Phytoremediation Potential of Different Genotypes of Salix alba and S. viminalis.

Elevated concentrations of heavy metals result in soil degradation, a reduction in plant yields, and a lower quality of agricultural products, which directly endangers people, animals, and the ecosystem. The potential of three clones of Salix alba (347, NS 73/6, and B-44) and one genotype of S. viminalis for the phytoextraction of heavy metals was investigated, with the aim of identifying the most physiologically suitable willow genotypes for use in soil phytoremediation. The experiment was placed on the contaminated soil substrate collected in Kolubara Mining Basin (Serbia), enriched by high loads of heavy metal salts, and a control medium. Significant differences in the concentrations of heavy metals were recorded between the contaminated and control plant material, especially when it comes to nickel (Ni), copper (Cu), cadmium (Cd), and lead (Pb), confirming that S. alba and S. viminalis are hyperaccumulator species of heavy metals. Clone 347 shows the greatest uptake of Cd and chromium (Cr), and clone B-44 takes up these metals only to a lesser extent, while clone NS 73/6 shows a less pronounced uptake of Cr. The roots have the greatest ability to accumulate Ni and Pb, Cu is absorbed by all plant organs, while Cd is absorbed by the leaves. The organ that showed the greatest ability to accumulate heavy metals was the root, which means that willows have a limited power to translocate heavy metals to above-ground organs. The studied genotypes of S. alba have a higher potential for the phytostabilization of Cu and Cd, as well as the phytoextraction of Cd, compared with S. viminalis. The results confirm the assumption of differences between different willow genotypes in terms of the ability to phytoextract certain heavy metals from soil, which is important information when selecting genotypes for soil phytoremediation.

Adrenal Abscesses: A Systematic Review of the Literature.

Objective: To summarize the existing knowledge about adrenal gland abscesses, including etiology, clinical presentation, common laboratory and imaging findings, management and overall morbidity and mortality. Design: Systematic literature review. Methods: We performed a search in the PubMed database using search terms: 'abscess and adrenal glands', 'adrenalitis', 'infection and adrenal gland', 'adrenal abscess', 'adrenal infection' and 'infectious adrenalitis'. Articles from 2017 to 2022 were included. We found total of 116 articles, and after applying exclusion criteria, data from 73 articles was included in the final statistical analysis. Results: Of 84 patients included in this review, 68 were male (81%), with a mean age of 55 years (range: 29 to 85 years). Weight loss was the most frequent symptom reported in 58.3% patients, followed by fever in 49%. Mean duration of symptoms was 4.5 months. The most common laboratory findings were low cortisol (51.9%), elevated ACTH (43.2%), hyponatremia (88.2%) and anemia (83.3%). Adrenal cultures were positive in 86.4% cases, with Histoplasma capsulatum (37.3%) being the leading causative agent. Blood cultures were positive in 30% of patients. The majority of the adrenal infections occurred through secondary dissemination from other infectious foci and abscesses were more commonly bilateral (70%). A total of 46.4% of patients developed long-term adrenal insufficiency requiring treatment. Abscess drainage was performed in 7 patients (8.3%) and adrenalectomy was performed in 18 (21.4%) patients. The survival rate was 92.9%. Multivariate analysis showed that the only independent risk factor for mortality was thrombocytopenia (p = 0.048). Conclusion: Our review shows that adrenal abscesses are usually caused by fungal pathogens, and among these, Histoplasma capsulatum is the most common. The adrenal glands are usually involved in a bilateral fashion and become infected through dissemination from other primary sources of infection. Long-term adrenal insufficiency develops in 46% of patients, which is more common than what is observed in non-infectious etiology of adrenal gland disorders. Mortality is about 7%, and the presence of thrombocytopenia is associated with worse prognosis. Further prospective studies are needed to better characterize optimal testing and treatment duration in patients with this relatively rare but challenging disorder.

Glucocorticoid Hormones as Modulators of the Kynurenine Pathway in Chronic Pain Conditions.

The pathogenesis of chronic pain entails a series of complex interactions among the nervous, immune, and endocrine systems. Defined as pain lasting or recurring for more than 3 months, chronic pain is becoming increasingly more prevalent among the US adult population. Pro-inflammatory cytokines from persistent low-grade inflammation not only contribute to the development of chronic pain conditions, but also regulate various aspects of the tryptophan metabolism, especially that of the kynurenine pathway (KP). An elevated level of pro-inflammatory cytokines exerts similar regulatory effects on the hypothalamic-pituitary-adrenal (HPA) axis, an intricate system of neuro-endocrine-immune pathways and a major mechanism of the stress response. As the HPA axis counters inflammation through the secretion of endogenous cortisol, we review the role of cortisol along with that of exogenous glucocorticoids in patients with chronic pain conditions. Considering that different metabolites produced along the KP exhibit neuroprotective, neurotoxic, and pronociceptive properties, we also summarize evidence rendering them as reliable biomarkers in this patient population. While more in vivo studies are needed, we conclude that the interaction between glucocorticoid hormones and the KP poses an attractive venue of diagnostic and therapeutic potential in patients with chronic pain.

