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Background: Following an update to the provincial Infection Prevention and Control Complaint Protocol in 2015, Ontario public health units have been mandated to investigate infection prevention and control (IPAC) complaints in various settings, including those where regulated health professionals work. No surveillance system exists for IPAC complaints; therefore, little is known about their occurrence. Anecdotal evidence suggests a recent increase in IPAC complaints resulting in increased demand on public health resources. Objectives: To describe the occurrence of IPAC complaints and lapses in Ontario in 2015–2018 and the public health response to these. Methods: Ontario public health units were surveyed about the occurrence and key challenges of IPAC complaint investigations through closed- and open-ended questions. The survey was disseminated through the Council of Ontario Medical Officers of Health listserv. Data collection spanned February 4–28, 2019. Descriptive statistical analyses and thematic analysis of free-text responses were performed. Results: Twenty-one public health units responded for a 60% response rate; fewer responding health units had a population size of less than 100,000. A nearly six-fold increase in IPAC complaints was found, from a total of 79 complaints in 2015 to 451 in 2018. IPAC lapses nearly tripled, with 61 identified in 2015 and 168 in 2018. Whereas variation in the number of IPAC complaints and lapses among public health units was noted, the most common IPAC lapse involved inadequate reprocessing of reusable equipment. Key challenges in investigating IPAC complaints included lack of staff expertise/training, increased workload and costs, interjurisdictional inconsistencies and lack of guidance. Conclusion: IPAC complaints and lapses have increased in Ontario since 2015 when the Ministry of Health and Long-Term Care changed the IPAC complaint protocol. Public health units identified lack of expertise, increased workload, interjurisdictional inconsistencies and lack of guidance as challenges. Further research to confirm these findings, identify best practices to address these challenges as well as interventions to prevent IPAC lapses would be useful. Prospective surveillance of IPAC complaints, like for reportable diseases, would also be useful. [ABSTRACT FROM AUTHOR]

Background: In late 2016 and early 2017, a number of countries began reporting hepatitis A virus (HAV) outbreaks involving person-to-person transmission among men who have sex with men (MSM), people using illicit drugs and homeless or underhoused persons. Objective: To describe the epidemiology and public health response to an outbreak of HAV disproportionately affecting MSM in Toronto, Canada from January 2017 to November 2018. Methods: Following an increase in the number of cases of HAV in MSM being reported in other countries, enhanced surveillance was performed for all non-travel-related cases of HAV reported from June 1, 2017 to November 1, 2018, including a retrospective analysis of cases reported from January 2017 to June 2017. Descriptive analysis and viral sequencing were performed to describe person-to-person transmission patterns and target interventions. Control strategies included interventions to promote the uptake of preexposure HAV vaccination, including social media campaigns geared to MSM, messaging to healthcare providers and vaccine clinics. Results: Based on the outbreak case definitions, 52 confirmed and probable cases of HAV were identified. Over 80% of outbreak cases were male (n=43/52) and, among those for whom data were available, 64% (n=25/39) reported an MSM exposure. Data on hospitalization was available for 51 cases; 56% of confirmed cases (n=23/41) and 40% of probable cases (n=4/10) required hospitalization. Of the cases with serum samples that had HAV sequencing, 83% (n=30/36) had one of the three strains seen circulating in outbreaks among MSM internationally; 72% (n=26/36) were VRD_521_2016, which had been detected in recently reported European outbreaks among MSM. Targeted promotion of publicly-funded vaccination using social media platforms popular with MSM and targeted vaccine clinics were developed to promote HAV awareness and vaccine uptake among MSM. Conclusion: Outbreaks of HAV, attributed to person-to-person transmission of strains of HAV that disproportionately affected MSM and were likely to have been imported from international MSM outbreaks, have now occurred in Canada. Genetic sequencing of HAV, risk factor analysis of cases, monitoring trends of vaccine coverage in high-risk groups and initiation of vaccination campaigns that address barriers to HAV preexposure vaccine coverage in the MSM population may prevent future outbreaks. [ABSTRACT FROM AUTHOR]

Graphene is considered a promising catalyst candidate due to its 2D nature, single-atom thickness, zero bandgap and very high surface to volume ratio. Further, graphene oxide (GO) has been used as a catalytic support material for metal/metal oxide nanoparticles due to its tunable electrical properties. In addition, its high chemical stability and ultrahigh thermal conductivity may possibly promote high loading of catalytically active sites. This review article focuses on the recent progress in the catalytic applications of GO especially (i) as catalytic-support material (GO/reduced graphene oxide supported metal/metal oxide nanohybrids) for the green synthesis of biologically relevant molecules, (ii) for metal-free catalysis and (iii) for electrocatalysis, with special focus on graphene contribution to catalytic efficiency. The critical overview and future perspectives are also discussed.

