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The work is devoted to the study of the second-harmonic generation (SHG) process as a result of random quasi-phase-matching of thulium laser radiation in ZnSe polycrystals. A linear dependence of the SHG efficiency on the nonlinear medium length has been observed in the experiment. The efficiencies of SHG in ZnSe polycrystals with average grain sizes from 35 μ m to 380 μ m were compared. The obtained results are in good agreement with the theory in the case of a Gaussian grain size distribution. [ABSTRACT FROM AUTHOR]

In this study, we investigated autonomous vessel obstacle avoidance using advanced techniques within the Guidance, Navigation, and Control (GNC) framework. We propose a Mixed Integer Linear Programming (MILP) based Guidance system for robust path planning avoiding static and dynamic obstacles. For Navigation, we suggest a multi-modal neural network for perception, demonstrating the identification of obstacle type, position, and orientation using imaging sensors. Additionally, the paper compares an error-based PID control strategy and a Model Predictive Control (MPC) scheme as well. This evaluation aids in better evaluating their performance and determining their applicability within the GNC scheme. We detail the implementation of these systems, present simulation results, and offer a performance evaluation using an experimental dataset. Our findings, analysed through qualitative discussion and quantitative performance indicators, contribute to advancements in autonomous navigation and the control strategies to achieve it. [ABSTRACT FROM AUTHOR]

This clinical report describes the rehabilitation of an edentulous mandible with an implant-supported fixed prosthesis using an all-ceramic framework fabricated from zirconium oxide. Four interforaminal implants were inserted and allowed to heal submerged. The implant-supported fixed prosthesis was then fabricated using CAD/CAM and electroforming technology. No clinical complications were observed at the 6-month follow-up examination, and the patient was highly satisfied with function and esthetics. All-ceramic frameworks provide a high standard of esthetics; reduce the number of metals used in the oral cavity; and have a lower density compared to metals, which reduces weight in the case of large frameworks. [ABSTRACT FROM AUTHOR]

A conservative method of replacing missing teeth is described. The fixed partial denture incorporates a resin-bonded retainer for the intact tooth and a telescopic coping for the carious or fractured tooth. A permanently cemented coping beneath a provisionally cemented superstructure provides the opportunity to recement the prosthesis if the acid-etched retainer is debonded. The advantages of this technique include conservation of enamel on the intact abutment and protection from leakage caused by dissolution of temporary cement on the abutment with a telescopic coping. [ABSTRACT FROM AUTHOR]

We aimed to understand the underlying mechanism that regulates successively expressed cuticular protein (CP) genes around pupation in Bombyx mori. Quantitative PCR was conducted to clarify the expression profile of CP genes and ecdysone-responsive transcription factor (ERTF) genes around pupation. Ecdysone pulse treatment was also conducted to compare the developmental profiles and the ecdysone induction of the CP and ERTF genes. Fifty-two CP genes (RR-1 13, RR-2 18, CPG 8, CPT 3, CPFL 2, CPH 8) in wing discs of B. mori were examined. Different expression profiles were found, which suggests the existence of a mechanism that regulates CP genes. We divided the genes into five groups according to their peak stages of expression. RR-2 genes were expressed until the day of pupation and RR-1 genes were expressed before and after pupation and for longer than RR-2 genes; this suggests different construction of exo- and endocuticular layers. CPG, CPT, CPFL and CPH genes were expressed before and after pupation, which implies their involvement in both cuticular layers. Expression profiles of ERTFs corresponded with previous reports. Ecdysone pulse treatment showed that the induction of CP and ERTF genes in vitro reflected developmental expression, from which we speculated that ERTFs regulate CP gene expression around pupation. [ABSTRACT FROM AUTHOR]

Reports on the introduction of severe acute respiratory syndrome (SARS) in Toronto, Ontario during 2003 and the resulting outbreak at several Greater Toronto Area hospitals. Discussion of public health measures to prevent the transmission of SARS-associated coronavirus among health-care workers and the second outbreak about four weeks after the first, which was thought to be over; The CDC editorial note discussing the importance of controlling health-care-related SARS transmission and deciding when SARS precautions are necessary.

Objectives: The global mpox (clade II) outbreak of 2022 primarily affected gay, bisexual, and other men who have sex with men (GBM) and was met with swift community and public health responses. We aimed to estimate the relative impact of changes in sexual behaviours, contact tracing/isolation, and first-dose vaccination on transmission in Canadian cities., Methods: We estimated changes in sexual behaviours during the outbreak using 2022 data from the Engage Cohort Study which recruited self-identified GBM in Montréal, Toronto, and Vancouver (n=1,445). We developed a transmission dynamic model to estimate the averted fraction of new infections attributable to the three interventions in each city., Results: The empirical estimates of sexual behaviours changes were imprecise: 20% (RR=0.80; 95% credible intervals [95%CrI]: 0.47-1.36) fewer sexual partners in the past 6 months among those reporting ≤7 partners and 33% (RR=0.67; 95%CrI: 0.31-1.43) fewer among those with >7 partners. The three interventions combined averted 46%-58% of cases. Reductions in sexual partners, contact tracing/isolation prevented approximately 12% and 14% of cases, respectively. Vaccination's effect varied across cities by start date and coverage, with 21%-39% mpox infections prevented., Conclusions: Reduction in sexual activity, contact tracing/isolation, and vaccination all contributed to accelerating epidemic control. Early vaccination had the largest impact., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joseph Cox reports research grants from Gilead Sciences Canada and ViiV Healthcare, all outside of the submitted work. Mathieu Maheu-Giroux reports contractual arrangements from the World Health Organization, the Joint United Nations Programme on HIV/AIDS (UNAIDS), and the Public Health Agency of Canada, all outside of the submitted work. Trevor A. Hart reports educational grants from being an Advisory Committee member for the Canadian Institutes of Health Research (CIHR)’s Institute of Infection and Immunity and funds for community engagement events from ViiV Healthcare and Gilead Sciences Canada, all outside of the submitted work. Darrell H.S. Tan's institution has received investigator-initiated grants from Abbvie and Gilead, and support for participation in clinical trials sponsored by Glaxo Smith Kline, all outside of the submitted work. All other authors report no conflict of interest., (Copyright © 2025. Published by Elsevier Ltd.)

