One size does not fit all: community views on choices for TB treatment and prevention.

Treatment and prevention paradigms in TB have been dominated by a 'one-size-fits-all' approach, in which all persons are given the same treatment regimens. This stands in contrast to other health conditions, where differentiated models of care have been shown to be effective. In this Viewpoint, we make the case for considering multiple factors when deciding which regimens should be offered to people with TB infection and disease. Choice about which regimens to use should be made in conjunction with people who have TB and consider efficacy, safety, duration, pill burden, formulation, drug interactions, time spent in monitoring, drug susceptibility, compatibility with other areas of life, and availability of support services. Ideally, these choices should be considered within an equity framework with the most intensified services being offered to those considered most vulnerable.

Les paradigmes de traitement et de prévention de la TB ont été dominés par une approche « unique ¼, dans laquelle toutes les personnes reçoivent les mêmes schémas thérapeutiques. Cette approche contraste avec d'autres problèmes de santé, pour lesquels des modèles de soins différenciés se sont avérés efficaces. Dans ce point de vue, nous plaidons en faveur de la prise en compte de multiples facteurs au moment de décider des schémas thérapeutiques à proposer aux personnes atteintes de infection tuberculeuse et de TB maladie. Le choix des traitements doit être fait en collaboration avec les personnes atteintes de TB et tenir compte de l'efficacité, de l'innocuité, de la durée, du nombre de comprimés, de la formulation, des interactions médicamenteuses, du temps consacré à la surveillance, de la sensibilité aux médicaments, de la compatibilité avec d'autres domaines de la vie et de la disponibilité des services d'aide. Idéalement, ces choix devraient être envisagés dans un cadre d'équité, les services les plus intensifs étant proposés aux personnes considérées comme les plus vulnérables.

Electrochemical and Photoelectrochemical Immunosensors for the Detection of Ovarian Cancer Biomarkers.

Photoelectrochemical (PEC) sensing is an emerging technological innovation for monitoring small substances/molecules in biological or non-biological systems. In particular, there has been a surge of interest in developing PEC devices for determining molecules of clinical significance. This is especially the case for molecules that are markers for serious and deadly medical conditions. The increased interest in PEC sensors to monitor such biomarkers can be attributed to the many apparent advantages of the PEC system, including an enhanced measurable signal, high potential for miniaturization, rapid testing, and low cost, amongst others. The growing number of published research reports on the subject calls for a comprehensive review of the various findings. This article is a review of studies on electrochemical (EC) and PEC sensors for ovarian cancer biomarkers in the last seven years (2016-2022). EC sensors were included because PEC is an improved EC; and a comparison of both systems has, expectedly, been carried out in many studies. Specific attention was given to the different markers of ovarian cancer and the EC/PEC sensing platforms developed for their detection/quantification. Relevant articles were sourced from the following databases: Scopus, PubMed Central, Web of Science, Science Direct, Academic Search Complete, EBSCO, CORE, Directory of open Access Journals (DOAJ), Public Library of Science (PLOS), BioMed Central (BMC), Semantic Scholar, Research Gate, SciELO, Wiley Online Library, Elsevier and SpringerLink.

Canonical correlation analysis on the association between HIV-related stress and health-related quality of life among newly diagnosed people living with HIV.

The overall negative correlation between HIV-related stress and health related quality of life (HRQoL) among people living with HIV (PLWH) has been established, but less is known about the associations between them from various dimensions. We aimed to give a deep understanding of the relationship between these two multidimensional variables. A cross-sectional study of 557 PLWH with diagnosis less than 1 month was conducted. The HIV/AIDS Stress Scale (SS-HIV) and the Medical Outcomes Study HIV Survey (MOS-HIV) were used to assess the HIV-related stress and HRQoL, respectively. Canonical correlation analysis was performed to analyze their correlation. The association between HIV-related stress and HRQoL among PLWH was mainly determined by the emotional stress and four HRQoL dimensions including health transition, heath stress, mental health function and the attitude towards general quality of life, which should be taken as important considerations in the management of HIV.

Bioinspired Synthesis of Pinoxaden Metabolites Using a Site-Selective C-H Oxidation Strategy.

