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Abstract Background Although regular health screening is recommended, long‐term follow‐up data in healthy aged cats are lacking. Objectives Determine the most common conditions in a large group of apparently healthy older cats and which diseases are manifested within 2 years in cats confirmed to be healthy based on extensive health screening. Animals Client‐owned cats. Methods Prospective study. Thorough history, physical examination, blood tests, and urinalysis were performed in 259 apparently healthy mature adult (7‐10 years) and senior (>10 years) cats. Semi‐annual follow‐up examinations were performed in 201 confirmed healthy cats. Results At baseline, 21% of apparently healthy cats were not considered healthy but were diagnosed with International Renal Interest Society (IRIS) ≥ stage 2 chronic kidney disease (CKD; 7.7%) or hyperthyroidism (4.6%), among other disorders. Disease occurred significantly more frequently in senior cats compared with mature adult cats. In addition, 40% cats were overweight, 35% had moderate to severe dental disease, and 22% had abnormal cardiac auscultation findings. Within 2 years, 28% of mature adult and 54% of senior cats that were confirmed healthy at inclusion developed new diseases, most commonly IRIS ≥ stage 2 CKD (cumulative incidence, 13.4%), hyperthyroidism (8.5%), chronic enteropathy, hepatopathy or pancreatitis (7.5%), or neoplasia (7%). Conclusions and Clinical Importance The high prevalence and 2‐year incidence of physical examination abnormalities and systemic diseases in apparently healthy older cats argue for regular health screening in cats ≥7 years of age. Although more common in senior cats, occult disease also occurs in mature adult cats, and owners should be informed accordingly.

Abstract Background Basal cell carcinoma (BCC) is the most common form of skin cancer, typically developing in sun‐exposed areas such as the face. Surgery is the treatment of choice, with a overall good prognosis. However, some scars can be unsightly or bothersome, and some tumours are too large or badly located to be eligible for surgery. Plasmonic photothermal therapy is presented here as an alternative treatment. Our team has developed green gold nanoparticles that have demonstrated their efficacy in inducing hyperthermia in the tumour‐microenvironment when combined with near‐infrared laser (NIR laser). Objectives The aim of this study is to demonstrate the effectiveness of gold nanoparticles combined with laser treatment against BCC. Methods In vitro, BCC cells were exposed to gold nanoparticles, both with and without laser treatment, to study the effects of this therapy on skin cells. Subsequently, mice bearing BCC were treated with photothermal therapy to assess tumour growth. Results Gold nanoparticles were found to be nontoxic to the cell line, and photothermal therapy induced apoptosis. In vivo studies showed complete regression of tumours without unsightly scarring and no recurrence after 40 days. Conclusions Plasmonic photothermal therapy using gold nanoparticles proved its efficacy in the destruction of BCC.

Abstract Background The diagnosis of pyelonephritis in cats is challenging and development of a noninvasive and accurate biomarker is needed. Hypotheses Serum amyloid A (SAA) is increased in cats with pyelonephritis, but not in cats with other urinary tract diseases. Animals A cohort of 125 cats (149 observations). Methods This was a prospective study. Group 1 included cats with a diagnosis of pyelonephritis either confirmed by bacterial culture of pelvic urine (Group 1a) or presumed (1b). Group 2 included cats for which pyelonephritis was ruled out (with certainty: Group 2a or judged unlikely: Group 2b). SAA concentration was compared between groups, and accuracy of SAA for the diagnosis of pyelonephritis was calculated using a Receiver Operating Characteristic (ROC) curve analysis. Results Median SAA concentration was significantly higher in Group 1a (86.8 mg/L [73.3; 161.5]; n = 8) than in Group 2a (4 mg/L [1.8; 5.6], n = 19; P

Abstract Background In 2018, the European Medicines Agency authorized adjuvant therapy for patients with resected stage III melanoma. Objectives The objective of the present study (performed in France) was to assess dermatologists' and oncologists' opinions and prescribing habits in this context. Methods From 28 May to 8 June 2021, we performed an online survey of members of the French Groupe de Cancérologie Cutanée (GCC) skin cancer interest group. Results Thirty‐eight practitioners replied to the survey. For BRAF‐mutant melanoma, 58% of the practitioners favoured immunotherapy (IT). If they themselves were to suffer from melanoma with a BRAFV600 mutation, 65% would choose IT for stage IIIB disease, and 72% would choose IT for stage IIID disease. For stage IIIA melanoma with a positive sentinel lymphatic node (SLN) biopsy

