Resource-Efficient Use of Residues from Medicinal and Aromatic Plants for Production of Secondary Plant Metabolites.

Although people's interest in green and healthy plant-based products and natural active ingredients in the cosmetic, pharmaceutical, and food industries is steadily increasing, medicinal and aromatic plants (MAPs) represent a niche crop type.It is possible to increase cultivation and sales of MAPs, by utilizing plant components that are usually discarded. This chapter provides an overview of studies concerning material flows and methods used for sustainable production of valuable metabolites from MAPs between 2018 and 2023. Additionally, it describes new developments and strategies for extraction and isolation, as well as innovative applications. In order to use these valuable resources almost completely, a systematic recycling of the plant material is recommended. This would be a profitable way to increase sustainability in the cultivation and usage of MAPs and provide new opportunities for extraction in plant science.

Prior medial meniscus arthroscopy is not associated with worst functional outcomes in patients undergoing primary total knee arthroplasty: A retrospective single-center study with a minimum follow-up of 5 years.

INTRODUCTION: There have been controversial studies on the impact of prior knee arthroscopy (KA) on outcomes of total knee arthroplasty (TKA). The purpose of this comparative study is to investigate the impact of prior KA of medial meniscus on patients undergoing TKA by evaluating the International Knee Society Score (IKS), the complications, and revisions. METHODS: This retrospective study reviewed 84 patients with TKA who had undergone prior KA of the medial meniscus and compared them to 84 cases, without a history of prior KA as a control group. Outcomes were assessed with the original IKS scores and complications. The mean follow-up was 8 years. RESULTS: There was no significant difference between groups with respect to demographics, or pre-operative IKS. The mean pre and postoperative IKS was not different between groups. The all-cause reoperation, revision, and complication rates of the KA group were not significantly higher than those of the control group. CONCLUSION: The present study seems to reveal that previous KA of the medial meniscus does not negatively affect a subsequent TKA. Nevertheless, larger studies may be necessary to confirm this observation.

De novo variants in RNF213 are associated with a clinical spectrum ranging from Leigh syndrome to early-onset stroke.

PURPOSE: RNF213, encoding a giant E3 ubiquitin ligase, has been recognized for its role as a key susceptibility gene for moyamoya disease. Case reports have also implicated specific variants in RNF213 with an early-onset form of moyamoya disease with full penetrance. We aimed to expand the phenotypic spectrum of monogenic RNF213-related disease and to evaluate genotype-phenotype correlations. METHODS: Patients were identified through reanalysis of exome sequencing data of an unselected cohort of unsolved pediatric cases and through GeneMatcher or ClinVar. Functional characterization was done by proteomics analysis and oxidative phosphorylation enzyme activities using patient-derived fibroblasts. RESULTS: We identified 14 individuals from 13 unrelated families with (de novo) missense variants in RNF213 clustering within or around the Really Interesting New Gene (RING) domain. Individuals presented either with early-onset stroke (n = 11) or with Leigh syndrome (n = 3). No genotype-phenotype correlation could be established. Proteomics using patient-derived fibroblasts revealed no significant differences between clinical subgroups. 3D modeling revealed a clustering of missense variants in the tertiary structure of RNF213 potentially affecting zinc-binding suggesting a gain-of-function or dominant negative effect. CONCLUSION: De novo missense variants in RNF213 clustering in the E3 RING or other regions affecting zinc-binding lead to an early-onset syndrome characterized by stroke or Leigh syndrome.

Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability and autistic features.

Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males that inherited the variants from their heterozygous carrier mothers. We show that PPP1R3F is predominantly expressed in brain astrocytes and localizes to the endoplasmic reticulum in cells. Glycogen content in PPP1R3F knockout astrocytoma cells appears to be more sensitive to fluxes in extracellular glucose levels than in wild-type cells, suggesting that PPP1R3F functions in maintaining steady brain glycogen levels under changing glucose conditions. We performed functional studies on nine of the identified variants and observed defects in PP1 binding, protein stability, subcellular localization and regulation of glycogen metabolism in most of them. Collectively, the genetic and molecular data indicate that deleterious variants in PPP1R3F are associated with a new X-linked disorder of glycogen metabolism, highlighting the critical role of GTSs in neurological development. This research expands our understanding of neurodevelopmental disorders and the role of PP1 in brain development and proper function.

