Unwanted Effects Research Articles

A Review on Indole-triazole Molecular Hybrids as a Leading Edge in Drug Discovery: Current Landscape and Future Perspectives.

Molecular hybridization is a rational design strategy used to create new ligands or pro-totypes by identifying and combining specific pharmacophoric subunits from the molecular struc-tures of two or more known bioactive derivatives. Molecular hybridization is a valuable technique in drug discovery, enabling the modulation of unwanted side effects and the creation of potential dual-acting drugs that combine the effects of multiple therapeutic agents. Indole-triazole conju-gates have emerged as promising candidates for new drug development. The indole and triazole moieties can be linked through various synthetic strategies, such as click chemistry or other cou-pling reactions, to generate a library of diverse compounds for biological screening. The achieva-ble structural diversity with indole-triazole conjugates offers avenues to optimize their pharmaco-kinetic and pharmacodynamic attributes, amplifying their therapeutic efficacy. Researchers have extensively tailored both indole and triazole frameworks with diverse modifications to compre-hend their impact on the drug's pharmacokinetic and pharmacodynamic characteristics. The cur-rent review article endeavours to explore and discuss various research strategies to design indole-triazole hybrids and elucidate their significance in a variety of pathological conditions. The in-sights provided herein are anticipated to be beneficial for the researchers and will likely encour-age further exploration in this field.

Safety strategies and harm reduction for methamphetamine users in the era of fentanyl contamination: A qualitative analysis

IntroductionIn the United States, methamphetamine use is increasing and the context of its use has changed, with reports of illicitly manufactured fentanyl being mixed with methamphetamine (either deliberately or inadvertently). We explore risk-mitigating actions taken by people who use drugs to protect their health when using methamphetamine in that context. MethodsWe conducted qualitative interviews with 48 adults (18+) who used methamphetamine in the past three months at two sites in Nevada, USA and two sites in New Mexico, USA. Interviews were recorded, transcribed, and analyzed using thematic analysis. ResultsRespondents described two rationales for employing harm reduction strategies. First, to prevent harm from methamphetamine containing illicit fentanyl, and second, to maintain their general wellbeing while using methamphetamine. Regarding methamphetamine containing illicit fentanyl, our findings highlight how respondents employ primary strategies like buying from trusted sources and secondary strategies such as spotting and selective use of harm reduction tools (i.e., fentanyl test strips) to reduce risks. To maintain their general wellbeing, participants reduced their use of methamphetamine as reasonably as possible, and used other substances like marijuana and alcohol alongside methamphetamine to counter the unwanted side effects of methamphetamine (i.e., hallucinations and paranoia). Use of these harm reduction strategies varied within situational and social contexts, and respondents usually developed these strategies based on their lived experiences. ConclusionOur findings uniquely demonstrate that people who use methamphetamine prioritize community driven, trust-based strategies within their social networks to mitigate risks in a fentanyl-contaminated drug environment. Additionally, our results indicate that harm reduction behaviors are influenced by multilevel risk environments, which include social, physical, economic, and political factors. Overall, these results highlight the potential for targeted interventions at the network level, which are responsive to complexities and shifts in drug market dynamics- such as illicit fentanyl in methamphetamine.

Patient perspectives on the unwanted effects of multidisciplinary pain management programmes: A qualitative study.

This study aimed to understand the impact of pain management programmes, focusing on the unwanted effects and their influence on patients' long-term use of self-management strategies. Qualitative study. Specialist musculoskeletal hospital in North London, England. Patients with chronic musculoskeletal pain that have completed a pain management programme. Multidisciplinary pain management programmes. Data were collected regarding patients' experiences and unwanted effects from the pain management programme using semi-structured interviews. Data were analysed using thematic analysis. Fourteen participant interviews were included in the analysis (median age 54 years, 12 females). Four themes were generated from the data: Benefits and burdens, Pain management programme and real life, Social support and Healthcare interventions. Unwanted effects included heightened anxiety related to negative interactions with peers, being in a new environment, worries about ability to cope with the programme, social anxiety from being in a group, the strain on families due to participants being away from home and a sense of abandonment at end of the programme. Burdens associated with implementing pain management strategies were identified, including the emotional burden of imposing their self-management on close family and competing demands with time and energy spent on self-management at the expense of work or home commitments. Pain management programmes have an important role in helping patients to learn how to self-manage chronic pain. Their unwanted effects and the treatment burdens associated with long-term self-management may be an important consideration in improving the longevity of their beneficial effects.