Abstract Background Laboratory results are influenced by presence and severity of disease, as well as preanalytical factors, analytical variation, and biological variation. Biological variation data for urinary protein: creatinine ratio (UPC) and urine specific gravity (USG) in cats are lacking. Objectives Determine the biological variation of UPC and USG in cats. Animals Eighty healthy client‐owned cats. Methods Prospective study. Urine was collected on days 0, 14, and 56 from all 80 cats to investigate the persistence of borderline or overt proteinuria or suboptimal urine concentration. In 15 of these cats, urine was collected weekly from day 0 to 42 to calculate the index of individuality (II) and reference change value (RCV), and on days 56 and 57 to evaluate day‐to‐day variability of UPC and USG. Results Borderline or overt proteinuria (UPC ≥0.2) was present in 18/80 (23%) cats at baseline and persisted on 3 occasions in 2 months in 8/18 (44%) cats. Urine concentration was suboptimal at inclusion (USG 82% increase in UPC in a healthy cat is not solely attributable to physiological and analytical variation. For USG, a decrease of >36% is considered clinically relevant.

Abstract Background Stability of serum symmetric dimethylarginine (sSDMA) during short‐ and long‐term storage has not been assessed for the immunoassay of the Point‐of‐Care IDEXX Catalyst DX (POC) analyzer and the Enzyme Multiplied Immunoassay Technique of IDEXX commercial laboratory (CL). Also, the agreement between both analyzers is questioned. Objectives To determine (a) the effect of storage time and temperature on sSDMA measured by POC and CL; (b) the agreement between sSDMA measured by POC and CL; and (c) the imprecision of the POC. Animals Serum of cats (n = 17) and dogs (n = 18) with a range of SDMA concentrations (6 to >100 μg/dL). Methods Based on an equivalence trial with predefined equivalence range (−3.0 to +3.0 μg/dL) and using T0 as baseline, stability was evaluated after 24 hours at 22°C and 4°C (POC); after 7 days at 4°C (POC and CL) and after 10 and 24 months at −24°C and −80°C (CL). Bland‐Altman plots enabled method comparison. Imprecision of the POC was assessed by duplicate sSDMA measurements at T0. Results The POC analyzer produced equivalent sSDMA measurements if samples were stored for 24 hours at 4°C (95% confidence interval [CI]: −2.5‐2.0 μg/dL), but not when stored for 24 hours at room temperature (RT; 95% CI: −4.1 to 0.5 μg/dL) or after 7 days at 4°C (95% CI: −3.6‐1.0 μg/dL). The CL analyzer was less affected by preanalytical variation with clinically similar results obtained when samples were stored for 7 days at 4°C (95% CI: −2.2 to 2.4 μg/dL) and for at least 24 months at −24°C (95% CI: −1.7 to 2.9 μg/dL) and −80°C (95% CI: −1.5 to 3 μg/dL). A relevant mean difference of −2.3 μg/dL between both analyzers was found. Duplicate POC measurements were equivalent (95% CI: −2.6 to 2.0 μg/dL). Conclusions Delayed analysis may significantly change sSDMA depending on storage and measurement conditions. Interchangeable use of assays should be done with caution because analytical variation could be interpreted as clinically relevant change.

Abstract Background Urinalysis is necessary for the diagnostic evaluation of chronic kidney disease in cats. Performing cystocentesis is not always feasible, but data comparing urine obtained by cystocentesis in the clinic with voided samples collected at home are lacking in cats. Objectives To compare urinary protein:creatinine ratio (UPC) and urine specific gravity (USG) and to detect clinically relevant changes in proteinuria substage or urine concentration between urine collected at home and in‐clinic by cystocentesis in cats. Animals Ninety‐two healthy and diseased client‐owned cats. Methods Prospective study. Owners collected voided urine at home and within 1 to 15 hours, cystocentesis was performed in the clinic. Results In a subset of motivated owners, 55% succeeded in collecting urine at home. Overall, UPC was higher (mean ±SD difference = 0.09 ±0.22; P 0.4) was present in paired urine samples from 28% of cats. In 18% of cats, urine concentrating ability (USG