A total of 18 patients with amebic peritonitis were studied. Fourteen of these cases were due to rupture of amebic liver abscess into the peritoneum and the remaining cases were due to perforation of amebic colitis. No initial suspicion of amebic etiology was made in more than half of the cases. In the group of ruptured liver abscesses, nearly half of the patients showed right lower lung syndrome. The diagnosis in 13 of 14 cases of rupture of liver abscess was confirmed on aspiration. Patients with ruptured amebic Kver abscess were of two types: 1. Diffuse type with diffuse signs, shorter duration of illness and poor prognosis. 2. Localized type with longer duration of illness, marked signs of peritonitis and better prognosis. Once the diagnosis of peritonitis was made, the management was surgical. Conservative treatment was tried only in cases with signs of localization. The mortality rate had been 33% in amebic liver abscess rupturing into the peritoneum and 75% in perforation of the intestine. A high index of suspicion of amebiasis in patients with an acute abdomen and institution of early treatment are recommended to help in reducing this mortality. Amebic liver abscess and amebic dysentery should be treated energetically to avoid this fatal complication and surgical intervention whenever indicated should not be delayed. [ABSTRACT FROM AUTHOR]

Operationally simple condensation of dl-alanine amino acid with substituted aromatic aldehydes/heterocyclic aldehyde occurs to afford Schiff bases in quantitative yield under organic solvent-free conditions efficiently in the presence of water as a green solvent. The operational simplicity, environmentally friendly conditions and high yield achieved are major benefits that meet the requirements of green production, including saving energy and high efficiency. Structural assignments are based on spectroscopic data. The compounds have also been screened for antibacterial and antifungal activities and most of the Schiff bases have shown potent antibac­terial and antifungal activity.

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.)

Plants have been used as healing agents since humanity began. This review presents the plant profiles inhabiting the world regarding their traditional usage by various tribes/ethnic groups for the treatment of epilepsy. The bibliographic investigation was carried out by analyzing standard reference textbooks, Science Direct, Google Scholar, Scopus, Medline, Web of Science, and PubMed databases. Search terms and keywords used for the search were epilepsy, medicinal plants for epilepsy, herbal remedies used in the treatment of epilepsy, and traditional antiepilepsy medication. This review article was prepared by including the biological names of plants/their parts/extracts/compounds/doses/models/results. Further, experimentally explored 15 potential medicinal plants have also been explored in detail. The present review was prepared by including 114 plants from 3 books, 83 research, and 59 review articles. This review indicates that the list of medicinal plants presented in this review might be useful to researchers for preliminary screening of potential antiepileptic agents., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Sunishtha Kalra et al.)

We consider how the genetic architecture underlying locally adaptive traits determines the strength of a barrier to gene flow in a mainland-island model. Assuming a general life cycle, we derive an expression for the effective migration rate when local adaptation is due to genetic variation at many loci under directional selection on the island, allowing for arbitrary fitness and dominance effects across loci. We show how the effective migration rate can be combined with classical single-locus diffusion theory to accurately predict multilocus differentiation between the mainland and island at migration-selection-drift equilibrium and determine the migration rate beyond which local adaptation collapses, while accounting for genetic drift and weak linkage. Using our efficient numerical tools, we then present a detailed study of the effects of dominance on barriers to gene flow, showing that when total selection is sufficiently strong, more recessive local adaptation generates stronger barriers to gene flow. We then study how heterogeneous genetic architectures of local adaptation affect barriers to gene flow, characterizing adaptive differentiation at migration-selection balance for different distributions of fitness effects. We find that a more heterogeneous genetic architecture generally yields a stronger genome-wide barrier to gene flow and that the detailed genetic architecture underlying locally adaptive traits can have an important effect on observable differentiation when divergence is not too large. Lastly, we study the limits of our approach as loci become more tightly linked, showing that our predictions remain accurate over a large biologically relevant domain., Competing Interests: Conflicts of interest The author(s) declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Background and Objectives: The COVID-19 pandemic prompted the scientific community to collaborate in an unprecedented way, with the rapid and urgent generation and translation of new knowledge about the disease and its causative agent. Iteratively, and at different levels of government and globally, population-level guidance was created and updated, resulting in the need for a living catalog of guidelines, the eCOVID-19 Recommendations Map and Gateway to Contextualization (RecMap). This article focuses on the approach that was used to analyze barriers and opportunities associated with using the RecMap in public health in Canada., Study Design and Setting: A mixed qualitative and quantitative approach data were used to inform this knowledge mobilization project and inform feedback on implementation of the eCOVID-19 RecMap. This approach involved surveying 110 attendees from a public health webinar. Following this webinar, an evidence brief and series of case studies were created and disseminated to 24 Canadian public health practitioners who attended a virtual workshop. This workshop identified barriers and opportunities to improve RecMap use., Results: This study helped to shed light on the needs that public health practitioners have when finding, using, and disseminating public health guidelines. Through the workshop that was conducted, opportunities for public health guidelines can be categorized into 4 categories: 1) information access, 2) awareness, 3) public health development, and 4) usability. Barriers that were identified can also be categorized into 4 categories: 1) usability, 2) information maintenance, 3) public health guidance, 4) awareness., Conclusion: This work will help to inform the development and organization of future public health guidelines, and the needs that public health practitioners have when engaging with them., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Traumatic brain injury (TBI) causes substantial mortality and morbidity globally. Current treatments only alleviate symptoms and do not halt secondary injury progression., Objectives: Evaluate the neuroprotective potential of Acorus calamus Linn. (AC) in a Drosophila melanogaster model of high-impact TBI., Methods: Fruit flies (Drosophila melanogaster) of the Oregon R + strain were administered hydroalcoholic extracts of Acorus calamus Linn. (HAEAC) at concentrations of 25 and 50 µg/mL, 24 h and continuously for 72 h, respectively, following TBI induction. Mortality rate, locomotor function, neurotransmitter levels, and oxidative stress markers were assessed at 24 and 72 h post-injury as outcomemeasures., Results: AC significantly reduced post-TBI mortality and improved locomotor function in a dose-dependent manner. Additionally, AC increased acetylcholinesterase, gamma-aminobutyric acid, serotonin, and dopamine levels while reducing glutamate. It also boosted antioxidant activity (superoxide dismutase, glutathione, and catalase) and lowered markers of oxidative damage (malondialdehyde, nitrite)., Conclusions: AC mitigated behavioral deficits, oxidative damage, and neurotransmitter imbalance in fruit flies after TBI. These findings indicate AC may be more effective than individual drugs for TBI therapy. Further research into its neuroprotective phytochemicals is warranted., 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 B.V. All rights reserved.)

