Lassa fever research priorities: towards effective medical countermeasures by the end of the decade.

In 2016, WHO designated Lassa fever a priority disease for epidemic preparedness as part of the WHO Blueprint for Action to Prevent Epidemics. One aspect of preparedness is to promote development of effective medical countermeasures (ie, diagnostics, therapeutics, and vaccines) against Lassa fever. Diagnostic testing for Lassa fever has important limitations and key advancements are needed to ensure rapid and accurate diagnosis. Additionally, the only treatment available for Lassa fever is ribavirin, but controversy exists regarding its effectiveness. Finally, no licensed vaccines are available for the prevention and control of Lassa fever. Ongoing epidemiological and behavioural studies are also crucial in providing actionable information for medical countermeasure development, use, and effectiveness in preventing and treating Lassa fever. This Personal View provides current research priorities for development of Lassa fever medical countermeasures based on literature published primarily in the last 5 years and consensus opinion of 20 subject matter experts with broad experience in public health or the development of diagnostics, therapeutics, and vaccines for Lassa fever. These priorities provide an important framework to ensure that Lassa fever medical countermeasures are developed and readily available for use in endemic and at-risk areas by the end of the decade.

Measures to prevent and treat Nipah virus disease: research priorities for 2024-29.

Nipah virus causes highly lethal disease, with case-fatality rates ranging from 40% to 100% in recognised outbreaks. No treatments or licensed vaccines are currently available for the prevention and control of Nipah virus infection. In 2019, WHO published an advanced draft of a research and development roadmap for accelerating development of medical countermeasures, including diagnostics, therapeutics, and vaccines, to enable effective and timely emergency response to Nipah virus outbreaks. This Personal View provides an update to the WHO roadmap by defining current research priorities for development of Nipah virus medical countermeasures, based primarily on literature published in the last 5 years and consensus opinion of 15 subject matter experts with broad experience in development of medical countermeasures for Nipah virus or experience in the epidemiology, ecology, or public health control of outbreaks of Nipah virus. The research priorities are organised into four main sections: cross-cutting issues (for those that apply to more than one category of medical countermeasures), diagnostics, therapeutics, and vaccines. The strategic goals and milestones identified in each section focus on key achievements that are needed over the next 6 years to ensure that the necessary tools are available for rapid response to future outbreaks of Nipah virus or related henipaviruses.

ICTV Virus Taxonomy Profile: Filoviridae 2024.

Filoviridae is a family of negative-sense RNA viruses with genomes of about 13.1-20.9 kb that infect fish, mammals and reptiles. The filovirid genome is a linear, non-segmented RNA with five canonical open reading frames (ORFs) that encode a nucleoprotein (NP), a polymerase cofactor (VP35), a glycoprotein (GP1,2), a transcriptional activator (VP30) and a large protein (L) containing an RNA-directed RNA polymerase (RdRP) domain. All filovirid genomes encode additional proteins that vary among genera. Several filovirids (e.g., Ebola virus, Marburg virus) are pathogenic for humans and highly virulent. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Filoviridae, which is available at www.ictv.global/report/filoviridae.

E-Stilbenes: General Chemical and Biological Aspects, Potential Pharmacological Activity Based on the Nrf2 Pathway.

Stilbenes are phytoalexins, and their biosynthesis can occur through a natural route (shikimate precursor) or an alternative route (in microorganism cultures). The latter is a metabolic engineering strategy to enhance production due to stilbenes recognized pharmacological and medicinal potential. It is believed that in the human body, these potential activities can be modulated by the regulation of the nuclear factor erythroid derived 2 (Nrf2), which increases the expression of antioxidant enzymes. Given this, our review aims to critically analyze evidence regarding E-stilbenes in human metabolism and the Nrf2 activation pathway, with an emphasis on inflammatory and oxidative stress aspects related to the pathophysiology of chronic and metabolic diseases. In this comprehensive literature review, it can be observed that despite the broad number of stilbenes, those most frequently explored in clinical trials and preclinical studies (in vitro and in vivo) were resveratrol, piceatannol, pterostilbene, polydatin, stilbestrol, and pinosylvin. In some cases, depending on the dose/concentration and chemical nature of the stilbene, it was possible to identify activation of the Nrf2 pathway. Furthermore, the use of some experimental models presented a challenge in comparing results. In view of the above, it can be suggested that E-stilbenes have a relationship with the Nrf2 pathway, whether directly or indirectly, through different biological pathways, and in different diseases or conditions that are mainly related to inflammation and oxidative stress.

