rs28371685), SLCO1B1 (rs4149056, rs2306283) and ABCG2 (rs2231142) using competitive allele specific polymerase chain reaction (KASPar). Results Presented patient suffered from an acute myocardial infarction in October 2023. She was treated with percutaneous coronary intervention, antiaggregation therapy and hypolipidemic therapy (rosuvastatin 40 mg/ezetimibe 10 mg). Her creatinine was 55 μM (eGFR 61 ml/min) at the time of statin prescription. Several months later she was admitted septic with myoglobin >50.000 μg/L and creatinine approximately 1600 μM. Infection was treated with piperacillin/tazobactam. Myoglobin was removed with Theranova dialyzer. The patient was dismissed home two weeks later with creatinine 230 μM. As potential patient's risk factors for rhabdomyolysis we considered high dose of rosuvastatin, patient's higher age and slower rosuvastatin disposition due to SNPs in DMET. Sepsis may have been an additional contributory factor. Genotyping revealed polymorphisms in all three genes involved in rosuvastatin metabolism and transport: CYP2C9, SLCO1B1 and ABCG2 (Table 1). Two genotypes resulted in the phenotypes with slower rosuvastatin metabolism, probably leading to gradual accumulation of plasma rosuvastatin, which may have manifested in rhabdomyolysis that contributed to ARF. Heterozygous CYP2C9*2 and *3 carriers have, in comparison to the wild type carriers, approximately 30% and 80% slower rosuvastatin metabolism, respectively. Heterozygous ABCG2 c.421C>A carrier state may also contribute slightly to rosuvastatin accumulation. Furthermore, the potential interaction with inflammation should not be overlooked, as inflammation may have a major effect on drug metabolism and transport through downregulation of CYP enzymes as well as drug transporters. If genotypes of the respective DMET genes were known in advance, high dose rosuvastatin could have been avoided despite relatively good kidney function at the time of rosuvastatin prescription. Conclusion Statins should be prescribed with caution and their dose adapted to the risk factors that should always be checked for at the time of statin prescription. We recommend periodical surveillance of serum creatinine, eGFR, urine protein to creatinine ratio, liver tests, creatine kinase and myoglobin in patients treated with high dose statins. Furthermore, SLCO1B1, ABCG2 and CYP2C9 genotyping before rosuvastatin prescription would enable insight into its metabolism. Genotype information could lead to more cautious statin prescribing, especially in the presence of other factors, such as infection or concomitant drug treatment that may modify the activity of DMET. In the case of chronic kidney disease drug dosing should be appropriately adjusted in accordance with drug's Summary of product characteristics and KDIGO guidelines.

Alloy composition dependent built-in polarization fields and quantized carrier states in III-nitride multi-quantum well structures

In this paper, mole fraction dependent strain in a III-nitride alloy and its effects on built-in polarization and quantized states in multi-quantum-wells (MQWs) have been investigated. The internal electric field arising out of spontaneous and piezoelectric polarizations in the presence of strain has been calculated. Then, the energy eigenvalues and wavefunctions of carriers in the modified potential well configurations have been computed by solving a time-independent Schrödinger equation using a finite difference method. Next, the overlap integrals between the wavefunctions of bound states in conduction and valence bands, an important consideration for optical transitions, have been computed and plotted. The results are shown taking three nitride-based MQW structures InGaN/GaN, GaN/AlGaN, and InGaN/InAlN as examples. The study helps choose suitable mole fractions for the improved and desired performance of the nitride MQW based devices.

Synthesis and characterization of uniform 3R phase bilayer MoS2 on sapphire

Bilayer (BL) two-dimensional transition metal dichalcogenides (TMDs) exhibit excellent properties in carrier mobility, state density, and room temperature stability, which attract considerable attention. However, previous efforts on synthesis BL TMDs have lacked homogeneity and control over the number of layers. Here, we demonstrate an effective and controllable approach to synthesize highly uniform 3R phase BL MoS2 on a c-plane sapphire substrate. The number of MoS2 layer can be controlled by adjusting the confinement distance, sapphire step height (annealing temperature), and growth temperature. These influencing factors have been thoroughly investigated. Raman and PL analyses demonstrate bilayer properties and remarkable uniformity. SHG and HAADF-STEM measurements reveal 3R stacking structure of BL MoS2. Furthermore, field-effect-transistor (FET) devices fabricated using BL MoS2 domains exhibit high carrier mobility and on/off ratio. This work provides an efficient method for layer-controlled MoS2 growth and offers new insights into the growth mechanism of BL MoS2.