Objectives: Preeclampsia (PET) is a serious pregnancy complication with potential adverse maternal and fetal outcomes. Recent research has examined the soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio for predicting PET. The study aimed to assess the efficacy of the sFlt-1/PlGF ratio in ruling out unnecessary hospital admission and PET., Methods: sFlt-1/PlGF ratio was performed in patients as clinically indicated., Results: The sFlt-1/PlGF ratio at a cutoff value of 51 predicted hospital admission with AUC, PPV, NPV, sensitivity, and specificity of 85%, 44%, 98%, 88%, and 85%, respectively. Additionally, at a cutoff value of 38, the sFlt-1/PlGF ratio predicted the short-term development of PET with PPV, NPV, sensitivity, and specificity of 42%, 100%, 100%, and 81%, respectively. The PlGF alone at a cutoff value of 193.36 predicted hospital admission with AUC, PPV, NPV, sensitivity, and specificity of 87%, 80%, 97%, 67%, and 98%, respectively. Moreover, at a cutoff value of 51.35, the PlGF alone predicted the development of PET with PPV, NPV, sensitivity, and specificity of 54%, 98%, 88%, and 90%, respectively. There was a significant association between a high sFlt-1/PlGF ratio and developing PET., Conclusion: The sFlt-1/PlGF ratio and PlGF are promising for ruling out PET and hospital admission in pregnant women.

Elevated global pollution level is the prime reason that contributes to the onset of various harmful health diseases. The products of Biginelli reaction are enormously used in the pharmaceutical industry as they have antiviral, antibacterial, and calcium channel modulation abilities. This work reports a novel eosin Y sensitized boron graphitic carbon nitride (EY-B en- g-C 3 N 4 ) as a photocatalyst that efficiently produced 3,4-dihydropyrimidine-2-(1H)-one by the Biginelli reaction of benzaldehyde, urea, and methyl acetoacetate. The photocatalyst EY-B en- g-C 3 N 4 showed a successful generation of 3,4-dihydropyrimidine-2-(1H)-one (Biginelli product) in good yield via photocatalysis which is an eco-friendly method and has facile operational process. In addition to the production of Biginelli products, the photocatalyst also showed a remarkable NADH regeneration of 81.18%. The incorporation of g-C 3 N 4 with boron helps increase the surface area and the incorporation of eosin Y which is an inexpensive and non-toxic dye, and in B en -g-C 3 N 4 , enhanced the light-harvesting capacity of the photocatalyst. The production of 3,4-dihydropyrimidine-2-(1H)-one and NADH by the EY-B en -g-C 3 N 4 photocatalyst is attributed to the requisite band gap, high molar absorbance, low rate of charge recombination, and increased capacity of the photocatalyst to harvest solar light energy., (© 2024 American Society for Photobiology.)

A solvent-free sulfur-bridge-eosin-Y (SBE-Y) polymeric framework photocatalyst was prepared for the first time through an in situ thermal polymerization route using elemental sulfur (S 8 ) as a bridge. The addition of a sulfur bridge to the polymeric framework structure resulted in an allowance of the harvesting range of eosin-Y (E-Y) for solar light. This shows that a wider range of solar light can be used by the bridge material's photocatalytic reactions. In this context, supercharged solar spectrum: enhancing light absorption and hole oxidation with sulfur bridges. This suggests that the excited electrons and holes through solar light can contribute to oxidation-reduction reactions more potently. As a result, the photocatalyst-enzyme attached artificial photosynthesis system developed using SBE-Y as a photocatalyst performs exceptionally well, resulting in high 1,4-NADH regeneration (86.81%), followed by its utilization in the exclusive production of formic acid (210.01 μmol) from CO 2 and synthesis of fine chemicals with 99.9% conversion yields. The creation of more effective photocatalytic materials for environmental clean-up and other applications that depend on the solar light-driven absorption spectrum of inorganic and organic molecules could be one of the practical ramifications of this research., (© 2023 American Society for Photobiology.)