Rapid Lignin Thermal Property Prediction through Attenuated Total Reflectance-Infrared Spectroscopy and Chemometrics.

To expedite the valorisation of lignin as a sustainable component in materials applications, rapid and generally available analytical methods are essential to overcome the bottleneck of lignin characterisation. Where features of a lignin's chemical structure have previously been found to be predicted by Partial Least Squares (PLS) regression models built on Infrared (IR) data, we now show for the first time that this approach can be extended to prediction of the glass transition temperature (Tg), a key physicochemical property. This methodology is shown to be convenient and more robust for prediction of Tg than prediction through empirically derived relationships (e. g., Flory-Fox). The chemometric analysis provided root mean squared errors of prediction (RMSEP) as low as 10.0 °C for a botanically, and a process-diverse set of lignins, and 6.2 °C for kraft-only samples. The PLS models could separately predict both the Tg as well as the degree of allylation (%allyl) for allylated lignin fractions, which were all derived from a single lignin source. The models performed exceptionally well, delivering RMSEP of 6.1 °C, and 5.4 %, respectively, despite the conflicting influences of increasing molecular weight and %allyl on Tg. Finally, the method provided accurate determinations of %allyl with RMSEP of 5.2 %.

Microbiological, physicomechanical, and surface evaluation of an experimental self-curing acrylic resin containing halloysite nanotubes doped with chlorhexidine.

OBJECTIVE: The objective was to synthesize halloysite nanotubes loaded with chlorhexidine (HNT/CHX) and evaluate the antimicrobial activity, microhardness, color change, and surface characteristics of an experimental self-curing acrylic resin containing varying concentrations of the synthesized nanomaterial. METHODS: The characterization of HNT/CHX was carried out by calculating incorporation efficiency, morphological and compositional, chemical and thermal evaluations. SAR disks were made containing 0 %, 3 %, 5 %, and 10 % of HNT/CHX. Specimens (n = 3) were immersed in distilled water and spectral measurements were carried out using UV/Vis spectroscopy to evaluate the release of CHX for up to 50 days. The antimicrobial activity of the composite against Candida albicans and Streptococcus mutans was evaluated by disk-diffusion test. Microhardness, color analyses (ΔE), and surface roughness (Ra) (n = 9) were performed before and after 30 days of immersion. Data were analyzed using ANOVA/Bonferroni. {Results.} The incorporation efficiency of CHX into HNT was of 8.15 %. All test groups showed controlled and cumulative CHX release up to 30 or 50 days. Significant antimicrobial activity was verified against both microorganisms (p < 0.001). After the 30-day immersion period, the 10 % HNT/CHX group showed a significant increase in hardness (p < 0.05) and a progressive color change (p < 0.001). At T0, the 5 % and 10 % groups exhibited Ra values similar to the control group (p > 0.05), while at T30, all groups showed similar roughness values (p > 0.05). {Significance.} The modification of a SAR with HNT/CHX provides antimicrobial effect and controlled release of CHX, however, the immediate surface roughness in the 3 % group was compromised when compared to the control group.

Establishing a national indicator-based surveillance system for hospital bed utilization by COVID-19 patients in the Philippines.