Porcine Circovirus Type 3 (PCV3) in Poland: Prevalence in Wild Boar Population in Connection with African Swine Fever (ASF).

Human health is dependent on food safety and, therefore, on the health of farm animals. One of the most significant threats in regard to swine diseases is African swine fever (ASF). Infections caused by porcine circoviruses (PCVs) represent another important swine disease. Due to the ubiquitous nature of PCV2, it is not surprising that this virus has been detected in ASFV-affected pigs. However, recent data indicate that coinfection of PCV3 and ASFV also occurs. It is still unclear whether PCV infection plays a role in ASFV infection, and that subject requires further analysis. The aim of this study was to assess whether PCV3 and PCV4 are present in the wild boar population in Poland (real-time PCR). The analysis was performed on wild boar samples collected for routine ASF surveillance in Poland, between 2018 and 2021. By extension, the obtained data were compared in regard to ASFV presence in these samples, thus investigating the odds of ASFV infection on the grounds of the PCV carrier state in free-ranging Suidae in Poland. In addition, sequencing of PCV3 and phylogenetic analysis were performed, based on a full genome and a capsid gene. In the current study, we demonstrated the high prevalence of PCV3 in the wild boar population in Poland; meanwhile, PCV4 was not detected. The odds of ASFV infection on the grounds of the PCV3 carrier state in free-ranging Suidae in Poland was more than twice as high. Ten full genome sequences of PCV3 were obtained, all of them belonging to clade 3a. The similarity between them was in the range of 98.78-99.80%.

Possibility of Lunar Crustal Magmatism Producing Strong Crustal Magnetism

AbstractThe Moon generated a long‐lived core dynamo magnetic field, with intensities at least episodically reaching ∼10–100 μT during the period prior to ∼3.56 Ga. While magnetic anomalies observed within impact basins are likely attributable to the presence of impactor‐added metal, other anomalies such as those associated with lunar swirls are not as conclusively linked to exogenic materials. This has led to the hypothesis that some anomalies may be related to magmatic features such as dikes, sills, and laccoliths. However, basalts returned from the Apollo missions are magnetized too weakly to produce the required magnetization intensities (>0.5 A/m). Here, we test the hypothesis that subsolidus reduction of ilmenite within or adjacent to slowly cooled mafic intrusive bodies could locally enhance metallic FeNi contents within the lunar crust. We find that reduction within hypabyssal dikes with high‐Ti or low‐Ti mare basalt compositions can produce sufficient FeNi grains to carry the minimum >0.5 A/m magnetization intensity inferred for swirls, especially if ambient fields are >10 μT or if fine‐grained Fe‐Ni metals in the pseudo‐single domain grain size range are formed. Therefore, there exists a possibility that certain magnetic anomalies exhibiting various shapes such as linear, swarms, and elliptical patterns may be magmatic in origin. Our study highlights that the domain state of the magnetic carriers is an under‐appreciated factor in controlling a rock's magnetization intensity. The results of this study will help guide interpretations of lunar crustal field data acquired by future rovers that will traverse lunar magnetic anomalies.

FINAL SIZE RELATIONS FOR SOME COMPARTMENTAL MODELS IN EPIDEMIOLOGY

The summary measurement of an epidemic such as the final size is an important quantity that allows us to approximate the impact of the disease on the affected region. In recent years, final size measurements for vector-transmitted diseases have acquired importance because of the increased concern for mosquito-borne diseases like dengue, Zika, Chikungunya, etc. However, analytical expressions for this estimate in the stage-structured models applicable to vector-borne diseases are less, mostly focused on the classical Kermack–McKendrick model. In this paper, we first calculate the final size expressions for an SIR model with carrier state and a SEIR–SI host–vector model. Then we extend this for the SEIR–SI host–vector model with treatment class in the host, as well as for the model with vertical transmission in the vector population. Finally, we verify our final size expression with some real scenarios.