The Kynurenine Pathway and Polycystic Ovary Syndrome: Inflammation as a Common Denominator.

Polycystic ovary syndrome (PCOS) is a complex metabolic disorder commonly seen in females of reproductive age. The pathophysiology of PCOS is multifactorial and includes dysfunction in ovarian steroidogenesis and folliculogenesis, impaired gonadotropin levels, insulin resistance, gut microbiota imbalance, genetic predisposition, and lifestyle preferences. Low-grade inflammatory conditions such as obesity and impaired glucose tolerance are common metabolic disturbances in women with PCOS. A growing body of literature suggests strong evidence rendering PCOS in close proximity with chronic inflammation as documented by high levels of serum white blood cells, C-reactive protein, and various proinflammatory cytokines seen in this condition. Inflammation seems to be the most common metabolic denominator between the kynurenine pathway and PCOS. The association of tryptophan and kynurenine pathway has already been well documented in mood disorders, neurodegenerative diseases, chronic pain conditions, and different inflammatory states. In this manuscript, we describe the influence of sex steroid hormones on different enzymes of the KP; inflammatory nature of PCOS and CRP as a marker of IDO/TDO activity; and the effects of altered gut flora in women with PCOS. This review provides a novel view of the available evidence of tryptophan and downstream metabolites in PCOS in the context of underlying inflammation.

Impact of an Extremely Dry Period on Tree Defoliation and Tree Mortality in Serbia.

This paper presents research results on forest decline in Serbia. The results were obtained through monitoring defoliation of 34 tree species at 130 sample plots during the period from 2004 to 2018. This research aimed to determine whether the occurrence of defoliation and tree mortality were caused by drought. Defoliation was assessed in 5% steps according to the International Co-operative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests) methodology. All the trees recorded as dead were singled out, and annual mortality rates were calculated. To determine changes in air temperature and precipitation regimes during the study period, we processed and analysed climatic data related to air temperature and precipitation throughout the year and in the growing season at 28 main weather stations in Serbia. Tree mortality patterns were established by classifying trees into three groups. The first group of trees exhibited a gradual increase in defoliation during the last few years of monitoring, with dying as the final outcome. The second group was characterised by sudden death of trees. The third group of trees reached a higher degree of defoliation immediately after the first monitoring year, and the trees died after several years. Tree mortality rates were compared between years using the Standardised Precipitation Evaporation Index (SPI) and the Standardised Precipitation Evapotranspiration Index (SPEI), the most common methods used to monitor drought. The most intensive forest decline was recorded during the period from 2013 to 2016, when the largest percentage of the total number of all trees died. According to the annual mortality rates calculated for the three observation periods (2004-2008, 2009-2013, and 2014-2018) the highest forest decline rate was recorded in the period from 2014 to 2018, with no statistically significant difference between broadleaved and coniferous tree species. As the sample of coniferous species was small, the number of sample plots should be increased in order to achieve better systematic forest condition monitoring in Serbia. The analysis of the relationship between defoliation and climatic parameters proved the correlation between them. It was noted that the forest decline in Serbia was preceded by an extremely dry period with high temperatures from 2011 to 2013, supporting the hypothesis that it was caused by drought. We therefore conclude that these unfavourable climatic conditions had serious and long-term consequences on forest ecosystems in Serbia.

Comparative safety review of current treatment options for chronic low back pain and unmet needs: a narrative review.

Introduction: The healthcare expenditures in the United States are substantial for the management of refractory, chronic low back pain (CLBP). The objective of this review is to summarize and evaluate the safety profiles of different pharmacological treatment options used in the management of CLBP.Areas covered: The authors conducted a search of randomized controlled trials (RCTs) assessing the safety profiles of different pharmacological agents used in the management of CLBP. This narrative review covered corticosteroids, opioids, antidepressants, gabapentinoids, nonsteroidal anti-inflammatory drugs, muscle relaxants, anti-nerve growth factor antibodies and topical agents, as monotherapy or in combination.Expert opinion: The risk-benefit ratio of a particular treatment is a subject driving the ongoing development of pharmaceuticals. The most commonly reported AEs across all drug classes are of gastrointestinal nature, followed by neurological and skin-related. These AEs include nausea, dizziness, constipation, arthralgia, headache, dry mouth, pruritus, etc. The majority of the AEs reported are not life-threatening, although they may lower patients' quality of life, thus, affecting their compliance. One of the biggest limitations of our review stems from the paucity of safety assessments in published RCTs. Advances in our understanding of the neurobiology of pain will promote development of new therapeutic strategies.