Abstract Background Urinary protein:creatinine ratio (UPC) results affect the diagnosis, prognosis, and therapy of chronic kidney disease in cats. Objectives To investigate the interlaboratory and intralaboratory variability and the effect of storage on UPC and International Renal Interest Society (IRIS) proteinuria substaging in cats. Animals Healthy and diseased client‐owned cats. Methods Prospective study. Urine of 60 cats was randomly sent to 4 (of 9) participating laboratories (to assess interlaboratory variability) and per cat, 2 laboratories each received 2 aliquots (to determine intralaboratory variability). Samples of 23 cats were analyzed in the same laboratory the day of collection, after preservation at 22°C for 1 day and at 4°C during 1‐7 days (short‐term storage) and at −24°C and −80°C for 6‐12 months (long‐term storage). Storage conditions were compared by equivalence testing. Results UPCs showed good interclass correlation (ICC‐inter, 0.90) and excellent intraclass correlation (ICC‐intra, 0.99). However, in 30/60 (50%) cats at least 1 of 4 laboratories assigned a different IRIS proteinuria substage. Urinary protein:creatinine ratio remained stable with short‐term storage, but not after 6 months storage at −24°C and after 12 months storage at −24°C or −80°C. Long‐term storage caused a change in IRIS proteinuria substage in 27% of cats, whereas a shift occurred only in 4% of cats during short‐term storage. Conclusions and Clinical Importance Laboratory choice for UPC measurement can result in different IRIS substaging for the same cat, whereas urine storage at room temperature for 1 day or in the refrigerator for up to 7 days does not clinically affect UPC.

Abstract Background Treatment of nasal tumors in dogs is associated with high morbidity and reliable prognostic factors are lacking. Dynamic contrast‐enhanced computed tomography (DCECT) can be used to assess tumor perfusion. Objectives To assess perfusion parameters of nasal tumors (correlating with tumor type) before and during radiotherapy (RT) and find potential correlation with survival. Animals Twenty‐four client‐owned dogs with nasal tumors, including 16 epithelial tumors and 8 sarcomas. Methods Prospective cross‐sectional study. All dogs had baseline DCECT to assess fractional vascular volume (BV), blood flow (BF), and transit time (TT). Thirteen dogs had repeat DCECT after 12 Gy of megavoltage RT. Survival times were calculated. Results Median BV was 17.83 mL/100 g (range, 3.63‐66.02), median BF was 122.63 mL/100 g/minute (range, 23.65‐279.99), and median TT was 8.91 seconds (range, 4.57‐14.23). Sarcomas had a significantly lower BF than adenocarcinomas (P = .002), carcinomas (P = .01), and other carcinomas (P = .001), and significantly lower BV than adenocarcinomas (P = .03) and other carcinomas (P = .004). Significant associations were found between epithelial tumors and sarcoma for change in tumor volume (P = .01), width (P = .004), and length (P = .02) in that epithelial tumors decreased in volume whereas sarcomas increased in volume. Perfusion parameters were not correlated with survival. Conclusions and Clinical Importance Nasal sarcomas have lower BV and BF than nasal carcinomas, and sarcomas have a lower size reduction than carcinomas early on during RT. Baseline results and changes in perfusion parameters may not be correlated with survival.

Abstract Background Urinary liver‐type fatty acid‐binding protein (uL‐FABP) is a promising biomarker to detect early chronic kidney disease (CKD) in cats. Few healthy cats show increased uL‐FABP for unknown reasons. Objectives The objective of this study was to evaluate uL‐FABP in a large healthy elderly cat population comparing cats with and without International Renal Interest Society (IRIS) stage 1 CKD and with and without borderline proteinuria. Methods This was a cross‐sectional study. One hundred ninety‐six clinically healthy client‐owned cats of ≥7 years old were subdivided based on two criteria: (1) having either IRIS stage 1 CKD or no evidence of CKD and (2) having borderline proteinuria or no proteinuria. Urinary L‐FABP was measured using a validated commercially available feline L‐FABP ELISA. Results Overall, uL‐FABP was detectable in 6/196 (3%) healthy elderly cats. For the first subdivision, nine (5%) cats had IRIS stage 1 CKD, 184 cats had no evidence CKD and three cats were excluded. All cats with IRIS stage 1 CKD had uL‐FABP concentrations below the detection limit, whereas 6/184 (3%) cats without IRIS stage 1 CKD had detectable uL‐FABP concentrations (median 1.79 ng/ml, range 0.79–3.66 ng/ml). For the second subdivision, 47 (24%) cats had borderline proteinuria, 147 cats had no proteinuria and two cats were excluded. One of the borderline proteinuric cats had a detectable uL‐FABP concentration, whereas the other five cats with detectable uL‐FABP concentrations were non‐proteinuric. Conclusion With the current assay, the screening potential of uL‐FABP as an early biomarker for feline CKD is limited as uL‐FABP was rarely detected in clinically healthy elderly cats independently of the presence of either IRIS stage 1 CKD or borderline proteinuria.