In March 2020, the Philippine Department of Health (DOH) designed and rapidly implemented a national surveillance system for the utilization of hospital beds by patients with coronavirus disease (COVID-19) to produce complete and timely data for use by various levels of governance in response to the COVID-19 pandemic. The DOH launched the DOH DataCollect (DDC) Bed Tracker system, a web-based application that collects information from all 1906 public and private hospitals and infirmaries across the country using a modular data collection tool. Data on the maximum number of occupied COVID-19-designated beds (n = 28 261), hospital bed utilization rate (71.7%), and mechanical ventilator number (n = 1846) and utilization rate (58.5%) were recorded in September 2021 during the Delta surge of cases in the Philippines. Data on human resources, personal protective equipment and supplies, and other operational indicators were added to the system during various modifications. Information from the DDC was used to inform the COVID-19 response and operations at national and local levels and facilitated research at academic and nongovernmental agencies. The development of the DDC system demonstrates that an effective surveillance system for use by all health-care facilities is achievable through strong national leadership, the use of available technology and adaptive information systems, and the establishment of networks across different health facilities and stakeholders.

Expanding lignin thermal property space by fractionation and covalent modification.

To fully exploit kraft lignin's potential in material applications, we need to achieve tight control over those key physicochemical lignin parameters that ultimately determine, and serve as proxy for, the properties of lignin-derived materials. Here, we show that fractionation combined with systematic (incremental) modification provides a powerful strategy to expand and controllably tailor lignin property space. In particular, the glass transition temperature (Tg) of a typical kraft lignin could be tuned over a remarkable and unprecedented 213 °C. Remarkably, for all fractions the Tg proved to be highly linearly correlated with the degree of derivatisation by allylation, offering such tight control over the Tg of the lignin and ultimately the ability to 'dial-in' this key property. Importantly, such control over this proxy parameter indeed translated well to lignin-based thiol-ene thermosetting films, whose Tgs thus covered a range from 2-124 °C. This proof of concept suggests this approach to be a powerful and generalisable one, allowing a biorefinery or downstream operation to consciously and reliably tailor lignins to predictable specifications which fit their desired application.

Gcm counteracts Toll-induced inflammation and impacts hemocyte number through cholinergic signaling.

Hemocytes, the myeloid-like immune cells of Drosophila, fulfill a variety of functions that are not completely understood, ranging from phagocytosis to transduction of inflammatory signals. We here show that downregulating the hemocyte-specific Glial cell deficient/Glial cell missing (Glide/Gcm) transcription factor enhances the inflammatory response to the constitutive activation of the Toll pathway. This correlates with lower levels of glutathione S-transferase, suggesting an implication of Glide/Gcm in reactive oxygen species (ROS) signaling and calling for a widespread anti-inflammatory potential of Glide/Gcm. In addition, our data reveal the expression of acetylcholine receptors in hemocytes and that Toll activation affects their expressions, disclosing a novel aspect of the inflammatory response mediated by neurotransmitters. Finally, we provide evidence for acetylcholine receptor nicotinic acetylcholine receptor alpha 6 (nAchRalpha6) regulating hemocyte proliferation in a cell autonomous fashion and for non-cell autonomous cholinergic signaling regulating the number of hemocytes. Altogether, this study provides new insights on the molecular pathways involved in the inflammatory response.

Renaming of genera Ebolavirus and Marburgvirus to Orthoebolavirus and Orthomarburgvirus, respectively, and introduction of binomial species names within family Filoviridae.

The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group continues to prospectively refine the established nomenclature for taxa included in family Filoviridae in an effort to decrease confusion of genus, species, and virus names and to adhere to amended stipulations of the International Code of Virus Classification and Nomenclature (ICVCN). Recently, the genus names Ebolavirus and Marburgvirus were changed to Orthoebolavirus and Orthomarburgvirus, respectively. Additionally, all established species names in family Filoviridae now adhere to the ICTV-mandated binomial format. Virus names remain unchanged and valid. Here, we outline the revised taxonomy of family Filoviridae as approved by the ICTV in April 2023.

Chemical, structural and cytotoxicity characterisation of experimental fluoride-doped calcium phosphates as promising remineralising materials for dental applications.