Variants in FGF10 cause early onset of severe childhood interstitial lung disease: A detailed description of four affected children.

INTRODUCTION: Fibroblast growth factor 10 (FGF10) is a signaling molecule with a well-established role for lung branching morphogenesis. Rare heterozygous, deleterious variants in the FGF10 gene are known causes of the lacrimo-auriculo-dento-digital (LADD) syndrome and aplasia of lacrimal and salivary glands. Previous studies indicate that pathogenic variants in FGF10 can cause childhood Interstitial Lung Disease (chILD) due to severe diffuse developmental disorders of the lung, but detailed reports on clinical presentation and follow-up of affected children are lacking. METHODS: We describe four children with postnatal onset of chILD and heterozygous variants in FGF10, each detected by exome or whole genome sequencing. RESULTS: All children presented with postnatal respiratory failure. Two children died within the first 2 days of life, one patient died at age of 12 years due to right heart failure related to severe pulmonary hypertension (PH) and one patient is alive at age of 6 years, but still symptomatic. Histopathological analysis of lung biopsies from the two children with early postpartum demise revealed diffuse developmental disorder representing acinar dysplasia and interstitial fibrosis. Sequential biopsies of the child with survival until the age of 12 years revealed alveolar simplification and progressive interstitial fibrosis. DISCUSSION: Our report extends the phenotype of FGF10-related disorders to early onset chILD with progressive interstitial lung fibrosis and PH. Therefore, FGF10-related disorder should be considered even without previously described syndromic stigmata in children with postnatal respiratory distress, not only when leading to death in the neonatal period but also in case of persistent respiratory complaints and PH.

Retrospective analysis of return to impact sport after medial unicompartmental knee arthroplasty based on a cohort of 92 patients.

BACKGROUND: Return to sport after Knee Arthroplasty has been investigated reporting modifications in the physical activities with a trend towards to lower impact sports after Unicompartemental Knee Arthroplasty. The purpose of this study was to analyze the return to sport level after medial unicompartmental knee arthroplasty (MUKA) in a population of osteoarthritic patients having practiced impact sport, defined with a University of California at Los Angeles activity scale (UCLA)≥9 in their pre-symptomatic arthritic period. HYPOTHESIS: Return to an impact sport after MUKA was possible for a population of osteoarthritic patients having practiced impact sport in their pre-symptomatic arthritic period. METHODS: Ninety-two MUKA with a pre-symptomatic arthritic UCLA score≥9, including 60 men (65.2%) and operated between January 2009 and September 2014, were evaluated by a dedicated survey. Informations were obtained concerning the physical activities (intensity, frequency, kind of sport, reasons to decrease or stop the physical activities in the pre- and the postoperative period). The average age was 64.9 years±6.4 (range 49-74.4). Three different periods were compared: pre-symptomatic arthritic, preoperative and postoperative period. The mean follow-up was 7.3±1.7 years. RESULTS: The mean pre-symptomatic arthritic UCLA score was 9.9±0.3, the mean preoperative UCLA score was 7.0±2.5 (2-10) and the mean postoperative UCLA score was 7.2±2.0 (3-10). There were significant differences for the mean UCLA score values between pre-symptomatic arthritis and postoperative UCLA scores (p=0.034), however no difference was detected in mean score values before and after surgery (p=0.09). Only 32.6% (30/92) of patients had a postoperative UCLA score≥9. For patients practicing an impact sport activity (UCLA≥9) in the preoperative period (23/92; 25%), the postoperative UCLA score was at 8±1.1 (range 4-10). In this subgroup, 47.8% (11/23) of patients had a postoperative UCLA score≥9. The decline in sports in postoperative was predominantly explained by residual pain of the operated knee (31/92; 34%), precaution to not damage the prosthesis (25/92; 27%) and restrictions due to another joint (19/92; 21%). DISCUSSION: Return to impact sport after MUKA seems to be limited to a restrained number of patients. The main reasons to the decline in sporting activity level are linked to the residual pain of the operated knee and the precaution to not damage the prosthesis. LEVEL OF EVIDENCE: IV, retrospective cohort study.