Can Implementation of Genetics and Pharmacogenomics Improve Treatment of Chronic Low Back Pain?

Etiology of back pain is multifactorial and not completely understood, and for the majority of people who suffer from chronic low back pain (cLBP), the precise cause cannot be determined. We know that back pain is somewhat heritable, chronic pain more so than acute. The aim of this review is to compile the genes identified by numerous genetic association studies of chronic pain conditions, focusing on cLBP specifically. Higher-order neurologic processes involved in pain maintenance and generation may explain genetic contributions and functional predisposition to formation of cLBP that does not involve spine pathology. Several genes have been identified in genetic association studies of cLBP and roughly, these genes could be grouped into several categories, coding for: receptors, enzymes, cytokines and related molecules, and transcription factors. Treatment of cLBP should be multimodal. In this review, we discuss how an individual's genotype could affect their response to therapy, as well as how genetic polymorphisms in CYP450 and other enzymes are crucial for affecting the metabolic profile of drugs used for the treatment of cLBP. Implementation of gene-focused pharmacotherapy has the potential to deliver select, more efficacious drugs and avoid unnecessary, polypharmacy-related adverse events in many painful conditions, including cLBP.

The Role of the Kynurenine Signaling Pathway in Different Chronic Pain Conditions and Potential Use of Therapeutic Agents.

Tryptophan (TRP) is an essential, aromatic amino acid catabolized by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) enzymes into kynurenine. The IDO enzyme is expressed in peripheral tissues and the central nervous system. Another enzyme of interest in the kynurenine signaling pathway is kynurenine 3-monooxygenase (KMO). The purpose of this review is to discuss the role of TRP and the kynurenine signaling pathway in different chronic pain patients. The IDO-1, IDO-2, and KMO enzymes and the kynurenine metabolite have been shown to be involved in the pathogenesis of neuropathic pain and other painful conditions (migraine, cluster headache, etc.) as well as depressive behavior. We highlighted the analgesic potential of novel agents targeting the enzymes of the kynurenine signaling pathway to explore their efficacy in both future basic science and transitional studies. Upcoming studies conducted on animal models will need to take into consideration the differences in TRP metabolism between human and non-human species. Since chronic painful conditions and depression have common pathophysiological patterns, and the kynurenine signaling pathway is involved in both of them, future clinical studies should aim to have outcomes targeting not only pain, but also functionality, mood changes, and quality of life.

Oral pharmacotherapeutics for the management of peripheral neuropathic pain conditions - a review of clinical trials.

INTRODUCTION: Epidemiological studies have shown that 6.9-10% of people suffer from neuropathic pain, a complex painful condition which is often undertreated. Data regarding the effectiveness of treatment options for patients with neuropathic pain is inconsistent, and there is no single treatment option that shows cost-effectiveness across studies. AREAS COVERED: In this narrative review, the authors present the results of different prospective, randomized controlled trials, systematic reviews and meta-analyses assessing the effects of different oral medications in the management of various peripheral neuropathic pain conditions. The authors discuss the effectiveness of commonly used oral medications such as voltage-gated calcium channels antagonists, voltage-gated sodium channel antagonists, serotonin-norepinephrine reuptake inhibitors, NMDA antagonists, and medications with other mechanisms of action. EXPERT OPINION: Most of the presented medications were more effective than placebo; however, when compared to each other, none of them were significantly superior. The heterogeneity of the studies looking into different oral neuropathic conditions has been the major issue that prevents us from making stronger recommendations. There are multiple reasons including high placebo responsiveness, improperly treated underlying comorbidities (particularly anxiety and depression), and inter-patient variability. Different sensory phenotypes should also be taken into consideration when designing future clinical trials for neuropathic pain.

Do Corticosteroids Still Have a Place in the Treatment of Chronic Pain?

Corticosteroids have played a standard role in the multimodal pain management in the treatment of chronic spinal pain (cervical and lumbar) and osteoarthritis pain over the past three decades. In this review we discuss different types of injectable steroids that are mainly used for injection into the epidural space (for the treatment of radicular back and neck pain), and as intra-articular injections for different types of osteoarthritis related pain conditions. Furthermore, we discuss different approaches taken for epidural corticosteroid injections and spinal surgical rates when injections fail to resolve painful conditions, as well as the possibility of using local anesthetics alone for neuraxial injections, instead of in combination with corticosteroids. While we present some beneficial effects of newly available treatment options for low back pain and osteoarthritis pain, such as use of PRP and hyaluronic acid, corticosteroids remain important considerations in the management of these chronic pain conditions.