We consider how a population of N haploid individuals responds to directional selection on standing variation, with no new variation from recombination or mutation. Individuals have trait values z 1 ,…,z N , which are drawn from a distribution ψ; the fitness of individual i is proportional to [Formula: see text] . For illustration, we consider the Laplace and Gaussian distributions, which are parametrised only by the variance V 0 , and show that for large N, there is a scaling limit which depends on a single parameter NV 0 . When selection is weak relative to drift (NV 0 ≪1), the variance decreases exponentially at rate 1/N, and the expected ultimate gain in log fitness (scaled by V 0 ), is just NV 0 , which is the same as Robertson's (1960) prediction for a sexual population. In contrast, when selection is strong relative to drift (NV 0 ≫1), the ultimate gain can be found by approximating the establishment of alleles by a branching process in which each allele competes independently with the population mean and the fittest allele to establish is certain to fix. Then, if the probability of survival to time t∼1/V 0 of an allele with value z is P(z), with mean P¯, the winning allele is the fittest of NP¯ survivors drawn from a distribution ψP/P¯. The expected ultimate change is ∼2log(1.15NV 0 ) for a Gaussian distribution, and ∼-12log0.36NV 0 -log-log0.36NV 0 for a Laplace distribution. This approach also predicts the variability of the process, and its dynamics; we show that in the strong selection regime, the expected genetic variance decreases as ∼t -3 at large times. We discuss how these results may be related to selection on standing variation that is spread along a linear chromosome., (Copyright © 2024 The Authors. Published by Elsevier Inc. 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.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and dementia. One of the major pathologies underlying AD is chronic neuroinflammation mediated by microglia and astrocytes in the brain. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling pathway is a key regulator of inflammation and has been implicated in the neuroinflammatory processes associated with AD. This review comprehensively summarizes current findings on the complex role of NF-κB signalling in AD pathogenesis. The canonical and non-canonical NF-κB activation pathways are described, along with evidence from human studies and animal models demonstrating increased NF-κB activity in AD brains. The deleterious effects of NF-κB-mediated neuroinflammation are discussed, including the upregulation of inflammatory cytokines, chemokines, and enzymes that exacerbate neuronal damage over time. Targeting the NF-κB pathway is proposed as a promising therapeutic approach to dampen neuroinflammation in AD. Preclinical studies utilizing genetic or pharmacological inhibition of NF-κB are reviewed, and key challenges in translating these findings to clinical applications are analyzed. Overall, this review unveils the multifaceted contributions of NF-κB signalling to AD neuropathology and highlights anti-neuroinflammatory NF-κB modulation as a potential avenue for future AD treatments. Further research is warranted to fully elucidate the complex interactions between NF-κB and AD pathogenesis.

