The neurophysiology of sensorimotor prosthetic control.

Movement is a central behavior of daily living; thus lost or compromised movement due to disease, injury, or amputation causes enormous loss of productivity and quality of life. While prosthetics have evolved enormously over the years, restoring natural sensorimotor (SM) control via a prosthesis is a difficult problem which neuroengineering has yet to solve. With a focus on upper limb prosthetics, this perspective article discusses the neurophysiology of motor control under healthy conditions and after amputation, the development of upper limb prostheses from early generations to current state-of-the art sensorimotor neuroprostheses, and how postinjury changes could complicate prosthetic control. Current challenges and future development of smart sensorimotor neuroprostheses are also discussed.

Digital Cognitive Behavioral Therapy vs Education for Pain in Adults with Sickle Cell Disease.

Despite the significant burden of chronic pain in sickle cell disease (SCD), non-pharmacological approaches to manage pain in SCD are lacking. Behavioral interventions incorporating digital cognitive-behavioral therapy CBT) for pain should be compared to available education efforts. To compare a CBT intervention tailored for adults with SCD to a digital pain/SCD education intervention (Education) on improving pain and associated symptoms. Multisite randomized comparative effectiveness trial. Seven comprehensive SCD centers and virtual recruitment through community organizations in the United States. Adults (age 18+) with SCD-related chronic pain and/or daily opioid use randomized to CBT or Education. Over 12 weeks, the CBT arm received an app-based intervention for pain management; the Education arm received digital pain/SCD education. Both groups received interactive chatbot lessons plus personalized health coach support. Changes in pain interference scale (primary); and other patient-reported outcomes (secondary), including pain intensity, depression, anxiety, quality of life, and self-efficacy over 6 months. 453 participants completed screening, 359 (79%) were randomized to CBT (n=181) or Education (n=178), 332 (92%) were Black African American, 238 (66.3%) female. At 6 months, 250 (70%) participants (n=125 per arm) completed follow-up assessments, 93 (26%) missed their follow-up window, 16 (4%) withdrew. Engagement with the chatbot content was variable (76% connected, 48% completed ≥1 lesson). However, 80% of participants completed ≥1 session with a health coach via phone, video, or text. The 6 month change in pain interference for CBT (-2.13; 95% CI, -3.42 to -0.84) and Education (-2.66; 95%CI, -3.97 to -1.36) was not significantly different (mean difference: 0.54; 95%CI, -1.30 to 2.37; *P=*0.57). Daily pain intensity ratings did not change for either group. There were no between-arm differences in depression, anxiety, and quality of life. CBT and Education did not differ in their effect on pain and mental health in SCD when combined with health coaching. Variable engagement with digital components and high engagement with health coaching may explain the lack of between-group differences, but these findings also provide insights into delivering digital interventions in racial minority and hard-to-reach populations. Trial Registration: ClinicalTrials.gov NCT04419168.

Myricetin-loaded SBA-15 silica nanoparticles for enhanced management of pyrexia, pain, and inflammation through modulation of MAPK/NF-κB and COX-2/PGE-2 pathways: Evidence from the biochemical, histological, and metabolomic analysis.

Myricetin (MYR) is a natural flavonoid that has several biological functions. However, some of its beneficial effects are diminished due to low water solubility, stability, and bioavailability. Herein, several kinds of silica nanoparticles (MCM-41 and SBA-15) were loaded with MYR to improve its biological activity as an analgesic, antipyretic, and anti-inflammatory component, thereby overcoming its drawbacks. The nanoparticles (MYR@SBA-15) were formulated optimally, transforming MYR into an amorphous state. This transformation was confirmed via several strategies, including differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder x-ray diffraction. As a result, there was a significant enhancement in the solubility and rate of dissolution in water. The anti-inflammatory benefits as an innovative strategy and the underlying mechanism of action of MYR and its SBA-15 silica nanoparticles (MYR@SBA-15) were investigated based on the biochemical, histological, immunohistochemical, and metabolomic assays alongside their antipyretic and analgesic characteristics. Compared to the usage of raw MYR, the administration of MYR@SBA-15 at doses of 25, 50, and 100 mg/kg significantly decreases pain perception by inhibiting the body's writhing motions induced by acetic acid. Furthermore, it helps regulate increased body temperature caused by baking yeast and effectively stabilizes it. It reduces the release of NO and PGE-2 in a concentration-dependent manner by down-regulating iNOS and COX-2 expression in the inflammatory model. MYR and MYR@SBA-15 also inhibit the nuclear translocation of NF-κB, downregulate the expression of mitogen-activated protein kinases (MAPKs), such as p38, ERK1/2, and JNK protein, and reduce the generation of proinflammatory cytokines, such as TNF-α. In addition, inflammatory cardinal signs like paw edema caused by carrageenan in rats are greatly suppressed by MYR and MYR@SBA-15 treatment when compared to the untreated group. More noteworthy outcomes are shown in the MYR@SBA-15, particularly at a dose of 100 mg/kg. These results of biochemical and immuno-histochemistry suggest that MYR@SBA-15 may be a useful analgesic antipyretic and may also help reduce inflammation by altering MAPKs/NF-κB and COX-2/PGE-2 signaling cascades. Serum metabolomics study demonstrated modifications in various low molecular weight metabolites with arthritis development. These metabolite levels were restored to normal when MYR@SBA-15 was administered via modulating several metabolic pathways, i.e., pyrimidine, energy metabolism, and proteins. Overall, MYR-loaded SBA-15 silica nanoparticles have demonstrated significant promise in enhancing the disturbed metaboloic pathways and providing a substantial capacity to regulate several oxidative stress and inflammatory mediators.