Importance of good hosting: reviewing the bi-directionality of the microbiome-gut-brain-axis

Gut microorganisms have been shown to significantly impact on central function and studies that have associated brain disorders with specific bacterial genera have advocated an anomalous gut microbiome as the pathophysiological basis of several psychiatric and neurological conditions. Thus, our knowledge of brain-to-gut-to microbiome communication in this bidirectional axis seems to have been overlooked. This review examines the known mechanisms of the microbiome-to-gut-to-brain axis, highlighting how brain-to-gut-to-microbiome signaling may be key to understanding the cause of disrupted gut microbial communities. We show that brain disorders can alter the function of the brain-to-gut-to-microbiome axis, which will in turn contribute to disease progression, while the microbiome-to gut-to brain direction presents as a more versatile therapeutic axis, since current psychotropic/neurosurgical interventions may have unwanted side effects that further cause disruption to the gut microbiome. A consideration of the brain-to-gut-to-microbiome axis is imperative to better understand how the microbiome-gut-brain axis overall is involved in brain illnesses, and how it may be utilized as a preventive and therapeutic tool.

Effectiveness of Segmental Thoracic Spinal Anaesthesia in Breast Surgery: An Observational Study

Background: General anaesthesia is usually performed for breast surgery but the risks and complications of general anaesthesia outweigh its benefits. For this, segmental thoracic spinal anesthesia might be an alternative to general anesthesia. Objectives: The objective of this study was to evaluate the effectiveness segmental thoracic spinal anaesthesia in breast surgery. Methods: This prospective observational study was conducted at surgery operation theatre in the Shaheed Suhrawardy Medical College and Hospital, Dhaka, Bangladesh from January 2023 to December 2023. Patients of ASA (American Society of Anesthesiologist) class I and II, ageing above 18 years, and BMI < 35 kg/m2 scheduled for breast surgery (modified radical mastectomy for carcinoma breast, lumpectomy for breast lump/gynaecomastia, and wide local excision for phylloids tumor) were included in this study. Segmental thoracic spinal anaesthesia was performed at T5-T6 space with injection 0.5% hyperbaric bupivacaine 1 ml (5mg) and fentanyl 0.5 ml (25 microgram). Perioperative hemodynamic changes, unwanted effects, time of first rescue analgesic, total opioid consumption in first 24 h, patient and surgeon satisfaction score were recorded in a data sheet. Results: Sixty patients were eligible for the study but 55 patients completed the study successfully. Modified radical mastectomy, Lumpectomy and Wide local excision were done in 42 (76%), 8 (15%) and 5 (9%) patients, respectively. The mean age of the patients was 50.78±8.98 years. There were no significant changes in haemodynamic parameters during the intraoperative period. The frequency of adverse effects were minimal. Mean time for 1st dose of analgesic was 5.8±1.8 hours and total opioid consumption was 76.77±15.7 mg in first 24 hours. Both patient (91%) and surgeon (95%) were highly satisfied with this technique. Conclusions: Segmental thoracic spinal anaesthesia provides better satisfaction and fewer complications in patients undergoing breast surgery. This regional anaesthesia technique can be used effectively for breast surgeries. J Shaheed Suhrawardy Med Coll 2022; 14(2): 47-52

Three-Dimensional Cone Beam Computed Tomography (CBCT)-Derived Soft Tissue Changes in Patients with Unilateral Cleft Lip, Alveolus, and Palate with Midfacial Deficiency after 1.5 Years of Bone-Anchored Maxillary Protraction

Three-Dimensional Cone Beam Computed Tomography (CBCT)-Derived Soft Tissue Changes in Patients with Unilateral Cleft Lip, Alveolus, and Palate with Midfacial Deficiency after 1.5 Years of Bone-Anchored Maxillary Protraction

Numerical Simulation and Modeling of Mechano–Electro–Thermal Behavior of Electrical Contact Using COMSOL Multiphysics