Role of synthetic coordination chemistry in pharmaceutical science is expeditiously increased due to its sundry relevances in this field. The present review endows the synthesized macrocyclic complexes of transition metal ions containing isatin and its derivatives as ligand precursors, their characterization and their copious pharmaceutical applications. Isatin (1 H -Indole-2,3-dione) is a protean compound (presence of lactam and keto moiety permits to change its molecular framework) that can be obtained from marine animals, plants, and is also found in mammalian tissues and in human fluids as a metabolite of amino acids. It can be used for the synthesis of miscellaneous organic and inorganic complexes and for designing of drugs since it has remarkable utility in pharmaceutical industry due to its wide range of biological and pharmacological activities, for instance anti-microbial, anti-HIV, anti-tubercular, anti-cancer, anti-viral, anti-oxidant, anti-inflammatory, anti-angiogenic, analgesic activity, anti-Parkinson's disease, anti-convulsant etc. This review provides extensive information about the latest methods for the synthesis of isatin or its substituted derivatives based macrocyclic complexes of transition metals and their plentiful applications in medicinal chemistry., Competing Interests: Conflict of interestAuthors declare there is no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Oxygen- and sulphur-based heterocycles form the core structure of many biologically active molecules as well as U.S. FDA-approved drugs. Moreover, they possess broad range of biological activities, viz. anticancer, antiinflammatory, antioxidant, antitumour, antibacterial, antiviral, antidiabetic, anticonvulsant, anti-tubercular, analgesic, anti-leishmanial, antimalarial, antifungal, and anti-histaminic, Hence, O- and S-based heterocycles are gaining more attention in recent years on the road to the discovery of innovative anticancer drugs after the extensive investigation of nitrogen-based heterocycles as anticancer agents. Several attempts have been made to synthesize fused oxygen- and sulphur-based heterocyclic derivatives as joining one heterocyclic moiety with another may lead to improvement in the biological profile of a molecule. Humans have been cursed with cancer since long time. Despite the development of several heterocyclic anticancer medications such as 5-fluorouracil, doxorubicin, methotrexate, and daunorubicin, cure of cancer is difficult. Hence, researchers are trying to synthesize new fused/spiro heterocyclic molecules to discover novel anticancer drugs which may show promising anticancer effects with fewer side effects. Furthermore, fused heterocycles behave as DNA intercalating agents which have the ability to interact with DNA, leading to cell death thereby exerting anticancer effect. This review article highlights the synthesis and anticancer potentiality of oxygen- and sulphur-containing heterocyclic compounds covering the period from 2011 to 2021., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A laryngoscopically benign lesion with minimal hoarseness may turn out to be mimickers of malignancy or malignancy itself. Histopathological study is mandatory in such cases to rule out malignancy. A descriptive study of histopathological and laryngoscopic findings of benign laryngeal lesions were studies over a period of 4.5 years. Among the thirty-six patients studied, the mean age of the patients was 42 years. The most common presenting complaint was hoarseness of voice seen in 87.5% of cases. Twelve cases of vocal cord polyps were diagnosed based on clinical, laryngoscopical and histopathological features. Seven cases of vocal cord nodules, presenting with hoarseness of voice and laryngoscopic finding of a small nodular growth over the cord. Nine cases of laryngeal papillomas and papillomatosis showed branching papillae, lined by squamous epithelium with fibrovascular cores. A single case of amyloidosis and four cases of granulomatous lesions suggestive of tuberculosis were studied. One case each of rhabdomyoma and granular cell tumour was reported and confirmed by immunohistochemistry. Rare benign tumours and tumour-like lesions mimicking malignancy on laryngoscopy need histopathological evaluation. It is mandatory to study excised biopsies of the larynx as grossly similar lesions can vary from non-neoplastic to frankly malignant., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Otolaryngologists of India 2020.)

This paper considers how polygenic local adaptation and reproductive isolation between hybridizing populations is influenced by linkage disequilibria (LD) between loci, in scenarios where both gene flow and genetic drift counteract selection. It shows that the combined effects of multi-locus LD and genetic drift on allele frequencies at selected loci and on heterozygosity at neutral loci are predicted accurately by incorporating (deterministic) effective migration rates into the diffusion approximation (for selected loci) and into the structured coalescent (for neutral loci). Theoretical approximations are tested against individual-based simulations and used to investigate conditions for the maintenance of local adaptation on an island subject to one-way migration from a differently adapted mainland, and in an infinite-island population with two habitats under divergent selection. The analysis clarifies the conditions under which LD between sets of locally deleterious alleles allows these to be collectively eliminated despite drift, causing sharper and (under certain conditions) shifted migration thresholds for loss of adaptation. Local adaptation also has counter-intuitive effects on neutral (relative) divergence: FST is highest for a pair of subpopulations belonging to the same (rare) habitat, despite the lack of reproductive isolation between them., Competing Interests: The authors have declared that no competing interests exist.

We analyse how migration from a large mainland influences genetic load and population numbers on an island, in a scenario where fitness-affecting variants are unconditionally deleterious, and where numbers decline with increasing load. Our analysis shows that migration can have qualitatively different effects, depending on the total mutation target and fitness effects of deleterious variants. In particular, we find that populations exhibit a genetic Allee effect across a wide range of parameter combinations, when variants are partially recessive, cycling between low-load (large-population) and high-load (sink) states. Increased migration reduces load in the sink state (by increasing heterozygosity) but further inflates load in the large-population state (by hindering purging). We identify various critical parameter thresholds at which one or other stable state collapses, and discuss how these thresholds are influenced by the genetic versus demographic effects of migration. Our analysis is based on a 'semi-deterministic' analysis, which accounts for genetic drift but neglects demographic stochasticity. We also compare against simulations which account for both demographic stochasticity and drift. Our results clarify the importance of gene flow as a key determinant of extinction risk in peripheral populations, even in the absence of ecological gradients. This article is part of the theme issue 'Species' ranges in the face of changing environments (part I)'.