The need for sunlight chemical renewal and contemporary organic transformation has fostered the advancement of environmentally friendly photocatalytic techniques. For the first time, we report on the novel crafting of a bright future with selenium-infused Eosin-B (Se in -E-B) nanocomposite photocatalysts in this work. The Se in -E-B nanocomposite materials were created using a hydrothermal process for solar chemical regeneration and organic transformation under visible light. The synthesized samples were subjected to UV-DRS-visible spectroscopy, FT-IR, SEM, EDX, EIS and XRD analysis. The energy band gap of the Se in -E-B nanocomposite photocatalyst was measured using UV-DRS, and the result was around 2.06 eV. to investigate the generated Se in -E-B catalytic activity as a nanocomposite for 1,4-NADH/NADPH re-formation and C-N bond activation. This novel photocatalyst offers a promising alternative for the regeneration of solar chemicals and C-N bond creation between pyrrole and aryl halides., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The combination of excellent electronic properties and thermal stability positions orange-derived graphene quantum dots (GQDs) as promising materials for solar light-based applications. Researchers are actively exploring their potential in fields such as photovoltaics, photocatalysis, optoelectronics, and energy storage. Their abundance, cost-effectiveness, and eco-friendly nature further contribute to their growing relevance in cutting-edge scientific research. Furthermore, only GQDs are not much more effective in the UV-visible region, therefore, required band gap engineering in GQDs material. In this context, we designed GQDs-based light harvesting materials, which is active in UV-visible region. Herein we synthesized GQDs coupled with 2,6-diaminoanthrquninone (AQ), that is, GQDs@AQ light harvesting photocatalyst the first time for the oxidation of sulfide to sulfoxide under visible light. For the integrating reactions of sulfide in aerobic conditions under visible light by GQDs@AQ photocatalyst exhibit utmost higher photocatalytic activity than simple GQDs due to low molar extinction coefficient and slow recombination charges. The use of GQDs@AQ light harvesting photocatalyst, showed the excellent organic transformation efficiency of sulfide to sulfoxide with excellent yield (94%). The high efficiency and excellent yield of 94% indicate the effectiveness of GQDs@AQ as a photocatalyst for these specific organic transformations., (© 2023 American Society for Photobiology.)

Photocatalysis has emerged as a promising approach for generating solar chemical and organic transformations under the solar light spectrum, employing polymer photocatalysts. In this study, our aim is to achieve the regeneration of NADH and fixation of nitroarene compounds, which hold significant importance in various fields such as pharmaceuticals, biology, and chemistry. The development of an in-situ nature-inspired artificial photosynthetic pathway represents a challenging task, as it involves harnessing solar energy for efficient solar chemical production and organic transformation. In this work, we have successfully synthesized a novel artificial photosynthetic polymer, named TFc photocatalyst, through the Friedel-Crafts alkylation reaction between triptycene (T) and a ferrocene motif (Fc). The TF C photocatalyst is a promising material with excellent optical properties, an appropriate band gap, and the ability to facilitate the regeneration of NADH and the fixation of nitroarene compounds through photocatalysis. These characteristics are necessary for several applications, including organic synthesis and environmental remediation. Our research provides a significant step forward in establishing a reliable pathway for the regeneration and fixation of solar chemicals and organic compounds under the solar light spectrum., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: With many global jurisdictions, Toronto, Canada, experienced an mpox outbreak in spring/summer 2022. Cases declined following implementation of a large vaccination campaign. A surge in early 2023 led to speculation that asymptomatic and/or undetected local transmission was occurring in the city., Methods: Mpox cases and positive laboratory results are reported to Toronto Public Health. Epidemic curves and descriptive risk factor summaries for the 2022 and 2023 outbreaks were generated. First- and second-dose vaccination was monitored. Mpox virus wastewater surveillance and whole genome sequencing were conducted to generate hypotheses about the source of the 2023 resurgence., Results: An overall 515 cases were reported in spring/summer 2022 and 17 in the 2022-2023 resurgence. Wastewater data correlated with the timing of cases. Whole genome sequencing showed that 2022-2023 cases were distinct from 2022 cases and closer to sequences from another country, suggesting a new importation as a source. At the start of the resurgence, approximately 16% of first-dose vaccine recipients had completed their second dose., Conclusions: This investigation demonstrates the importance of ongoing surveillance and preparedness for mpox outbreaks. Undetected local transmission was not a likely source of the 2022-2023 resurgence. Ongoing preexposure vaccine promotion remains important to mitigate disease burden., Competing Interests: Potential conflicts of interest. D. H. S. T.’s institution has received support for investigator-initiated research from Abbvie and Gilead and for industry-sponsored clinical trials from Glaxo Smith Kline, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Indeed, the development of ecologically benign molecular fabrication methods for highly efficient graphene quantum dots-based photocatalysts is of great significant. Graphene quantum dots-based photocatalysts have promising applications in various field, including environmental remediation, energy conversion, and splitting of water. However, ensuring resource reusability and minimizing the environmental impact are crucial considerations in the development. From this perspective, attention has also been paid to the creation of easy to make solar light harvesting graphene quantum dots-based photocatalysts for synthesising pharmaceuticals and functional imines compounds. Imines are excellent significant building blocks in pharmaceutical chemistry and excellent examples of these valuable compounds' synthetic intermediates, and the environmentally friendly oxidative synthesis of imines from amines. Therefore, herein, we designed a facile and efficient condensation route to synthesize the Nen-GQDs@PH photocatalyst. This route involves coupling of 2,4-dinitrophenylhydrazine (PH) with nitrogen-enriched graphene quantum dots (Nen-GQDs). The Nen-GQDs@PH as photocatalyst functions in a highly selective and efficient manner, leading to high amines conversion efficiency to imines (95%). Our results highlight a novel and environmentally safe approach for generating highly selective imines from various types of amines, setting a new benchmark in the current research field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Frequent inspections on sorghum and maize crops during seasons of 2021 and 2022 in some regions in Bani-Suef governorate, Egypt, discovered unprecedented invasions of Spodoptera frugiperda (J. E. Smith). Accordingly, our study on Beauveria bassiana and spinetoram was supporter to the Food and Agriculture Organization's tendency in adopting biorational insecticides against S. frugiperda in Egypt. Exposure toxicity of LC 25 values at 48 h of B. bassiana were 2.7 × 10 6 and 5.2 × 10 6 conidia mL -1 and spinetoram were 0.019 and 0.048 mg L -1 against the 2nd and 4th instar larvae laboratory strain of S. frugiperda, respectively. Sub-lethal effects (LC 25 ) were accomplished on biological parameters against both instar larvae. LC 25 of B. bassiana reduced adult emergency (89.91 and 91.05%) more than spinetoram (75.99 and 79.49%) against the 2nd and 4th instar larvae, respectively. The 2nd instar larvae exposed to LC 25 of B. bassiana suppressed female fecundity (0.00 eggs) more than spinetoram (19.74 eggs). Enzymatic activity of lipase in hemolymph, fat bodies, and mid-gut of the 4th instars at 48 h showed significant drop in B. bassiana more than spinetoram. Glutathione-S-transferase (GST) levels in hemolymph for both insecticides were equal and exceeded the control. Fat bodies and mid-gut possessed the highest GST activity in B. bassiana followed by spinetoram and the control. Residual efficacy of spinetoram exceled B. bassiana at their field rates under semi-field condition in Bani-Suef along the two seasons of maize crop against both instars. Eventually, B. bassiana alongside spinetoram could afford good control especially on early instar larvae of S. frugiperda., (© 2023. The Author(s).)

