Pseudomonas aeruginosa senses and responds to epithelial potassium flux via Kdp operon to promote biofilm.

Mucosa-associated biofilms are associated with many human disease states, but the host mechanisms promoting biofilm remain unclear. In chronic respiratory diseases like cystic fibrosis (CF), Pseudomonas aeruginosa establishes chronic infection through biofilm formation. P. aeruginosa can be attracted to interspecies biofilms through potassium currents emanating from the biofilms. We hypothesized that P. aeruginosa could, similarly, sense and respond to the potassium efflux from human airway epithelial cells (AECs) to promote biofilm. Using respiratory epithelial co-culture biofilm imaging assays of P. aeruginosa grown in association with CF bronchial epithelial cells (CFBE41o-), we found that P. aeruginosa biofilm was increased by potassium efflux from AECs, as examined by potentiating large conductance potassium channel, BKCa (NS19504) potassium efflux. This phenotype is driven by increased bacterial attachment and increased coalescence of bacteria into aggregates. Conversely, biofilm formation was reduced when AECs were treated with a BKCa blocker (paxilline). Using an agar-based macroscopic chemotaxis assay, we determined that P. aeruginosa chemotaxes toward potassium and screened transposon mutants to discover that disruption of the high-sensitivity potassium transporter, KdpFABC, and the two-component potassium sensing system, KdpDE, reduces P. aeruginosa potassium chemotaxis. In respiratory epithelial co-culture biofilm imaging assays, a KdpFABCDE deficient P. aeruginosa strain demonstrated reduced biofilm growth in association with AECs while maintaining biofilm formation on abiotic surfaces. Furthermore, we determined that the Kdp operon is expressed in vivo in people with CF and the genes are conserved in CF isolates. Collectively, these data suggest that P. aeruginosa biofilm formation can be increased by attracting bacteria to the mucosal surface and enhancing coalescence into microcolonies through aberrant AEC potassium efflux sensed by the KdpFABCDE system. These findings suggest host electrochemical signaling can enhance biofilm, a novel host-pathogen interaction, and potassium flux could be a therapeutic target to prevent chronic infections in diseases with mucosa-associated biofilms, like CF.

Polyamines and linear DNA mediate bacterial threat assessment of bacteriophage infection.

Monitoring the extracellular environment for danger signals is a critical aspect of cellular survival. However, the danger signals released by dying bacteria and the mechanisms bacteria use for threat assessment remain largely unexplored. Here, we show that lysis of Pseudomonas aeruginosa cells releases polyamines that are subsequently taken up by surviving cells via a mechanism that relies on Gac/Rsm signaling. While intracellular polyamines spike in surviving cells, the duration of this spike varies according to the infection status of the cell. In bacteriophage-infected cells, intracellular polyamines are maintained at high levels, which inhibits replication of the bacteriophage genome. Many bacteriophages package linear DNA genomes and linear DNA is sufficient to trigger intracellular polyamine accumulation, suggesting that linear DNA is sensed as a second danger signal. Collectively, these results demonstrate how polyamines released by dying cells together with linear DNA allow P. aeruginosa to make threat assessments of cellular injury.

Apidima Cave fossils provide earliest evidence of Homo sapiens in Eurasia.

Two fossilized human crania (Apidima 1 and Apidima 2) from Apidima Cave, southern Greece, were discovered in the late 1970s but have remained enigmatic owing to their incomplete nature, taphonomic distortion and lack of archaeological context and chronology. Here we virtually reconstruct both crania, provide detailed comparative descriptions and analyses, and date them using U-series radiometric methods. Apidima 2 dates to more than 170 thousand years ago and has a Neanderthal-like morphological pattern. By contrast, Apidima 1 dates to more than 210 thousand years ago and presents a mixture of modern human and primitive features. These results suggest that two late Middle Pleistocene human groups were present at this site-an early Homo sapiens population, followed by a Neanderthal population. Our findings support multiple dispersals of early modern humans out of Africa, and highlight the complex demographic processes that characterized Pleistocene human evolution and modern human presence in southeast Europe.

Measuring the total photon economy of molecular species through fluorescent optical cycling.

