Investigating the Promising Anticancer Activity of Cetuximab and Fenbendazole Combination as Dual CBS and VEGFR-2 Inhibitors and Endowed with Apoptotic Potential.

In this work, the cytotoxicity of monoclonal antibody (Cetuximab, Ce) and Fenbendazole (Fen), as well as their combination therapy were tested with the MTT assay. On the other side, Ce, Fen, and a combination between them were subjected to a colchicine-tubulin binding test, which was conducted and compared to Colchicine as a reference standard. Besides, Ce, Fen, and the combination of them were tested against the VEGFR-2 target receptor, compared to Sorafenib as the standard medication. Moreover, the qRT-PCR technique was used to investigate the levels of apoptotic genes (p53 and Bax) and anti-apoptotic gene (Bcl-2) as well. Also, the effect of Ce, Fen, and the combination of them on the level of ROS was studied. Furthermore, the cell cycle analysis and Annexin V apoptosis assay were carried out for Ce, Fen, and a combination of them. In addition, the molecular docking studies were used to describe the molecular levels of interactions for both (Fen and colchicine) or (Fen and sorafenib) within the binding pockets of the colchicine binding site (CBS) and vascular endothelial growth factor-2 receptor (VEGFR-2), respectively.

The first report of triple anthelmintic resistance on a French Thoroughbred stud farm.

This study assessed the anthelmintic resistance in strongylid nematodes against commonly used anthelmintic (AH) drugs in a French galloping racehorse stud farm from March to December 2023. Faecal egg count reduction tests (FECRTs) were conducted in three different groups of Thoroughbred yearlings (a group of 6 males, a group of 13 females and a group of 8 females and 3 males) following the new World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines. The efficacy of fenbendazole was tested in two groups once during the monitoring period (in March), the efficacy of ivermectin in 3 groups twice (in March-April and in November-December) and the efficacy of pyrantel in one group once (in May-June). For each FECRT, the 90% confidence interval of the percentage faecal egg count reduction was calculated using the hybrid Frequentist/Bayesian analysis method. The resistance in strongylids was observed to fenbendazole, pyrantel and ivermectin in all the groups in which these drugs were tested. The number of animals in each group was sufficient to reach ≥80% power for the resistance test. The results highlight the first case of triple AH resistance in strongylids in France. Further studies involving more farms and equids are required to assess the prevalence of AH resistance in France and refine recommendations for owners.

Concurrent use of two dual-combination drenches containing monepantel/abamectin and oxfendazole/levamisole in sheep: effect on marker residues 21 and 28 days after administration.

AIMS: To determine the concentration, in comparison with the maximum residue limit (MRL), of anthelmintic marker residues in the target tissues (liver and fat) of sheep treated concurrently with two oral drenches, one containing monepantel and abamectin and the other oxfendazole and levamisole. METHODS: On day 0 of the study, 12 sheep (six male and six female; 8-9-months old) were dosed according to individual body weight determined the day prior. Zolvix Plus (dual-active oral drench containing 25 g/L monepantel and 2 g/L abamectin) was administered to all animals prior to administration of Scanda (dual-active oral drench containing 80 g/L levamisole hydrochloride and 45.3 g/L oxfendazole). Six sheep (three male and three female) were slaughtered 21 and 28 days after treatment and renal fat and liver samples were collected.Using validated methods, analyses for monepantel sulfone, abamectin, levamisole and oxfendazole (expressed as total fenbendazole sulfone following conversion of the combined concentrations of oxfendazole, fenbendazole and fenbendazole sulfone) were performed on liver samples while renal fat specimens were analysed for monepantel sulfone and abamectin residues only. Detected concentrations were compared to the established MRL in sheep for each analyte determined by the Ministry for Primary Industries. RESULTS: All residues detected in samples of liver and fat collected 21 and 28 days after treatment were below the MRL for each analyte. All liver samples collected on day 21 had detectable monepantel sulfone (mean 232 (min 110, max 388) µg/kg) and oxfendazole (mean 98.7 (min 51.3, max 165) µg/kg) residues below the MRL (5,000 and 500 µg/kg, respectively). Monepantel sulfone (mean 644 (min 242, max 1,119) µg/kg; MRL 7,000 µg/kg) residues were detected in 6/6 renal fat samples. Levamisole residues were detected in 3/6 livers (mean 40.0 (min 14.3, max 78.3) µg/kg; MRL 100 µg/kg), and abamectin residues in 1/6 livers (0.795 µg/kg; MRL 25 µg/kg) and 2/6 fat samples, (mean 0.987 (min 0.514, max 1.46) µg/kg; MRL 50 µg/kg) 21 days after treatment. CONCLUSION AND CLINICAL RELEVANCE: These results suggest that concurrent administration of Zolvix Plus and Scanda to sheep is unlikely to result in an extended residue profile for any of the active ingredients, with all analytes measured being under the approved New Zealand MRL 21 days after treatment. This work was not completed in line with guidance for establishing official residue profiles, nor is it sufficient to propose a new withholding period.