OBJECTIVES: This study aimed at evaluating the cytotoxicity, chemical and structural properties of experimental fluoride-doped calcium-phosphates as potential remineralising materials for dental applications. METHODS: Experimental calcium phosphates were formulated using ß-tricalcium phosphate, monocalcium phosphate monohydrate, calcium hydroxide, and different concentrations of calcium/sodium fluoride salts [(5 wt%: VSG5F), (10 wt%: VSG10F), (20 wt%: VSG20F)]. A fluoride-free calcium phosphate (VSG) was used as control. Each tested material was immersed in simulated body fluid (SBF), (24 h, 15 and 30 days) to assess their ability to crystallise into apatite-like. Cumulative fluoride release was assayed up to 45 days. Moreover, each powder was placed into a medium containing human dental pulp stem cells (200 mg/mL) and their cytotoxicity was analysed using the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay (24 h, 48 h and 72 h incubation). These latter results were statistically analysed by ANOVA and Tukey's test (α = 0.05). RESULTS: All the experimental VSG-F materials produced fluoride-containing apatite-like crystals after SBF immersion. VSG20F presented prolonged release of fluoride ions into the storage media (45d). VSG, VSG10F and VSG20F showed a significant cytotoxicity at dilution of 1:1, while at 1:5, only VSG and VSG20F demonstrated a reduction in cell viability. At lower dilutions (1:10, 1:50 and 1:100) all specimens showed no significant toxicity to hDPSCs, but an increase in cell proliferation. SIGNIFICANCE: The experimental fluoride-doped calcium-phosphates are biocompatible and possess a clear ability to evoke fluoride-containing apatite-like crystallisation. Hence, they may be promising remineralising materials for dental applications.

Updates in Traumatic Lower Extremity Free Flap Reconstruction.

SUMMARY: Lower extremity reconstruction, particularly in the setting of trauma, remains one of the most challenging tasks for the plastic surgeon. Advances in wound management and microsurgical techniques in conjunction with long-term outcomes studies have expanded possibilities for limb salvage, but many aspects of management have continued to rely on principles set forth by Gustilo and Godina in the 1980s. The purpose of this article is to provide a comprehensive update on the various management aspects of traumatic lower extremity microvascular reconstruction based on the latest evidence, with an examination of recent publications.

Perioperative Medication Management in Elective Plastic Surgery Procedures.

BACKGROUND: Perioperative medication management is vital to maintain patient safety while under anesthesia, as well as to avoid postoperative complications. Plastic surgeons make daily decisions on whether to ask a patient to stop taking medication before their surgery. These important decisions can affect bleeding risk, wound healing, and interactions with anesthetics, which can range from minor to life-threatening. Current plastic surgery literature lacks a comprehensive review of perioperative medication management, with existing reports focusing on specific procedures and specific medication classes. METHODS: A PubMed database search was conducted for articles through July 2021. The bibliographies of included studies were also examined for articles not acquired in the initial search queries. The authors included studies on medication usage and perioperative guidance in patients undergoing elective plastic surgery procedures. The authors excluded studies unrelated to plastic surgery and studies where the medications were used as an intervention. Abstracts, animal studies, studies involving the pediatric population, and book chapters were also excluded, as well as articles not published in English. RESULTS: A total of 801 papers were identified by our search terms. After title and abstract screening, 35 papers were selected for full-text review. After full-text review, 20 papers were selected for inclusion, with an additional 6 papers from cited references added. Of the 26 papers, 6 papers discussed psychotropic drugs, 6 papers discussed medications affecting hemostasis, 4 papers discussed hormone-containing medications, 3 papers discussed antilipid medications, 2 papers discussed antihypertensive medications, 2 papers discussed herbal supplements, 1 paper discussed both psychotropic and herbal supplements, 1 paper discussed medications affecting wound healing, and 1 paper discussed rheumatologic medications. A summary of those recommendations was then compiled together. CONCLUSIONS: The perioperative medication management in elective plastic surgery procedures remains a complex and multidisciplinary process. It is important to manage these patients in a case-by-case manner and to consult a specialist when necessary. Careful medication reconciliation is essential to decrease the likelihood of adverse outcomes and interactions with perioperative anesthetics.