Electrical contacts are important circuit components with diverse industrial applications, and their failure can lead to multiple unwanted effects. Hence, the behavior of electrical contacts is a widely studied topic in the scientific literature based on various approaches, tools, and techniques. The present study proposes a new approach to numerical modeling and simulation based on the Holm contact theory, aiming to study the dependence between the electric potential and the temperature within an electrical contact. Structured in five sections, the research was conducted using COMSOL Multiphysics software and its solid-state mechanics, electric current, and heat transfer modules in order to highlight contact behavior from mechanical, electrical and thermal points of view: the von Mises stress, contact force, electric field amplitude, variation of the electrical potential along the current path, temperature gradient, and dependence of temperature along the contact elements edges were obtained by simulation, and are graphically represented. The results show that the temperature increase follows a parabolic curve, and that for values higher than 4 mV of voltage drop, the temperature of the contact increases to 79.25 degrees (and up to 123.81 degrees for 5 mV) over the ambient temperature, thus the integrity of insulation can be compromised. These values are close (10–12%) to the analytically calculated ones, and also in line with research assessed in the literature review.

Drugs as organizers of cell populations

The aim of the review is to draw attention to the multifaceted biological action of medications, especially their infl uence on direct intercellular interactions. The data are summarized on the fact that common medications such as dopamine, glutamic acid, melatonin, phenylephrine-containing agents can, depending on the stimulated receptors, both organize and disorganize intercellular connections. The action can be predicted considering information on agonism or antagonism of receptor eff ects on intracellular calcium or cAMP. Information is provided on the possibility of mitigating unwanted eff ects. The data on the prospects of using gangliosides in therapy are summarized.

Cell selective BCL-2 inhibition enabled by lipid nanoparticles alleviates lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with a high mortality rate due to limited treatment options. Current therapies cannot effectively reverse the damage caused by IPF. Research suggests that promoting programmed cell death (apoptosis) in myofibroblasts, the key cells driving fibrosis, could be a promising strategy. However, inducing apoptosis in healthy cells like epithelial and endothelial cells can cause unwanted side effects. This project addresses this challenge by developing a targeted approach to induce apoptosis specifically in myofibroblasts. We designed liposomes (LPS) decorated with peptides that recognize VCAM-1, a protein highly expressed on myofibroblasts in fibrotic lungs. These VCAM1-targeted LPS encapsulate Venetoclax (VNT), a small molecule drug that inhibits BCL-2, an anti-apoptotic protein. By delivering VNT directly to myofibroblasts, we hypothesize that VCAM1-VNT-LPS can selectively induce apoptosis in these cells, leading to reduced fibrosis and improved lung function. We successfully characterized VCAM1-VNT-LPS for size, surface charge, and drug loading efficiency. Additionally, we evaluated their stability over three months at different temperatures. In vitro and in vivo studies using a bleomycin-induced mouse model of lung fibrosis demonstrated the therapeutic potential of VCAM1-VNT-LPS. These studies showed a reduction in fibrosis-associated proteins (collagen, α-SMA, VCAM1) and BCL-2, while simultaneously increasing apoptosis in myofibroblasts. These findings suggest that VCAM1-targeted delivery of BCL-2 inhibitors using liposomes presents a promising and potentially selective therapeutic approach for IPF.

“All employees are equal … but some are more equal than others”. Role identity and nonfamily member discrimination in family SMEs

PurposeThis paper aims to investigate if, under which conditions, and with which consequences, nonfamily members have the perception of being discriminated against as a consequence of nepotism and adverse selection practices. This research also aims to investigate whether the carried-out role influences the perception of being discriminated against among nonfamily member employees.Design/methodology/approachA quantitative approach was carried out by adopting a structural equation model (SEM) analysis. The survey investigated a sample of Italian family SMEs (participating companies N = 186, total questionnaires collected N = 838).FindingsDrawing on the multiple identities theory, findings show that role salience (RS) effectively contributes to reducing the unwanted effects of perceived discrimination (PD) among nonfamily member employees. In doing so, this study deepens the knowledge of nonfamily member employment conditions and their consequences on strategic outcomes such as organizational commitment (OC), organizational justice (OJ) and intention to quit (ITQ).Research limitations/implicationsBy adopting a self-categorization approach, this study also advances current theoretical literature, as this methodological lens could help scholars further understand diversity in family business.Practical implicationsThis study suggests it would be advisable to implement human resource management practices based on job rotation to promote cohesion and reduce perceived distances.Social implicationsSMEs are the most widespread type of firm in the world; as a consequence, avoiding PD among nonfamily member employees has general ethical relevance.Originality/valueThis study expands current literature by showing that RS plays an important role in determining levels of PD. This study also advances current literature by focusing on the impact of multiple identities on fairness and commitment at individual and group levels of analysis of family businesses.