The total photon economy of a chromophore molecular species represents a study of how absorbed photons partition among various electronic states and ultimately dissipate their excited energy into the environment. A complete accounting of these rates and pathways would allow one to optimize chromophores and their environments for applications. We describe a technique, fluorescent optical cycling (FOC), which allows for simultaneous observation of prompt and delayed emission during and after multiple pulsed excitation, ultimately granting access to multi-state photophysical rates. We exercise control over the excitation pulse train, which allows us to "optically shelve" long-lived intermediate states without the use of diode or flashlamp excitation. By recording all photon arrival times in the visible and shortwave infrared, we can simultaneously resolve fluorescence, phosphorescence, and singlet oxygen sensitization in a single experiment. We use FOC to examine the photophysics of dual emitting bis(di-R-phosphino)alkanethiophene-pyridine-platinum ([Pt(thpy)(dppm)]+) under different solvation conditions, revealing changes in intersystem crossing and phosphorescent rates induced by the external heavy atom effect. Coupling FOC with decay associated Fourier spectroscopy (DAFS), we demonstrate simultaneous correlated spectral and lifetime data in this dual emitting complex. Finally, FOC combined with superconducting nanowire single photon detectors (SNSPDs) allows us to observe the shortwave infrared region (SWIR) phosphorescence of singlet oxygen sensitized by Rose Bengal. Overall, FOC provides a powerful tool to simultaneously study multiple photophysics across timescales, even in weakly populated electronic states.

A smartphone-integrated aptasensor for pesticide detection using gold-decorated microparticles.

The increasing incidence of environmental concerns related to excessive use of pesticides, such as imidacloprid and carbendazim, poses risks to pollinators, water bodies, and human health, prompting regulatory scrutiny and bans in developed countries. In this study, we propose a portable smartphone-based biosensor for rapid and label-free colorimetric detection by using the gold-decorated polystyrene microparticles (Ps-AuNP) functionalized with specific aptamers to imidacloprid and carbendazim on a microfluidic paper-based analytical device (µ-PAD). Four aptamers were selected for the detection of these pesticides and their sensitivity and selectivity performance was evaluated. The sensitivity results show a detection limit for imidacloprid of 3.12 ppm and 1.56 ppm for carbendazim. The aptamers also exhibited high selectivity performance against other pesticides, such as thiamethoxam, fenamiphos, isoproturon, and atrazine. However, the platform presented cross-selectivity when detecting imidacloprid, carbendazim, and linuron, which is discussed herein. Overall, we present a promising platform for simple, on-site, and rapid colorimetric screening of specific pesticides, while highlighting the challenges of aptasensors in achieving selectivity amidst diverse molecular structures.

Exploring Career Choice Among Black Psychiatry Interns: an Exploratory Qualitative Study.

OBJECTIVE: Relative to the Black American population size, there is an underrepresentation of Black psychiatrists in the USA. In order to address this issue, it is important to explore factors that contribute to Black medical students' decision to pursue a career in psychiatry. METHODS: First-year psychiatry residents who identify as Black (N = 7) were interviewed. Career Construction Theory provided a structured framework for the interview process. For qualitative analysis of data, codes were assigned to reflect concepts and develop themes. RESULTS: All participants mentioned the impact of being a Black psychiatrist in the Black community, the influence of strong female role models on their life, and the importance of the fit between their personality and the work done within psychiatry. The majority of interviewees identified macro-level and cultural events that had influenced them and discussed a desire for advocacy and the influence of Black role models, perseverance, and the importance of work-life balance. CONCLUSION: This qualitative study identified many influential factors that were deemed important to Black interns in their decision to pursue a residency in psychiatry. With the information learned from these interviews, educators within psychiatry can bolster their support of Black medical students, encourage pursuit of a career in psychiatry, and ultimately, work toward reducing disparities in psychiatric care. Future research should examine additional collective notions of career decision-making.

Associations of reproductive and breastfeeding history with anti-Müllerian hormone concentration among African-American women of reproductive age.

