Calcium isotope fractionation by intracellular amorphous calcium carbonate (ACC) forming cyanobacteria.

The formation of intracellular amorphous calcium carbonate (ACC) by various cyanobacteria is a widespread biomineralization process, yet its mechanism and importance in past and modern environments remain to be fully comprehended. This study explores whether calcium (Ca) isotope fractionation, linked to ACC-forming cyanobacteria, can serve as a reliable tracer for detecting these microorganisms in modern and ancient settings. Accordingly, we measured stable Ca isotope fractionation during Ca uptake by the intracellular ACC-forming cyanobacterium Cyanothece sp. PCC 7425. Our results show that Cyanothece sp. PCC 7425 cells are enriched in lighter Ca isotopes relative to the solution. This finding is consistent with the kinetic isotope effects observed in the Ca isotope fractionation during biogenic carbonate formation by marine calcifying organisms. The Ca isotope composition of Cyanothece sp. PCC 7425 was accurately modeled using a Rayleigh fractionation model, resulting in a Ca isotope fractionation factor (Δ44Ca) equal to -0.72 ± 0.05‰. Numerical modeling suggests that Ca uptake by these cyanobacteria is primarily unidirectional, with minimal back reaction observed over the duration of the experiment. Finally, we compared our Δ44Ca values with those of other biotic and abiotic carbonates, revealing similarities with organisms that form biogenic calcite. These similarities raise questions about the effectiveness of using the Ca isotope fractionation factor as a univocal tracer of ACC-forming cyanobacteria in the environment. We propose that the use of Δ44Ca in combination with other proposed tracers of ACC-forming cyanobacteria such as Ba and Sr isotope fractionation factors and/or elevated Ba/Ca and Sr/Ca ratios may provide a more reliable approach.

Current Status and Future Directions: The Application of Artificial Intelligence/Machine Learning for Precision Medicine.

Technological innovations, such as artificial intelligence (AI) and machine learning (ML), have the potential to expedite the goal of precision medicine, especially when combined with increased capacity for voluminous data from multiple sources and expanded therapeutic modalities; however, they also present several challenges. In this communication, we first discuss the goals of precision medicine, and contextualize the use of AI in precision medicine by showcasing innovative applications (e.g., prediction of tumor growth and overall survival, biomarker identification using biomedical images, and identification of patient population for clinical practice) which were presented during the February 2023 virtual public workshop entitled "Application of Artificial Intelligence and Machine Learning for Precision Medicine," hosted by the US Food and Drug Administration (FDA) and University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI). Next, we put forward challenges brought about by the multidisciplinary nature of AI, particularly highlighting the need for AI to be trustworthy. To address such challenges, we subsequently note practical approaches, viz., differential privacy, synthetic data generation, and federated learning. The proposed strategies - some of which are highlighted presentations from the workshop - are for the protection of personal information and intellectual property. In addition, methods such as the risk-based management approach and the need for an agile regulatory ecosystem are discussed. Finally, we lay out a call for action that includes sharing of data and algorithms, development of regulatory guidance documents, and pooling of expertise from a broad-spectrum of stakeholders to enhance the application of AI in precision medicine.

Diagnostic challenges in tuberculous meningitis: a case report with negative genexpert result.

Introduction: Tuberculous meningitis (TBM) is a severe form of tuberculosis affecting the meninges, primarily caused by Mycobacterium tuberculosis. Diagnosis of TBM poses numerous challenges due to its nonspecific clinical presentation and the limitations of diagnostic tests like GeneXpert. Case presentation: The authors report a case of a 22-year-old female from Eastern Nepal presenting with acute-onset fever, headache, vomiting, and neck pain. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, elevated protein, low glucose levels, and cobweb coagulum indicative of TBM. However, the GeneXpert test revealed negative results. Discussion: In resource-limited settings like Nepal, where access to GeneXpert MTB/Rif is limited, CSF analysis and clinical algorithms play a crucial role in diagnosing TBM. Relying solely on GeneXpert results may lead to false negatives, so a high level of suspicion based on patient risk factors is essential. Prompt initiation of empirical antitubercular therapy is vital for a favorable outcome in TBM cases. Conclusion: Negative MTB PCR results from CSF can be misleading in diagnosis of tubercular meningitis. Therefore, comprehensive evaluations, including detailed patient history, physical examination, and CSF fluid analysis, are crucial in high tuberculous prevalence countries to ensure accurate and timely diagnosis.