Amelioration of Dextran Sodium Sulfate-Induced Colitis in Mice through Oral Administration of Palmitoylethanolamide

Inflammatory bowel disease (IBD) is a group of chronic disorders characterized by pain, ulceration, and the inflammation of the gastrointestinal tract (GIT) and categorized into two major subtypes: ulcerative colitis (UC) and Crohn’s disease. The inflammation in UC is typically restricted to the mucosal surface, beginning in the rectum and extending through the entire colon. UC patients typically show increased levels of pro-inflammatory cytokines, leading to intestinal epithelial apoptosis and mucosal inflammation, which impair barrier integrity. Chronic inflammation is associated with the rapid recruitment and inappropriate retention of leukocytes at the site of inflammation, further amplifying the inflammation. While UC can be managed using a number of treatments, these drugs are expensive and cause unwanted side effects. Therefore, a safe and effective treatment for UC patients is needed. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide and an analog of the endocannabinoid anandamine. PEA administration has been found to normalize intestinal GIT motility and reduce injury in rodents and humans. In the current study, we examined the efficacy of PEA encapsulated in phytosomes following oral administration in experimental ulcerative colitis. Here, we showed that PEA at a human-equivalent dose of 123 mg/kg (OD or BID) attenuated DSS-induced experimental colitis as represented by the reduction in clinical signs of colitis, reduction in gross mucosal injury, and suppression of leukocyte recruitment at inflamed venules. These findings add to the growing body of data demonstrating the beneficial effects of PEA to control the acute phase of intestinal inflammation occurring during UC.

Activity of pyridyl-pyrazolone derivatives against Trypanosoma cruzi

New affordable drugs are needed for the treatment of infection with the protozoan parasite Trypanosoma cruzi responsible for the Chagas disease (CD). Only two old drugs are currently available, nifurtimox and benznidazole (Bz) but they exhibit unwanted side effects and display a weak activity in the late chronic phase of the disease. In this context, we evaluated the activity of a series of aryl-pyrazolone derivatives against T cruzi, using both bloodstream trypomastigote and intracellular amastigote forms of the parasite. The test compounds originate from a series of anticancer agents targeting the immune checkpoint ligand PD-L1 and bear an analogy with known anti-trypanosomal pyrazolones. A first group of 6 phenyl-pyrazolones was tested, revealing the activity of a single pyridyl-pyrazolone derivative. Then a second group of 8 compounds with a common pyridyl-pyrazolone core was evaluated. The in vitro testing process led to the identification of two non-cytotoxic and highly potent molecules against the intracellular form of T. cruzi, with an activity comparable to Bz. Moreover, one compound revealed an activity largely superior to that of Bz against bloodstream trypomastigotes, while being non-cytotoxic (selectivity index >1000). Unfortunately, the compound showed little activity in vivo, most likely due to its very limited plasma stability. However, the study opens novel perspectives for the design of new anti-trypanosomal products and the mechanism of action of the compounds is discussed.

Reactivities of acrylamide warheads toward cysteine targets: a QM/ML approach to covalent inhibitor design.