RESEARCH QUESTION: Are gravidity, parity and breastfeeding history associated with anti-Müllerian hormone concentration among African-American women of reproductive age? DESIGN: This study included baseline data from the Study of the Environment, Lifestyle and Fibroids, a 5-year longitudinal study of African-American women. Within this community cohort, data from 1392 women aged 25-35 years were analysed. The primary outcome was serum anti-Müllerian hormone concentration measured using the Ansh Labs picoAMH assay, an enzyme-linked immunosorbent assay. Multivariable linear regression models were used to estimate mean differences in anti-Müllerian hormone concentration (ß) and 95% CI by self-reported gravidity, parity and breastfeeding history, with adjustment for potential confounders. RESULTS: Of the 1392 participants, 1063 had a history of gravidity (76.4%). Of these, 891 (83.8%) were parous and 564 had breastfed. Multivariable-adjusted regression analyses found no appreciable difference in anti-Müllerian hormone concentration between nulligravid participants and those with a history of gravidity (ß = -0.025, 95% CI -0.145 to 0.094). Among participants with a history of gravidity, there was little difference in anti-Müllerian hormone concentration between parous and nulliparous participants (ß = 0.085, 95% CI -0.062 to 0.232). There was also little association between anti-Müllerian hormone concentration and breastfeeding history (ever versus never: ß = 0.009, 95% CI -0.093 to 0.111) or duration of breastfeeding (per 1-month increase: ß = -0.002, 95% CI -0.010 to 0.006). CONCLUSIONS: Gravidity, parity and breastfeeding history were not meaningfully associated with anti-Müllerian hormone concentration in this large sample of the Study of the Environment, Lifestyle and Fibroids cohort.

Anxiety, attitudes, and education about fertility among medical students in the United States.

BACKGROUND: As delayed family building is common among physicians, the goal of this study was to evaluate childbearing plans, anxiety related to future fertility, and interest in fertility education among medical students. METHODS: Using convenience and snowball sampling methods, an electronic REDCap survey was distributed via social media and group messaging applications to medical students enrolled in medical schools across the United States. Answers were collected, and analysis of the descriptive statistics was performed. RESULTS: The survey was completed by 175 participants, 72% of which were female (assigned at birth). The mean (± SD) age of participants was 24.9 ± 1.9 years. Of all participants, 78.3% desire to have children and 65.1% of these individuals plan to delay childbearing. On average, the planned age of first pregnancy is 31.0 ± 2.3 years. "Lack of time" was the greatest influence on decision regarding timing of childbearing. Of all respondents, 58.9% reported at least some anxiety related to future fertility. When females and males were compared, significantly more females (73.8%) versus males (20.4%) reported worrying about future fertility (p < 0.001). Participants reported that greater knowledge about infertility and potential treatments would help ease fertility related anxiety, and 66.9% of respondents showed interest in learning about how things such as age and lifestyle can impact fertility, preferably through medical curricula, videos, and podcasts. CONCLUSION: A majority of the medical students in this cohort intend to have children and most plan to delay childbearing. A large percentage of female medical students reported anxiety related to future fertility, but many students showed interest in receiving fertility education. This study highlights an opportunity for medical school educators to incorporate targeted fertility education into their curriculum with the intention of decreasing anxiety and improving future reproductive success.

The anti-sigma factor MucA is required for viability in Pseudomonas aeruginosa.

During decades-long infections in the cystic fibrosis (CF) airway, Pseudomonas aeruginosa undergoes selection. One bacterial genetic adaptation often observed in CF isolates is mucA mutations. MucA inhibits the sigma factor AlgU. Mutations in mucA lead to AlgU misregulation, resulting in a mucoid phenotype that is associated with poor CF disease outcomes. Due to its ability to be mutated, mucA is assumed to be dispensable for bacterial viability. Here we show that, paradoxically, a portion of mucA is essential in P. aeruginosa. We demonstrate that mucA is no longer required in a strain lacking algU, that mucA alleles encoding for proteins that do not bind to AlgU are insufficient for viability, and that mucA is no longer essential in mutant strains containing AlgU variants with reduced sigma factor activity. Furthermore, we found that overexpression of algU prevents cell growth in the absence of MucA, and that this phenotype can be rescued by the overproduction of RpoD, the housekeeping sigma factor. Together, these results suggest that in the absence of MucA, the inability to regulate AlgU activity results in the loss of bacterial viability. Finally, we speculate that the essentiality of anti-sigma factors that regulate envelope function may be a widespread phenomenon in bacteria.

Comparison of MRI Features of Fat Fraction and ADC for Early Treatment Response Assessment in Participants with Multiple Myeloma.