Exploring COVID-19 vaccine adverse events among pregnant women: a cross-sectional study, 2022.

Background: Clear and trustworthy information is crucial to improving public acceptance of COVID-19 vaccinations, especially among pregnant women. Given the increased risk of severe viral pneumonia in pregnant women, it is critical to foster confidence in the vaccine's safety and understand any potential adverse events (AEs). So, we did this study in Jeddah, Saudi Arabia (SA), from March to May 2022 to compare women who did not get any doses of the COVID-19 vaccine during pregnancy (Group A) to women who did get at least one dose during pregnancy (Group B) regarding (1) the frequency, types, AEs, and management of its AEs of the COVID-19 vaccination; and (2) exploring pregnancy, delivery, and fetus-related complications (e.g., miscarriage, birth defects, and preterm labor). Methods: A cross-sectional study targeted 438 women who gave birth or were pregnant within the previous 8 weeks. Data was collected through face-to-face interviews with skilled nurses in 13 randomly selected primary healthcare facilities, using a validated, well-structured questionnaire that included the Centers for Disease Control (CDC) COVID-19 vaccination-related AEs. We analyzed the collected data using SPSS version 27. Results: Most participants were aged 25 to less than 35 (58.8%), and 287 (61.3%) were university graduates. There was no statistically significant difference among the studied groups regarding demographics. However, women in Group B had a significantly higher rate of abortions, oligohydramnios (24.4%), abnormal placentas (size and location), 103 (42.7%) abnormal fetal growth, 122 (53.7%) problems breastfeeding, blood pressure problems, and more cases of malaise, headaches, chest pain, breathing problems, and sleep problems than women in Group A. After the second and third doses, the confirmed post-vaccination COVID-19 rates in Group B were lower than those in Group A. Conclusion: The COVID-19 vaccine significantly reduces post-vaccination COVID-19. Although COVID-19 vaccine-related AES are prevalent, analgesics and antipyretics effectively treat most of them.

Background: Clear and trustworthy information is essential for increasing public acceptance of COVID-19 vaccinations, particularly among pregnant women who face higher risks of severe illness. This study, conducted from March to May 2022 in Jeddah, Saudi Arabia, aimed to explore issues related to COVID-19 vaccination in pregnant women. The study focused to compare those who did not receive any vaccination doses during pregnancy (Group A) and those who received at least one dose or more during pregnancy (Group B) regarding 1) the frequency, types, AEs, and management of the COVID-19 vaccination among moms; and 2) exploring pregnancy, delivery, and fetus-related complications (e.g., miscarriage, birth defects, preterm labor, etc.). Methods: We conducted the study on 438 women who had given birth within the past 8 weeks. Data were collected through face-to-face interviews with skilled nurses at 13 randomly selected primary healthcare facilities using a validated questionnaire. Results: In this study, it is observed:• Most participants were aged 25 to less than 35 years old (58.8%), and 61.3% were university graduates.• No significant demographic differences were found between groups.• The study groups showed a statistically significant difference in the occurrence of spontaneous abortions, oligohydramnios, abnormal placentas (size and location), abnormal fetal growth, blood pressure problems, breastfeeding problems, malaise, headaches, chest pain, breathing problems, and sleep problems. However, most reported AEs required only analgesics and antipyretics.• Post-vaccination COVID-19 rates were lower in vaccinated women after the second and third doses. Conclusions: The COVID-19 vaccine significantly reduces post-vaccination COVID-19. Although COVID-19 vaccine-related AES are prevalent, analgesics and antipyretics effectively treat most of them.