Background: People Who Use Drugs (PWUD) have lower vaccination uptake than the general population, and disproportionately experience the burden of harms from vaccine-preventable diseases. We conducted a national qualitative study to: (1) identify the barriers and facilitators to receiving COVID-19 vaccinations among PWUD; and (2) identify interventions to support PWUD in their decision-making., Methods: Between March and October 2022, semi-structured interviews with PWUD across Canada were conducted. Fully vaccinated (2 or more doses) and partially or unvaccinated (1 dose or less) participants were recruited from a convenience sample to participate in telephone interviews to discuss facilitators, barriers, and concerns about receiving COVID-19 vaccines and subsequent boosters, and ways to address concerns. A total of 78 PWUD participated in the study, with 50 participants being fully vaccinated and 28 participants partially or unvaccinated. Using thematic analysis, interviews were coded based on the capability, opportunity, and motivation-behavior (COM-B) framework., Results: Many partially or unvaccinated participants reported lacking knowledge about the COVID-19 vaccine, particularly in terms of its usefulness and benefits. Some participants reported lacking knowledge around potential long-term side effects of the vaccine, and the differences of the various vaccine brands. Distrust toward government and healthcare agencies, the unprecedented rapidity of vaccine development and skepticism of vaccine effectiveness were also noted as barriers. Facilitators for vaccination included a desire to protect oneself or others and compliance with government mandates which required individuals to get vaccinated in order to access services, attend work or travel. To improve vaccination uptake, the most trusted and appropriate avenues for vaccination information sharing were identified by participants to be people with lived and living experience with drug use (PWLLE), harm reduction workers, or healthcare providers working within settings commonly visited by PWUD., Conclusion: PWLLE should be supported to design tailored information to reduce barriers and address mistrust. Resources addressing knowledge gaps should be disseminated in areas and through organizations where PWUD frequently access, such as harm reduction services and social media platforms., (© 2023. The Author(s).)

Background: Canadian clinical guidelines recommend at least annual and up to quarterly bacterial sexually transmitted infection (STI) testing among sexually active gay, bisexual, and other men who have sex with men (GBM). However, testing rates are suboptimal. Innovative solutions are needed to close the gap because there is currently limited knowledge on how best to approach this issue., Objective: Our aim was to build consensus regarding interventions with the greatest potential for improving local STI testing services for GBM communities in Toronto, Ontario, Canada, using a web-based e-Delphi process., Methods: The e-Delphi method involves using a panel format to conduct successive rounds of prioritization, with feedback between rounds, to determine priorities among groups. We recruited experts separately from the community (GBM who sought or underwent STI testing in the preceding 18 months; conducted between October 2019 and November 2019) and health care providers (those who offered STI testing to GBM in the past 12 months; conducted between February 2020 and May 2020). The experts prioritized 6 to 8 potential interventions on a 7-point Likert scale ranging from definitely not a priority to definitely a priority over 3 survey rounds and ranked their top 3 interventions. Consensus was defined as ≥60% within a ±1 response point. Summaries of responses were provided in successive rounds. We reported the percentage of a priority (encompassing somewhat a priority, a priority, and definitely a priority responses) at the end of the final round of the survey., Results: Of the community experts (CEs), 84% (43/51) completed all rounds; 19% (8/43) were living with HIV; 37% (16/43) were HIV negative and on pre-exposure prophylaxis; and 42% (18/43) were HIV negative and not on pre-exposure prophylaxis. We reached consensus on 6 interventions: client reminders (41/43, 95%), express testing (38/43, 88%), routine testing (36/43, 84%), an online booking app (36/43, 84%), online-based testing (33/43, 77%), and nurse-led testing (31/43, 72%). The CEs favored convenient interventions that also maintain a relationship with their provider. Of the provider experts (PEs), 77% (37/48) completed all rounds; 59% (22/37) were physicians. Consensus was reached on the same 6 interventions (range 25/37, 68%, to 39/39, 100%) but not for provider alerts (7/37, 19%) and provider audit and feedback (6/37, 16%). Express testing, online-based testing, and nurse-led testing were prioritized by >95% (>37/39) of the PEs by the end of round 2 because of streamlined processes and decreased need to see a provider., Conclusions: Both panels were enthusiastic about innovations that make STI testing more efficient, with express testing rating highly in both the prioritizations and top 3 rankings. However, CEs preferred convenient interventions that involved their provider, whereas PEs favored interventions that prioritized patient independence and reduced patient-provider time., International Registered Report Identifier (irrid): RR2-10.2196/13801., (©Anna Yeung, Ryan Lisk, Jayoti Rana, Charlie B Guiang, Jean Bacon, Jason Brunetta, Mark Gilbert, Dionne Gesink, Ramandip Grewal, Michael Kwag, Carmen H Logie, Leo Mitterni, Rita Shahin, Darrell HS Tan, Ann N Burchell. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 29.06.2023.)