Background An imaging-based predictor of response could provide prognostic information early during treatment course in patients with multiple myeloma (MM). Purpose To investigate if very early changes in bone marrow relative fat fraction (rFF) and apparent diffusion coefficient (ADC) histogram metrics, occurring after one cycle of induction therapy in participants with newly diagnosed MM, could help predict overall best response status. Materials and Methods This prospective study included participants with MM who were enrolled between August 2014 and December 2017. Histogram metrics were extracted from ADC and rFF maps from MRI examinations performed before treatment and after the first treatment cycle. Participants were categorized into the very good partial response (VGPR) or better group and the less than VGPR group per the International Myeloma Working Group response criteria. ADC and rFF map metrics for predicting treatment response were compared using the Wilcoxon rank test, and the false discovery rate (FDR) was used to correct for multiple comparisons. Results A total of 23 participants (mean age, 65 years ± 11 [SD]; 13 men) were evaluated. There was no evidence of a difference in ADC metrics between the two responder groups after correcting for multiple comparisons. The rFF histogram changes between pretreatment MRI and MRI after the first treatment cycle (ΔrFF) that provided significant differences between the VGPR or better and less than VGPR groups were as follows: ΔrFF_10th Percentile (median, 0.5 [95% CI: 0, 1] vs -2.5 [95% CI: -5.1, 0.1], respectively), ΔrFF_90th Percentile (median, 2 [95% CI: 1, 6.8] vs -0.5 [95% CI: -1, 0]), ΔrFF_Mean (median, 3.4 [95% CI: 0.3, 7.6] vs -1.1 [95% CI: -1.8, -0.7]), and ΔrFF_Root Mean Squared (median, 3.2 [95% CI: 0.3, 6.1] vs -0.7 [95% CI: -1.3, -0.4]) (FDR-adjusted P = .03 for all), and the latter two also presented mean group increases in the VGPR or better group that were above the upper 95% CI limit for repeatability. Conclusion Very early changes in bone marrow relative fat fraction histogram metrics, calculated from MRI examination at baseline and after only one cycle of induction therapy, may help to predict very good partial response or better in participants with newly diagnosed multiple myeloma. © RSNA, 2022 Online supplemental material is available for this article.

Recent Advances in Aptamer-Based Biosensors for Global Health Applications.

Since aptamers were first reported in the early 2000s, research on their use for the detection of health-relevant analytical targets has exploded. This review article provides a brief overview of the most recent developments in the field of aptamer-based biosensors for global health applications. The review provides a description of general aptasensing principles and follows up with examples of recent reports of diagnostics-related applications. These applications include detection of proteins and small molecules, circulating cancer cells, whole-cell pathogens, extracellular vesicles, and tissue diagnostics. The review also discusses the main challenges that this growing technology faces in the quest of bringing these new devices from the laboratory to the market.

Early ß-hCG levels predict live birth after single embryo transfer.

PURPOSE: Specific serum beta human chorionic gonadotropin (ß-hCG) parameters that can predict live birth after an embryo transfer have yet to be defined. METHODS: We performed a retrospective cohort study of 1,028 patients with a detectable ß-hCG who underwent a single embryo transfer between 2002 and 2019 at a large academic center. Two ß-hCG parameters were examined in relation to live birth: 1) "doubling" defined as ß-hCG doubling over 48 h and 2) "reaching 100" defined as a ß-hCG ≥ 100 mIU/mL by 15 days after oocyte retrieval (AOR). RESULTS: One thousand three hundred forty cycles involving a single embryo were analyzed. Two thirds were frozen embryos and 86% were blastocyst transfers. Preimplantation genetic testing was performed in almost 30% of cycles. When ß-hCG levels "doubled," a live birth occurred in 80.7% of cycles and when ß-hCG levels "reached 100" by 15 days AOR, live birth occurred in 81.6% of cycles. When ß-hCG levels both doubled and reached 100 by 15 days, AOR 85.4% cycles resulted in live birth. A multiple logistic regression model to control for patient and cycle level factors revealed a live birth odds ratio (OR) of 8.0 (95% CI 5.7-11.1) when ß-hCG "doubled" and an OR of 21.2 (95% CI 14.3-31.5) when ß-hCG "reached 100." When both these latter parameters were met, the OR was 12.5 (95% CI 8.9-17.8). CONCLUSION: ß-hCG parameters of "doubling" and "reaching 100" by 15 days AOR are robust predictors of live birth and can aid in patient counseling regarding pregnancy outcomes soon after single embryo transfer.