Prevalence and issues of COVID-19 vaccine adverse events among pregnant women.

Unusual association of cervical arachnoid cyst and idiopathic intracranial hypertension.

Arachnoid cysts (ACs) are more commonly seen intracranially rather than intraspinally, with most being asymptomatic. This case report presents a rare association between symptomatic AC and idiopathic intracranial hypertension (IIH). In a 71-year-old man who exhibited long-standing bilateral shoulder pain and severe left brachialgia despite an unremarkable physical examination. Radiologic investigations revealed a left C5-6 cervical arachnoid cyst, and during treatment, the patient was diagnosed with IIH. Surgical excision of the cyst failed, so the patient was treated with a lumbar puncture (LP) shunt that required several revisions. During these revisions, IIH was diagnosed, leading to the insertion of a ventriculoperitoneal (VP) shunt, which improved the symptoms. Early diagnosis of IIH through lumbar puncture in cases of spinal arachnoid cysts allows for earlier treatment with cerebrospinal fluid (CSF) diversion via a VP shunt, reducing repeated hospital admissions and surgical interventions.

Cilostazol Combats Lipopolysaccharide-Induced Hippocampal Injury in Rats: Role of AKT/GSK3ß/CREB Curbing Neuroinflammation.

Neuroinflammation is important in the pathophysiology of several degenerative brain disorders. This study looked at the potential neuroprotective benefits of cilostazol, a phosphodiesterase inhibitor, against LPS-induced hippocampus damage in rodents and the principal molecular involvement of AKT/GSK3ß/CREB signaling pathways. Behavioral tests revealed that cilostazol successfully corrected LPS-induced neurobehavioral impairments. Furthermore, cilostazol therapy lowered hippocampal levels of amyloid beta 1-42 (Aß1-42) and p-tau protein, both of which are critical pathological indicators of neurodegenerative disorders. Furthermore, cilostazol administration suppressed LPS-induced rises in hippocampus caspase-3 and NF-κB levels while elevating rat B-cell/lymphoma 2 (BCL2) and brain-derived neurotrophic factor (BDNF) levels, which are implicated in neuronal survival and synaptic plasticity. Cilostazol treatment also restored the decreased phosphorylation of protein kinase B (p-AKT) and reduced the elevated levels of phosphorylated glycogen synthase kinase-3 beta (p-GSK3ß) and cAMP response element-binding protein (CREB) in the hippocampus of LPS-treated rats. Histopathological examination revealed that cilostazol ameliorated LPS-induced brain damage with reduced neuronal loss and gliosis. Immunohistochemistry analysis showed a decrease in Iba-1 expression, indicating a reduction in microglial activation in the cilostazol-treated group compared to the LPS group. The findings advocate that cilostazol exerts neuroprotective effects against LPS-induced hippocampal injury by modulating the AKT/GSK3ß/CREB pathway and curbing neuroinflammation. Cilostazol may hold promise as a therapeutic agent for neuroinflammatory conditions associated with neurodegenerative diseases.

MRSA Inhibitory Activity of Some New Pyrazolo[1,5-a]pyrimidines Linked to Arene and/or Furan or Thiophene Units.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major contributor to hospital-acquired infections and is highly resistant to treatment. Ongoing research focuses on developing new antimicrobial medications to prevent the spread of resistance. A facile method was employed to efficiently synthesize new pyrazolo[1,5-a]pyrimidines in 84-93% yields by reacting 4-benzyl-1H-pyrazole-3,5-diamine with the respective α,ß-unsaturated ketones. The reaction was carried out in ethanol containing 1.2 equivalents of potassium hydroxide at reflux for 5-6 h. The new products are attached to a para-substituted aryl group with variable electronic properties at pyrazolopyrimidine-C5, in addition to one of three units at C7, namely phenyl, thiophen-2-yl, or furan-2-yl units. A wide spectrum of antibacterial activity was displayed by the new pyrimidines against six different bacterial strains. In general, pyrimidines attached to furan-2-yl units at C7, in addition to another aryl unit at C5, attached to 4-Me or 4-OMe groups, demonstrate significant antibacterial activity, particularly against S. aureus strain. They had MIC/MBC of 2.5/5.1 and 2.4/4.9 µM, respectively, which exceeded that of ciprofloxacin. Moreover, they demonstrate more effective MRSA inhibitory activity than linezolid, with MIC/MBC values up to 4.9/19.7 and 2.4/19.7 µM against MRSA ATCC:33591 and ATCC:43300 strains, respectively.

