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Substance use refers to the consumption of drugs that have varying degrees of impact on a persons’ physical, mental and emotional well-being. While the adverse health effects of drugs have been extensively documented, further research is needed to understand their impact on fertility. Studies have indicated that substance use affects both the male and female reproductive systems. As substance use is more prevalent among young adults compared with the elderly, it appears that individuals of reproductive age are particularly vulnerable to the reproductive impairments associated with substance use. Although numerous studies have reported detrimental effects of substance use on pregnant women and their foetus during the post-implantation stages, there are limited studies on critical pre-implantation period and gamete stages. In this narrative review, we aimed to focus on the most significant evidence regarding the impact of substances on gametes and pre-implantation embryos.
Biobased content analysis is a well-established, analytically independent, standardized method to determine the biobased content of fuels and plastics, based on differences of the specific radiocarbon (14C) activity of fossil and recent biogenic compounds. This biogenic content analysis can be useful for the producers as a quality assurance tool, for the customers as feedback about the truly biobased products and for the control organizations as an independent analytical tool to prove the biological origin. More than 100 commercially available foods, cosmetics, and drug samples have been used for biobased carbon content analysis by accelerator mass spectrometry (AMS) 14C measurement to demonstrate the potential of this technique. Our results show that this measurement technique is a unique tool for the determination of biocontent in foodstuff and medical products. Most of the tested materials were nearly or completely biobased (≥ 98 pMC), and no completely fossil-based final product was detected. The lowest biogenic compound was measured in a vanilla aroma flavor. In 45 of the 102 samples selected a wide range (2–98%) presented fossil-based carbon content. The method can be applied for monitoring raw materials and final products for biobased content in the industry and consumer protection as well.
How do you read a patent and what subject matter is patentable? What is the purpose of a patent? Who is an inventor on the patent if work is done by many people on the project? What is the process of obtaining a patent in my country and globally? Read this chapter to see how you could lose commercialization rights to your own invention. When exactly does an invention or idea become patentable? Once you own a patent, how can you make money from it? What is the process of licensing and the key terms that should be negotiated in such a license agreement? What is the use of a copyright or a trade secret in biotech? What exactly constitutes patent infringement ? These questions and many others are addressed in this chapter on intellectual property.
From the long path through preclinical development, entering the regulatory field of interactions for human clinical trials can sometimes feel like you are walking into the lion’s den. This chapter guides you through an understanding of how to interact and how to prepare for FDA meetings so that they are on your side rather than fighting you. The common goals of companies and the FDA are highlighted here. Specific issues with identifying the appropriate regulatory approval pathway are discussed here with cautionary case studies. Complex new technologies which combine diagnostics and drugs, or devices and software, or AI-based dynamic software are reviewed here. The best approach to the appropriate regulatory pathway will be clear after reading this chapter. Case studies are used to show successful pathways taken by cutting-edge developments, such as cell-based therapy.
Lorazepam is a benzodiazepine derivative that is globally used for the therapy of anxiety and insomnia.
Objectives
The objective of our work was to show that Lorazepam can be a cause of unexpected liver injury even though it is a rare entity.
Methods
We reported the case of a patient who had a Drug-Induced Liver Injury (DILI) under Lorazepam. We performed a literature review based on a PubMed search with the following keywords: “Lorazepam,DILI”.
Results
A 20 year-old-Tunisian woman was hospitalized in the psychiatry department of the hospital of Nabeul in Tunisia for a brief psychotic episode.She had a DILI under Olanzapine, Chlorpromazine and Lorazepam, which conducted us to interrupt her treatments except for the Lorazepam(5mg/day). The hepatic tests went back to normal even under Lorazepam. Few days later, the liver enzymes increased again to reach very high levels. Extensive workup was negative for other causes of liver injury, including viral hepatitis A, B, C and E.; capillary electrophoresis of serum proteins was normal; Exhaustive immunological tests were performed searching for auto immune hepatitis(anti-smooth muscle antibodies, anti-LKM1, anti-LC1, anti-SLA/LP) primary biliary cholangitis(anti-mitochondrial antibodies, anti-GP210, anti-sp100) and other antibodies like antinuclear antibodies were negative. Liver biopsy showed polymorphic inflammatory infiltrate including some eosinophilic polynuclear cells and rare vaguely epitheloid macrophages, with necrotico-inflammatory foci in the lobules, all of which were consistent with DILI. Lorazepam was discontinued and within 10 days her liver enzymes decreased and completely normalized.