Glycyrrhizic Acid Derivatives Bearing Amino Acid Residues in the Carbohydrate Part as Dengue Virus E Protein Inhibitors: Synthesis and Antiviral Activity.

Dengue virus (DENV) is one of the most geographically distributed mosquito-borne flaviviruses, like Japanese encephalitis virus (JEV), and Zika virus (ZIKV). In this study, a library of the known and novel Glycyrrhizic acid (GL) derivatives bearing amino acid residues or their methyl/ethyl esters in the carbohydrate part were synthesized and studied as DENV inhibitors in vitro using the cytopathic effect (CPE), viral infectivity and virus yield assays with DENV1 and DENV-2 in Vero E6 and A549 cells. Among the GL conjugates tested, compound hits GL-D-ValOMe 3, GL-TyrOMe 6, GL-PheOEt 11, and GL-LysOMe 21 were discovered to have better antiviral activity than GL, with IC50 values ranging from <0.1 to 5.98 µM on the in vitro infectivity of DENV1 and DENV2 in Vero E6 and A549 cells. Compound hits 3, 6, 11, and 21 had a concentration-dependent inhibition on the virus yield in Vero E6, in which GL-D-ValOMe 3 and GL-PheOEt 11 were the most active inhibitors of DENV2 yield. Meanwhile, the time-of-addition assay indicated that conjugates GL-D-ValOMe 3 and GL-PheOEt 11 exhibited a substantial decrease in the DENV2 attachment stage. Subsequently, chimeric single-round infectious particles (SRIPs) of DENV2 C-prM-E protein/JEV replicon and DENV2 prM-E/ZIKV replicon were utilized for the DENV envelope I protein-mediated attachment assay. GL conjugates 3 and 11 significantly reduced the attachment of chimeric DENV2 C-prM-E/JEV and DENV2 prM-E/ZIKV SRIPs onto Vero E6 cells in a concentration-dependent manner but did not impede the attachment of wild-type JEV CprME/JEV and ZIKV prM-E/ZIKV SRIPs, indicating the inhibition of Compounds 3 and 11 on DENV2 E-mediated attachment. Molecular docking data revealed that Compounds 3 and 11 have hydrophobic interactions within a hydrophobic pocket among the interfaces of Domains I, II, and the stem region of the DENV2 envelope (E) protein. These results displayed that Compounds 3 and 11 were the lead compounds targeting the DENV E protein. Altogether, our findings provide new insights into the structure−activity relationship of GL derivatives conjugated with amino acid residues and can be the new fundamental basis for the search and development of novel flavivirus inhibitors based on natural compounds.

Psychiatry Residency Directors' Attitudes Toward and Uses of the Medical Student Performance Evaluation and Other Potential Tools for Residency Selection.

OBJECTIVE: A survey was conducted to determine US psychiatry residency directors' attitudes regarding current measures of medical student performance and their preferences for the future. METHODS: A team of psychiatry medical student educators and residency program directors developed a 23-question survey. In July 2021, links to the survey were sent out to all program directors registered with the American Association of Directors of Psychiatric Residency Training. RESULTS: Seventy program directors out of 223 initiated the survey, resulting in a response rate of 31.4%. Forty percent of respondents reported that the most important use of the Medical Student Performance Evaluation (MSPE) is in screening out applicants for interviews, and only 26.1% reported that the MSPE in its current form could be trusted to provide a valid and reliable assessment of a student's medical school performance. Most respondents agreed that in the absence of United States Medical Licensing Examination (USMLE) step 1 numerical scores, the existing MSPE format/content requirements should be modified, use a set of ranking categories that are uniform across all medical schools, and be supplemented with additional measures of the student's character and ability specific to psychiatry. CONCLUSIONS: US psychiatry program directors are eager for change when it comes to the MSPE and how it reports rankings, grades, and professionalism. The transition of the USMLE step 1 score reporting to pass/fail presents an opportunity to pursue this change and for stakeholders from all medical specialties to work together toward a shared goal of an improved residency selection process.

Whole-Body Low-Dose CT in Multiple Myeloma: Diagnostic Value of Appendicular Medullary Patterns of Attenuation.