Higher knee survivorship in young patients with monocompartmental osteoarthritis and constitutional deformity treated by high tibial osteotomy then total knee arthroplasty compared to an early total knee arthroplasty : a comparative study at a minimum follow-up of ten years.

AIMS: The use of high tibial osteotomy (HTO) to delay total knee arthroplasty (TKA) in young patients with osteoarthritis (OA) and constitutional deformity remains debated. The aim of this study was to compare the long-term outcomes of TKA after HTO compared to TKA without HTO, using the time from the index OA surgery as reference (HTO for the study group, TKA for the control group). METHODS: This was a case-control study of consecutive patients receiving a posterior-stabilized TKA for OA between 1996 and 2010 with previous HTO. A total of 73 TKAs after HTO with minimum ten years' follow-up were included. Cases were matched with a TKA without previous HTO for age at the time of the HTO. All revisions were recorded. Kaplan-Meier survivorship analysis was performed using revision of metal component as the endpoint. The Knee Society Score, range of motion, and patient satisfaction were assessed. RESULTS: Mean follow-up was 13 years (SD 3) after TKA in both groups. The 20-year Kaplan-Meier survival estimate was 98.6% in TKA post-HTO group (HTO as timing reference) and 81.4% in control group (TKA as timing reference) (p = 0.030). There was no significant difference in clinical outcomes, radiological outcomes, and complications at the last follow-up. CONCLUSION: At the same delay from index surgery (HTO or TKA), a strategy of HTO followed by TKA had superior knee survivorship compared to early TKA at long term in young patients.Level of evidence: IIICite this article: Bone Jt Open 2023;4(2):62-71.

At 10-Year Minimum Follow-Up, One-Third of Patients Have Patellofemoral Arthritis After Isolated Medial Patellofemoral Ligament Reconstruction Using Gracilis Tendon Autograft.

PURPOSE: To report the long-term clinical outcomes after isolated medial patellofemoral ligament reconstruction (MPFLr) to treat recurrent patellar instability. METHODS: This was a single-center study of patients undergoing an isolated MPFLr between 2000 and 2011. All patients underwent reconstruction using hamstring autograft. The inclusion criteria were a minimum 10-year follow-up period and skeletally mature patients with more than 1 episode of patellar dislocation who underwent MPFLr without an associated bony procedure. RESULTS: A total of 54 knees were available for final analysis. The mean follow-up period was 12.3 years (range, 10-14 year). The mean age at surgery was 25 years. No patients had patellofemoral arthritis (PFA) prior to surgery. Preoperatively, the mean Caton-Deschamps index was 1.1 and the mean tibial tubercle-trochlear groove distance was 14.9 ± 2 mm (range, 7-17 mm). All patients had trochlear dysplasia according to the Dejour classification. At final follow-up, the mean Kujala score was 82.9 ± 15.3; mean International Knee Documentation Committee score, 78.3 ± 18.5; and mean Tegner score, 4.0 ± 1.7. Patients with an unsatisfactory outcome as determined by a Kujala score lower than 80 had a higher Caton-Deschamps index preoperatively and were more likely to be female patients; however, neither factor reached significance. Of the patients, 33 (66%) had no radiographic evidence of PFA whereas 15 (30%) had Iwano stage 1 and 2 had Iwano stage 2 (4%). At final follow-up, 4 patients (7.4%) had recurrent instability requiring revision surgery. CONCLUSIONS: Isolated MPFLr with gracilis tendon autograft in appropriately selected patients is an effective long-term treatment for recurrent patellofemoral instability with low rates of recurrence. One-third of patients exhibit radiographic evidence of PFA more than 10 years after isolated MPFLr. LEVEL OF EVIDENCE: Level IV, case series.