Assessing the effectiveness of fenbendazole supramolecular complexes against schistosomiasis, monieziosis and parabronemosis in sheep.

Helminth infections pose a significant economic threat to livestock production, causing productivity declines and, in severe cases, mortality. Conventional anthelmintics, exemplified by fenbendazole, face challenges related to low solubility and the necessity for high doses. This study explores the potential of supramolecular complexes, created through mechanochemical modifications, to address these limitations. The study focuses on two key anthelmintics, praziquantel (PZQ) and fenbendazole (FBZ), employing mechanochemical techniques to enhance their solubility and efficacy. Solid dispersions (SD) of PZQ with polymers and dioctyl sulfosuccine sodium (DSS) and fenbendazole with licorice extract (ES) and DSS were prepared. The helminthicidal activity of these complexes was assessed through helminthological dissections of sheep infected with Schistosoma turkestanicum, moniesiasis, and parabronemosis. In the assessment of supramolecular complex of FBZ (SMCF) at doses ranging from 1.0 to 3.0 mg/kg for the active substance (AS), optimal efficacy was observed with the fenbendazole formulation containing arabinogalactan and polyvinylpyrrolidone at a 3.0 mg/kg dosage. At this concentration, the formulation demonstrated a remarkable 100% efficacy in treating spontaneous monieziosis in sheep, caused by Moniezia expansa (Rudolphi, 1810) and M. benedenii (Moniez, 1879). Furthermore, the SMCF, administered at doses of 1.0, 2.0, and 3.0 mg/kg, exhibited efficacy rates of 42.8%, 85.7%, and 100%, respectively, against the causative agent of parabronemosis (Parabronema skrjabini Rassowska, 1924). Mechanochemical modifications, yielding supramolecular complexes of PZQ and FBZ, present a breakthrough in anthelmintic development. These complexes address solubility issues and significantly reduce required doses, offering a practical solution for combating helminth infections in livestock. The study underscores the potential of supramolecular formulations for revolutionizing helminthiasis management, thereby enhancing the overall health and productivity of livestock.

Toltrazuril + fenbendazole for cattle: Pharmacokinetics and efficacy against Eimeria spp. and gastrointestinal nematodes.