Association of the Complement System with Subclinical Atherosclerosis in Psoriasis: Findings from an Observational Cohort Study.

Psoriasis is a chronic and inflammatory disease that affects the skin and joints and is associated with multiple comorbidities and cardiovascular risk factors. Consequently, patients with psoriasis have an increased risk of cardiovascular diseases such as atherosclerosis, a chronic pathology that shares common inflammatory and immune-response mechanisms with psoriasis, including vascular inflammation and complement activation. To better understand the relationship between atherosclerosis and psoriasis, a proteomics study followed by a bioinformatics analysis was carried out, with a subsequent validation step using ELISA and western blotting. When the plasma from patients with psoriasis alone was compared with that from patients with psoriasis and atherosclerosis, 31 proteins of interest related to the complement system and oxygen transport were identified. After the validation phase, 11 proteins appeared to define the presence of subclinical atherosclerosis in patients with psoriasis, indicating the importance of complement cascades in the development of atherosclerotic plaques in individuals with psoriasis. These results are a step forward in understanding the pathological pathways implicated in the cardiovascular risk associated with this population, which may represent an interesting starting point for developing predictive tools that improve the follow-up of these patients and design more effective therapies.

Mortality Among Children Aged <5 Years Living with HIV Who Are Receiving Antiretroviral Treatment - U.S. President's Emergency Plan for AIDS Relief, 28 Supported Countries and Regions, October 2020-September 2022.

Globally, children aged <5 years, including those living with HIV who are not receiving antiretroviral treatment (ART), experience disproportionately high mortality. Global mortality among children living with HIV aged <5 years receiving ART is not well described. This report compares mortality and related clinical measures among infants aged <1 year and children aged 1-4 years living with HIV with those among older persons aged 5-14, 15-49, and ≥50 years living with HIV receiving ART services at all clinical sites supported by the U.S. President's Emergency Plan for AIDS Relief. During October 2020-September 2022, an average of 11,980 infants aged <1 year and 105,510 children aged 1-4 years were receiving ART each quarter; among these infants and children receiving ART, 586 (4.9%) and 2,684 (2.5%), respectively, were reported to have died annually. These proportions of infants and children who died ranged from four to nine times higher in infants aged <1 year, and two to five times higher in children aged 1-4 years, than the proportions of older persons aged ≥5 years receiving ART. Compared with persons aged ≥5 years living with HIV, the proportions of children aged <5 years living with HIV who experienced interruptions in treatment were also higher, and the proportions who had a documented HIV viral load result or a suppressed viral load were lower. Prioritizing and optimizing HIV and general health services for children aged <5 years living with HIV receiving ART, including those recommended in the WHO STOP AIDS Package, might help address these disproportionately poorer outcomes.

Esthetic rehabilitation of mutilated maxillary anterior alveolar segment by combining orthodontic osseous distraction and implant-supported crowns: A clinical report.

Bony defects in the esthetic zone, especially in the maxillary anterior region, increase the complexity of surgical and prosthetic procedures. Moving teeth with preprosthetic osseous distraction techniques can be an alternative nonsurgical option to traditional regenerative or reparative surgical therapies to increase bone volume. Healthy peri-implant bone, periodontium, and adjacent teeth provide a favorable environment for implant restorations. The esthetic rehabilitation of the maxillary region after the removal of 2 ankylosed central incisors is presented. The lateral incisors were moved mesially to the central incisor positions, and implants placed in the lateral incisor positions after new healthy bone had been induced.

Coexistence of cerebral venous thrombosis and dural arteriovenous fistula in an adolescent: A case report.