Abstract A 3‐year‐old female German Shepherd dog was presented with generalized tonic‐clonic epileptic seizures, right‐sided central vestibular syndrome, and right trigeminal nerve dysfunction. Acute lacunar ischemic strokes within both thalami, right side of the mesencephalon, left side of the myelencephalon, both sides of the cervical spinal cord, and acute hemorrhagic strokes within the rostral part of the right cerebellar hemisphere and right rostral colliculus were identified on magnetic resonance imaging. Additional evaluation identified multiple renal infarcts and complete splenic torsion, with entrapment of the left pancreatic lobe. Medical management, splenectomy, partial pancreatectomy, and intensive physical rehabilitation led to clinical improvement. The histology of the spleen was consistent with hemorrhagic infarction. Three months after onset, neurological examination identified only mild vestibular sequelae. The final diagnosis was multiple ischemic strokes secondary to primary splenic torsion. Spontaneous early hemorrhagic transformation, a well‐known condition in human medicine, also was found in this case.

Abstract Serum creatinine concentration, the classical biomarker of chronic kidney disease (CKD) in cats, has important limitations that decrease its value as a biomarker of early CKD. Recently, serum symmetric dimethylarginine concentration was introduced as a novel glomerular filtration rate biomarker for the early detection of CKD in cats. However, data on its specificity are still limited. The limitations of conventional biomarkers and the desire for early therapeutic intervention in cats with CKD to improve outcomes have prompted the discovery and validation of novel renal biomarkers to detect glomerular or tubular dysfunction. Changes in the serum or urinary concentrations of these biomarkers may indicate early kidney damage or predict the progression of kidney before changes in conventional biomarkers are detectable. This review summarizes current knowledge on renal biomarkers in CKD in cats, a field that has progressed substantially over the last 5 years.

Abstract Background Lobar emphysema in dogs and cats is caused by bronchial collapse during expiration and subsequent air trapping. Congenital causes such as bronchial cartilage defects or acquired causes such as compressive neoplastic lesions have been reported. Morbidity results from hyperinflation of the affected lung lobe and compression of adjacent thoracic structures. Objective To describe patient characteristics and imaging findings in dogs and cats with lobar emphysema. Animals Fourteen dogs and 3 cats with lobar emphysema diagnosed by imaging findings were retrospectively identified from veterinary referral hospital populations over a 10‐year period. Methods Cases that included thoracic radiography, thoracic computed tomography (CT), or both were included. All images were reviewed by a European College of Veterinary Diagnostic Imaging diplomate. Relevant case information included signalment, clinical findings, treatment, and histopathology where available. Results Ten of 17 (59%) patients were presented for evaluation of dyspnea and 6 (35%) for coughing. Eleven (65%) patients were

Abstract Background Liver‐type fatty acid‐binding protein (L‐FABP) and neutrophil gelatinase‐associated lipocalin (NGAL) are candidate biomarkers for the detection of early chronic kidney disease (CKD) in cats. Objective To evaluate urinary and serum L‐FABP and NGAL concentrations in CKD cats and in hyperthyroid cats before and after radioiodine (131I) treatment. Animals Nine CKD cats, 45 healthy cats and hyperthyroid cats at 3 time points including before (T0, n = 49), 1 month (T1, n = 49), and 11 to 29 months after (T2, n = 26) 131I treatment. Methods Cross‐sectional and longitudinal study. Serum L‐FABP (sL‐FABP), serum NGAL (sNGAL), urinary L‐FABP (uL‐FABP), and urinary NGAL (uNGAL) were compared between the 3 groups and between hyperthyroid cats before and after treatment. Data are reported as median (min‐max). Results CKD cats had significantly higher sL‐FABP (13.50 [3.40‐75.60] ng/ml) and uL‐FABP/Cr (4.90 [0.97‐2139.44] µg/g) than healthy cats (4.25 [1.34‐23.25] ng/ml; P = .01 and 0.46 [0.18‐9.13] µg/g; P < .001, respectively). Hyperthyroid cats at T0 had significantly higher uL‐FABP/Cr (0.94 [0.15‐896.00] µg/g) than healthy cats (P < .001), thereafter uL‐FABP/Cr significantly decreased at T2 (0.54 [0.10‐76.41] µg/g, P = .002). For the detection of CKD, uL‐FABP/Cr had 100% (95% confidence interval [CI], 66.4‐100.0) sensitivity and 93.2% (95% CI, 81.3‐98.6) specificity. There were no significant differences in sNGAL and uNGAL/Cr between the 3 groups. Conclusions and Clinical Importance L‐FABP, but not NGAL, is a potential biomarker for the detection of early CKD in cats. Utility of uL‐FABP to predict azotemia after treatment in hyperthyroid cats remains unknown.