The present work evaluated the pharmacokinetics and efficacy of the association of 15cmg/kg toltrazuril +5cmg/kg fenbendazole against Eimeria spp. and gastrointestinal nematodes (GINs) in calves of different regions of Brazil (Center-West, Southeast, and South). A total of seven experiments were carried out, five of which determined formulation efficacy against Eimeria spp., considering the following aspects: therapeutic, preventive, metaphylactic, and residual efficacy. Therapeutic efficacy experiments for GINs were carried out by parasitological necropsy. The toltrazuril + fenbendazole association demonstrated ≥95% efficacy against Eimeria spp. for 21 days post-treatment (DPT). When used preventively and metaphylatically, the same association demonstrated ≥97% efficacy against E. zuernii, E. ellipsoidalis, E. cylindrica, E. bovis, E. wyomingensis and E. auburnensis. Toltrazuril + fenbendazole administered seven days before challenge was 100% effective against all these Eimeria species. Results of therapeutic, preventive, metaphylactic and residual efficacies can be related to the pharmacokinetic results, especially considering toltrazuril sulfone, which was detected in animal plasma for a longer period than the parent compound. Toltrazuril + fenbendazole achieved 100% anthelminthic efficacy against the GINs Haemonchus placei (L4), Cooperia pectinata and Oesophagostomum radiatum; 99.94% against adult H. placei; and 99.98% against C. puntacta. The association of toltrazuril + fenbendazole, associated with other measures, is an important and suitable tool for the control and treatment of Eimeria spp. and GINs in young cattle.

Impaired efficacy of fenbendazole and ivermectin against intestinal nematodes in adult horses in Iran.

This study aimed to evaluate the efficacy of fenbendazole and ivermectin on strongyles and Parascaris sp. infecting adult riding horses in three regions with different climates. During 2021 and 2022 fecal specimens were randomly collected from 483 horses older than three years in 31 equestrian clubs in Hamedan (n = 217), Yazd (n = 146) and Tabriz cities (n = 120). Eggs were counted by McMaster technique, and the strongyle larvae were identified using coproculture, PCR and sequencing. Horses with strongyles and Parascaris egg counts ≥150 were enrolled in fecal egg count reduction (FECR) examination following treatment with ivermectin or fenbendazole. In total, 26.5% of examined horses were positive with at least one parasite. Infection rates varied in three cities i.e., 25.8% in Hamedan, 28.8% in Yazd, 25% in Tabriz. Fifty-seven horses had FECR measured. FECR below <90% was observed for IVM-strongyle in two horses in Tabriz, for FBZ-strongyle in two horses in Tabriz and two horses in Hamedan, for IVM-Parascaris in one horse in all three cities, and for FBZ-Parascaris in one horse in Yazd. Furthermore, FECR 90-100% was observed in IVM-Parascaris and FBZ -Parascaris groups in Tabriz. Data herein presented demonstrate different degrees of resistance of strongyles and Parascaris infecting horses in Iran against both ivermectin and fenbendazole. Since non-principled use of anthelminthics is common among horse owners, urgency of test-and-treatment strategy should be educated and implemented by policy-making organizations. Evaluating efficacy of different anthelminthics and choosing the most effective treatment in each region is suggested.

Identification and treatment of Strongyloides stercoralis infection in a Boston Terrier dog from south-eastern Australia.

Strongyloides stercoralis, the causative agent of strongyloidiasis, is a potentially zoonotic intestinal nematode endemic to northern Australia. Strongyloidiasis is typically observed in immunocompromised hosts and is characterised by gastrointestinal signs, respiratory symptoms and a failure to thrive. In immunocompromised hosts, hyperinfection syndrome and disseminated infections can prove life-threatening. A 24-month-old Boston Terrier dog was referred for investigation of chronic small and large intestinal watery hematochezic diarrhoea, emaciation and hematemesis. Small intestinal histology identified a nematode despite consecutive negative faecal flotations. A real-time polymerase chain reaction and Baermann test subsequently confirmed infection with S. stercoralis. The dog had received an oral parasiticide comprising milbemycin oxime and afoxolaner every month for the 11 months prior to this diagnosis. Despite fenbendazole being reported as successful in the treatment of canine strongyloidiasis, a course of fenbendazole failed to clear the infection. Eradication of S. stercoralis infection was confirmed after the administration of off-label ivermectin fortnightly for 12 doses. Attention should be paid to this nematode as the failure of routine copromicroscopic methods to diagnose S. stercoralis infections can result in misdiagnosis, mistreatment and progression of the disease. Off-label ivermectin may be an alternative to fenbendazole for the treatment of Strongyloides spp. infection in dogs.