Introduction: Opioid overdose epidemic is a public health crisis that is impacting communities around the world. Overdose education and naloxone distribution programs equip and train lay people to respond in the event of an overdose. We aimed to understand factors to consider for the design of naloxone distribution programs in point-of-care settings from the point of view of community stakeholders., Methods: We hosted a multi-stakeholder co-design workshop to elicit suggestions for a naloxone distribution program. We recruited people with lived experience of opioid overdose, community representatives, and other stakeholders from family practice, emergency medicine, addictions medicine, and public health to participate in a full-day facilitated co-design discussion wherein large and small group discussions were audio-recorded, transcribed and analysed using thematic approaches., Results: A total of twenty-four participants participated in the multi-stakeholder workshop from five stakeholder groups including geographic and setting diversity. Collaborative dialogue and shared storytelling revealed seven considerations for the design of naloxone distribution programs specific to training needs and the provision of naloxone, these are: recognizing overdose, how much naloxone, impact of stigma, legal risk of responding, position as conventional first aid, friends and family as responders, support to call 911., Conclusion: To create an naloxone distribution program in emergency departments, family practice and substance use treatment services, stigma is a central design consideration for training and naloxone kits. Design choices that reference the iconography, type, and form of materials associated with first aid have the potential to satisfy the need to de-stigmatize overdose response., (© 2023. The Author(s).)

Through investigating the two different enhanced cell division stages, we tried to clarify the switch from the growth to differentiation in the wing disc of the last larval instar of Bombyx mori. The response to insulin and 20E in vitro was stage specific. Bmmyc expression in V1 wing discs showed differences after being cultured with and without insulin. Bmmyc expression in V5 wing discs also showed differences after being cultured with and without 20E. Cell cycle-related genes, BmE2F1 and BmcycE, were upregulated with insulin or 20E in cultured wing discs of V1 or V5, respectively. Bmwnt1 and Bmras1 showed upregulation with 20E in cultured wing discs. Bmwnt1 showed upregulation with insulin in cultured wing discs, but Bmras1 did not show clear upregulation with insulin treatment. In contrast, Bmdpp showed upregulation with insulin, but did not show clear upregulation with 20E. The addition of PI3K or TOR inhibitors inhibited the upregulation of Bmmyc expression that was upregulated with insulin or 20E. The upregulation of Bmmyc and Bmwnt1 with insulin or 20E was inhibited with the addition of Myc or Wnt inhibitors, respectively. Genes related to matrix metalloprotease showed upregulation with 20E, and the upregulation was inhibited by the addition of Myc or Wnt inhibitors. From the present results, we concluded that cell division during the feeding stage occurred through PI3K/TOR cascade, and that at the wandering stage occurred through ecdysone and PI3K/TOR cascade; the former is for growth and the latter for differentiation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Overdose education and naloxone distribution (OEND) programmes equip and train people who are likely to witness an opioid overdose to respond with effective first aid interventions. Despite OEND expansion across North America, overdose rates are increasing, raising questions about how to improve OEND programmes. We conducted an iterative series of codesign stakeholder workshops to develop a prototype for take-home naloxone (THN)-kit (i.e., two doses of intranasal naloxone and training on how to administer it)., Methods: We recruited people who use opioids, frontline healthcare providers and public health representatives to participate in codesign workshops covering questions related to THN-kit prototypes, training on how to use it, and implementation, including refinement of design artefacts using personas and journey maps. Completed over 9 months, the workshops were audio-recorded and transcribed with visible results of the workshops (i.e., sticky notes, sketches) archived. We used thematic analyses of these materials to identify design requirements for THN-kits and training., Results: We facilitated 13 codesign workshops to identify and address gaps in existing opioid overdose education training and THN-kits and emphasize timely response and stigma in future THN-kit design. Using an iterative process, we created 15 prototypes, 3 candidate prototypes and a final prototype THN-kit from the synthesis of the codesign workshops., Conclusion: The final prototype is available for a variety of implementation and evaluation processes. The THN-kit offers an integrated solution combining ultra-brief training animation and physical packaging of nasal naloxone to be distributed in family practice clinics, emergency departments, addiction medicine clinics and community settings., Patient or Public Contribution: The codesign process was deliberately structured to involve community members (the public), with multiple opportunities for public contribution. In addition, patient/public participation was a principle for the management and structuring of the research team., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: Composition of gut microbiota has recently been suggested as a key factor persuading the pathogenesis of numerous human diseases including hepatic cirrhosis., Objective: To evaluate the potential impact of Lactobacillus acidophilus and Bifidobacterium bifidum microbiota on the progression of hepatic histopathological changes among patients with non-cirrhotic chronic hepatitis C (HCV) infection with different viral load. Additionally, to assess fecal composition of Lactobacillus acidophilus ATCC-4356 and Bifidobacterium bifidum ATCC-11863 microbiota genotypes MATERIAL AND METHODS: This study was carried out on 40 non-cirrhotic chronically infected HCV patients, and 10 healthy-controls. Liver biopsy and HCV genomic viral load were assessed for all patients after full clinical examination. Lactobacillus acidophilus ATCC-4356 and Bifidobacterium bifidum ATCC-11863 microbiota were assessed in all fecal samples using PCR assay, after counting total lactic acid bacteria., Results: There was a significantly higher difference between the count of both total lactic acid and Lactobacillus acidophilus of healthy controls compared to patients (P-value < 0.001). Though the count of total lactic acid bacteria, and Lactobacillus acidophilus were higher in the cases with early stage of fibrosis (score ≤ 1) compared to those with score > 1, there were no statistically significant differences with both the serum level of hepatitis C viremia (P = 0.850 and 0.977 respectively) and the score of fibrosis (P = 0.246 and 0.260 respectively). Genotypic analysis for the composition of the studied microbiota revealed that diversity was higher in healthy controls compared to patients., Conclusions: The progression of hepatic fibrosis in HCV chronically infected patients seems to be plausible based on finding the altered Lactobacillus acidophilus and Bifidobacterium bifidum gut microbiota composition. Thus, modulation of these microbiota seems to be a promising target for prevention and control of HCV infection., (© 2022. The Author(s).)