Conclusions
Lorazepam, with an unknown action mechanism, can be a cause of DILI.
The emergence of the COVID-19 pandemic has presented the addiction services with an unprecedented set of challenges. Opioid users are particularly vulnerable because of their high level of pre-existing health problems and lifestyle factors. In order to minimise their risks to self and to others in the current Covid-19 crisis, addiction services sought to urgently identify vulnerable individuals, and induct them into opioid substitution treatment (OST) promptly. Additionally, several guidelines were created and regularly updated by the health and safety executive (HSE) for any healthcare staff working with opioid users. These include guidance documents, to facilitate prompt induction of patients onto the OST programme, the prescribing of naloxone to all patients at risk of overdose, eConsultation, medication management for those in self-isolation, and the delivery of injecting equipment. The guidance documents and resources will provide a template for a new way of working for the sector during these challenging times and into the future.
The association of leishmaniasis and malignancies in human and animal models has been highlighted in recent years. The misdiagnosis of coexistence of leishmaniasis and cancer and the use of common drugs in the treatment of such diseases prompt us to further survey the molecular biology of Leishmania parasites and cancer cells. The information regarding common expressed proteins, as possible therapeutic targets, in Leishmania parasites and cancer cells is scarce. Therefore, the current study reviews proteins, and investigates the regulation and functions of several key proteins in Leishmania parasites and cancer cells. The up- and down-regulations of such proteins were mostly related to survival, development, pathogenicity, metabolic pathways and vital signalling in Leishmania parasites and cancer cells. The presence of common expressed proteins in Leishmania parasites and cancer cells reveals valuable information regarding the possible shared mechanisms of pathogenicity and opportunities for therapeutic targeting in leishmaniasis and cancers in the future.
Therapeutic drug monitoring is performed to ensure drug levels in the blood are in the therapeutic (not toxic) range, thus imporving efficacy of the drug and patient outcomes. While not all drugs require this, those that do have a recognised desired serum concentration which provides optimal effect. The chapter describes some general rules, including when to take levels and how to calculate ideal and corrected body weight, and runs through some common examples, including gentamicin, phenytoin and aminophylline.
Forty-five cases of psychotic patients with admission urinalysis positive for cannabis were compared with psychotic controls without evidence of cannabis use. Cases and controls were matched for age, sex and year of admission, and were compared for socio-demographic data, circumstances of admission, diagnosis, and symptoms at admission. Three differences were found: cases were more likely to be Afro-Caribbean than white (P = 0.01), to manifest incoherence of speech (P= 0.02) and agitation (P= 0.01). In other respects the case and control groups were indistinguishable, and no pattern of symptoms characterised the “cannabis psychosis“group. These findings do not support the view that “cannabis psychosis” has a distinct psycho-phenomenological pattern Epidemiological studies are required to further clarify the association for psychotic patients between Afro-Caribbean ethnic groups and the likelihood of having a positive urine test for cannabis.
Little information is available on the use of brief psychotherapy among subjects with generalised anxiety disorder (GAD) within community mental health services. This study compared results among subjects treated with brief Adlerian psychodynamic psychotherapy (B-APP), those treated with medication (MED), or those who experienced combined treatment (COM). Symptomatology and occupational functioning were assessed using the Hamilton Anxiety and Depression scales (HAM-A; HAM-D), Clinical Global Impression (CGI), and Social and Occupational Functioning Assessment Scale (SOFAS) at intake (T1) and at 3, 6, and 12 months later (T3, T6, T12). The study sample included 87 patients with GAD (B-APP 34; MED 33; COM 20), and an ANOVA was applied for analysing repeated measures while controlling for personality disorder. After 6 months, CGI, HAM-A, HAM-D, and SOFAS scores significantly improved independently from the type of treatment. Subjects with personality disorders treated with B-APP exhibited superior results to those treated using other methods only in SOFAS scores at T6. These results were generally maintained at T12. Remission rates among subjects (HAM-A scores <7) varied between 55% (MED) and 74% (B-APP) at T6 and between 63% (MED) and 78% (COM) at T12; no significant differences appeared between the three treatment groups. A logistic regression model predicted anxiety remission only by CGI at T1. This paper discusses these results in relation to the use of brief psychotherapy within community mental health services.