Late effects after allogeneic haematopoietic cell transplantation in children and adolescents with non-malignant disorders: a retrospective cohort study.

BACKGROUND: Continued advances in haematopoietic cell transplantation (HCT) for children with non-malignant diseases (NMDs) have led to a growing population of survivors in whom late occurring toxic effects remain a challenge. We investigated the incidence of and risk factors for post-transplant toxicities in a contemporary cohort of children and adolescents undergoing HCT for NMDs. METHODS: In this retrospective cohort study, we extracted data from the Center for International Blood and Marrow Transplantation Research (CIBMTR) database to analyse timing and incidence of effects and risk factors associated with late effects of HCT for treatment of NMDs at age 21 years or younger. Late effects of interest were avascular necrosis, cataracts, congestive heart failure, myocardial infarction, diabetes, gonadal dysfunction, growth hormone deficiency, hypothyroidism, renal failure requiring dialysis, and neurological events (stroke and seizure). Cumulative incidence of each late effect was calculated at 5 years and 7 years after HCT. Risk factors were evaluated in Cox proportional hazards regression analyses. Main exposures were primary NMD, age, sex, ethnicity and race, insurance, donor and graft type, myoablative conditioning, total-body irradiation exposure, graft-versus-host disease (GVHD), and transplant year. Primary outcomes were rates, cumulative incidence probability (95% CI), and risk-factors for organ-specific late effects. FINDINGS: Between Jan 1, 2000, and Dec 31, 2017, 7785 patients aged 21 years or younger underwent HCT. 1995 patients were ineligible or did not consent to be included. 5790 patients from 171 centres were included in the analysis. 3505 (60·5%) of 5790 patients were male and 2285 (39·5%) were female. 2106 (36·4%) patients were White, 771 (13·3%) were Hispanic, and 773 (12·7%) were Black. 1790 (30·9%) patients were non-USA residents. Median age at HCT was 5·5 years (range 0·0-21·0). 1127 (19%) of 5790 patients had one late effect, and 381 (7%) had at least two. At 7 years post-HCT, the cumulative incidence probability was 1·9 (95% CI 1·5-2·3) for cataracts, 4·9 (4·3-5·6) for diabetes, 2·6 (2·1-3·1) for gonadal dysfunction, 3·2 (2·7-3·8) for hypothyroidism, 5·0 (4·4-5·7) for growth disturbance, 8·1 (7·4-8·9) for renal failure, 1·6 (1·3-2·0) for avascular necrosis, 0·6 (0·4-0·8) for congestive heart failure, 0·2 (0·1-0·3) for myocardial infarction, and 9·4 (8·6-10·2) for neurological effects. Age 10 years or older at HCT, unrelated donor source, total-body irradiation, and GVHD were identified as risk factors for long-term effects. INTERPRETATION: The findings highlight the need for, and access to, multidisciplinary and lifelong follow-up for children undergoing HCT for NMDs. As more children undergo treatment with cellular therapies for non-malignant conditions, further analyses of post-transplant data could increasingly guide treatment decisions and subsequent long-term surveillance. FUNDING: National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration, and Office of Naval Research.

Impacts of circulating cytokine levels and gene polymorphism predisposition on type 1 diabetes mellitus.

PURPOSE: A wide range of cytokines has been demonstrated to be involved in the etiology of type 1 diabetes mellitus (T1DM). Gene polymorphisms may potentially contribute to a hereditary predisposition toward circulating cytokine levels as (high, intermediate, or low) since they can affect cytokine production or function. The aim of this study was to investigate the roles of cytokine levels and the association of single-nucleotide polymorphisms (SNPs) within cytokine genes with T1DM in Saudi children. METHODS: Totals of 91 well-characterized T1DM patients and 91 T1DM-free control subjects were enrolled in this study. RESULTS: The levels of 3 circulating cytokines (transforming growth factor [TGF]-ß1, interleukin [IL]-10, and IL-6) and 6 SNPs in 3 cytokine genes (TGF-ß1 [rs1800470 and rs1800471], IL-10 [rs1800896, rs1800871, and rs1800872], and IL-6 [rs1800795]) that contribute to genetic susceptibility were measured by enzyme-linked immunosorbent assay and polymerase chain reaction with sequence-specific primers. Our fn dings show that TGF-ß1 serum levels were signifcantly lower in the children with T1DM than in the control participants. The TGF-ß1 genotypes with a high-production phenotype were signifcantly less frequent and those with a lowproduction phenotype were signifcantly more frequent in the children with T1DM compared to the control participants. respectively. Furthermore, the IL-6 genotype frequency with low level of IL-6 production were signifcantly increased in the T1DM group compared to the control group. Moreover, our data demonstrated no appreciable diferences in circulating serum level or genotype and phenotype of IL- 10 between the patients and controls. CONCLUSION: This kind of measurement, which considers the prediction of T1DM, may be useful in assessing the severity of T1DM and susceptibility to T1DM among Saudi children.