Unravelling drug-drug interactions in pigs: Induction of hepatic cytochrome P450 1A (CYP1A) metabolism after the in-feed medication with the anthelmintic fenbendazole.

The anthelmintic fenbendazole (FBZ) undergoes hepatic S­oxygenation by monooxygenases belonging to the cytochrome P450 (CYP) and flavin-monooxygenase (FMO) families. The in-feed medication with FBZ induced CYP1A-dependent metabolism in pig liver. This fact may alter the metabolism of the anthelmintic itself, and of CYP1A substrates like aflatoxin B1 (AFB1). This work evaluated the effect of the in-feed administration of FBZ on CYP1A-dependent metabolism, on its own pattern of hepatic S­oxygenation, and on the metabolism of AFB1. Landrace piglets remained untreated (n = 5) or received a pre-mix of FBZ (n = 6) in feed for 9 days. Pigs were slaughtered for preparation of liver microsomes used for: CYP content determination; monitoring the CYP1A-dependent enzyme activities, 7-ethoxyresorufin O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD); measurement of FBZ (50 µM) S­oxygenation, and AFB1 (16 nM) disappearance from the incubation medium. In microsomes of FBZ-treated animals, EROD and MROD increased 19-fold (p = 0.002) and 14-fold (p = 0.003), respectively. An enhanced (3-fold, p = 0.004) participation of the CYP pathway in FBZ S­oxygenation was observed in the liver of piglets treated with the anthelmintic (210 ± 69 pmol/min.nmol CYP) compared to untreated animals (68 ± 34 pmol/min.nmol CYP). AFB1 metabolism was 93% higher (p = 0.009) in the liver of FBZ-treated compared to untreated pigs. Positive and significant (p < 0.05) correlations were observed between CYP1A-dependent enzyme activities and FBZ or AFB1 metabolism. The sustained administration of FBZ caused an auto-induction of the CYP1A-dependent S­oxygenation of this anthelmintic. The CYP1A induction triggered by the anthelmintic could amplify the production of AFB1 metabolites in pig liver, including the hepatotoxic AFB1-derived epoxide.+.

The Success Factors of Rest Defense in Soccer - A Mixed-Methods Approach of Expert Interviews, Tracking Data, and Machine Learning.

While the tactical behavior of soccer players differs between specific phases of play (offense, defense, offensive transition, defensive transition), little is known about successful behavior of players during defensive transition (switching behavior from offense to defense). Therefore, this study aims to analyze the group tactic of rest defense (despite in ball possession, certain players safeguard quick counterattacks in case of ball loss) in defensive transition. A mixed-methods approach was used, involving both qualitative and quantitative analysis. Semi-structured expert interviews with seven professional soccer coaches were conducted to define rest defense. In the quantitative analysis, several KPIs were calculated, based on tracking and event data of 153 games of the 2020/21 German Bundesliga season, to predict the success of rest defense situations in a machine learning approach. The qualitative interviews indicated that rest defense can be defined as the positioning of the deepest defenders during ball possession to prevent an opposing counterattack after a ball loss. For instance, the rest defending players created a numerical superiority of 1.69 ± 1.00 and allowed a space control of the attacking team of 11.51 ± 9.82 [%] in the area of rest defense. The final machine learning model showed satisfactory prediction performance of the success of rest defense (Accuracy: 0.97, Precision: 0.73, f1-Score: 0.64, AUC: 0.60). Analysis of the individual KPIs revealed insights into successful behavior of players in rest defense, including controlling deep spaces and dangerous counterattackers. The study concludes regaining possession as fast as possible after a ball loss is the most important success factor in defensive transition.

[Alveolar echinococcosis in fattening pigs in a conventional housing system]. / Alveoläre Echinokokkose bei Mastschweinen in einem konventionellen Haltungssystem.