Magnetic solid phase extraction as a nonchromatographic method for the quantification of ultratrace inorganic arsenic in rice by inductively coupled plasma-optical emission spectrometry (ICP OES).

An alternative analytical method was developed for the quantification of inorganic arsenic (iAs) in rice by ICP OES. Iron nanoparticles modified with an organophosphorus compound were used as the solid phase for MSPE of iAs from the plant matrix. The MSPE procedure was performed using 4 mL of a buffer solution with pH 4.0, 20 mg of the nanomaterial, and a 15-min extraction time. The total As (tAs) by ICP OES was also quantified using the same MSPE procedure after solubilization of the samples by a block digester. The accuracy of tAs and iAs quantification was verified using CRM NIST 1568b (97 % and 101 % recovery, respectively). The precision (RSD < 15 %) and LOD and LOQ (1.08 and 3.70 µg kg-1, respectively) of the proposed method were satisfactory. The rice samples had tAs contents between 0.090 and 0.295 mg kg-1 and iAs mass fractions between 0.055 and 0.109 mg kg-1.

Ozone use in the treatment of subclinical mastitis in dairy cows.

This research communication paper addresses the hypothesis that the use of therapeutic alternatives for mastitis, such as intramammary ozone, can cure the disease with lower costs and without harmful residues for human consumption and without formation of microbial resistance like the ones caused by indiscriminate use of antibiotics in dairy farms. The study was performed in 36 mammary quarters from 12 dairy cows with subclinical mastitis grade three. The experimental units were randomly assigned into four groups and each group received a treatment. Treatments comprised (a) 20 µg/ml ozone gas; (b) 40 µg/ml ozone gas; (c) negative control treatment of 12.5 µg/ml ozonated saline and (d) positive control treatment of 100 mg of cephalexin + 100 mg of neomycin + 10 mg of prednisolone, all by intramammary injection. In all quarters, milk was collected before and after the application of treatments for California mastitis test and evaluation of milk composition, somatic cell count, and bacterial cultures. The results indicated that the use of intramammary ozone did have a therapeutic effect, and whilst this was less than that of antibiotics, ozone does confer some advantages. Treated milk had a good composition, the treatment cost was low, milk withdrawal may not be necessary and there is no risk of antibiotic resistance.

An anti-inflammatory transcriptional cascade conserved from flies to humans.

Innate immunity is an ancestral process that can induce pro- and anti-inflammatory states. A major challenge is to characterize transcriptional cascades that modulate the response to inflammation. Since the Drosophila glial cells missing (Gcm) transcription factor has an anti-inflammatory role, we explored its regulation and evolutionary conservation. Here, we show that the murine Gcm2 (mGcm2) gene is expressed in a subpopulation of aged microglia (chronic inflammation) and upon lysophosphatidylcholine (LPC)-induced central nervous system (CNS) demyelination (acute inflammation). Moreover, mGcm2 conditional knockout mice show an increased inflammatory phenotype upon aging or LPC injection, and hGCM2 is expressed in active demyelinating lesions of patients with multiple sclerosis. Finally, Drosophila Gcm expression is induced upon aging and acute challenge, and its overexpression decreases the inflammatory phenotype. Altogether, these data indicate that the inducible Gcm cascade is conserved from flies to humans and represents a potential therapeutic target in the control of the inflammatory response.

The First Successful Combined Full Face and Bilateral Hand Transplant.