Key Clinical Message: Clinicians should consider central venous thrombosis (CVT) as a differential diagnosis in young adolescents with persistent headaches. It is essential to assess for concurrent CVT and dural arteriovenous fistula (DAVF), particularly in those with a history of CVT. Abstract: Cerebral venous thrombosis (CVT) and dural arteriovenous fistula (DAVF) are uncommon vascular disorders with diverse clinical presentations. The coexistence of CVT and DAVF is a rare but important association that may impact the management and prognosis of affected patients. Prothrombotic conditions generally ranging from acquired to genetic, oral contraceptives, malignancy, puerperium, infection, and head injury are the common risk factors for cerebral venous thrombosis. Here, we present a case of 18 years males who developed recurrent cerebral thrombosis on the background of the presence of an arteriovenous fistula.

Molecular epidemiology of Clostridioides difficile isolates in a non-outbreak setting at a comprehensive cancer center.

Ribotyping was performed on Clostridioides difficile isolates from patients with malignancies. Thirty-one (27.9%) isolates from 111 episodes of colitis were recovered representing 14 ribotypes with 25 (80.6%) belonging to 6 ribotypes (014/020, 1/VPI/077/087, 05/015, 015/046, 05/053, 106/174). We identified three novel ribotypes with 1 carrying gene encoding for binary toxin.

Cytomegalovirus hemorrhagic colitis in an immunocompetent patient with COVID-19 infection: A case report.

In coronavirus disease-19, we should suspect the opportunistic coinfections even in immunocompetent individuals. In the presence of recurrent gastrointestinal problems, colonoscopy should be done with biopsy and histopathology to diagnose the opportunistic infection, such as cytomegalovirus colitis, in patient with coronavirus disease-19. Here, we report a case of immunocompetent male with coronavirus disease-19 presenting with per rectal bleeding diagnosed as cytomegalovirus colitis.

Expanded triazolophanes: a topological analysis of vesicular assembly.

Triazolophanes with larger ring sizes such as 40- and 42- were designed and synthesized. Ultramicroscopic studies on a variety of expanded triazolophanes and larger acyclic systems revealed vesicular self-assembly. The role of molecular topology on vesicular assembly was systematically investigated by studying a series of molecules with increasing curvature.

Widespread formation of intracellular calcium carbonates by the bloom-forming cyanobacterium Microcystis.

The formation of intracellular amorphous calcium carbonates (iACC) has been recently observed in a few cultured strains of Microcystis, a potentially toxic bloom-forming cyanobacterium found worldwide in freshwater ecosystems. If iACC-forming Microcystis are abundant within blooms, they may represent a significant amount of particulate Ca. Here, we investigate the significance of iACC biomineralization by Microcystis. First, the presence of iACC-forming Microcystis cells has been detected in several eutrophic lakes, indicating that this phenomenon occurs under environmental conditions. Second, some genotypic (presence/absence of ccyA, a marker gene of iACC biomineralization) and phenotypic (presence/absence of iACC) diversity have been detected within a collection of strains isolated from one single lake. This illustrates that this trait is frequent but also variable within Microcystis even at a single locality. Finally, one-third of publicly available genomes of Microcystis were shown to contain the ccyA gene, revealing a wide geographic and phylogenetic distribution within the genus. Overall, the present work shows that the formation of iACC by Microcystis is common under environmental conditions. While its biological function remains undetermined, this process should be further considered regarding the biology of Microcystis and implications on the Ca geochemical cycle in freshwater environments.

Protecting the gains: analysis of HIV treatment and service delivery programme data and interventions implemented in 19 African countries during COVID-19.