Unveiling the Neem (Azadirachta indica) Effects on Biofilm Formation of Food-Borne Bacteria and the Potential Mechanism Using a Molecular Docking Approach.

Biofilms currently represent the most prevalent bacterial lifestyle, enabling them to resist environmental stress and antibacterial drugs. Natural antibacterial agents could be a safe solution for controlling bacterial biofilms in food industries without affecting human health and environmental safety. A methanolic extract of Azadirachta indica (neem) leaves was prepared and analyzed using gas chromatography-mass spectrometry for the identification of its phytochemical constituents. Four food-borne bacterial pathogens (Bacillus cereus, Novosphingobium aromaticivorans, Klebsiella pneumoniae, and Serratia marcescens) were tested for biofilm formation qualitatively and quantitatively. The antibacterial and antibiofilm properties of the extract were estimated using liquid cultures and a microtiter plate assay. The biofilm inhibition mechanisms were investigated using a light microscope and molecular docking technique. The methanolic extract contained 45 identified compounds, including fatty acids, ester, phenols, flavonoids, terpenes, steroids, and antioxidants with antimicrobial, anticancer, and anti-inflammatory properties. Substantial antibacterial activity in relation to the extract was recorded, especially at 100 µg/mL against K. pneumoniae and S. marcescens. The extract inhibited biofilm formation at 100 µg/mL by 83.83% (S. marcescens), 73.12% (K. pneumoniae), and 54.4% (N. aromaticivorans). The results indicate efficient biofilm formation by the Gram-negative bacteria S. marcescens, K. pneumoniae, and N. aromaticivorans, giving 0.74, 0.292, and 0.219 OD at 595 nm, respectively, while B. cereus was found to have a low biofilm formation potential, i.e., 0.14 OD at 595 nm. The light microscope technique shows the antibiofilm activities with the biofilm almost disappearing at 75 µg/mL and 100 µg/mL concentrations. This antibiofilm property was attributed to DNA gyrase inhibition as illustrated by the molecular docking approach.

Surface topography changes and wear resistance of different non-metallic telescopic crown attachment materials in implant retained overdenture (prospective comparative in vitro study).

BACKGROUND: The purpose of this study was to evaluate the effect of using different types of metallic and non-metallic telescopic crown attachment materials on wear resistance and surface tomography changes in implant-retained mandibular overdentures. MATERIALS AND METHODS: Completely edentulous mandibular epoxy models were fabricated, in which two implants were placed in the canine region and retained to the implants with three different material combinations used for the construction of telescopic attachments. Thirty-three identical mandibular overdentures were fabricated using the conventional standardized technique. The study groups were divided into three categories according to the material used for the construction of the secondary copings. The primary copings in all the study groups were constructed of PEEK, while the secondary coping in group I was PEEK, group II was ZrO2 and CoCr for group III. Primary copings were cemented on a ready-made abutment. Secondary copings were placed over the primary copings in the desired path of insertion, then picked up into the intaglio surface of the overdentures. A cyclic loading machine was used to apply repeated insertion-removal cycles simulating nearly 10 years of clinical use. Stereomicroscope with a built-in camera was used to monitor the reduction in width of the primary copings to evaluate the wear resistance of each material combination. RESULTS: There was highly statistically significant difference between the study groups after the application of 1.000, 5.000 and 10.000 cycles. The highest level of wear resistance was recorded for the PEEK/PEEK combination, whereas PEEK/ZrO2 and PEEK/CoCr showed no significant differences. CONCLUSIONS: Implant retained overdenture with PEEK-PEEK telescopic crown attachment is associated with the highest wear resistance among all the study groups. PEEK-PEEK combination may be the treatment of choice for fabrication of telescopic attachment in implant retained overdenture as it provides better resistance to wear. It offers the advantages for geriatric patients as it decreases the possibility for repeated repair and replacement of attachment, increase long-term patient satisfaction and shelf life of prosthesis.