OBJECTIVE. The purpose of this article is to analyze whole-body low-dose CT-detected appendicular medullary patterns of attenuation in patients with newly diagnosed multiple myeloma and to determine the diagnostic performance of whole-body low-dose CT in detecting diffuse marrow infiltration. MATERIALS AND METHODS. A total of 76 patients with myeloma who underwent whole-body low-dose CT and spinal MRI at initial assessment were retrospectively analyzed. The medullary cavities of femurs and humeri were evaluated qualitatively and quantitatively on CT. Medullary attenuation and SD-to-mean attenuation ratio were recorded for each long bone. The pattern of marrow involvement on spinal MRI was used as reference. The chi-square test was used to evaluate the relationship between the CT-based appendicular medullary cavity pattern and the MRI pattern, and ROC analysis was performed to assess the diagnostic accuracy of CT attenuation measurements for the differentiation between diffuse and mixed CT-based appendicular medullary cavity patterns. RESULTS. Medullary attenuation differed significantly among mixed, nodular, and diffuse CT-based appendicular medullary cavity patterns in the femurs (mean, 34.23 HU and range, 15-61 HU; mean, 66.26 HU and range, 26-104 HU; mean, 92.80 HU and range, 53-127 HU, respectively) and humeri (mean, 22.18 HU and range, 9-41; mean, 61.18 HU and range, 23-93 HU; mean, 77.50 and range, 25-105 HU, respectively). To discriminate between diffuse and mixed CT-based appendicular medullary cavity patterns, optimal cutoff attenuation values were 63 HU (sensitivity, 97.7%; specificity, 100.0%) for the femurs, and 52 HU (sensitivity, 97.4%; specificity, 100.0%) for the humeri. A total of 24 of 30 (80.0%) patients with a diffuse MRI pattern showed a diffuse CT-based appendicular medullary cavity pattern on whole-body low-dose CT, and all patients with a diffuse CT-based appendicular medullary cavity pattern also showed a diffuse pattern on MRI. CONCLUSION. According to analysis of peripheral medullary patterns of attenuation, whole-body low-dose CT can identify patients with multiple myeloma with diffuse marrow involvement.

Glycyrrhetinic acid derivatives as Zika virus inhibitors: Synthesis and antiviral activity in vitro.

Zika virus (ZIKV) is an arbovirus of the Flaviviridae family (Flavivirus genus), causing serious neurological complications, such as Guillain-Barre Syndrome (GBS) in adults and fetal microcephaly. Licensed vaccines or specific antiviral agents against ZIKV do not currently exist. Therefore, the search and development of anti-ZIKV agents are particularly relevant and necessary. Glycyrrhetinic (3ß-hydroxy-11-oxo-18ßH-Olean-12-en-30-oic acid) (GA) 1 is one of the well-known pentacyclic triterpenoids isolated from licorice root (Glycyrrhiza glabra L., Gl. uralensis Fisher) (Leguminosae) possessing many biological features, including antiviral activity. This paper is devoted to the synthesis and studies of a number of nitrogen and sulfur-containing GA derivatives as ZIKV inhibitors. Sixteen GA and related triterpenoids (3ß-hydroxy-18ßH-Olean-12-en-30-oic acid and 3ß-hydroxy-11-oxo-18ßH-Olean-12(13),18(19)-dien-30-oic acid) derivatives were synthesized (amides, semi- and thiosemicarbazones, and 1,2,3-thiadiazoles) and antiviral activity against ZIKV was studied in vitro, including the inhibitory assays on cytopathic effect (CPE), viral protein synthesis, and replication stages. Four active compounds were found among GA derivatives tested, 13 (3-O-acetyl-30-aminopyridine GA), 16 (3-semicarbazone-30-butyl GA), 18 (1,2,3-thiadiazole-30-methyl GA), and 19 (1,2,3-thiadiazole-30-butyl GA) with IC50 < 1 µM against ZIKV replication. These compounds had a stronger inhibitory activity on ZIKV-induced CPE and viral protein translation in infected cells as compared to derivatives of 11-desoxo-GA. The most active compound was amide 13 (IC50 0.13 µM, TI ˃ 384). Time-of-addition assays indicated that 1,2,3-thiadiazole ring is important for inhibiting viral entry stage (compounds 18 and 19), while the 30-butyl ester group influenced on post-entry stage (compound 19). The molecular docking analysis demonstrated that lead compounds 13 and 19 forms a hydrogen-bond interaction with the catalytic triad (His51-Asp75-Ser135) of ZIKV NS2B-NS3 protease. Therefore, the active GA derivatives are promising for developing new antiviral agents against ZIKV infection.