In a conventional fattening farm in southern Germany, up to 100 % of the livers of individual slaughter groups were condemned due to parasitic lesions during 2022. Intensification of antiparasitic metaphylaxis with fenbendazole to control Ascaris suum in the herd was unsuccessful. A pathomorphologic examination of 6 livers from two slaughter groups revealed oligofocal fibrotic inflammation. Histologically, chronic granulomatous hepatitis with massive involvement of eosinophilic granulocytes and central parasitic structures of a helminth were detected. Examination of the liver lesions by PCR revealed evidence of Echinococcus (E.) multilocularis. To determine the source of introduction into the herd, fecal samples were collected from semi-feral domestic cats near the feed mixer and in the corridor of the barn. Parasitologically, cestode eggs were detected in the fecal samples. Genome fragments of E. multilocularis could not be amplified by PCR. In the present case, domestic cats were suspected as the most likely source of entry into the herd. Control measures were aimed at preventing parasite entry by therapy of the domestic cats with antiparasitics. Differentially, no other possible pathogens could be detected by PCR and bacteriological examination.

The Fasciola hepatica egg development and hatching test (EDHT) using commercial drugs: a simple protocol for tackling anthelminthic resistance and promoting cattle productivity.

Fasciolosis is an important zoonotic disease caused by the trematode Fasciola hepatica, and it causes great losses in bovine production. The anthelmintic resistance is a major problem in the control of fasciolosis. In this study, the F. hepatica egg development and hatching test (EDHT) was used for the evaluation of the ovicidal activity of commercial drugs, commonly used for treating infected cattle, which reflects F. hepatica anthelminthic resistance in infected bovines, according to recent literature. Bile samples from F. hepatica naturally parasitized cattle were obtained from slaughterhouses in the cities of Lages and Otacílio Costa, Santa Catarina State, Brazil. The bile was washed, the eggs were recovered, quantified, and distributed in universal collectors, with a minimum of 1,000 eggs per vial. Four commercial drugs were used in this study, containing albendazole sulfoxide (ABDZ), closantel (CSTL), nitroxynil (NTXL), and triclabendazole with fenbendazole (TBZF). The drugs were diluted according to the manufacturer instructions. All drugs, and the respective control, were tested in triplicates, with the quantity of recovered eggs determining the number of drugs to be tested. The vials were incubated for 28 days at 27 °C, and the eggs were classified according to their degree of development under a stereomicroscope. In total, 121 egg samples were analyzed. Two samples were identified as resistant to TBZF. Undetermined resistance/susceptibility has been found in two isolates treated with ABDZ, one treated with NTXL and six treated with TBZF. CSTL did not present ovicidal activity and cannot be used in EDHT. This is the first time that commercial drugs were used in F. hepatica EDHT.

A fecal egg count reduction test in grazing beef steers using topical pioneer and generic eprinomectin and fenbendazole oral suspension.

Many generic anthelmintics are commercially available; however, little information exists regarding product effectiveness compared to pioneer brands. The objective of this study was to compare the effectiveness of a generic eprinomectin to the pioneer eprinomectin, as well as to fenbendazole and fenbendazole in combination with the pioneer eprinomectin in grazing beef steers via a fecal egg count reduction test. Forty naturally infected steers were allocated into five treatment groups based on ranked fecal egg counts: 1. pioneer eprinomectin (Eprinex®, topical), 2. generic eprinomectin (Eprizero®, topical), 3. fenbendazole (Safeguard® 0.5% oral suspension), 4. combination of pioneer eprinomectin topical and fenbendazole oral suspension, 5. negative control. Fecal samples were collected on days -14, 0, 14, and 29. Data were analyzed using the MIXED procedure of SAS 9.4. Neither the pioneer nor the generic eprinomectin groups reached a 90% fecal egg count reduction (FECR) throughout the study with reductions of 50% and 11% for pioneer eprinomectin and 79% and - 5% for generic eprinomectin at days 14 and 29 post-treatment, respectively. Both the fenbendazole and combination groups showed 98% and 99% FECR, respectively, at 14 days post-treatment; these reductions dropped slightly at day 29 post-treatment to 94% and 89%, respectively. Primarily Cooperia punctata, Cooperia oncophora and Ostertagia ostertagi larvae were recovered from the coprocultures across all treatment groups. Interestingly, the proportions of C. punctata and C. oncophora essentially demonstrated a post-treatment reversal in the both the fenbendazole and combination treatment groups when comparing days 0 and 29, demonstrating prepatency period differences or a fenbendazole treatment effect.