BACKGROUND: Vascularized composite allotransplantation has redefined the frontiers of plastic and reconstructive surgery. At the cutting edge of this evolving paradigm, the authors present the first successful combined full face and bilateral hand transplant. METHODS: A 21-year-old man presented for evaluation with sequelae of an 80 percent total body surface area burn injury sustained after a motor vehicle accident. The injury included full face and bilateral upper extremity composite tissue defects, resulting in reduced quality of life and loss of independence. Multidisciplinary evaluation confirmed eligibility for combined face and bilateral hand transplantation. The operative approach was validated through 11 cadaveric rehearsals utilizing computerized surgical planning. Institutional review board and organ procurement organization approvals were obtained. The recipient, his caregiver, and the donor family consented to the procedure. RESULTS: Combined full face (i.e., eyelids, ears, nose, lips, and skeletal subunits) and bilateral hand transplantation (i.e., forearm level) was performed over 23 hours on August 12 to 13, 2020. Triple induction and maintenance immunosuppressive therapy and infection prophylaxis were administered. Plasmapheresis was necessary postoperatively. Minor revisions were performed over seven subsequent operations, including five left upper extremity, seven right upper extremity, and seven facial secondary procedures. At 8 months, the patient was approaching functional independence and remained free of acute rejection. He had significantly improved range of motion, motor power, and sensation of the face and hand allografts. CONCLUSIONS: Combined face and bilateral hand transplantation is feasible. This was the most comprehensive vascularized composite allotransplantation procedure successfully performed to date, marking a new milestone in plastic and reconstructive surgery for patients with otherwise irremediable injuries.

Laser-power dependence effects on the structural stability of nanocomposite catalysts studied by Raman spectroscopy: On the structure-activity correlations in glycerol acetylation.

Structural properties of binary CeAl, CeMn, NiAl, CeZr, SnTi and ZrMn nanocomposite oxide catalysts were monitored towards the Laser Raman spectroscopy investigations providing new insights to control catalytic applications upon temperature ranges at which the laser power was varied. The lattice vibrational properties were investigated by varying the incident laser power during Raman measurements from 0.017 mW to 4.0 mW. Structural changes in nanocomposites were achieved upon increasing laser power, which induced local heating disorder causing the sintering of CeMn, SnTi, and ZrMn nanocomposites. The laser-power dependence effects on the structural stability of CeAl, NiAl, and CeZr were observed with high amounts of oxygen vacancy defects over CeAl upon laser power heating. Both CeMn and ZrMn exhibited phase transitions from MnO2 to α-Mn2O3 being the use of the latter nanocomposites limited to work at 1.1 mW. The structure-activity correlations for the nanocomposite oxide catalysts were evaluated through the acetylation of glycerol with acetic acid reaction to produce valuable acetins. Remarkable shifts in the Raman bands wavenumbers and other spectral changes in the lattice mode were caused by laser-induced phenomena accounting for the undesired phase formation and particle growths, as well. This resulted in a low catalytic performance of the NiAl, SnTi, CeMn and ZrMn owing to the thermal effects. Contrary, CeAl and CeZr were more active for acetins products avoiding the phase transformations due to their structural stability at high temperatures, which in turn avoided leaching of the active Ce sites during the reaction.

Chiropractic techniques and treatment modalities included in academic programs: A survey of chiropractic educational institutions.

OBJECTIVE: The chiropractic techniques that chiropractors learn during their training strongly influence the nature of treatments provided by chiropractors and their professional identity. The objective of this project is to provide an exhaustive description of all chiropractic techniques and treatment modalities taught in chiropractic educational institutions. METHODS: International experts were solicited to provide feedback on the exhaustivity and clarity of our preliminary questionnaire. Following the expert suggestions, we administered our cross-sectional survey representatives of all chiropractic education institutions listed on the World Federation of Chiropractic website. We also asked the contact information for an additional contact from each institution and surveyed them for triangulation purposes. RESULTS: Among the 47 chiropractic education institutions surveyed, 29 completed our survey (response rate: 62%) of which 18 (62%) had 2 respondents. Among all the chiropractic techniques and treatment modalities investigated, only the Diversified technique was included in the core curriculum of all responding institutions. A considerable proportion of the techniques or modalities studied were not included in the educational activities of the institutions, particularly within the manual tonal or reflex techniques, instrument-assisted articular techniques, as well as the other techniques or modalities categories. Surprisingly, exercise prescription was not included in the core curriculum of all the institutions. Some scientifically challenged approaches were included in the educational activities of more than 40% of the institutions. CONCLUSION: The portfolio of therapeutic teaching varies greatly between chiropractic educational institutions. A more standardized therapeutic curriculum could be beneficial to reduce public and interprofessional confusion toward therapeutic approaches in chiropractic.