Tritium labelling to study humic substance-nanodiamond composites.

Nanodiamonds produced by the detonation method are used as lubricants, polishing compositions, polymer composites, etc. To reveal how nanodiamonds differ in terms of surface properties and interact with natural organic matter, we used tritium-labelled humic substances to quantitively describe their adsorption onto the nanodiamond surface. It was shown that the adsorption of humic substances onto nanodiamonds resulted in fractionation of humic substances that was strongly dependent on the zeta potential of nanodiamonds in water but did not significantly affect the uptake of nanodiamonds by wheat seedlings. The uptake of nanodiamond particles by plants was determined by the functional composition of the particle surface.

Entropically driven aggregation of bacteria by host polymers promotes antibiotic tolerance in Pseudomonas aeruginosa.

Bacteria causing chronic infections are generally observed living in cell aggregates suspended in polymer-rich host secretions, and bacterial phenotypes induced by aggregated growth may be key factors in chronic infection pathogenesis. Bacterial aggregation is commonly thought of as a consequence of biofilm formation; however the mechanisms producing aggregation in vivo remain unclear. Here we show that polymers that are abundant at chronic infection sites cause bacteria to aggregate by the depletion aggregation mechanism, which does not require biofilm formation functions. Depletion aggregation is mediated by entropic forces between uncharged or like-charged polymers and particles (e.g., bacteria). Our experiments also indicate that depletion aggregation of bacteria induces marked antibiotic tolerance that was dependent on the SOS response, a stress response activated by genotoxic stress. These findings raise the possibility that targeting conditions that promote depletion aggregation or mechanisms of depletion-mediated tolerance could lead to new therapeutic approaches to combat chronic bacterial infections.

Green Synthesis of Silver Nanoparticles Using Extract of Cilembu Sweet Potatoes (Ipomoea batatas L var. Rancing) as Potential Filler for 3D Printed Electroactive and Anti-Infection Scaffolds.

Electroactive biomaterials are fascinating for tissue engineering applications because of their ability to deliver electrical stimulation directly to cells, tissue, and organs. One particularly attractive conductive filler for electroactive biomaterials is silver nanoparticles (AgNPs) because of their high conductivity, antibacterial activity, and ability to promote bone healing. However, production of AgNPs involves a toxic reducing agent which would inhibit biological scaffold performance. This work explores facile and green synthesis of AgNPs using extract of Cilembu sweet potato and studies the effect of baking and precursor concentrations (1, 10 and 100 mM) on AgNPs' properties. Transmission electron microscope (TEM) results revealed that the smallest particle size of AgNPs (9.95 ± 3.69 nm) with nodular morphology was obtained by utilization of baked extract and ten mM AgNO3. Polycaprolactone (PCL)/AgNPs scaffolds exhibited several enhancements compared to PCL scaffolds. Compressive strength was six times greater (3.88 ± 0.42 MPa), more hydrophilic (contact angle of 76.8 ± 1.7°), conductive (2.3 ± 0.5 × 10-3 S/cm) and exhibited anti-bacterial properties against Staphylococcus aureus ATCC3658 (99.5% reduction of surviving bacteria). Despite the promising results, further investigation on biological assessment is required to obtain comprehensive study of this scaffold. This green synthesis approach together with the use of 3D printing opens a new route to manufacture AgNPs-based electroactive with improved anti-bacterial properties without utilization of any toxic organic solvents.

Guidelines for Acquisition, Interpretation, and Reporting of Whole-Body MRI in Myeloma: Myeloma Response Assessment and Diagnosis System (MY-RADS).

Acknowledging the increasingly important role of whole-body MRI for directing patient care in myeloma, a multidisciplinary, international, and expert panel of radiologists, medical physicists, and hematologists with specific expertise in whole-body MRI in myeloma convened to discuss the technical performance standards, merits, and limitations of currently available imaging methods. Following guidance from the International Myeloma Working Group and the National Institute for Clinical Excellence in the United Kingdom, the Myeloma Response Assessment and Diagnosis System (or MY-RADS) imaging recommendations are designed to promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI in myeloma and allow response assessment. This consensus proposes a core clinical protocol for whole-body MRI and an extended protocol for advanced assessments. Published under a CC BY 4.0 license. Online supplemental material is available for this article.