Covalent inhibition offers many advantages over non-covalent inhibition, but covalent warhead reactivity must be carefully balanced to maintain potency while avoiding unwanted side effects. While warhead reactivities are commonly measured with assays, a computational model to predict warhead reactivities could be useful for several aspects of the covalent inhibitor design process. Studies have shown correlations between covalent warhead reactivities and quantum mechanic (QM) properties that describe important aspects of the covalent reaction mechanism. However, the models from these studies are often linear regression equations and can have limitations associated with their usage. Applications of machine learning (ML) models to predict covalent warhead reactivities with QM descriptors are not extensively seen in the literature. This study uses QM descriptors, calculated at different levels of theory, to train ML models to predict reactivities of covalent acrylamide warheads. The QM/ML models are compared with linear regression models built upon the same QM descriptors and with ML models trained on structure-based features like Morgan fingerprints and RDKit descriptors. Experiments show that the QM/ML models outperform the linear regression models and the structure-based ML models, and literature test sets demonstrate the power of the QM/ML models to predict reactivities of unseen acrylamide warhead scaffolds. Ultimately, these QM/ML models are effective, computationally feasible tools that can expedite the design of new covalent inhibitors.

Investigating the safety and feasibility of osteopathic manipulative medicine in hospitalized children and adolescent young adults with cancer.

Children and adolescents young adults (AYAs) undergoing treatment for oncologic diagnoses are frequently hospitalized and experience unwanted therapy-induced side effects that diminish quality of life. Osteopathic manipulative treatment (OMT) is a medical intervention that utilizes manual techniques to diagnose and treat body structures. Few studies have investigated the implementation of OMT in the pediatric oncology outpatient setting. To date, no studies have investigated the safety and feasibility of OMT in the pediatric oncology inpatient setting. The objective of this study is to investigate the safety and feasibility of OMT in the pediatric oncology inpatient setting. This is a prospective, single-institution pilot study evaluating children and AYAs aged≥2 years to≤30 years with a diagnosis of cancer hospitalized at Riley Hospital for Children (RH) from September 2022 to July 2023. Approval was obtained from the Indiana University Institutional Review Board (IRB). Patients were evaluated daily with a history and physical examination as part of routine inpatient management. Patients who reported chemotherapy side effects commonly encountered and managed in the inpatient setting, such as pain, headache, neuropathy, constipation, or nausea, were offered OMT. Patients provided written informed consent/assent prior to receiving OMT. OMT was provided by trained osteopathic medical students under the supervision of a board-certified osteopathic physician and included techniques commonly taught in first- and second-year osteopathic medical school curricula. Safety was assessed by a validated pain (FACES) scale immediately pre/post-OMT and by adverse event grading per Common Terminology Criteria for Adverse Events (CTCAE) 24 h post-OMT. All data were summarized utilizing descriptive statistics. A total of 11 patients were screened for eligibility. All patients met the eligibility criteria and were enrolled in the study. The majority of patients were male (n=7, 63.6 %) with a median age of 18.2 years at time of enrollment (range, 10.2-29.8 years). Patients had a variety of hematologic malignancies including B-cell acute lymphoblastic leukemia (ALL) (n=5, 45.5 %), T-cell ALL (n=1, 9.1 %), acute myeloid leukemia (AML) (n=2, 18.2 %), non-Hodgkin's lymphoma (n=2, 18.2 %), and Hodgkin's lymphoma (n=1, 9.1 %). All patients were actively undergoing cancer-directed therapy at the time of enrollment. There were 40 unique reasons for OMT reported and treated across 37 encounters, including musculoskeletal pain (n=23, 57.5 %), edema (n=7, 17.5 %), headache (n=5, 12.5 %), peripheral neuropathy (n=2, 5.0 %), constipation (n=2, 5.0 %), and epigastric pain not otherwise specified (n=1, 2.5 %). Validated FACES pain scores were reported in 27 encounters. Of the 10 encounters for which FACES pain scores were not reported, 8 encounters addressed lower extremity edema, 1 encounter addressed peripheral neuropathy, and 1 encounter addressed constipation. The total time of OMT was documented for 33 of the 37 encounters and averaged 9.8 min (range, 3-20 min). Hospitalized children and AYAs with cancer received OMT safely with decreased pain in their reported somatic dysfunction(s). These findings support further investigation into the safety, feasibility, and efficacy of implementing OMT in the pediatric oncology inpatient setting and to a broader inpatient pediatric oncology population.