Bioactivity screening and molecular identification of Anchusa milleri L. sunflower crud extract for antioxidant, antiviral, antimicrobial, and anticancer properties.

The current study evaluates hot water A. milleri sunflower extracts at 40 °C temperature (AMSE40) for their antibacterial, anti-biofilm, antiviral and anticancer activities. AMSE40 exhibited excellent antioxidant activity with an IC50 of 1.17 mg/mL (ascorbic acid) and was found to be rich in phytochemical compounds such as alkaloids, flavonoids, phenolics, saponins, and tannins, with concentrations of 1.23%, 351.60 mg/g, 152.50 mg/g, 0.98%, and 146.35 mg/g, respectively. AMSE40 showed strong antibacterial and anti-biofilm activity against four multidrug-resistant isolates, comprising E. faecalis, S. aureus, P. aeruginosa, and K. pneumonia with minimum bactericidal concentrations (25 mg/mL) and minimum inhibitory concentrations (12.5 mg/mL) for all isolates. The AMSE40 (62.5 µg/mL) showed antiviral efficacy against CoxB4 (9.1%) and HSV-1 (34.4%). Additionally, AMSE40 induced DNA fragmentation in liver cell lines, indicating cell death. The cytotoxic concentration of AMSE40 had a mild impact on Vero (283.2 µg) and HepG2 cells (76.4 µg). A. milleri has the potential to serve as a natural and eco-friendly source for innovative pharmaceutical and medical applications.

Silence is not always golden: A closer look at potential environmental and ecotoxicological impacts of large-scale dsRNA application.

RNA interference (RNAi) technology has emerged as a pivotal strategy in sustainable pest management, offering a targeted approach that significantly mitigates the environmental and health risks associated with traditional insecticides. Originally implemented through genetically modified organisms (GMOs) to produce specific RNAi constructs, the technology has evolved in response to public and regulatory concerns over GMOs. This evolution has spurred the development of non-transgenic RNAi applications such as spray-induced gene silencing (SIGS), which employs double-stranded RNA (dsRNA) to silence pest genes directly without altering the plant's genetic makeup. Despite its advantages in specificity and reduced ecological footprint, SIGS faces significant obstacles, particularly the instability of dsRNA in field conditions, which limits its practical efficacy. To overcome these limitations, innovative delivery mechanisms have been developed. These include nanotechnology-based systems, minicells, and nanovesicles, which are designed to protect dsRNA from degradation and enhance its delivery to target organisms. While these advancements have improved the stability and application efficiency of dsRNA, comprehensive assessments of their environmental safety and the potential for increased exposure risks to non-target organisms remain incomplete. This comprehensive review aims to elucidate the environmental fate of dsRNA and evaluate the potential risks associated with its widespread application on non-target organisms, encompassing soil microorganisms, beneficial insects, host plants, and mammals. The objective is to establish a more refined framework for RNAi risk assessment within environmental and ecotoxicological contexts, thereby fostering the development of safer, non-transgenic RNAi-based pest control strategies.

Lessons Learned From Shared Decision-Making With Oral Anticoagulants: Viewpoint on Suggestions for the Development of Oral Chemotherapy Decision Aids.

Oral chemotherapy is commonly prescribed, and by using decision aids (DAs), clinicians can facilitate shared decision-making (SDM) to align treatment choices with patient goals and values. Although products exist commercially, little evidence informs the development of DAs targeting the unique challenges of oral chemotherapy. To address this gap in the literature, our objective was to review DAs developed for oral anticoagulation, DA use in oncology, and patient preference surveys to guide the development of DAs for oral chemotherapy. We focused on reviewing SDM, patient preferences, and specifically the development, efficacy, and patient experience of DAs in oral anticoagulation and oncologic conditions, ultimately including conclusions and data from 30 peer-reviewed publications in our viewpoint paper. We found that effective DAs in oral anticoagulation improved knowledge, lowered decisional conflict, increased adherence, and covered a broad range of SDM elements; however, limited information on patient experience was a common shortcoming. In oncology, DAs increased knowledge and aligned decisions with the values of the patients. Ineffective oncology DAs provided general, unclear, or overly optimistic information, while providing "too much" information was not shown to do harm. Patients preferred DAs that included pros and cons, side effects, questions to ask, and expected quality of life changes. In developing DAs for oral chemotherapy, patients should be included in the development process, and DA content should be specifically tailored to patient preferences. Providing DAs ahead of appointments proved more effective than during, and additional considerations included addressing barriers to efficacy. There is a need for evidence-based DAs to facilitate SDM for patients considering oral chemotherapy. Developers should use data from studies in oral anticoagulation, oncology, and preference surveys to optimize SDM.