INTRODUCTION: The potential disruption in antiretroviral therapy (ART) services in Africa at the start of the COVID-19 pandemic raised concern for increased morbidity and mortality among people living with HIV (PLHIV). We describe HIV treatment trends before and during the pandemic and interventions implemented to mitigate COVID-19 impact among countries supported by the US Centers for Disease Control and Prevention (CDC) through the President's Emergency Plan for AIDS Relief (PEPFAR). METHODS: We analysed quantitative and qualitative data reported by 10,387 PEPFAR-CDC-supported ART sites in 19 African countries between October 2019 and March 2021. Trends in PLHIV on ART, new ART initiations and treatment interruptions were assessed. Viral load coverage (testing of eligible PLHIV) and viral suppression were calculated at select time points. Qualitative data were analysed to summarize facility- and community-based interventions implemented to mitigate COVID-19. RESULTS: The total number of PLHIV on ART increased quarterly from October 2019 (n = 7,540,592) to March 2021 (n = 8,513,572). The adult population (≥15 years) on ART increased by 14.0% (7,005,959-7,983,793), while the paediatric population (<15 years) on ART declined by 2.6% (333,178-324,441). However, the number of new ART initiations dropped between March 2020 and June 2020 by 23.4% for adults and 26.1% for children, with more rapid recovery in adults than children from September 2020 onwards. Viral load coverage increased slightly from April 2020 to March 2021 (75-78%) and viral load suppression increased from October 2019 to March 2021 (91-94%) among adults and children combined. The most reported interventions included multi-month dispensing (MMD) of ART, community service delivery expansion, and technology and virtual platforms use for client engagement and site-level monitoring. MMD of ≥3 months increased from 52% in October 2019 to 78% of PLHIV ≥ age 15 on ART in March 2021. CONCLUSIONS: With an overall increase in the number of people on ART, HIV programmes proved to be resilient, mitigating the impact of COVID-19. However, the decline in the number of children on ART warrants urgent investigation and interventions to prevent further losses experienced during the COVID-19 pandemic and future public health emergencies.

Facile Synthesis and Life Cycle Assessment of Highly Active Magnetic Sorbent Composite Derived from Mixed Plastic and Biomass Waste for Water Remediation.

Plastic and biomass waste pose a serious environmental risk; thus, herein, we mixed biomass waste with plastic bottle waste (PET) to produce char composite materials for producing a magnetic char composite for better separation when used in water treatment applications. This study also calculated the life cycle environmental impacts of the preparation of adsorbent material for 11 different indicator categories. For 1 functional unit (1 kg of pomace leaves as feedstock), abiotic depletion of fossil fuels and global warming potential were quantified as 7.17 MJ and 0.63 kg CO2 equiv for production of magnetic char composite materials. The magnetic char composite material (MPBC) was then used to remove crystal violet dye from its aqueous solution under various operational parameters. The kinetics and isotherm statistical theories showed that the sorption of CV dye onto MPBC was governed by pseudo-second-order, and Langmuir models, respectively. The quantitative assessment of sorption capacity clarifies that the produced MPBC exhibited an admirable ability of 256.41 mg g-1. Meanwhile, the recyclability of 92.4% of MPBC was demonstrated after 5 adsorption/desorption cycles. Findings from this study will inspire more sustainable and cost-effective production of magnetic sorbents, including those derived from combined plastic and biomass waste streams.

Safety and efficacy of coronavirus disease-19 vaccines in chronic kidney disease patients under maintenance hemodialysis: A systematic review.

Background and aims: Patients on maintenance dialysis are a high-risk, immune-compromised population with 15%-25% coronavirus disease (COVID-19) mortality rate that has been underrepresented in COVID-19 vaccination clinical trials. The aim of study was to review of those studies to determine the safety and efficacy of the COVID-19 vaccination in chronic kidney disease (CKD) patients receiving maintenance hemodialysis systematically. Methods: The effectiveness was assessed by looking at the humoral and cellular responses. The humoral response is defined as de novo IgG- or IgA-anti-SpikeS1 antibody positivity. The establishment of de novo T-cell immunity after immunization was used to measure cellular response. Adverse results were also reported of the included studies to analyze the safety of COVID-19 vaccines. Eight previous works were included in our study. Results: Two doses of COVID-19 vaccines were shown to be effective with seroconversion rate of humoral response ranging from 81% to 97% among eight studies. The T-cell response was shown 67% and 100% in two studies. COVID-19 vaccines did not have notable adverse events and hence can be considered safe. Conclusion: Although a single dosage has not shown to improve humoral immune response in most hemodialysis trials, a double dose has been reported to improve seroconversion rate and humoral immune response. Further research are required to observe if hemodialysis patients generate effective T-cell responses.

Detection of biogenic amorphous calcium carbonate (ACC) formed by bacteria using FTIR spectroscopy.