The United States does not yet have a comprehensive legal regime to manage germline editing. However, the US Congress, which appropriates funds annually to support the Food and Drug Administration (FDA), has enacted a rider that prevents the agency from using those funds to receive applications for clinical trials. In this manner, Congress has imposed a de facto moratorium that prevents scientists from creating children with modified genomes. In most of the fifty states, scientists remain free to edit human gametes and embryos in the lab as long as they mind federal regulations governing research.In the future, Congress and state legislatures may ban germline editing, in whole or in part. Such bans may face legal challenges. To be sure, the United States has not ratified the International Covenant on Economic, Social and Cultural Rights, and is not bound by its requirement that parties respect scientific freedom. Nor does the US Constitution expressly state a right to engage in scientific research. However, some academics argue that such a right can be derived from the First Amendment. Further, those who cannot conceive a healthy child without germline editing may claim that a ban violates their constitutional right to privacy.
Causes of the comorbidity of substance misuse with anxiety-related and depressive disorders (anxiety/depression) remain poorly known. We estimated associations of substance misuse and anxiety/depression in the general population and tested them while accounting for genetic and shared environmental factors.
Methods
We studied individuals born in Sweden 1968–1997 (n = 2 996 398) with follow-up in nationwide register data for 1997–2013. To account for familial effects, stratified analyses were conducted within siblings and twin pairs. Substance misuse was defined as ICD-10 alcohol or drug use disorder or an alcohol/drug-related criminal conviction. Three dimensions of ICD-10 anxiety and depressive disorders and a substance misuse dimension were identified through exploratory factor analysis.
Results
Substance misuse was associated with a 4.5-fold (95% CI 4.50–4.58) elevated risk of lifetime generalized anxiety/depression, 4.7-fold (95% CI 4.63–4.82) elevated risk of panic disorder and agora/social phobia, and 2.9-fold elevated risk of phobias/OCD (95% CI 2.82–3.02) as compared to those without substance misuse. The associations were attenuated in within-family analyses but we found elevated risks in monozygotic twin pairs discordant for substance misuse as well as significant non-shared environmental correlations. The association between anxiety/depression and substance misuse was mainly driven by generalized anxiety/depression, whereas other anxiety/depression dimensions had minor or no independent associations with substance misuse.
Conclusions
Substance misuse and anxiety/depression are associated at the population level, and these associations are partially explained by familial liabilities. Our findings indicate a common genetic etiology but are also compatible with a potential partially causal relationship between substance misuse and anxiety/depression.
The protozoan parasite Leishmania is endemic in large parts of the world which causes leishmaniasis. Its visceral form is fatal if not treated and is caused mostly by Leishmania donovani, Leishmania infantum and Leishmania chagasi. Given the difficulties linked to vector (sandfly) control and the lack of an effective vaccine, the control of leishmaniasis relies mostly on chemotherapy. Unfortunately, the prevalence of parasites becoming resistant to the first-line drug pentavalent antimony (SbV) is increasing worldwide. Few alternative drugs are available that includes amphotericin B, pentamidine and miltefosine (oral). Already, decreases in efficacy, resistance and toxicity have been noted against these drugs. Dry antileishmanial pipeline further indicates the slow pace of drug discovery in this field where resistance as a major barrier. Full understanding of the genetic and molecular basis of the parasite is lagging. Since leishmaniasis is a neglected disease and occurs predominantly in the developing world largely, therefore, it is unaddressed. The pharma industry argues that development of the new drug is too costly and risky to invest in low return neglected diseases is very high. Research is also needed to identify new and effective drug targets. The lack of drug research and development for neglected diseases will require some new strategies. We have discussed the various cause of slow pace of antileishmanial drug discovery in this review to pay attention of researchers and also take the public and private initiative to make the process fast for new antileishmanial drug development.
As clinical impartiality is an accepted basic principle of ethical practice, any proactive exercises that may inform selection, training, clinical placements, and other interventions, which promote future positive and equitable professional conduct, thus guarding against future discriminatory attitudes are germane. Within this context, the purpose of this review was to identify trends and patterns in health student, namely future practitioners’, regard for substance-using patients using the Medical Condition Regard Scale.
Methods
Six electronic databases were systematically searched for studies that used the Medical Condition Regard Scale as an outcome measure in assessing health student regard for drug-using patients. Academics who had published in this area were also consulted to recommend texts that would complement the above citation sourcing process. Following an elimination of duplicates, the application of inclusion and exclusion criteria, as well as conducting citation searches, 16 studies were incorporated in the final review. Although the quality of all included studies was satisfactory, no study was free from a potential source of bias.