Computed tomographic and bronchoscopic diagnosis of Oslerus osleri infection in a dog.

A 16-month-old Sarplaninac Shepherd cross dog presented for a 1-month history of a productive cough that was unresponsive to an empirical 10-day course of cephalexin. Thoracic computed tomography (CT) showed multifocal, well-defined, smoothly marginated, soft tissue attenuating, minimally contrast enhancing nodular airway mural thickenings protruding into the airway lumen in the caudal trachea and principal bronchi. These nodules were also visualized on bronchoscopy, and cytology revealed parasitic larvae consistent with Oslerus osleri. The dog was treated with oral fenbendazole for 26 days. Clinical signs resolved within 3 weeks of treatment initiation and had not relapsed at 7-month follow-up.

The Occurrence of Non-Regulated Mycotoxins in Foods: A Systematic Review.

The aim of this systematic review is to provide an update on the occurrence and co-occurrence of selected non-regulated mycotoxins and provide an overview of current regulations. Fifteen non-regulated mycotoxins were found in 19 food categories worldwide. On top of that, 38 different combinations of non-regulated mycotoxins were found, with mixtures varying from binary combinations up to 12 mycotoxins. Taking into consideration the amount of evidence regarding the prevalence and co-occurrence of non-regulated mycotoxins, future steps should be taken considering continuous monitoring, scientific exchange, and generation of high-quality data. To enhance data quality, guidelines outlining the minimum quality criteria for both occurrence data and metadata are needed. By doing so, we can effectively address concerns related to the toxicity of non-regulated mycotoxins. Furthermore, obtaining more data concerning the co-occurrence of both regulated and non-regulated mycotoxins could aid in supporting multiple chemical risk assessment methodologies. Implementing these steps could bolster food safety measures, promote evidence-based regulations, and ultimately safeguard public health from the potential adverse effects of non-regulated mycotoxins.

Helminth infection in horses - a cross-sectional study from stables in Lower Silesia (Poland).

Parasitosis in horses may be uncontrolled and expose breeders and owners to serious financial losses or, possibly, to the loss of animals. Therefore, the prevention and monitoring of the development of parasitic diseases should play an important role in the breeding process. The aim of this study was to confirm the influence of factors such as age, breed, herd size, deworming program, and type of anthelmintics, on the prevalence and intensity of parasites (helminths) in domestic horses in Lower Silesia. The study was carried out between August and November of 2020. The samples of horse feces were collected from 50 different stables in the area of Lower Silesia, Poland. A total of 286 individuals from various breeds were examined. Detailed analysis revealed that the mean age of infected horses was significantly lower than in uninfected horses. The mean time since the last deworming procedure was almost twice as low in uninfected horses than in infected ones. Additionally, the deworming agent affects the prevalence of infection. The analysis was also performed for the same factors in reference to quantitative data. The mean EPG was four-fold higher in juvenile horses than in adults and three-fold higher when the horses were dewormed with the use of fenbendazole instead of ivermectin or ivermectin with praziquantel combined.

Study on thermal health and its safety management mode for the working environment.