Adult-Onset Neurodegeneration in Nucleotide Excision Repair Disorders (NERDND ): Time to Move Beyond the Skin.

BACKGROUND: Variants in genes of the nucleotide excision repair (NER) pathway have been associated with heterogeneous clinical presentations ranging from xeroderma pigmentosum to Cockayne syndrome and trichothiodystrophy. NER deficiencies manifest with photosensitivity and skin cancer, but also developmental delay and early-onset neurological degeneration. Adult-onset neurological features have been reported in only a few xeroderma pigmentosum cases, all showing at least mild skin manifestations. OBJECTIVE: The aim of this multicenter study was to investigate the frequency and clinical features of patients with biallelic variants in NER genes who are predominantly presenting with neurological signs. METHODS: In-house exome and genome datasets of 14,303 patients, including 3543 neurological cases, were screened for deleterious variants in NER-related genes. Clinical workup included in-depth neurological and dermatological assessments. RESULTS: We identified 13 patients with variants in ERCC4 (n = 8), ERCC2 (n = 4), or XPA (n = 1), mostly proven biallelic, including five different recurrent and six novel variants. All individuals had adult-onset progressive neurological deterioration with ataxia, dementia, and frequently chorea, neuropathy, and spasticity. Brain magnetic resonance imaging showed profound global brain atrophy in all patients. Dermatological examination did not show any skin cancer or pronounced ultraviolet damage. CONCLUSIONS: We introduce NERDND as adult-onset neurodegeneration (ND ) within the spectrum of autosomal recessive NER disorders (NERD). Our study demonstrates that NERDND is probably an underdiagnosed cause of neurodegeneration in adulthood and should be considered in patients with overlapping cognitive and movement abnormalities. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Restricted kinematic alignment may be associated with increased risk of aseptic loosening for posterior-stabilized TKA: a case-control study.

PURPOSE: The purpose of the study was to compare clinical and radiological results between kinematic alignment (KA) and mechanical alignment (MA) with a posterior-stabilized (PS) total knee arthroplasty (TKA) with a post-cam mechanism at a minimum follow-up of 3 years. The authors hypothesized a higher risk of aseptic loosening when performing KA using PS TKA. METHODS: A retrospective monocentric single surgeon case control study was performed comparing 100 matched patients who had TKA performed using a MA philosophy to 50 patients receiving TKA with a KA technique between January 2016 and October 2017. All patients had the same knee prosthesis (GMK primary posterior-stabilized, Medacta®, Switzerland). Patient specific cutting blocks were used in both groups and a restricted KA (rKA) was aimed in the KA group. A hybrid cementation technique was performed. The new Knee Society Score (KSS) and radiological assessment were collected preoperatively and at the final follow-up. Comparisons between groups were done with the T test or Fisher exact test. Global survival curves were estimated with Kaplan-Meier model. Significance was set at p < 0.05. RESULTS: Mean follow-up was 42.9 months ± 3.6 (range 37.6-46.7) and 53.3 months ± 4.1 (range 45.5-59.8) for rKA and MA groups. Postoperatively, no significant differences were found for clinical scores between both groups. Radiological assessment found similar postoperative Hip-Knee-Ankle angle for rKA and MA groups (178° versus 179° respectively, NS). At last follow-up, a significant higher survivorship was found for the MA group compared to the rKA group (97 versus 84%; p < 0.001) for aseptic loosening revision as the endpoint. CONCLUSION: An increased risk of tibial implant loosening was found with rKA compared to MA using a posterior-stabilized TKA with a post-cam system at short-term follow-up. Caution should be taken when choosing the TKA design while performing rKA. LEVEL OF EVIDENCE: Retrospective case-control study, Level IV.

Mechanical alignment for primary TKA may change both knee phenotype and joint line obliquity without influencing clinical outcomes: a study comparing restored and unrestored joint line obliquity.