A Novel Intrauterine Device for the Spatio-Temporal Release of Norethindrone Acetate as a Counter-Estrogenic Intervention in the Genitourinary Syndrome of Menopause

The genitourinary syndrome of menopause (GSM) is a widely occurring condition affecting millions of women worldwide. The current treatment of GSM involves the use of orally or vaginally administered estrogens, often with the risk of endometrial hyperplasia. The utilization of progestogens offers a means to counteract the effects of estrogen on the endometrial tissue, decreasing unwanted side effects and improving therapeutic outcomes. In this study, a norethindrone acetate (NETA)-loaded, hollow, cylindrical, and sustained release platform has been designed, fabricated, and optimized for implantation in the uterine cavity as a counter-estrogenic intervention in the treatment of GSM. The developed system, which comprises ethyl cellulose (EC) and polycaprolactone (PCL), has been statistically optimized using a two-factor, two-level factorial design, with the mechanical properties, degradation, swelling, and in vitro drug release of NETA from the device evaluated. The morphological characteristics of the platform were further investigated through scanning electron microscopy in addition to cytocompatibility studies using NIH/3T3 cells. Results from the statistical design highlighted the platform with the highest NETA load and the EC-to-PCL ratio that exhibited favorable release and weight loss profiles. The drug release data for the optimal formulation were best fitted with the Peppas–Sahlin model, implicating both diffusion and polymer relaxation in the release mechanism, with cell viability results noting that the prepared platform demonstrated favorable cytocompatibility. The significant findings of this study firmly establish the developed platform as a promising candidate for the sustained release of NETA within the uterine cavity. This functionality serves as a counter-estrogenic intervention in the treatment of GSM, with the platform holding potential for further advanced biomedical applications.

Biological degradation of organic micropollutants in GAC filters–temporal development and spatial variations

The capacity for organic micropollutant removal in granular activated carbon (GAC) filters for wastewater treatment changes over time. These changes are in general attributed to changes in adsorption, but may in some cases also be affected by biological degradation. Knowledge on the degradation of organic micropollutants, however, is scarce. In this work, the degradation of micropollutants in several full-scale GAC and sand filters was investigated through incubation experiments over a period of three years, using 14C-labeled organic micropollutants with different susceptibilities to biological degradation (ibuprofen, diclofenac, and carbamazepine), with parallel 16S rRNA gene sequencing. The results showed that the degradation of diclofenac and ibuprofen in GAC filters increased with increasing numbers of bed volumes when free oxygen was available in the filter, while variations over filter depth were limited. Despite relatively large differences in bacterial composition between filters, a degradation of diclofenac was consistently observed for the GAC filters that had been operated with high influent oxygen concentration (DO >8 mg/L). The results of this comprehensive experimental work provide an increased understanding of the interactions between microbial composition, filter material, and oxygen availability in the biological degradation of organic micropollutants in GAC filters.

A Simple Artificial Neural Model to Predict Dambovita River Temperature Affected by Urban Heat Islands in Bucharest City

Water bodies can offer local microclimates that have the potential to attenuate the effects of urban heat islands by reducing local temperature. This capability is shaded when the river is channelized. In such cases, the river temperature rises during hot periods, leading to negative impacts on the water quality. The main aim of this paper is to develop a local simple model to predict the temperature of the Dâmbovița River at its exit from Bucharest City, the capital of Romania. The location is chosen based on the historical critical impacts, in terms of extreme heatwaves that took place during hot summers, as well as future possible risks due to climate change. The water temperature prediction model is based on an artificial neural network that uses the Levenberg–Marquardt algorithm, due to its stability and rapid convergence capabilities. The model forecasts, with an accuracy of ±1 °C, the water temperature in an ungauged, downstream location, as a function of measured air and upstream water temperatures. The proposed model represents a first attempt to provide water managers in Bucharest City with a useful tool that will allow them to take timely measures to counteract the unwanted effects that can be generated by high water temperatures.