The lack of HBsAg secretion does neither facilitate induction of antiviral T cell responses nor Hepatitis B Virus clearance in mice

Immune tolerance to the hepatitis B virus (HBV) is crucial for developing chronic hepatitis B, and the HBV surface antigen (HBsAg) produced and secreted in high amounts is regarded as a key contributor. HBsAg is expressed in HBV-infected hepatocytes and those carrying an HBV integration. Whether either HBsAg secretion or the high antigen amount expressed in the liver determines its immunomodulatory properties, however, remains unclear. We, therefore, developed a novel HBV animal model that allowed us to study the role of secreted HBsAg. We introduced a previously described HBs mutation, C65S, abolishing HBsAg secretion into a replication-competent 1.3-overlength HBV genome and used adeno-associated virus vectors to deliver it to the mouse liver. The AAV-HBV established a carrier state of wildtype and C65S mutant HBV, respectively. We investigated antiviral B- and T-cell immunity in the HBV-carrier mice after therapeutic vaccination. Moreover, we compared the effect of a lacking HBsAg secretion with that of an antiviral siRNA. While missing HBsAg secretion allowed for higher levels of detectable anti-HBs antibodies after therapeutic vaccination, it did neither affect antiviral T-cell responses nor intrahepatic HBV gene expression, irrespective of the starting level. A treatment with HBV siRNA restricting viral antigen expression within hepatocytes, however, improved the antiviral efficacy of therapeutic vaccination, irrespective of the ability of HBV to secrete HBsAg. Our data indicate that clearing HBsAg from blood cannot significantly impact HBV persistence or T-cell immunity. This indicates that a restriction of hepatic viral antigen expression will be required to break HBV immunotolerance.

Carrier state of enterotoxigenic Escherichia coli virulence markers in pigs: Effects on gut microbiota modulation and immune markers transcription

Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in pigs at early age, leading to high mortality rates and significant economic losses in the swine industry. ETEC effect on gut microbiota and immune system is mostly studied in diarrheic model under controlled laboratory conditions, however its impact on asymptomatic carriers remains unknown. Thus, we investigated whether ETEC can modulate gut microbiota or regulate the transcription of immune markers in asymptomatic pigs in farm environment. Stool samples from newborn piglets, nursery and growing pigs, and sows were screened for ETEC markers, then submitted to 16S-rDNA sequencing to explore gut microbiota composition in carriers (ETEC+) and non-carriers (ETEC-) animals. We observed a reduced α-diversity in ETEC+ animals (p < 0.05), while bacterial compositions were mostly driven by ageing (p > 0.05). Prevotella marked ETEC-carrier group, while Rikenellaceae RC9 gut group was a marker for a healthy gut microbiota, suggesting that they might be biomarker candidates for surveillance and supplementation purposes. Furthermore, we observed transcription regulation of il6 and tff2 genes in ETEC+ in newborn and nursery stages, respectively. Our findings indicate that ETEC presence modulate gut microbiota and the immune response in asymptomatic pigs; nevertheless, further studies using a probabilistic design must be performed to assess the effect of ETEC presence on gut imbalance in pigs despite the age bias.

Broadband Emission Induced by Band-Edge Carrier Reconfiguration in 2D Hybrid Lead Halide Perovskites.

Broadband emission in hybrid lead halide perovskites (LHPs) has gained significant attention due to its potential applications in optoelectronic devices. The origin of this broadband emission is primarily attributed to the interactions between electrons and phonons. Most investigations have focused on the impact of structural characteristics of LHPs on broadband emission, while neglecting the role of electronic mobility. In this work, the study investigates the electronic origins of broadband emission in a family of 2D LHPs. Through spectroscopic experiments and density functional theory calculations, the study unveils that the electronic states of the organic ligands with conjugate effect in LHPs can extend to the band edges. These band-edge carriers are no longer localized only within the inorganic layers, leading to electronic coupling with molecular states in the barrier and giving rise to additional interactions with phonon modes, thereby resulting in broadband emission. The high-pressure photoluminescence measurements and theoretical calculations reveal that hydrostatic pressure can induce the reconfiguration of band-edge states of charge carriers, leading to different types of band alignment and achieving macroscopic control of carrier dynamics. The findings can provide valuable guidance for targeted synthesis of LHPs with broadband emission and corresponding design of state-of-the-art optoelectronic devices.

Genome-Wide Analysis of Exertional Rhabdomyolysis in Sickle Cell Trait Positive African Americans.