An ultrasensitive green synchronous factorized spectrofluorimetric approach for the simultaneous determination of Favipiravir and Molnupiravir: Application to pharmaceutical, environmental, and biological matrices.

During the pandemic, Favipiravir (FVP) and Molnupiravir (MPV) have been widely used for COVID-19 treatment, leading to their presence in the environment. A green synchronous spectrofluorimetric method was developed to simultaneously detect them in environmental water, human plasma, and binary mixtures. Maximum fluorescence intensity was achieved at pH 8, with MPV exhibiting two peaks at 300 and 430 nm, and FVP showing one peak at 430 nm. A fluorescence subtraction method effectively removed interference, enabling direct determination of MPV at 300 nm and FVP at 430 nm. The method showed linearity within 2-13 ng/mL for FVP and 50-600 ng/mL for MPV, with recoveries of 100.35% and 100.12%, respectively. Limits of detection and quantification were 0.19 and 0.57 ng/mL for FVP and 10.52 and 31.88 ng/mL for MPV. Validation according to ICH and FDA guidelines yielded acceptable results. The method demonstrated good recoveries of FVP and MPV in pharmaceuticals, tap water and Nile water (99.62% ± 0.96% and 99.69% ± 0.64%) as per ICH guidelines and spiked human plasma (94.87% ± 2.111% and 94.79% ± 1.605%) following FDA guidelines, respectively. Its environmental friendliness was assessed using Green Analytical Procedure Index (GAPI) and the Analytical Greenness Metric (AGREE) tools.

Impact of Race and Ethnicity on Outcomes After Umbilical Cord Blood Transplantation.

BACKGROUND: Umbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients. OBJECTIVE: To compare outcomes by social determinants of health. STUDY DESIGN: We designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, following either a myeloablative (N = 1752) or reduced intensity conditioning (N = 759) for acute myeloid leukemia, acute lymphoid leukemia, or myelodysplasia. The primary outcome was 2-year OS. Secondary outcomes included disease free survival, transplant related mortality (TRM), acute and chronic graft vs host disease (GVHD), and GVHD free, relapse free survival (GRFS). RESULTS: For 1705 adults, in univariate analysis, 2-year OS was 41.5% (99% CI, 37.6 to 45.3) for Whites, 36.1% (99% CI, 28.2 to 44.5) for Latinx, 45.8% (99% CI, 36.7 to 55.1) for Blacks, and 44.5% (99% CI, 33.6 to 55.6) for Asians. In multivariate analysis of adults, Latinx patients had inferior OS compared to black patients (p = .0005, HR 1.45, 99% CI 1.18 to 1.79). OS improved over time for all racial/ethnic groups. GVHD rates were comparable among the different racial/ethnic groups. In the 807 children, the 2-year OS in univariate analysis was 66.1% (99% CI, 59.7 to 72.2) for Whites, 57.1% (99%CI, 49 to 64.9) for Latinx, 46.8% (99%CI, 35.3 to 58.4) for Blacks, and 53.8% (99%CI, 32.7 to 74.2) for Asians. In multivariate analysis, no difference in OS was observed among racial/ethnic groups (p = .051). Grade III/IV acute GVHD was higher in Blacks compared with Whites (p = .0016, HR 2.25, 99% CI 1.36 to 3.74) and Latinx (p = .0016, HR 2.17, 99% CI 1.43 to 3.30). There was no survival advantage to receiving a UCB unit from a donor of similar race and ethnicity, for any racial/ethnic groups, for both children and adults. Black and Latinx adult patients were more likely to live in areas defined as high poverty. Patients from high poverty level areas had worse OS (p = .03), due to a higher rate of TRM (p=0.04). Educational level, and type of insurance did not impact overall survival, GVHD, TRM or other transplant outcomes. Children from areas with a higher poverty level had higher TRM, regardless of race and ethnicity (p = .02). Public health insurance, such as Medicaid, was also associated with a higher TRM (p = .02). However, poverty did not impact pediatric OS, DFS, or other post-transplant outcomes. CONCLUSIONS: OS for UCBT has improved over time. In adults, OS is comparable among Whites, Blacks, and Asians and lower for Latinx patients. In children, OS is comparable among Whites, Blacks, Latinx, and Asians, but Grade III/IV acute GVHD was higher in Black patients. There was no survival benefit to matching UCB unit and patient by race and ethnicity for adults and children.