Rituximab versus tacrolimus as corticosteroid-sparing therapy for children with steroid-dependent nephrotic syndrome: A systematic review and meta-analysis of randomized and nonrandomized controlled trials

ABSTRACT Objectives: Prolonged use of corticosteroids induced complicated course in children with steroid-dependent nephrotic syndrome (SDNS), and the use of tacrolimus, a first-line alternative calcineurin inhibitor (CNI) agent was related to some unwanted adverse effects. Rituximab, a second alternative treatment has been proven to reliably reduce the number of relapses within 12 months with minimal adverse effects. Materials and Methods: Our review follows Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. All the databases were derived from MEDLINE, Proquest, EBSCOhost, Wiley, and Google Scholar within the past 11 years. The risk of bias was evaluated using the Revised Cochrane Risk of Bias Tool for Randomized Trials (RoB 2) and Risk of Bias in Non-Randomized Studies of Interventions. Meta-analysis used Review Manager (version 5.4) with a random effect model to obtain a pooled mean difference (MD) and odds ratio with 95% confidence intervals (CIs). Results: Four studies were included based on our eligibility criteria, and only three were included in the quantitative analysis. Three studies had low and one study had a moderate risk of bias. Pooled data results indicated that Rituximab was superior to tacrolimus in reducing the number of patients with 1–2 relapses (MD = 0.44, [95% CI: 0.21–0.91]) and had higher eGFR values (MD = 6.67; [CI − 2.92–10.61]). However, Rituximab showed insignificant superiority compared to tacrolimus in reducing the number of patients with 3 relapses, sustained remission, cumulative steroid use, serum cholesterol, and serum albumin concentrations. Conclusion: Rituximab exhibits more advantages in treating SDNS compared to tacrolimus, although the treatment options are highly individualized. Both regimens must also be weighed against their potential side effects to achieve a better overall health status.

Use of agricultural fields by Natterjack toads: Implications for pesticide exposure

Land sharing conservation strategies might not work if wildlife is exposed to plant protection products. Plant protection products are used to protect crops against harmful organisms yet they can also have unwanted side effects on non-target organisms. Amphibians are one group of non-target organisms for which there is evidence that plant protection products can have negative effects on individuals and populations. Despite much research on amphibian ecotoxicology, not much is known about the exposure of amphibians to plant protection products in agricultural landscapes. Here, we study habitat use and movement behaviour of an endangered amphibian, the Natterjack toad Epidalea calamita, in two study areas in Switzerland. We placed arrays of artificial cover boards in agricultural fields and adjacent non-agricultural habitats and used a photographic mark-recapture approach to track individual toads, both adults and juveniles, during and after the reproductive season in the terrestrial habitat. We used multistate and spatial mark-recapture models to analyse the data. Toads used the agricultural fields during spring and summer and set up their home ranges within the fields but there was a great turnover of individuals. Toad densities were higher in agricultural fields than other habitat types, including a nature reserve suitable for the species. Toads preferred open soils and avoided grassy meadows typical of agricultural set-asides, suggesting that the conservation of the species in agricultural landscapes requires new types of biodiversity promotion areas. The results of the study show that toads use agricultural fields during most of the growing season and are thus likely to be exposed to plant protection products.

Use of Minimal Amounts of Hyaluronidase in the Ultrasound-Guided Treatment of Acute Vascular Occlusion by Hyaluronic Acid: A Preliminary Report

Abstract Background Complications from hyaluronic acid fillers are increasingly frequent, given the very high number of treatments performed every day worldwide. They are routinely treated with high doses of hyaluronidase, which can cause significant local and general unwanted effects. Objectives aim of our work is to demonstrate that when the origin of the complication is precisely identified and treated under ultrasound guidance, few hyaluronidase units are enough to treat it effectively. Methods Five young female patients came to our observation for vascular lesions from injection of HA fillers performed in the immediately preceding days, in 4 cases, and a few weeks earlier in the fifth case. All lesions were accurately identified by ultrasound and treated with hyaluronidase. Results the four promptly treated patients, fully recovered with a hyaluronidase dose of 87 ± 44 IU (range 30-150 IU). The fifth patient, treated later, markedly improved regarding clinical picture and symptoms. No early or late side effects have been reported from this hyaluronidase dosage. Conclusions Our data confirm that if the lesion at the origin of the skin damage is precisely localized with ultrasound examination and treated under ultrasound guidance, a few units of hyaluronidase, injected directly into the hyaluronic acid accumulation, effectively resolve the skin damage. At the doses we used, which were much lower than those usually recommended, hyaluronidase proved to be not only effective but also free of any side effects.