Background: In recent years, there has been a crucial need for the design and development of novel anticancer drugs that can lessen the serious health problems and unwanted side effects associated with currently used anticancer drugs. The triazole nucleus is well-recognized to possess numerous pharmacological activities, including anticancer, as revealed by various investigations on anticancer drugs and the latest research findings., Objective: The aim of this review article is to summarise the anticancer potential of 1, 2, 3-triazole, 1, 2, 4-triazole and heterocycle-fused triazole derivatives against several human cancer cell lines, compiling research articles published between 2010 and 2021., Methods: Data were collected from PubMed, Google scholar and Research Gate using keywords "anticancer activity of 1, 2, 3-triazole derivatives", "anticancer activity of 1, 2, 4-triazole derivatives" and "anticancer activity of heterocycle- fused triazole derivatives" and reviewed comprehensively., Results: This review examines the anticancer potential of 1,2,3-triazole coupledoleanolic acid/dithiocarbamate/ pyrido[ 2,3-d] pyrimidine derivatives, 1,2,3-triazole linked pyrimidine/1,4-naphthoquinone hybrids, and 1,2,4-triazole substituted methanone derivatives, acridine-based 1,2,4-triazole derivatives, 1,2,4-thiadiazol coupled with 1,2,4- triazole and 5-ene-thiazolo[3,2-b][1,2,4]triazole-6(5H)-one derivatives against several human cancer cell lines., Conclusion: This review highlights the key findings in the area of cancer therapy. Triazole derivatives possess anticancer activity against various human cancer cell lines, and hence the triazole core may act as a lead molecule for the synthesis of novel anticancer drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neglected tropical diseases as termed by World Health Organization include a group of 20 diverse infectious diseases in the tropical and subtropical regions of the world. Amongst these diseases, high mortality rate is mostly associated with Chagas disease and leishmaniosis due to limited drugs, severe toxicity caused by the available drugs and drug resistance. The above hitches have triggered the researchers to focus on the development of novel alternative therapeutics. Studies reveal that several target-based drugs have emerged which affect the biochemical pathways of the causative parasite. An anti-cancerous molecule and its derivatives might be used as antiprotozoal agents due to biochemical similarities affecting DNA metabolism. Cisplatin is a widely used drug for the treatment of testicular, ovarian, head and neck cancers, melanoma, lymphomas and several others. It exerts anticancer activity via multiple mechanisms but most effective mechanism is binding with DNA, formation of intrastrand and interstrand cross-links and generation of DNA lesions. However, side effects of cisplatin limit its application and effectiveness in the cancer treatment. Moreover, to minimize the side effects of cisplatin, combination therapies are used and have proven to be effective against cancers. Thus, current review is aimed at highlighting potential of cisplatin alone and in combination therapies as an antileishmanial agent.

Background: Complex regional pain syndrome is a rare, neuropathic disorder that affects fewer than 200,000 individuals in the United States annually. Current treatments often focus on pain management and fall short of relieving symptoms of pain and dystonia in patients., Objective: The goal of this systematic qualitative review is to evaluate the evidence for the use of low-dose naltrexone in the treatment of chronic pain syndromes., Study Design: This is a systematic review., Methods: PubMed, Embase, and Web of Science were searched for articles containing the keywords "low-dose naltrexone" AND ("pain" OR "chronic pain" OR "fibromyalgia" OR "complex regional pain syndrome" OR "neuropathic pain" OR "nociceptive pain") between 1950 and July 17, 2020. A total of 30 publications were systematically reviewed. Exclusion criteria were articles that were unavailable in English, focused on acute pain only, and evaluated only animal models. Case studies were included for the purposes of our qualitative review., Results: Out of 29 articles, we reviewed 11 prospective studies, 10 case studies, 3 systematic reviews, 2 retrospective studies, 2 simulation models, and one combination study. Articles focused on chronic pain syndromes as well as painful rheumatologic disorders and neurological disorders. We found that low-dose naltrexone treatment was positively associated with symptom relief in patients experiencing chronic pain, dystonia, and sleep disturbances., Limitations: Due to the limited number of available articles focusing on the treatment of complex regional pain syndrome with low-dose naltrexone, the majority of studies analyzed focused on other chronic pain syndromes., Conclusions: There is a need for additional prospective and interventional studies addressing the use of low-dose naltrexone in the treatment of complex regional pain syndrome symptoms.

Background: Outbreaks cause significant morbidity and mortality in healthcare settings. Current testing methods can identify specific viral respiratory pathogens, yet the approach to outbreak management remains general., Objectives: Our aim was to examine pathogen-specific trends in respiratory outbreaks, including how attack rates, case fatality rates and outbreak duration differ by pathogen between hospitals and long-term care (LTC) and retirement homes (RH) in Ontario., Methods: Confirmed respiratory outbreaks in Ontario hospitals and LTC/RH reported between September 1, 2007, and August 31, 2017, were extracted from the integrated Public Health Information System (iPHIS). Median attack rates and outbreak duration and overall case fatality rates of pathogen-specific outbreaks were compared in both settings., Results: Over the 10-year surveillance period, 9,870 confirmed respiratory outbreaks were reported in Ontario hospitals and LTC/RH. Influenza was responsible for most outbreaks (32% in LTC/RH, 51% in hospitals), but these outbreaks were shorter and had lower attack rates than most non-influenza outbreaks in either setting. Human metapneumovirus, while uncommon (<4% of outbreaks) had high case fatality rates in both settings., Conclusion: Attack rates and case fatality rates varied by pathogen, as did outbreak duration. Development of specific outbreak management guidance that takes into account pathogen and healthcare setting may be useful to limit the burden of respiratory outbreaks., Competing Interests: Competing interests: The authors declare that they have no competing interests.