A bioinspired synthesis of Pinoxaden metabolites 2-5 is described herein. A site-selective C-H oxidation strategy validated by density functional theory (DFT) calculations was devised for preparing metabolites 2-4. Oxidation of the benzylic C-H bond in tertiary alcohol 7 using K2S2O8 and catalytic AgNO3 formed the desired metabolite 2 that enabled access to metabolites 3 and 4 in a single step. Unlike most metal/persulfate-catalyzed transformations reported for the C-C and C-O bond formation reactions wherein the metal acts as a catalyst, we propose that Ag(I)/K2S2O8 plays the role of an initiator in the oxidation of intermediate 7 to 2. Metabolite 2 was subjected to a ruthenium tetroxide-mediated C-H oxidation to form metabolites 3 and 4 as a mixture that were purified to isolate pure standards of these metabolites. Metabolite 5 was synthesized from readily available advanced intermediate 9 via a House-Meinwald-type rearrangement in one step using a base.

Preventing medication errors in dental practice: An australian perspective.

INTRODUCTION: Prescribing errors are a common type of medication error, even in dental practice. However, prescribing is a skill to which little attention is paid, as the profession is mostly focussed on performing dental procedures, eschewing the use of drugs, to treat dental conditions. Most dentists in Australia report learning little about prescribing during their university training, gaining these skills informally on the job after they graduate. Despite this, dentists are the second largest prescriber group in Australia and prescribe a wide variety of drugs including antibiotics, non-steroidal anti-inflammatory drugs, opioid analgesics, muscle relaxants and anxiolytics. OBJECTIVES: To summarise medication safety, medication and prescribing errors in the context of dental practice. DATA: The sources of medication and prescribing errors are reviewed. SOURCES: For this narrative review, pivotal concepts regarding sources of medication error and types of prescribing error are highlighted. The Swiss Cheese model of prescribing errors is also discussed, highlighting possible interventions when errors can be detected and averted. STUDY SELECTION: Case reports of prescribing error in dentistry in Australia are presented, highlighting examples of how dental prescribing is prone to error. CONCLUSIONS: Solutions lie in addressing the systems and processes in which dentists work. Examples include implementing forced functions such as checklists and electronic prescribing tools. CLINICAL SIGNIFICANCE: Dentists are the second largest prescriber group in Australia and prescribe a wide variety of drugs. As such, prescribing errors are common in dental practice. Solutions to reduce medication and prescribing errors lie in addressing the systems which govern dentistry, as well as implementing forced functions such as prescribing tools.

N-Ammonium Ylide Mediators for Electrochemical C-H Oxidation.

The site-specific oxidation of strong C(sp3)-H bonds is of uncontested utility in organic synthesis. From simplifying access to metabolites and late-stage diversification of lead compounds to truncating retrosynthetic plans, there is a growing need for new reagents and methods for achieving such a transformation in both academic and industrial circles. One main drawback of current chemical reagents is the lack of diversity with regard to structure and reactivity that prevents a combinatorial approach for rapid screening to be employed. In that regard, directed evolution still holds the greatest promise for achieving complex C-H oxidations in a variety of complex settings. Herein we present a rationally designed platform that provides a step toward this challenge using N-ammonium ylides as electrochemically driven oxidants for site-specific, chemoselective C(sp3)-H oxidation. By taking a first-principles approach guided by computation, these new mediators were identified and rapidly expanded into a library using ubiquitous building blocks and trivial synthesis techniques. The ylide-based approach to C-H oxidation exhibits tunable selectivity that is often exclusive to this class of oxidants and can be applied to real-world problems in the agricultural and pharmaceutical sectors.

The association between sibling bullying and psychotic-like experiences among children age 11-16 years in China.

BACKGROUND: Few studies exist on sibling bullying or even sibling aggression more generally in the past 30 years. Studies of sibling bullying have shown that sibling bullying may associate with depression, anxiety, self-harm, suicide ideation in early adulthood. Nevertheless, few studies have explored the relationship between sibling victimization types and the occurrence of psychosis, not to mention that psychotic-like experiences (PLEs) always occur before psychotic disorders. Therefore, the current study aims to examine the association between sibling bullying and PLEs among children age 11-16 years in China. METHOD: This is a cross-sectional study which included 3231 students from eight junior middle schools in three cities of Hunan Province, China. Frequency and types of sibling bullying was assessed with Sibling Bullying Questionnaire and PLEs was assessed with Community Assessment Psychic Experiences-42. RESULTS: The percentage of sibling bullying were 12.9% for victimization and 10.8% for perpetration. Sibling bullying plays as an independent influence factor for all subtypes of PLEs, and verbal victimization was the most important risk factor in developing different subtypes of PLEs followed by physical victimization and verbal perpetration. CONCLUSION: The current study found that sibling bullying is associated with PLEs. Intervention programs should be conducted to focus on those children and adolescents who are involved in multiple types of sibling victimization or perpetration.