Sickle cell trait (SCT), although generally a benign carrier state of hemoglobin S (HbAS), is a risk factor for exertional rhabdomyolysis (ERM), a rare but potentially fatal consequence of highly intense physical exercise, particularly among active-duty military personnel and high-performance athletes. The association between SCT and ERM is poorly understood. The objective of this study was to elucidate the genetic basis of ERM in an SCT-positive African American cohort. SCT-positive African Americans with a personal history of ERM (cases, n = 30) and without history of ERM (controls, n = 53) were enrolled in this study. Whole-genome sequencing was performed on DNA samples isolated from peripheral white blood cells. Participants' demographic, behavioral, and medical history information was obtained. An additional 131 controls were extracted from SCT-positive subjects of African descent from the 1000 Genomes Project. SCT carriers with ERM were characterized by myotoxicity features, significant muscle involvement dominated by muscle weakness, and severe pain and substantial increase in serum creatine kinase, with a mean value of 50,480 U/L. A distinctive feature of the SCT individuals with ERM was exertional collapse, which was reported in 53.3% of the cases in the study cohort. An important factor for the development of ERM was the duration and frequency of strenuous physical activity in the cases compared to the controls. Whole-genome sequencing identified 79,696 protein-coding variants. Genome-wide association analysis revealed that the p.C477R, rs115958260 variant in the SLC44A3 gene was significantly associated with ERM event in SCT-positive African Americans. The study results suggest that a combination of vigorous exercise and a genetic predisposing factor is involved in ERM.

Uptake rate of carrier screening among consanguineous couples.

To quantify the uptake rates of Carrier Screening (CS) in consanguineous couples and compare this rate to that of non-consanguineous couples. We performed a matched case control study of 82 consanguineous couples seen at Rutgers-Robert Wood Johnson Medical school who were offered carrier screening between January 1, 2012 and October 10, 2022. We then matched each consanguineous female patient to a non-consanguineous female control patient who was also offered CS at the time of their genetic counseling appointment. A 2×2 contingency table analysis was used to compare rates of acceptance and declination between the consanguineous and non-consanguineous groups. The overall acceptance rate among consanguineous couples was 82.9%, whereas the overall acceptance rate among non-consanguineous couples was 56.1%. After statistical analysis, consanguineous couples were significantly more likely to accept CS as compared to non-consanguineous couples (OR=3.801, 95% CI; p<0.0001). We also report the carrier couple rates and individual carrier statistics between these two groups. This study supports the idea that consanguineous couples are more likely to pursue CS and have a higher carrier couple yield.

Ultraweakly low-dispersion epsilon-negative response of GR-CNT/PVDF ternary metacomposites

The epsilon-negative (ε’ < 0) response displayed by metacomposites offers notable potential for diverse applications in the design of dielectric and electromagnetic (EM) devices, underpinned by novel principles. However, achieving a weakly low-dispersion ε′-negative performance within the radio frequency (RF) band remains challenging. In this study, we bypassed this issue by constructing three-dimensional (3D) conductive networks through the integration of graphene (GR) and carbon nanotubes (CNT) with polyvinylidene fluoride (PVDF) serving as the matrix material. Leveraging the modifiable GR-CNT network, a ε′-negative response at approximately −20 was attained spanning the 100 MHz-1 GHz range. This ultraweak ε′-negative response was attributed to the formation of a moderate plasmonic state of free carriers within the metacomposites. Further, simulations were conducted, assessing the electric field vector distribution of the ε′-negative materials, revealing promising EM shielding performance. Concurrently, this investigation elucidates the RF ε′-negative response mechanism, paving the way for the practical application of metacomposites.

Chronic Granulomatous Disease; Experience of a Rare Primary Immunodeficiency from a Tertiary Care Center in Pakistan

Objective: To determine the clinical parameters, consanguinity of parents, previous family history of primary immunodeficiency (PID) and Neutrophil oxidative index (NOI) of Dihydrorhodamine (DHR) assay in chronic granulomatous disease (CGD). Study Design: Cross-sectional study. Place and Duration of Study: Immunology Department, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from Jan 2015 to Dec 2020. Methodology: A total of 18 patients with chronic granulomatous disease were diagnosed over six years by Dihydrorhodamine assay on flow cytometry, in our institute. Results: The mean age of patients at the time of symptoms was 4.0±3.01 months, while diagnosis was made at the mean age of 42.02±46.00 months. In 6 years, 13(72%) males and 5(28%) females were diagnosed with chronic granulomatous disease by DHR assay on flow cytometry. Parents of fifteen patients (83%) had consanguineous marriages, and 8(44%) patients had positive family history of PIDs. DHR assay showed two mothers had carrier states. The commonest clinical presentation noted was recurrent respiratory tract infections in 16 (89%) patients, repeated abscesses were seen in 13 (72%) and 5(28%) patients had a history of tuberculosis. Conclusion: Chronic granulomatous disease should be suspected in patients with repeated chest infections (especially with catalase-positive organisms), abscesses, diarrhoea and death of siblings at an early age with undiagnosed PID.