Bringing to a halt the cell cycle in mitosis and interfering with its normal progression is one of the most successful anti-cancer strategies used nowadays. Classically, several kinds of anti-cancer drugs like taxanes and vinca alkaloids directly inhibit microtubules during cell division. These drugs exhibit serious side effects, most importantly, severe peripheral neuropathies. Alternatively, KSP inhibitors are grasping a lot of research attention as less toxic mitotic inhibitors. In this review, we track the medicinal chemistry developmental stages of KSP inhibitors. Moreover, we address the challenges that are faced during the development of KSP inhibitor therapy for cancer and future insights for the latest advances in research that are directed to find active KSP inhibitor drugs., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2022 Dr Rand Omar Shahin.)

We aimed to explain the reason and function of the successive expression of ecdysone-responsive transcription factors (ERTFs) and related cuticular protein (CP) genes during transformation from larva to pupa. The regulation of the expression of CP genes by ERTFs was examined by in vitro wing disc culture and reporter assay using a gene gun transduction system. Two CP genes that showed expression peaks at different stages-BmorCPG12 at W3L and BmorCPH2 at P0 stage-were selected and examined. Reporter constructs conveying putative BHR3, ßFTZ-F1, BHR39, and E74A binding sites of BmorCPG12 and BmorCPH2 showed promoter activity when introduced into wing discs. In the present study, we showed the functioning of the putative BHR3 and E74A binding sites, together with putative ßFTZ-F1 binding sites, on the activation of CP genes, and different ERTF binding sites functioned in one CP gene. From these, we conclude that BHR3, ßFTZ-F1, and E74A that are successively expressed bring about the successive expression of CP genes, resulting in insect metamorphosis. In addition to this, reporter constructs conveying putative BHR39 binding sites of BmorCPG12 and BmorCPH2 showed negative regulation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Targeting Polo-like kinase 1 (Plk1) by molecular inhibitors is being a promising approach for tumor therapy. Nevertheless, insufficient methodical analyses have been done to characterize the interactions inside the Plk1 binding pocket. In this study, an extensive combined ligand and structure-based drug design workflow was conducted to data-mine the structural requirements for Plk1 inhibition. Consequently, the binding modes of 368 previously known Plk1 inhibitors were investigated by pharmacophore generation technique. The resulted pharmacophores were engaged in the context of Genetic function algorithm (GFA) and Multiple linear regression (MLR) analyses to search for a prognostic QSAR model. The most successful QSAR model was with statistical criteria of (r 2  = 0.76, r 277 adj = 0.76, r 2 adj = 0.76, r 2 pred = 0.75, Q 2  = 0.73). Our QSAR-selected pharmacophores were validated by Receiver Operating Characteristic (ROC) curve analysis. Later on, the best QSAR model and its associated pharmacophoric hypotheses (HypoB-T4-5, HypoI-T2-7, HypoD-T4-3, and HypoC-T3-3) were used to identify new Plk1 inhibitory hits retrieved from the National Cancer Institute (NCI) database. The most potent hits exhibited experimental anti-Plk1 IC 50 of 1.49, 3.79. 5.26 and 6.35 μM. Noticeably, our hits, were found to interact with the Plk1 kinase domain through some important amino acid residues namely, Cys67, Lys82, Cys133, Phe183, and Asp194., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To examine the relationship between the use of hydroxychloroquine (HCQ) and risk of developing heart failure (HF) in rheumatoid arthritis (RA)., Methods: In this nested case-control study, cases were Olmsted County, Minnesota residents with incident RA (based on 1987 American College of Rheumatology criteria) from 1980 to 2013 who developed HF after RA incidence. Each case was matched on year of birth, sex, and year of RA incidence with an RA control who did not develop HF. Data on HCQ use including start and stop dates, as well as dose changes, were reviewed and used to calculate HCQ duration and cumulative dose. Age-adjusted logistic regression models were used to examine the association between HCQ and HF., Results: The study identified 143 RA cases diagnosed with HF (mean age 65.8 yrs, 62% females) and 143 non-HF RA controls (mean age 64.5, 62% female). HCQ cumulative dose was not associated with HF (OR 0.96 per 100-g increase in cumulative dose, 95% CI 0.90-1.03). Likewise, no association was found for patients with a cumulative dose ≥ 300 g (OR 0.92, 95% CI 0.41-2.08). The HCQ duration of intake in years prior to index was not associated with HF (OR 0.98, 95% CI 0.91-1.05)., Conclusion: Use of HCQ was not associated with development of HF in patients with RA in this study. Further studies are needed to understand the effect of higher doses of HCQ on the development of HF in RA., (Copyright © The Journal of Rheumatology.)