While the formation of intracellular amorphous calcium carbonate (ACC) by living organisms is widespread, its detection in prokaryotes remains difficult owing to its susceptibility to transform or dissolve upon sample preparation. Because of these challenges, a large number of ACC-forming prokaryotes may have been undetected and their abundance in the natural environment is possibly underestimated. This study identifies diagnostic spectral markers of ACC-forming prokaryotes that facilitate their detection in the environment. Accordingly, ACC formed by cyanobacteria was characterized using Fourier transform infrared (FTIR) spectroscopy in near-IR, mid-IR, and far-IR spectral regions. Two characteristic FTIR vibrations of ACC, at âˆ¼ 860 cm-1and âˆ¼ 306 cm-1, were identified as reliable spectral probes to rapidly detect prokaryotic ACC. Using these spectral probes, several Microcystis strains whose ACC-forming capability was unknown, were tested. Four out of eight Microcystis strains were identified as possessing ACC-forming capability and these findings were confirmed by scanning electron microscopy (SEM) observations. Overall, our findings provide a systematic characterization of prokaryotic ACC that facilitate rapid detection of ACC forming prokaryotes in the environment, a prerequisite to shed light on the role of ACC-forming prokaryotes in the geochemical cycle of Ca in the environment.

Semiconducting hematite facilitates microbial and abiotic reduction of chromium.

Semi-conducting Fe oxide minerals, such as hematite, are well known to influence the fate of contaminants and nutrients in many environmental settings through sorption and release of Fe(II) resulting from microbial or abiotic reduction. Studies of Fe oxide reduction by adsorbed Fe(II) have demonstrated that reduction of Fe(III) at one mineral surface can result in the release of Fe(II) on a different one. This process is termed "Fe(II) catalyzed recrystallization" and is believed to be the result of electron transfer through semi-conducting Fe (hydr)oxides. While it is well understood that Fe(II) plays a central role in redox cycling of elements, the environmental implications of Fe(II) catalyzed recrystallization require further exploration. Here, we demonstrate that hematite links physically separated redox reactions by conducting the electrons involved in those reactions. This is shown using an electrochemical setup where Cr reduction is coupled with a potentiostat or Shewanella putrefaciens, a metal reducing microbe, where electrons donated to hematite produce Fe(II) that ultimately reduces Cr. This work demonstrates that mineral semi-conductivity may provide an additional avenue for redox chemistry to occur in natural soils and sediments, because these minerals can link redox active reactants that could not otherwise react due to physical separation.

Cardiac Registries During the COVID-19 Pandemic: Lessons Learned.

PURPOSE OF THIS REVIEW: We discuss the role of observational studies and cardiac registries during the COVID-19 pandemic. We focus on published cardiac registries and highlight contributions to the field that have had clinical implications. RECENT FINDINGS: We included observational studies of COVID-19 patients published in peer-reviewed medical journals with defined inclusion and exclusion criteria, defined study design, and primary outcomes. A PubMed and MEDLINE literature review results in 437 articles, of which 52 include patients with COVID-19 with cardiac endpoints. From July 2020 to December 2021, the average time from last data collected to publication was 8.9 ± 4.1 months, with an increasing trend over time (R = 0.9444, p < 0.0001). Of the 52 articles that met our inclusion criteria, we summarize main findings of 4 manuscripts on stroke, 14 on acute coronary syndrome, 4 on cardiac arrest, 7 on heart failure, 7 on venous thromboembolism, 5 on dysrhythmia, and 11 on different populations at risk for cardiovascular. Registries are cost effective, not disruptive to essential health services, and can be rapidly disseminated with short intervals between last data point collected and publication. In less than 2 years, cardiac registries have filled important gaps in knowledge and informed the care of COVID-19 patients with cardiovascular conditions.

Lessons Learned from Programmatic Gains in HIV Service Delivery During the COVID-19 Pandemic - 41 PEPFAR-Supported Countries, 2020.