Results
This review found that patients with drug-use problems were consistently held in the lowest echelons of regard by trainee health practitioners. The impact of sex, age, year of course, and personal exposure to mental health difficulties in predicting negative regard was unclear.
Conclusions
Unless addressed, patients with drug problems may have a high potential for future treatment marginalisation by tomorrow’s health professionals. This scenario needs to be proactively managed by all stakeholders through a greater investment in educational and clinical training placement opportunities.
For many years, virtually all pharmaceutical companies had an agrochemical
division. This was partly to maximize the benefits of expensive chemical
synthesis efforts by searching for many types of useful biological
activities. Leads for pharmaceuticals and pesticides often overlap, in some
cases leading to similar compounds used for human health and weed management
purposes. This review will focus on herbicides and herbicide classes that
have potential pharmaceutical properties, both as therapeutic agents that
act through human molecular target sites and those that act on infectious
agents. An example of the first case is compounds that target plant acetyl
coenzyme A carboxylases, inhibiting fatty acid synthesis, and similar
compounds used in humans as anti-inflammatory agents. Another such example
is the triketone class of compounds that can act both as herbicides and as
treatments for the genetic disease tyrosinemia, targeting the same enzyme in
both cases. Examples of the second case are the relatively large number of
herbicides that have activity against the malaria protozoan
(Plasmodium spp.). It turns out that
Plasmodium spp. and related disease organisms have an
organelle that is apparently analogous to the plant plastid, the apicoplast.
Herbicides such as dinitroanilines are active against several protozoan
parasites by the same mechanism by which they kill plants, interaction with
tubulin to halt cell division and other tubulin-dependent processes. These
and other multiple activities of various herbicides and herbicide classes
provide perspective on the broad biological activity of herbicides and
related compounds.
Objectives: Companion diagnostic tests (CDx) are used to measure an individual's protein or gene expression (biomarkers) to inform choice of therapy. The increasing number of drugs requiring CDx poses challenges for regulatory and reimbursement policies. To better understand this issue, an environmental scan was conducted by the Canadian Agency for Drugs and Technologies in Health (CADTH).
Methods: The environmental scan was based on a focused literature search and feedback solicited from targeted stakeholders.
Results: The global market for CDx is expected to grow considerably until the end of this decade, with compound annual growth rate around 20 percent. Several factors may impact the adoption of CDx, including the potential cost-savings associated with reduced treatment failures and adverse reactions. Anticipating an expansion in drugs with CDx, some countries have updated their regulatory frameworks, including the United States where the FDA released new guidance in 2014. With respect to reimbursement, both the United Kingdom and Australia updated their evaluation frameworks to inform reimbursement decisions; however, several countries, including Canada, have not published policies for co-dependent technology.
Conclusion: The market size for CDx is expected to considerably expand in the future. The drive in uptake may be influenced by many factors including an increased knowledge of biomarkers and molecular drivers of disease and the potential cost-savings associated with fewer treatment failures and adverse reactions. Assessing whether such benefits materialize is important. Health technology assessment will play an important role in informing policies regarding the clinical use and funding of pharmaceuticals with CDx.
Previous studies on substance-dependent populations have shown that age of first use and duration of use are associated with alterations in regional brain volumes. However, it is not clear whether such alterations are factors that predispose young people to use, and so are also present in recreational users, or are a consequence of chronic exposure to substances and/or comorbid psychopathology.
Objective:
To investigate relationships between key brain structures and parameters of alcohol and cannabis use, in otherwise healthy male recreational users.
Method:
High-resolution magnetic resonance imaging was used to measure hippocampal, amygdala, whole-brain and intracranial cavity (ICC) volumes in 22 young men with a history of both alcohol and cannabis use.
Results:
Linear regression analyses with hippocampal, amygdala and whole-brain volumes as the dependent variables and age and ICC as covariates were performed. Findings showed that use of cannabis and alcohol at an earlier age were independently predictive of larger amygdala volumes, whereas longer duration of cannabis use was predictive of smaller hippocampal volumes.
Conclusions:
Our findings offer preliminary support for a relationship between patterns of substance use and regional brain volumes in recreational users. It is speculative, but possible that this relationship is an evidence of a neurobiological vulnerability to drug-taking behaviour.