The COVID-19 pandemic has affected the entire world and catapulted the United States into one of the deepest recessions in history. While this pandemic rages, the opioid crisis worsens. During this period, the pandemic has resulted in the decimation of most conventional medical services, including those of chronic pain management, with the exception of virtual care and telehealth. Many chronic pain patients have been impacted in numerous ways, with increases in cardiovascular disease, mental health problems, cognitive dysfunction, and early death. The epidemic has also resulted in severe economic and physiological consequences for providers. Drug deaths in America, which fell for the first time in 25 years in 2018, rose to record numbers in 2019 and are continuing to climb, worsened by the coronavirus pandemic. The opioid epidemic was already resurfacing with a 5% increase in overall deaths from 2018; however, the preliminary data show that prescription opioid deaths continued to decline, while at the same time deaths due to fentanyl, methamphetamine, and cocaine climbed, with some reductions in heroin deaths. The health tracker data also showed that along with an almost 88% decline in elective surgeries, pain-related prescriptions declined 15.1%. Despite increases in telehealth, outpatient services declined and only began returning towards normal at an extremely slow pace, accompanied by reduced productivity and increased practice costs. This review, therefore, emphasizes the devastating consequences of concurrent epidemics on chronic pain management and the need to develop best practice efforts to preserve access to treatment for chronic pain.

This article analyzes the conditions for local adaptation in a metapopulation with infinitely many islands under a model of hard selection, where population size depends on local fitness. Each island belongs to one of two distinct ecological niches or habitats. Fitness is influenced by an additive trait which is under habitat-dependent directional selection. Our analysis is based on the diffusion approximation and accounts for both genetic drift and demographic stochasticity. By neglecting linkage disequilibria, it yields the joint distribution of allele frequencies and population size on each island. We find that under hard selection, the conditions for local adaptation in a rare habitat are more restrictive for more polygenic traits: even moderate migration load per locus at very many loci is sufficient for population sizes to decline. This further reduces the efficacy of selection at individual loci due to increased drift and because smaller populations are more prone to swamping due to migration, causing a positive feedback between increasing maladaptation and declining population sizes. Our analysis also highlights the importance of demographic stochasticity, which exacerbates the decline in numbers of maladapted populations, leading to population collapse in the rare habitat at significantly lower migration than predicted by deterministic arguments., (© 2021 The Authors. Evolution published by Wiley Periodicals LLC on behalf of The Society for the Study of Evolution.)

Interspecific crossing experiments have shown that sex chromosomes play a major role in reproductive isolation between many pairs of species. However, their ability to act as reproductive barriers, which hamper interspecific genetic exchange, has rarely been evaluated quantitatively compared to Autosomes. This genome-wide limitation of gene flow is essential for understanding the complete separation of species, and thus speciation. Here, we develop a mainland-island model of secondary contact between hybridizing species of an XY (or ZW) sexual system. We obtain theoretical predictions for the frequency of introgressed alleles, and the strength of the barrier to neutral gene flow for the two types of chromosomes carrying multiple interspecific barrier loci. Theoretical predictions are obtained for scenarios where introgressed alleles are rare. We show that the same analytical expressions apply for sex chromosomes and autosomes, but with different sex-averaged effective parameters. The specific features of sex chromosomes (hemizygosity and absence of recombination in the heterogametic sex) lead to reduced levels of introgression on the X (or Z) compared to autosomes. This effect can be enhanced by certain types of sex-biased forces, but it remains overall small (except when alleles causing incompatibilities are recessive). We discuss these predictions in the light of empirical data comprising model-based tests of introgression and cline surveys in various biological systems., (© The Author(s) 2020. Published by Oxford University Press on behalf of Genetics Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The re-engineered definition of clinical guidelines in 2011 from the IOM (Institute of Medicine) states, "clinical practice guidelines are statements that include recommendations intended to optimize patient care that is informed by a systematic review of evidence and an assessment of the benefit and harms of alternative care options." The revised definition distinguishes between the term "clinical practice guideline" and other forms of clinical guidance derived from widely disparate development processes, such as consensus statements, expert advice, and appropriate use criteria., Objective: To assess the literature and develop methodology for evidence synthesis and development of comprehensive evidence-based guidelines for interventional techniques in chronic spinal pain., Methods: A systematic review of the literature including methodology of guideline development encompassing GRADE approach for guidance on evidence synthesis with recommendations., Results: Some of the many factors described in 2011 continue as of 2020 and impede the development of clinical practice guidelines. These impediments include biases due to a variety of conflicts and confluence of interest, inappropriate and poor methodological quality, poor writing and ambiguous presentation, projecting a view that these are not applicable to individual patients or too restrictive with the elimination of clinician autonomy, and overzealous and inappropriate recommendations, either positive, negative, or non-committal. Thus, ideally, a knowledgeable, multidisciplinary panel of experts with true lack of bias and confluence of interest must develop guidelines based on a systematic review of the existing evidence. This manuscript describes evidence synthesis from observational studies, various types of randomized controlled trials (RCTs), and, finally, methodological and reporting quality of systematic reviews. The manuscript also describes various methods utilized in the assessment of the quality of observational studies, diagnostic accuracy studies, RCTs, and systematic reviews., Limitations: Paucity of publications with appropriate evidence synthesis methodology in reference to interventional techniques., Conclusion: This review described comprehensive evidence synthesis derived from systematic reviews, including methodologic quality and bias measurement. The manuscript described various methods utilized in the assessment of the quality of the systematic reviews, RCTs, diagnostic accuracy studies, and observational studies.