The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) supports country programs in identifying persons living with HIV infection (PLHIV), providing life-saving treatment, and reducing the spread of HIV in countries around the world (1,2). CDC used Monitoring, Evaluation, and Reporting (MER) data* to assess the extent to which COVID-19 mitigation strategies affected HIV service delivery across the HIV care continuum† globally during the first year of the COVID-19 pandemic. Indicators included the number of reported HIV-positive test results, the number of PLHIV who were receiving antiretroviral therapy (ART), and the rates of HIV viral load suppression. Percent change in performance was assessed between countries during the first 3 months of 2020, before COVID-19 mitigation efforts began (January-March 2020), and the last 3 months of the calendar year (October-December 2020). Data were reviewed for all 41 countries to assess total and country-level percent change for each indicator. Then, qualitative data were reviewed among countries in the upper quartile to assess specific strategies that contributed to programmatic gains. Overall, positive percent change was observed in PEPFAR-supported countries in HIV treatment (5%) and viral load suppression (2%) during 2020. Countries reporting the highest gains across the HIV care continuum during 2020 attributed successes to reducing or streamlining facility attendance through strategies such as enhancing index testing (offering of testing to the biologic children and partners of PLHIV)§ and community- and home-based testing; treatment delivery approaches; and improvements in data use through monitoring activities, systems, and data quality checks. Countries that reported program improvements during the first year of the COVID-19 pandemic offer important information about how lifesaving HIV treatment might be provided during a global public health crisis.

Adsorptive removal of some Cl-VOC's as dangerous environmental pollutants using feather-like γ-Al2O3 derived from aluminium waste with life cycle analysis.

Herein, we designed a cost-effective preparation method of nanocomposite γ-Al2O3 derived from Al-waste. The produced material has a feather-like morphology, and its adsorption of some chlorinated volatile organic compounds (Cl-VOC's) such as benzyl chloride, chloroform and carbon tetrachloride (C7H7Cl, CHCl3 and CCl4) was investigated due to their potential carcinogenic effect on humans. It showed a characteristic efficiency towards the adsorptive removal of these compounds over a long period, i.e., eight continuous weeks, at ambient temperature and atmospheric pressure. After 8-weeks, the adsorbed amounts of these compounds were determined as: 325.3 mg C7H7Cl, 247.6 mg CHCl3 and 253.3 mg CCl4 per g of γ-Al2O3, respectively. CCl4 was also found to be dissociatively adsorbed on the surface of γ-Al2O3, whereas CHCl3 and C7H7Cl were found to be associatively adsorbed. The prepared γ-Al2O3 has a relatively high surface area (i.e., 192.2 m2. g-1) and mesoporosity with different pore diameters in the range of 25-47 Å. Furthermore, environmental impacts of the nanocomposite γ-Al2O3 preparation were evaluated using life cycle assessment. For prepartion of adsorbent utilising 1 kg of scrap aluminium wire, it was observed that potential energy demand was 288 MJ, climate change potential was 19 kg CO2 equivalent, acidification potential was 0.115 kg SO2 equivalent and eutrophication potential was 0.018 kg PO43- equivalent.

Integrating life cycle assessment and characterisation techniques: A case study of biodiesel production utilising waste Prunus Armeniaca seeds (PAS) and a novel catalyst.

Prunus Armeniaca seed (PAS) oil was utilised as a waste biomass feedstock for biodiesel production via a novel catalytic system (SrO-La2O3) based on different stoichiometric ratios. The catalysts have been characterised and followed by a parametric analysis to optimise catalyst results. The catalyst with a stoichiometric ratio of Sr: La-8 (Sr-La-C) using parametric analysis showed an optimum yield of methyl esters is 97.28% at 65 °C, reaction time 75 min, catalyst loading 3 wt% and methanol to oil molar ratio of 9. The optimum catalyst was tested using various oil feedstocks such as waste cooking oil, sunflower oil, PAS oil, date seed oil and animal fat. The life cycle assessment was performed to evaluate the environmental impacts of biodiesel production utilising waste PAS, considering 1000 kg of biodiesel produced as 1 functional unit. The recorded results showed the cumulative abiotic depletion of fossil resources over the entire biodiesel production process as 22,920 MJ, global warming potential as 1150 kg CO2 equivalent, acidification potential as 4.89 kg SO2 equivalent and eutrophication potential as 0.2 kg PO43- equivalent for 1 tonne (1000 kg) of biodiesel produced. Furthermore, the energy ratio (measured as output energy divided by input energy) for the entire production process was 1.97. These results demonstrated that biodiesel obtained from the valorisation of waste PAS provides a suitable alternative to fossil fuels.