Abstract Background Glomerular filtration rate (GFR) is the gold standard in assessing renal function but is impractical. Serum creatinine (sCr) has limited sensitivity in identifying early chronic kidney disease (CKD), whereas symmetric dimethylarginine (SDMA) has been commercialized as more accurate biomarker. Studies comparing SDMA and sCr with GFR in cats are limited. Objectives To further investigate the diagnostic performance of SDMA in nonazotemic and azotemic cats. Animals Forty‐nine client‐owned cats: 17 cats with CKD, 15 cats with diabetes mellitus (DM), and 17 healthy cats. Methods Retrospective study using spare blood samples from cats with documented sCr and GFR results for SDMA analysis. Diagnostic performances of SDMA and sCr were evaluated using correlation coefficients, sensitivities, specificities, and receiver operator characteristic curves. Results Compared to healthy cats and cats with DM, CKD cats had significantly higher SDMAplasma (26.7 ± 9.9 μg/dL) and sCr (249.7 ± 71.6 μmol/L [2.8 ± 0.8 mg/dL]; both P

Abstract Individuals moving in heterogeneous environments can improve their fitness considerably by habitat choice. Induction by past exposure, genetic preference alleles and comparison of local performances can all drive this decision‐making process. Despite the importance of habitat choice mechanisms for eco‐evolutionary dynamics in metapopulations, we lack insights on the connection of their cue with its effect on fitness optimization. We selected a laboratory population of Tetranychus urticae Koch (two‐spotted spider mite) according to three distinct host‐choice selection treatments for ten generations. Additionally, we tested the presence of induced habitat choice mechanisms and quantified the adaptive value of a choice before and after ten generations of artificial selection in order to gather insight on the habitat choice mechanisms at play. Unexpectedly, we observed no evolution of habitat choice in our experimental system: the initial choice of cucumber over tomato remained. However, this choice became maladaptive as tomato ensured a higher fitness at the end of the experiment. Furthermore, a noteworthy proportion of induced habitat choice can modify this ecological trap depending on past environments. Despite abundant theory and applied relevance, we provide the first experimental evidence of an emerging trap. The maladaptive choice also illustrates the constraints habitat choice has in rescuing populations endangered by environmental challenges or in pest control.

Abstract Background Percutaneous ultrasound (US)‐guided fine‐needle aspiration (FNA) of adrenal gland lesions is controversial in veterinary medicine. Objective To evaluate the frequency and radiologists' perception of the risk of the procedure as well as determining the incidence of complications. Methods Retrospective study. A first survey was submitted by e‐mail to all board‐certified radiologists of the American College of Veterinary Radiology (ACVR) and European College of Veterinary Diagnostic Imaging (ECVDI). A second survey was sent to radiologists who declared having performed the procedure at least once in their career (observational cross‐sectional case study). Results The first survey was sent to 977 diplomates and answered by 138. Of 138 diplomates, 40 currently performed the procedure and 98 did not; 44 of the 98 gave the hypertensive crisis risk in pheochromocytoma as a reason. To the second survey, 12 of 65 responded positively; 50 dogs with 58 lesions were recruited, including 23 pheochromocytomas. Complications were reported in 4 of 50 dogs; 3 hemorrhages (1 mild and 1 moderate) and 1 death from acute respiratory distress syndrome (possibly related to laryngeal paralysis). No hypertensive crisis was reported. There was no relationship between the method of FNA/type of needle used and occurrence of complications. Based on the recollection of these 65 radiologists, who performed approximately 200 FNA of adrenal lesions, a death rate of approximately 1% was estimated. Conclusions and Clinical Importance Percutaneous US‐guided FNA of adrenal lesions can be considered a minimally risky procedure, despite the negative perception by radiologists.

Abstract Background Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. Methods We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients. Results Pathogenic variants in ASPM and WDR62 were the most frequent causes in non‐consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non‐consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types. Conclusion Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients.