Aim: We plan to conduct a randomised clinical trial among people likely to witness opioid overdose to compare the educational effectiveness of point-of-care naloxone distribution with best-available care, by observing participants' resuscitation skills in a simulated overdose. This mixed methods feasibility study aims to assess the effectiveness of recruitment and retention strategies and acceptability of study procedures., Methods: We implemented candidate-driven recruitment strategies with verbal consent and destigmatizing study materials in a family practice, emergency department, and addictions service. People ≥16 years of age who are likely to witness overdose were randomized to point-of-care naloxone distribution or referral to an existing program. We evaluated participant skills as a responder to a simulated overdose 3-14 days post-recruitment. Retention strategies included flexible scheduling, reminders, cash compensation and refreshments. The primary outcome was recruitment and retention feasibility, defined as the ability to recruit 28 eligible participants in 28 days, with <50% attrition at the outcome simulation. Acceptability of study procedures and motivations for participation were assessed in a semi-structured interview., Results: We enrolled 30 participants over 24 days, and retained 21 participants (70%, 95%CI 56.7-100). The most common motivation for participation was a desire to serve the community or loved ones in distress. Participants reported that study procedures were acceptable and that the outcome simulation provided a supportive and affirming environment., Conclusion: The planned trial is ready for implementation. Recruitment and retention is feasible and study processes are acceptable for people who are likely to witness overdose. (Registration: NCT03821649)., (© 2021 The Authors.)

Pre-exposure prophylaxis (PrEP) is traditionally prescribed by HIV specialist physicians. Given finite specialist resources, there is a need to scale up PrEP delivery by decentralizing services via other healthcare professionals. We aimed to assess the feasibility of delivering PrEP to men who have sex with men (MSM) through primary care physicians and sexual health clinic nurses. We piloted a multi-component, implementation and dissemination research program to increase provision of PrEP through primary care physicians and sexual health clinic nurses in Toronto, Canada. Community-based organizations (CBOs) provided prospective participants with information cards that contained links to an online module on engaging providers in a conversation about PrEP. In our patient-initiated continuing medical education (PICME) strategy, participants saw their family doctors and gave them the card, which also contained a link to a Continuing Medical Education module. In the nurse-led strategy, participants visited one of two participating clinics to obtain PrEP. We administered an optional online questionnaire to patients and providers at baseline and six months. CBOs distributed 3043 cards. At least 339 men accessed the online module and 196 completed baseline questionnaires. Most (55%) intended to visit nurses while 21% intended to consult their physicians. Among 45 men completing follow-up questionnaires at 6 months, 31% reported bringing cards to their physicians and obtaining PrEP through them; sexual health clinics delivered PrEP to 244 patients. Participants who went through the PICME approach reported no changes in relationships with their providers. Nurses showed fidelity to PrEP prescribing guidelines. Nurse-led PrEP and patient-initiated continuing medical education (PICME) for primary care physicians are feasible strategies to increase PrEP uptake. Nurse-led PrEP delivery was preferred by most patients., Competing Interests: The authors have read the journal’s policy, and the authors of this study have the following competing interests to declare: DHST’s institution has received investigator-driven grants from Gilead Sciences, Abbvie and Viiv Healthcare, and DHST has served as a Site Principal Investigator for clinical trials sponsored by Glaxo Smith Kline, all outside the submitted work. DCK has been a consultant for Merck, Gilead Sciences and Viiv Healthcare, all outside of the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. All other authors have declared that no competing interests exist.