COVID-19 is a pandemic with over 5 million cases worldwide. The disease has imposed a huge burden on health resources. Evaluation of clinical and epidemiological profiles of such patients can help in understanding and managing the outbreak more efficiently. This study was a prospective observational analysis of 200 diagnosed COVID-19 patients admitted to a tertiary care center from 20th march to 8th May 2020. All these patients were positive for COVID-19 by an oro-nasopharyngeal swab-rtPCR based testing. Analyses of demographic factors, clinical characteristics, comorbidities, laboratory parameters, and the outcomes were performed. The mean age of the population was 40 years with a slight male predominance (116 patients out of 200, 58%). A majority of the patients (147, 73.5 %) were symptomatic, with fever being the most common symptom (109, 54.5%), followed by cough (91, 45.5%). An older age, presence of symptoms and their duration, leukocytosis, a high quick SOFA score, a high modified SOFA score, need for ventilator support, an AST level more than 3 times the upper limit of normal (ULN), and a serum creatinine level of 2 mg/dl or greater were at a significantly higher risk of ICU admission and mortality. Presence of diabetes mellitus, AST > three times ULN, serum creatinine 2 mg/dl or higher, and a qSOFA score of 1 or higher were all associated with significantly greater odds of critical care requirement. Triage and severity assessment helps in deciding the requirement for a hospital stay and ICU admission for COVID-19 which can easily be done using clinical and laboratory parameters. A mild, moderate and severe category approach with defined criteria and treatment guidelines will help in judicious utilization of health-care resources, especially for developing countries like India.   *Other members of the Safdarjung Hospital COVID-19 working group: Balvinder Singh (Microbiology), MK Sen (Pulmonary Medicine), Shibdas Chakrabarti (Pulmonary Medicine), NK Gupta (Pulmonary medicine), AJ Mahendran (Pulmonary Medicine), Ramesh Meena (Medicine), G Usha (Anaesthesiology), Santvana Kohli (Anaesthesiology), Sahil Diwan (Anaesthesiology), Rushika Saksena (Microbiology), Vikramjeet Dutta (Microbiology), Anupam Kr Anveshi (Microbiology).

Background: Since the late 1940s, corticosteroids have been a mainstay class of agents in multiple interventional techniques and intra-articular injections. Exogenous glucocorticoids are structurally and pharmacologically similar to the endogenous hormones. As such, multiple actions of corticosteroids are exhibited, including those of anti-inflammatory and immunosuppressive effects. Epidural injections, with or without steroids, have been extensively used throughout the world. There are reports of epidural injections starting in 1901, with steroids being added to the local anesthetic since 1952, when steroids were administered into the sacral foramen., Purpose: Due to the extensive side effects of steroids in various injections, some have proposed limiting their use in epidurals and intraarticular injections. With the COVID-19 pandemic, the multiple side effects of the steroids have elevated the level of concern and recommendations have been made to utilize local anesthetic alone or the lowest dose of steroids. Fashioned from common expressions of the day, the term "steroid distancing" began to be used and proposed for intraarticular injections of the knee. Consequently, we sought to evaluate the evidence and feasibility of steroid distancing in interventional pain management., Methods: This focused review of local anesthetics and steroids utilized in interventional pain management for epidural injections, peripheral nerve blocks, and intraarticular injections by multiple database searches. This is a focused narrative review and not a systematic review. Consequently, evidence synthesis was not performed traditionally, but was based on an overview of the available evidence., Results: No significant difference was identified based on whether steroids are added to local anesthetic or not for epidural as well as facet joint injections. However, there was not enough evidence to compare these two groups for peripheral intraarticular injections., Limitations: The present review is limited by the paucity of literature with bupivacaine alone or bupivacaine with steroids local anesthetic alone or with steroids of intraarticular injections of knee, hip, shoulder and other joints, and intraarticular facet joint injections., Conclusion: This review shows an overall lack of significant difference between lidocaine alone and lidocaine with steroids in epidural injections. However, available evidence is limited for bupivacaine alone or with steroids. Evidence is also not available comparing local anesthetic alone with steroids for facet joint or peripheral joint intraarticular injections. Thus, it is concluded that local anesthetic with lidocaine may be utilized for epidural injections, with appropriate patient selection and steroids reserved for non-responsive patients with local anesthetic and with significant radiculitis.

Background: The coronavirus disease 2019 (COVID-19) pandemic has drastically altered daily living and medical care for Ohio residents and the practice of medicine for the interventional pain management physician. As a state, Ohio tends to be demographically representative of the broader US population., Objective: Reviewing the efforts deployed by Ohio to flatten the COVID-19 infection curve and reduce the spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important component of determining optimal procedures for mitigating the effects of the COVID-19 pandemic., Methods: Over the course of several announcements and orders during the months of March and April, new policies were put into place to prevent COVID-19 transmission, which included efforts to facilitate social distancing and ensure the health care system could manage the number of COVID-19 cases at peak infection rate. Efforts directed toward medical providers included delay of elective procedures, expansion of telehealth options, and new temporary guidance for prescribing controlled substances., Results: The Ohio COVID-19 containment approach resulted in a substantial reduction in COVID-19 cases compared with early models of disease spread, and the state has begun a phased reopening. Continued vigilance in applying social distancing and infection control measures will be a critical component of preventing or reducing the impact of a second wave of COVID-19 in Ohio., Limitations: A narrative review with paucity of literature.