What is in a name: defining pediatric refractory ITP.

ABSTRACT: There are no agreed upon terminology to define "refractory" pediatric immune thrombocytopenia (ITP). Guidelines are therefore limited to arbitrary and outdated definitions. The Pediatric ITP Consortium of North America held a meeting in 2023 to define this entity. With 100% agreement, the faculty established that pediatric ITP that is refractory to emergent therapy could be defined as no platelet response after treatment with all eligible emergent pharmacotherapies. With 100% agreement, the working group established that pediatric patients with ITP that continue to demonstrate high disease burden and/or no platelet response despite treatment with multiple classes of disease-modifying therapies represent a challenging subset of ITP. These patients are at higher risk of ongoing disease burden and merit additional investigation as well as consideration for clinical trials or novel therapies. Future efforts to define disease burden and disease response will be completed in collaboration with the ITP International Working Group.

Association between suicidal ideation, negative symptoms and theory of mind in first episode psychosis.

PURPOSE: Suicidal thoughts are common among patients with first episode psychosis (FEP). The impact of symptoms' severity and social cognition on suicidal risk should be a focus of attention. This study aimed at assessment of the severity of suicidal ideation in patients with FEP and its potential association with the theory of mind (ToM) impairment and symptoms' severity. METHODS: Ninety-six participants were recruited consecutively and subdivided into three equal groups: FEP, schizophrenia, and healthy controls (HC). The symptoms' severity was assessed using Positive and Negative Syndrome Scale (PANSS) and Beck Depression Inventory (BDI). Suicidal ideation was evaluated using Beck Scale for Suicidal Ideation (BSSI). Reading the Mind in the Eyes revised version (RMET) was used to assess ToM. RESULTS: Suicidal ideation was significantly higher only in FEP compared to HC (p = 0.001). Both FEP and schizophrenia had substantially lower performance than HC on RMET (p < 0.001). Higher depression (ß = 0.452, p = 0.007) and negative symptoms (ß = 0.433, p = 0.027) appeared to be significantly associated with increased suicidal ideation severity in FEP while RMET did not. CONCLUSION: Patients with FEP and chronic schizophrenia have comparable deficits in theory of mind dimension of social cognition. The severity of negative and depressive symptoms potentially contributes to the increased risk of suicide in FEP.

Osteomyelitis of the Jaw: A 10-Year Retrospective Analysis at a Tertiary Health Care Centre in Canada.

BACKGROUND: Osteomyelitis (OM) of the jaw is a rare medical condition. In this review, we provide a descriptive analysis of the experience with this condition at a single tertiary health care centre in Canada over 10 years. MATERIALS AND METHODS: We conducted a retrospective chart review of adult patients aged ≥ 18 years presenting with OM of the jaw at the University of Manitoba Health Sciences Centre between January 2009 and May 2019. We included cases with consistent clinical symptoms and radiographic and/or microbiologic evidence of OM of the jaw. Excluded were cases with a previous history of head and neck cancer, radiation therapy in the head and neck regions and use of anti-resorptive medications. RESULTS: Of the 37 patients who met our criteria, the mean age was 44 years (standard deviation [SD] ± 16 years), 21 (56.8%) were male, 16 (43.2%) were diagnosed with acute OM and 21 (57.8%) with chronic OM. Underlying comorbidities, such as diabetes mellitus and chronic kidney diseases, were reported in 6 (16.2%) and 3 patients (8.1%), respectively. Traumatic injuries to the facial skeleton were the most common predisposing factor (11 patients [29.7%]). The most commonly isolated infective organisms were viridans group streptococci (VGS; 75.8%), followed by Prevotella spp. (45.4%). Results showed a higher level of resistance to penicillin of the isolated organisms in chronic OM compared with acute OM. CONCLUSIONS: This description of acute and chronic forms of OM of the jaw will enable clinicians to better understand OM patient profiles, leading to early diagnosis, improved patient care and better outcomes.

Experimental and numerical investigations on the bending capacity of cold-formed steel box headers.

The study investigates the bending strength of tracks of box headers beyond AISI, which considers the capacity of individual channels alone. Both experimental and FEM are used, and the results are compared to AISI. The findings highlight tracks' significant role in the overall bending capacity. AISI is found to be conservative by 34% to 152%. Failure mode is different from code theoretical expectations for a single channel. Fastener close spacing marginally improves the capacity, while side fasteners offer significant enhancement, but track widening limits this enhancement. A modification to AISI is proposed considering track strength, with outcomes showing good accuracy.