Thermal health concerns have gained significant attention due to the heightened health risks faced by workers who are exposed to extreme thermal environments for prolonged periods. To ensure the occupational health and safety of such workers, and to enhance work efficiency, it is imperative to examine the characteristics of thermal health in the working environment. This study proposes three key elements of thermal health in the working environment, namely thermal health states, absence of heat-related illnesses, and heat adaptability, which can be used to develop a safety management framework for thermal health. By exploring the interconnections between these elements, the study summarizes their features and outlines the necessary precautions to safeguard them. The PDCA (plan/do/check/action) cycle management mode is utilized as a framework, with the three components of thermal health forming the core, to establish a safety management mode for thermal health. To ensure that employees work in a safe, healthy, comfortable, and productive environment, the assessment and control objectives of the thermal environment are regularly revised through the use of labor protection technology and thermal environment control technology. This paper presents a PDCA cycle safety management mode based on the characteristics of thermal health, which offers novel insights and approaches for assessing and managing workers' thermal health.

The change of green space well-being during rapid urbanization: A case study in Jinan, China, 2006-2018.

With the rapid advancement of urbanization, the green space well-being (GSWB) of developing countries faces drastic changes and is increasingly threatened. Green and residential spaces are the core elements of GSWB; however, we know very little about the interaction and combination of the two in terms of their effect on GSWB. This study identified the spatiotemporal features of GSWB and critically examined how patterns of residential-green combinations affect GSWB. Based on land-use data for Jinan from 2006 to 2018, and using the spatial measurement tool GeoDa, we found that both green and residential space have increased significantly in central Jinan. At the macro level, the spatial correlation between the two decreased significantly; meanwhile, at the micro level, there are obvious differences in time and geography. This led to differences in the distribution of GSWB between regions with high value and those with low value. We revealed that the development, preservation, and demolition of residential and green spaces influence changes in GSWB. The positive effects on GSWB come from (1) mountain park development policy in built-up areas, (2) theme park development policy in new urban areas, and (3) urban renewal and demolition policy. The negative effects on GSWB come from (1) issues remaining from prior extensive urban development, (2) the replacement of central areas driven by urban branding, and (3) the lack of supervision of nearby facilities for new housing development. To better understand changes in GSWB, it is necessary to consider its internal residential-green spatial collaboration and propose targeted response strategies. This can help to better safeguard the quality of human settlements in the process of urbanization in developing countries.

Key normative, legal, and policy considerations for supporting pregnant and postpartum adolescents in high HIV-burden settings: a critical analysis.

Rates of adolescent pregnancy within sub-Saharan Africa are increasing. Adolescent mothers ages 10-19 years face a distinct set of risks to their own and their children's health, compounded by many economic, social, and epidemiological challenges, such as living with HIV. In navigating this complex developmental period, many adolescent mothers face structural barriers impeding safe transitions to adulthood and motherhood. Drawing on existing literature and emerging data, we outline three normative, legal, and policy issues - violence and gender inequity, access to sexual and reproductive health services, and access to social and structural supports - which affect the health, wellbeing and development of adolescent mothers and their children. We also highlight emergent evidence about programming and policy changes that can better support adolescent mothers and their children. These key proposed responses include removing barriers to SRH and HIV service integration; ensuring implementation of return-to-school policies; and extending social protection systems to cater for adolescent mothers. Despite ongoing global crises and shifts in funding priorities, these normative, legal, and policy considerations remain critical to safeguard the health and wellbeing of adolescent mothers and their children.

Conserving avian evolutionary history can effectively safeguard future benefits for people.

Phylogenetic diversity (PD)-the evolutionary history of a set of species-is conceptually linked to the maintenance of yet-to-be-discovered benefits from biodiversity or "option value." We used global phylogenetic and utilization data for birds to test the PD option value link, under the assumption that the performance of sets of PD-maximizing species at capturing known benefits is analogous to selecting the same species at a point in human history before these benefits were realized. PD performed better than random at capturing utilized bird species across 60% of tests, with performance linked to the phylogenetic dispersion and prevalence of each utilization category. Prioritizing threatened species for conservation by the PD they encapsulate performs comparably to prioritizing by their functional distinctiveness. However, species selected by each metric show low overlap, indicating that we should conserve both components of biodiversity to effectively conserve a variety of uses. Our findings provide empirical support for the link between evolutionary history and benefits for future generations.