Reproductive health challenges of male and female street beggars and use of reproductive health services by female street beggars in Ife-Ijesa, Nigeria.

OBJECTIVES: The aims of the study were to investigate the reproductive health challenges in Nigeria of male and female street beggars and the use of reproductive health services by female street beggars. METHODS: The study had a cross-sectional descriptive design. An interviewer-administered questionnaire, designed by the authors, was used to elicit information from 100 male and female street beggars recruited over a 4 week period in Ife-Ijesa zone, south-western Nigeria. Information was obtained about male and female participants' reproductive health challenges (symptoms and issues) and female participants' use of reproductive health services. RESULTS: More than a third of participants were aged ≥60 years (37%), 57% were men, 82% were from the Hausa tribe and 92% were Muslims. The main reasons given for street begging were poverty (30%) and physical handicap (66%). Although most of the street beggars were aware of the availability of reproductive health services (81%) and where to access them (89%), only a small proportion of female street beggars had given birth in hospital (9.3%) and family planning services (32.6%). CONCLUSION: Street beggars are a poor and vulnerable group with reproductive health challenges. They have difficulty accessing reproductive health services because of physical disabilities and related low socioeconomic status.

A review of drugs that contribute to bleeding risk in general dental practice.

The risk of postoperative bleeding is a daily concern for many general dental practitioners. A thorough medical and medication history must be taken to consider all risk factors, particularly drugs, that contribute to bleeding risk. While the risk from drugs such as aspirin, warfarin and clopidogrel are well known, the extent to which new antiplatelet agents and direct oral anticoagulants affect bleeding risk is less well understood. In addition, there are drugs other than antithrombotics, such as antidepressants and complementary medicines that also impair haemostasis. The aim of this paper is to provide dentists with an updated overview of the drugs commonly encountered in general dental practice that can contribute to a patient's postoperative bleeding risk.

Oral manifestations of illicit drug use.

The use of illicit and misuse of licit drugs is a global public health problem, with illicit drug use being responsible for 1.8% of the total disease burden in Australia in 2011. Oral adverse effects associated with illicit drug use are well-established, with aggressive caries, periodontitis, bruxism, poor oral hygiene and general neglect documented. Other factors such as a high cariogenic diet and lifestyle, social and psychological factors compound the poorer oral health in illicit drug users. Literature has shown that the oral health-related quality of life among injecting drug users is poorer compared with the Australian general population and the overall quality of life of addicted people correlates with caries experience. Thus, the role of the dentist is imperative in managing the oral health of these individuals. Given their widespread recreational use, it is likely that dental practitioners will encounter patients who are regular or past users of illicit drugs. The aim of this article is to describe the prevalence and mechanism of action of commonly used illicit drugs in Australia, including cannabis, methamphetamine, cocaine and heroin and to inform dentists about the common orofacial presentations of their side effects to help with patient management.

Photoelectrocatalytic application of palladium decorated zinc oxide-expanded graphite electrode for the removal of 4-nitrophenol: experimental and computational studies.

A novel Pd-ZnO-expanded graphite (EG) photoelectrode was constructed from a Pd-ZnO-EG nanocomposite synthesised by a hydrothermal method and characterised using various techniques such as X-ray diffractometry (XRD), Raman spectroscopy, UV-Vis diffuse reflectance spectroscopy, nitrogen adsorption-desorption analysis, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS). Cyclic voltammetry and photocurrent response measurements were also carried out on the electrode. The Pd-ZnO-EG electrode was employed in the photoelectrocatalytic removal of 4-nitrophenol as a target water pollutant at a neutral pH and with a current density of 7 mA cm-2. Optical studies revealed that the Pd-ZnO-EG absorbed strongly in the visible light region. The Pd-ZnO-EG electrode showed improved photoelectrocatalytic activity in relation to ZnO-EG and EG electrodes for the removal of the 4-nitrophenol. The photocurrent responses showed that the Pd-ZnO-EG nanocomposite electrode could be employed as a good photoelectrode for photoelectrocatalytic processes and environmental remediation such as treatment of industrial waste waters. Density functional theory method was used to model the oxidative degradation of 4-nitrophenol by the hydroxyl radical which generates hydroquinone, benzoquinone, 4-nitrocatechol, 4-nitroresorcinol and the opening of the 4-nitrophenol ring. Furthermore, the hydroxyl radical is regenerated and can further oxidise the ring structure and initiate a new degradation process.