Typhoidal salmonella disease in Mukuru informal settlement, Nairobi Kenya; carriage, diversity, and antimicrobial resistant genes.

Multiple studies have shown that typhoid fever is endemic in developing countries characterized by poor hygiene. A unique way of Salmonella Typhi (S.Typhi) pathogenicity is establishing a persistent, usually asymptomatic carrier state in some infected individuals who excrete large numbers of bacteria in faeces. This study aimed to determine the isolation rate of S.Typhi from blood and stool samples among cases and asymptomatic individuals in the Mukuru informal settlement and identify antibiotic resistance patterns within the same population. We recruited 1014 outpatient participants presenting with typhoid-like symptoms in selected health centres in Nairobi, Kenya. Bacterial isolation was done on Xylose Lysine Deoxycholate agar (XLD) and Mac Conkey agar (Oxoid), followed by standard biochemical tests. Identification was done using API20E, and S.Typhi was confirmed by serotyping using polyvalent antisera 0-9 and monovalent antisera d. The Kirby-Bauer disc diffusion method was used to test the antimicrobial susceptibility of S.Typhi isolates, while Multi-Drug Resistant (MDR) strains were characterized using conventional PCR. Of 1014 participants, 54 (5%) tested positive for S.Typhi. Thirty-eight (70%) of the S.Typhi isolated were from stool samples, while sixteen (30%) were from blood. Three (0.2%) of the isolates were from asymptomatic carriers. Of the 54 S.Typhi isolates, 20 (37%) were MDR. Resistance to ciprofloxacin and nalidixic acid was 43% and 52%, respectively. Resistance to amoxicillin-clavulanic acid (a beta-lactam inhibitor) was 2%. The BlaTEM-1 gene was present in 19/20 (95%) MDR isolates. MDR S.Typhi is prevalent in Mukuru Informal settlement. The sharp increase in nalidixic acid resistance is an indication of reduced susceptibility to fluoroquinolones, which are currently the recommended drugs for the treatment of typhoid fever. This study highlights the need for effective antimicrobial stewardship and routine surveillance of antimicrobial resistance (AMR) to inform policy on the prevention and control of MDR Typhoid disease.

The Many Hidden Faces of Gallbladder Carcinoma on CT and MRI Imaging-From A to Z.

Gallbladder carcinoma represents the most aggressive biliary tract cancer and the sixth most common gastrointestinal malignancy. The diagnosis is a challenging clinical task due to its clinical presentation, which is often non-specific, mimicking a heterogeneous group of diseases, as well as benign processes such as complicated cholecystitis, xanthogranulomatous cholecystitis, adenomyomatosis, porcelain gallbladder or metastasis to the gallbladder (most frequently derived from melanoma, renal cell carcinoma). Risk factors include gallstones, carcinogen exposure, porcelain gallbladder, typhoid carrier state, gallbladder polyps and abnormal pancreaticobiliary ductal junction. Typical imaging features on CT or MRI reveal three major patterns: asymmetric focal or diffuse wall-thickening of the gallbladder, a solid mass that replaces the gallbladder and invades the adjacent organs or as an intraluminal enhancement mass arising predominantly from the gallbladder fundus. The tumor can spread to the liver, the adjacent internal organs and lymph nodes. Depending on the disease stage, surgical resection is the curative treatment option in early stages and adjuvant combination chemotherapy at advanced stages. The purpose of this scientific paper is to fully illustrate and evaluate, through multimodality imaging findings (CT and MRI), different presentations and imaging scenarios of gallbladder cancer in six patients and thoroughly analyze the risk factors, patterns of spread and differential diagnosis regarding each particular case.

New Approaches to Tackling Intractable Issues in Infectious Disease.

Despite major progress in the last several decades in reducing the public and animal health burden of infectious disease a number of issues remain to be resolved and which have thus far been regarded as intractable. These include (i) the persistent carrier state in individuals convalescent from typhoid and typhoid-like infections, (ii) the increasing prevalence of multi-antibiotic resistance in enteric pathogens, much of which is mediated by self-transmissible plasmids, and (iii) parasite infections which are difficult to control by vaccination and where resistance to chemotherapeutics is also increasing. The author describes very recent work carried out by his group to look at resolving these problems in new and imaginative ways.