Background: Rates of bacterial sexually transmitted infections (STIs) continue to rise among gay, bisexual, and other men who have sex with men (GBMSM) globally. Testing and treatment can prevent morbidity and transmission. However, testing rates remain suboptimal., Methods: In 2018, we conducted an online cross-sectional survey to explore STI testing ordering practices, 14 potential barriers for testing and 11 possible ways to improve testing from the perspective of health care providers in Toronto, Ontario. An estimated 172 providers were invited from primary care and sexual health clinic settings. Providers were eligible to complete the survey if they provided care for ≥1 GBMSM per week and were involved in the decision-making process in providing STI tests. We used descriptive statistics to summarize survey responses., Results: Ninety-five providers (55% response rate) participated, of whom 68% worked in primary care and 32% in sexual health settings. Most (66%) saw ≤10 GBMSM clients per week. In primary care (65%) and sexual health (40%) clinic settings, insufficient consultation time was the most common barrier to STI testing. In primary care, other common barriers included difficulty introducing testing during unrelated consultations (53%), forgetting (47%), and patients being sexually inactive (31%) or declining testing (27%). The following were most likely to improve testing: express/fast-track testing services (89%), provider alerts when patients are due for testing (87%), patient-collected specimens (84%), nurse-led STI testing (79%), and standing orders (79%)., Conclusions: Promising interventions to improve bacterial STI testing included initiatives that simplify and expedite testing and expand testing delivery to other health care professionals., Competing Interests: Conflict of Interest and Sources of Funding: The authors disclose no competing interests. This study was supported by the Canadian Institutes of Health Research HIV Catalyst Grant (FRN 150082) and a foundation award to A.N.B. (FDN 148432). The funders had no role in the study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication., (Copyright © 2020 American Sexually Transmitted Diseases Association. All rights reserved.)

Introduction: African, Caribbean and Black (ACB) communities are disproportionately infected by HIV in Ontario, Canada. They constitute only 5% of the population of Ontario yet account for 25% of new diagnoses of HIV. The aim of this study is to understand underlying factors that augment the HIV risk in ACB communities and to inform policy and practice in Ontario., Methods and Analysis: We will conduct a cross-sectional study of first-generation and second-generation ACB adults aged 15-64 in Toronto (n=1000) and Ottawa (n=500) and collect data on sociodemographic information, sexual behaviours, substance use, blood donation, access and use of health services and HIV-related care. We will use dried blood spot testing to determine the incidence and prevalence of HIV infection among ACB people, and link participant data to administrative databases to investigate health service access and use. Factors associated with key outcomes (HIV infection, testing behaviours, knowledge about HIV transmission and acquisition, HIV vulnerability, access and use of health services) will be evaluated using generalised linear mixed models, adjusted for relevant covariates., Ethics and Dissemination: This study has been reviewed and approved by the following Research Ethics Boards: Toronto Public Health, Ottawa Public Health, Laurentian University; the University of Ottawa and the University of Toronto. Our findings will be disseminated as community reports, fact sheets, digital stories, oral and poster presentations, peer-reviewed manuscripts and social media., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We report the optimization of oleogel formulation based on sodium caseinate (CN, 0-4 g/100 g), xanthan gum (XG, 0-1 g/100 g), guar gum (GG, 0-1 g/100 g), and drying method (freeze and oven drier) using response surface methodology to achieve the desired oil binding capacity, textural, and rheological attributes. All the selected responses were successfully fitted by a quadratic model with determination coefficient values higher than .95 with the exception of firmness values which was fitted by linear model. There were considerable increases in all the responses for the samples containing ternary mixtures of protein-gum (CN:XG:GG) as well as binary mixtures (CN:GG and CN:XG) compared to samples containing protein or gums alone due to the synergistic effect of CN and gums on formation of highly ordered and strong gel network. Regression modeling demonstrated that freeze drying method led to significantly greater structure recovery values than those of oven drying method. The best formulation was the freeze dried oleogel containing 4 g/100 g CN, 0.43 g/100 g XG, and 0.98 g/100 g GG. Results showed that fabrication of oleogels with at least 94.5 g/100 g sunflower oil and characteristics similar to industrial shortening is feasible., (© 2019 Wiley Periodicals, Inc.)

Background: 3-Phosphoinositide Dependent Protein Kinase-1 (PDK1) is being lately considered as an attractive and forthcoming anticancer target. A Protein Data Bank (PDB) cocrystallized crystal provides not only rigid theoretical data but also a realistic molecular recognition data that can be explored and used to discover new hits., Objective: This incited us to investigate the co-crystallized ligands' contacts inside the PDK1 binding pocket via a structure-based receptor-ligand pharmacophore generation technique in Discovery Studio 4.5 (DS 4.5)., Methods: Accordingly, 35 crystals for PDK1 were collected and studied. Every single receptorligand interaction was validated and the significant ones were converted into their corresponding pharmacophoric features. The generated pharmacophores were scored by the Receiver Operating Characteristic (ROC) curve analysis., Results: Consequently, 169 pharmacophores were generated and sorted, 11 pharmacophores acquired good ROC-AUC results of 0.8 and a selectivity value above 8. Pharmacophore 1UU3&#95;2&#95;01 was used in particular as a searching filter to screen NCI database because of its acceptable validity criteria and its distinctive positive ionizable feature. Several low micromolar PDK1 inhibitors were revealed. The most potent hit illustrated anti-PDK1 IC50 values of 200 nM with 70% inhibition against SW480 cell lines., Conclusion: Eventually, the active hits were docked inside the PDK1 binding pocket and the recognition points between the active hits and the receptor were analyzed that led to the discovery of new scaffolds as potential PDK1 inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)