Design, synthesis, and pharmacological evaluation of JDTic analogs to examine the significance of replacement of the 3-hydroxyphenyl group with pyridine or thiophene bioisosteres.

The potent and selective KOR antagonist JDTic was derived from the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of pure opioid antagonists. In previous studies we reported that compounds that did not have a hydroxyl on the 3-hydroxyphenyl group and did not have methyl groups at the 3- and 4-position of the piperidine ring were still potent and selective KOR antagonists. In this study we report JDTic analogs 2, 3a-b, 4a-b, and 5, where the 3-hydroxyphenyl ring has been replaced by a 2-, 3-, or 4-pyridyl or 3-thienyl group and do not have the 3-methyl or 3,4-dimethyl groups, remain potent and selective KOR antagonists. Of these, (3R)-7-hydroxy-N-(1S)-2-methyl-[4-methyl-4-pyridine-3-yl-carboxamide (3b) had the best overall binding potency and selectivity in a [(35)S]GTPγS functional assay, with a Ke=0.18nM at the KOR and 273- and 16,700-fold selectivity for the KOR relative to the MOR and DOR, respectively. Calculated physiochemical properties for 3b suggest that it will cross the blood-brain barrier.

Design, Synthesis, and Biological Evaluation of Structurally Rigid Analogues of 4-(3-Hydroxyphenyl)piperidine Opioid Receptor Antagonists.

In order to gain additional information concerning the active conformation of the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (1) class of opioid receptor antagonists, procedures were developed for the synthesis of structurally rigid N-substituted-6-(3-hydroxyphenyl)3-azabicyclo[3.1.0]hexane and 3-methyl-4-(3-hydroxyphenyl)-4-azabicyclo[4.1.0]heptanes. Evaluation of the conformationally constrained series in a [35S]GTPγS assay showed that structural rigid compounds having the 3-hydroxyphenyl group locked in the piperidine equatorial orientation had potencies equal to or better than similar compounds having more flexible structures similar to 1. The studies of the rigid compounds also suggested that the 3-methyl group present in compound 1 type antagonists may not be necessary for their pure opioid antagonist properties.

The application of exfoliated graphite electrode in the electrochemical degradation of p-nitrophenol in water.

We report the application of exfoliated graphite (EG) as an electrode material in the electrochemical degradation of p-nitrophenol in water. Bulk electrolysis (degradation) of p-nitrophenol was carried out at a potential of 2.0 V (vs. Ag/AgCl) in the presence of 0.1 M Na2SO4 supporting electrolyte, while UV-Vis spectrophotometry was used to monitor the degradation efficiency. An initial p-nitrophenol load concentration of 0.2 mM for 3 h electrolysis time was studied under the optimized conditions of pH 7, and 10 mAcm(-2) current density. The electro-degradation reaction displayed a pseudo-first-order kinetic behavior with a rate constant (k(r)) of 11×10(-3) min(-1). The removal efficiency was found to be 91.5%. Chromatography coupled with time of flight mass spectrometry revealed p-benzoquinone as a major intermediate product. These results demonstrate the potential and viability of electrochemical technology as an alternative approach to water treatment using a low cost graphite electrode.

Design, synthesis, and pharmacological evaluation of JDTic analogs to examine the significance of the 3- and 4-methyl substituents.

The design and discovery of JDTic as a potent and selective kappa opioid receptor antagonist used the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine pharmacophore as the lead structure. In order to determine if the 3-methyl or 4-methyl groups were necessary in JDTic and JDTic analogs for antagonistic activity, compounds 4a-c, and 4d-f which have either the 3-methyl or both the 3- and 4-methyl groups removed, respectively, from JDTic and analogs were synthesized and evaluated for their in vitro opioid receptor antagonist activities using a [(35)S]GTPγS binding assay. Other ADME properties were also assessed for selected compounds. These studies demonstrated that neither the 3-methyl or 3,4-dimethyl groups present in JDTic and analogs are required to produce potent and selective κ opioid receptor antagonists.