Anti-biofilm, drug delivery and cytotoxicity properties of dendrimers.

Treatments using antimicrobial agents have faced many difficulties as a result of biofilm formation by pathogenic microorganisms. The biofilm matrix formed by these microorganisms prevents antimicrobial agents from penetrating the interior where they can exact their activity effectively. Additionally, extracellular polymeric molecules associated with biofilm surfaces can absorb antimicrobial compounds, lowering their bioavailability. This problem has resulted in the quest for alternative treatment protocols, and the development of nanomaterials and devices through nanotechnology has recently been on the rise. The literature on dendrimers was searched for in databases such as Google Scholar, PubMed, and ScienceDirect. As a nanomaterial, dendrimers have found useful applications as a drug delivery vehicle for antimicrobial agents against biofilm-mediated infections to circumvent these defense mechanisms. The distinctive properties of dendrimers, such as multi-valency, biocompatibility, high water solubility, non-immunogenicity, and biofilm matrix-/cell membrane fusogenicity (ability to merge with intracellular membrane or other proteins), significantly increase the efficacy of antimicrobial agents and reduce the likelihood of recurring infections. This review outlines the current state of dendrimer carriers for biofilm treatments, provides examples of their real-world uses, and examines potential drawbacks.

Exciton-carrier coupling in a metal halide perovskite nanocrystal assembly probed by two-dimensional coherent spectroscopy

The surface chemistry and inter-connectivity within perovskite nanocrystals play a critical role in determining the electronic interactions. They manifest in the Coulomb screening of electron–hole correlations and the carrier relaxation dynamics, among other many-body processes. Here, we characterize the coupling between the exciton and free carrier states close to the band-edge in a ligand-free formamidinium lead bromide nanocrystal assembly via two-dimensional coherent spectroscopy. The optical signatures observed in this work show: (i) a nonlinear spectral lineshape reminiscent of Fano-like interference that evidences the coupling between discrete electronic states and a continuum, (ii) symmetric excited state absorption cross-peaks that suggest the existence of a coupled exciton-carrier excited state, and (iii) ultrafast carrier thermalization and exciton formation. Our results highlight the presence of coherent coupling between exciton and free carriers, particularly in the sub-100 femtosecond timescales.

A comparative modeling study of the mitochondrial function of the proximal tubule and thick ascending limb cells in the rat kidney.

To reabsorb >99% of the glomerular filtrate, the metabolic demand of the kidney is high. Interestingly, renal blood flow distribution exhibits marked inhomogeneity, with typical tissue oxygen tension (Po2) of 50-60 mmHg in the well-perfused cortex and 10-20 mmHg in the inner medulla. Cellular fluid composition and acidity also varies substantially. To understand how different renal epithelial cells adapt to their local environment, we have developed and applied computational models of mitochondrial function of proximal convoluted tubule cell (baseline Po2 = 50 mmHg, cytoplasmic pH = 7.20) and medullary thick ascending limb (mTAL) cell (baseline Po2 = 10 mmHg, cytoplasmic pH = 6.85). The models predict key cellular quantities, including ATP generation, P/O (phosphate/oxygen) ratio, proton motive force, electrical potential gradient, oxygen consumption, the redox state of key electron carriers, and ATP consumption. Model simulations predict that close to their respective baseline conditions, the proximal tubule and mTAL mitochondria exhibit qualitatively similar behaviors. Nonetheless, because the mTAL mitochondrion has adapted to a much lower Po2, it can sustain a sufficiently high ATP production at Po2 as low as 4-5 mmHg, whereas the proximal tubule mitochondria would not. Also, because the mTAL cytosol is already acidic under baseline conditions, the proton motive force (pmf) exhibits higher sensitivity to further acidification. Among the different pathways that lead to oxidative phosphorylation impairment, the models predict that both the proximal tubule and mTAL mitochondria are most sensitive to reductions in Complex III activity.NEW & NOTEWORTHY Tissue fluid composition varies substantially within the mammalian kidney. The renal cortex is well perfused and pH neutral, whereas some medullary regions are hypoxic and acidic. How do these environments affect the mitochondrial function of proximal convoluted tubule and medullary thick ascending limb cells, which reside in the cortex and medulla, respectively? This computational modeling study demonstrates that these mitochondria can adapt to their contrasting environments and exhibit different sensitivities to perturbations to local environments.