Abstract Background Several options have been proposed for the treatment of congenital extrahepatic portosystemic shunts (cEHPSS) in dogs, but formal comparisons among different treatment options are currently unavailable. A previous evidence‐based review (2012) found low quality of evidence for papers assessing the treatment of cEHPSS in dogs. Objectives To assess the quality of evidence available in the treatment of cEHPSS, summarize the current state of knowledge with respect to outcome after cEHPSS management, and compare different treatment techniques. Animals Not used. Methods A bibliographic search was performed without date or language restrictions. Studies were assessed for quality of evidence (study design, study group sizes, subject enrollment quality, and overall risk of bias) and outcome measures reported (perioperative outcome, clinical outcome, and surgical or interventional outcome), all reported with 95% confidence intervals. A network meta‐analysis was performed. Results Forty‐eight studies were included. Six retrospective studies (grade 4b) compared 2 techniques and 7 were abstracts (grade 5). The quality of evidence was low and risk of bias high. Regarding surgical outcome, statistically significant superiority of ameroid constrictor over thin film band was observed (P = .003). No other comparisons were statistically significant. Conclusions and Clinical Importance The evidence base of choice of treatment of cEHPSS in dogs remains weak despite recent publications on the subject. Ameroid is superior to thin film band in causing EHPSS closure. Blinded randomized studies comparing different treatment modalities, which routinely include postoperative imaging to assess cEHPSS closure and acquired portosystemic shunt development are essential.

Logging roads in the Congo Basin are often associated with forest degradation through fragmentation and access for other land uses. However, in concessions managed for timber production, secondary roads are usually closed after exploitation and are expected to disappear subsequently. Little is known about the effectiveness of this prescription and the factors affecting vegetation recovery rate on abandoned logging roads. In a novel approach we assessed logging roads as temporary elements in the forest landscape that vary in persistence depending on environmental conditions. We analyzed road persistence during the period 1986–2013 in adjacent parts of Cameroon, Central African Republic and Republic of Congo. Three successive phases of road recovery were identified on LANDSAT images: open roads with bare soil, roads in the process of revegetation after abandonment and disappeared roads no longer distinguishable from the surrounding forest. Field based inventories confirmed significant differences between all three categories in density and richness of woody species and cover of dominant herbs. We used dead‐end road segments, built for timber exploitation, as sampling units. Only 6% of them were identified as being re‐opened. Survival analyses showed median persistence of four years for open roads before changing to the revegetating state and 20 years for revegetating roads before disappearance. Persistence of revegetating roads was 25% longer on geologically poor substrates which might result from slower forest recovery in areas with lower levels of soil nutrient content. We highlight the contrast amongst forests growing on different types of substrate in their potential for ecosystem recovery over time after roads have been abandoned. Forest management plans need to take these constraints into account. Logging activities should be concentrated on the existing road network and sites of low soil resource levels should be spared from business‐as‐usual exploitation.

Defects in the regulation of apoptosis are one main cause of cancer development and may result from overexpression of anti-apoptotic proteins such as the X-linked inhibitor of apoptosis protein (XIAP). XIAP is frequently overexpressed in human leukemia and prostate and breast tumors. Inhibition of apoptosis by XIAP is mainly coordinated through direct binding to the initiator caspase-9 via its baculovirus-IAP-repeat-3 (BIR3) domain. XIAP inhibits caspases directly making it to an attractive target for anti-cancer therapy. In the search for novel, non-peptidic XIAP inhibitors in this study we focused on the chemical constituents of sāng bái pí (mulberry root bark). Most promising candidates of this plant were tested biochemically in vitro by a fluorescence polarization (FP) assay and in vivo via protein fragment complementation analysis (PCA). We identified the Diels Alder adduct Sanggenon G (SG1) as a novel, small-molecular weight inhibitor of XIAP. As shown by FP and PCA analyses, SG1 binds specifically to the BIR3 domain of XIAP with a binding affinity of 34.26 μM. Treatment of the transgenic leukemia cell line Molt3/XIAP with SG1 enhances caspase-8, -3 and -9 cleavage, displaces caspase-9 from XIAP as determined by immunoprecipitation experiments and sensitizes these cells to etoposide-induced apoptosis. SG1 not only sensitizes the XIAP-overexpressing leukemia cell line Molt3/XIAP to etoposide treatment but also different neuroblastoma cell lines endogenously expressing high XIAP levels. Taken together, Sanggenon G (SG1) is a novel, natural, non-peptidic, small-molecular inhibitor of XIAP that can serve as a starting point to develop a new class of improved XIAP inhibitors.