Design, synthesis, and biological evaluation of (3R)-1,2,3,4-tetrahydro-7-hydroxy-N-[(1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl]-3-isoquinolinecarboxamide (JDTic) analogues: in vitro pharmacology and ADME profile.

JDTic analogues 4-15 which have the hydroxyl groups replaced with other groups were synthesized and their in vitro efficacy at the µ, δ, and κ opioid receptors determined and compared to JDTic using [(35)S]GTPγS assays. Compounds 4, 5, 6, 13, 14, and 15 had Ke = 0.024, 0.01, 0.039, 0.02, 0.11, and 0.041 nM compared to the Ke = 0.02 nM for JDTic at the κ receptor and were highly selective for the κ receptor relative to the µ and δ opioid receptors. Unexpectedly, replacement of the 3-hydroxyl substituent of the 4-(3-hydroxyphenyl) group of JDTic with a H, F, or Cl substituent leads to potent and selective KOR antagonists. In vitro studies to determine various ADME properties combined with calculated TPSA, clogP, and logBB values suggests that the potent and selective κ opioid receptors 4, 5, 13, and 14 deserve consideration for further development toward potential drugs for CNS disorders.

Effect of the 3- and 4-methyl groups on the opioid receptor properties of N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines.

N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines (2a,b) are opioid receptor antagonists where the antagonist properties are not due to the type of N-substituent. In order to gain a better understanding of the contribution that the 3- and 4-methyl groups make to the pure antagonist properties of 2a,b, we synthesized analogues of 2a,b that lacked the 4-methyl (5a,b), 3-methyl (6a,b), and both the 3- and 4-methyl group (7a,b) and compared their opioid receptor properties. We found that (1) all N-methyl and N-phenylpropyl substituted compounds were nonselective opioid antagonists (2) all N-phenylpropyl analogues were more potent than their N-methyl counterparts, and (3) compounds 2a,b which have both a 3- and 4-methyl substituent, were more potent antagonists than analogues 5a,b, 6a,b, and 7a,b. We also found that the removal of 3-methyl substituent of N-methyl and N-phenylpropyl 3-methyl-4-(3-hydroxyphenyl)piperazines (8a,b) gives (4a,b), which are opioid antagonists.

4ß-Methyl-5-(3-hydroxyphenyl)morphan opioid agonist and partial agonist derived from a 4ß-methyl-5-(3-hydroxyphenyl)morphan pure antagonist.

In previous studies we reported that addition of 7α-acylamino groups to N-phenylpropyl-4ß-methyl-5-(3-hydroxyphenyl)morphan (4) led to compounds that were pure opioid receptor antagonists. In contrast to these findings we report in this study that addition of a 7α-amino (5a), 7α-alkylamino (5b-e), or 7α-dialkylamino (5f-h) group to 4 leads to opioid receptor ligands with varying degrees of agonist/antagonist activity. The 7α-amino and 7α-methylamino analogues were full agonists at the µ and δ receptors and antagonists at the κ receptor. The 7α-cyclopropylmethylamino analogue 5h was a full agonist at the µ receptor with weaker agonist activity at the δ and κ receptors. Whereas the addition of a 7α-acylamino group to the pure nonselective opioid receptor antagonist N-phenylpropyl-4ß-methyl-5-(3-hydroxyphenyl)morphan (4) led to κ selective pure opioid receptor antagonist, the addition of a 7α-amino, 7α-alkylamino, or 7α-dialkylamino group to 4 leads to opioid ligands that are largely µ or δ agonist with mixed agonist/antagonist properties.

Preparation of a Series of 5-Methyl-3-(substituted)-[1,2,4]triazines.

Procedures for the synthesis of thirty-six 5-methyl-3-(substituted)-[1,2,4]triazines have been described. These compounds were evaluated for antagonism at metabotropic glutamate receptor subtype 5. Two compounds, 5b and 3c, were determined to be low micromolar inhibitors of mGluR5.