Objective: The WHISPER randomized controlled trial (RCT) evaluates safety and clinical effectiveness of subperception spinal cord stimulation (SCS) at ≤1.2 kHz in subjects previously implanted with an SCS system for treatment of chronic, neuropathic pain., Methods: WHISPER is a prospective, multicenter RCT with a crossover design sponsored by Boston Scientific, Marlborough, MA (ClinicalTrials.gov: NCT02314000). Eligible subjects were randomized (N = 140) to receive subperception or supraperception for three months and then crossed over to receive the alternative. Upon completion of crossover period, subjects who preferred subperception were followed up to one year. Overall pain, quality-of-life, and other outcomes were collected in the study. The primary endpoint was the overall pain responder rate (≥50% improvement from baseline) with no increase in medications. Secondary endpoints consisted of pain scores, physical disability, quality of life, and treatment preference., Results: The study met its primary endpoint and demonstrated noninferiority between supraperception and subperception in a prespecified cohort of 70 randomized subjects (Interim Analysis). Thirty-nine percent of subjects with subperception settings and 29% with supraperception settings had a greater than or equal to 50% reduction in their overall pain scores with no increase in average daily medication at three-months post-activation as compared with baseline. Further assessment of all participating study subjects (N = 140) revealed similar results. Subjects were previously implanted 3.8 ± 2 years and had a disability score (Oswestry Disability Index) of 70.2 ± 11.4 at study start. Of the randomized subjects that completed the End of Period 2 Visit, 93 (66%) preferred subperception SCS and their mean overall pain reduced from 7.3 ± 1.1 (N = 89) at baseline to 4.0 ± 2.1 (N = 80) at 12-months post-activation. Post hoc analysis also demonstrated that multiple options provide superior outcomes, as supported by a 74% increase in the responder rate when subjects could choose their most effective option (47%) compared with supraperception alone (27%)., Discussion: Subperception SCS at ≤1.2 kHz is safe and effective in subjects with extreme physical disability and previously implanted for chronic pain. Further, by providing study participants with different waveform options, increased pain relief was achieved., (© 2019 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.)

This article analyzes how partial selfing in a large source population influences its ability to colonize a new habitat via the introduction of a few founder individuals. Founders experience inbreeding depression due to partially recessive deleterious alleles as well as maladaptation to the new environment due to selection on a large number of additive loci. I first introduce a simplified version of the inbreeding history model to characterize mutation-selection balance in a large, partially selfing source population under selection involving multiple nonidentical loci. I then use individual-based simulations to study the eco-evolutionary dynamics of founders establishing in the new habitat under a model of hard selection. The study explores how selfing rate shapes establishment probabilities of founders via effects on both inbreeding depression and adaptability to the new environment, and also distinguishes the effects of selfing on the initial fitness of founders from its effects on the long-term adaptive response of the populations they found. A high rate of (but not complete) selfing is found to aid establishment over a wide range of parameters, even in the absence of mate limitation. The sensitivity of the results to assumptions about the nature of polygenic selection is discussed., (© 2019 The Authors. Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.)

We study how a block of genome with a large number of weakly selected loci introgresses under directional selection into a genetically homogeneous population. We derive exact expressions for the expected rate of growth of any fragment of the introduced block during the initial phase of introgression, and show that the growth rate of a single-locus variant is largely insensitive to its own additive effect, but depends instead on the combined effect of all loci within a characteristic linkage scale. The expected growth rate of a fragment is highly correlated with its long-term introgression probability in populations of moderate size, and can hence identify variants that are likely to introgress across replicate populations. We clarify how the introgression probability of an individual variant is determined by the interplay between hitchhiking with relatively large fragments during the early phase of introgression and selection on fine-scale variation within these, which at longer times results in differential introgression probabilities for beneficial and deleterious loci within successful fragments. By simulating individuals, we also investigate how introgression probabilities at individual loci depend on the variance of fitness effects, the net fitness of the introduced block, and the size of the recipient population, and how this shapes the net advance under selection. Our work suggests that even highly replicable substitutions may be associated with a range of selective effects, which makes it challenging to fine map the causal loci that underlie polygenic adaptation., (Copyright © 2018 by the Genetics Society of America.)

Background: Occipital neuralgia is an uncommon disorder characterized by severe pain involving the posterior scalp in the distribution of the greater and lesser occipital nerves. In cases refractory to pharmacotherapy, invasive treatment options may be warranted. The aim of the present study was to examine the effects of thermal radiofrequency ablation (TRF) on occipital neuralgia. We hypothesized that this procedure would result in long-term pain relief., Methods: All patients who underwent TRF of the greater and lesser occipital nerves between January 1, 2013 and March 23, 2016 were identified. Medical records were reviewed for preprocedure pain score, 1-month postprocedure pain score, patient-defined percent pain relief according to the visual analog scale (on which zero equals no pain and 10 represents the worst pain imaginable), and length of pain relief. The primary outcomes were the differences between preprocedure and 1-month postprocedure pain scores (mean change from baseline), percent pain relief, and patient-reported length of relief., Results: A total of 50 patients were identified; 4 patients were excluded because of insufficient data as a result of loss to follow-up. A significant difference was found between preprocedure and postprocedure patient-reported pain scores (6.7 vs 2.7, respectively; P < 0.001), equating to a mean reduction in pain scores 1-month postprocedure of 4.0 ± 3.3. The mean patient-defined percent pain relief was 76.3% ± 25.0%. The mean patient-reported length of relief was 6.5 ± 5.1 months., Conclusion: This study suggests that TRF may reduce pain scores for approximately 6 months.