PURPOSE: In total knee arthroplasty (TKA), knee phenotypes including joint line obliquity are of interest regarding surgical realignment strategies. The hypothesis of this study is that better clinical results, including decreased postoperative knee pain, will be observed for patients with a restored knee phenotype. METHODS: A retrospective analysis was performed on prospective data, including 1078 primary osteoarthritic knees in 936 patients. The male:female ratio was 780:298, mean age at surgery was 71.3 years ± 8.0. International Knee Society Scores and standardized long-leg radiographs (LLR) were collected preoperatively and at 2 years follow-up after TKA. Patients were categorized using the Coronal Plane Alignment of the Knee (CPAK) classification including the lateral distal femoral angle (LDFA) and medial proximal tibial angle (MPTA) measured on LLR by a single observer, allowing knee phenotypes to be categorized considering the arithmetic hip-knee-ankle (aHKA) angle (MPTA-LDFA) as measure of constitutional alignment, and joint line obliquity (JLO) (MPTA + LDFA). Clinical results were compared between patients with surgically restored preoperative constitutional knee phenotype to patients without restored constitutional knee phenotypes. Descriptive data analysis such as means, standard deviations and ranges were performed. T tests for independent samples were performed to compare group differences. Comparisons of categorical data were performed using the χ2 test. Significance was set at p < 0.05. RESULTS: A third of patients (33.4%) had constitutional knee varus with apex distal JLO. 63.5% of patients had preoperative apex distal JLO. Postoperatively, 57.8% of patients had a neutral HKA (- 2° to 2°) and a neutral JLO (- 3° and 3°), with only 18% of patients with restored constitutional knee phenotype. Of these patients, statistically less postoperative pain was observed in patients where apex distal JLO was restored compared to non-restored apex distal JLO (pain score 46.7 vs. 44.6; p = 0.02) without clinical relevance. Other categories of restored JLO or arithmetic HKA angle were not associated with improved outcomes. CONCLUSION: This study showed that performing mechanical alignment for primary TKA resulted in most cases in a change of the preoperative knee phenotype. These results emphasize the relevance of considering joint line obliquity to better understand preoperative knee deformity and better restore knee phenotypes with a more personalized realignment strategy to potentially improve TKA postoperative results. LEVEL OF EVIDENCE: III.

Assessing the drivers of syphilis among men who have sex with men in Switzerland reveals a key impact of screening frequency: A modelling study.

Over the last decade, syphilis diagnoses among men-who-have-sex-with-men (MSM) have strongly increased in Europe. Understanding the drivers of the ongoing epidemic may aid to curb transmissions. In order to identify the drivers of syphilis transmission in MSM in Switzerland between 2006 and 2017 as well as the effect of potential interventions, we set up an epidemiological model stratified by syphilis stage, HIV-diagnosis, and behavioral factors to account for syphilis infectiousness and risk for transmission. In the main model, we used 'reported non-steady partners' (nsP) as the main proxy for sexual risk. We parameterized the model using data from the Swiss HIV Cohort Study, Swiss Voluntary Counselling and Testing center, cross-sectional surveys among the Swiss MSM population, and published syphilis notifications from the Federal Office of Public Health. The main model reproduced the increase in syphilis diagnoses from 168 cases in 2006 to 418 cases in 2017. It estimated that between 2006 and 2017, MSM with HIV diagnosis had 45.9 times the median syphilis incidence of MSM without HIV diagnosis. Defining risk as condomless anal intercourse with nsP decreased model accuracy (sum of squared weighted residuals, 378.8 vs. 148.3). Counterfactual scenarios suggested that increasing screening of MSM without HIV diagnosis and with nsP from once every two years to twice per year may reduce syphilis incidence (at most 12.8% reduction by 2017). Whereas, increasing screening among MSM with HIV diagnosis and with nsP from once per year to twice per year may substantially reduce syphilis incidence over time (at least 63.5% reduction by 2017). The model suggests that reporting nsP regardless of condom use is suitable for risk stratification when modelling syphilis transmission. More frequent screening of MSM with HIV diagnosis, particularly those with nsP may aid to curb syphilis transmission.

Pediatric Tuberculosis Disease during Years of High Refugee Arrivals: A 6-Year National Prospective Surveillance Study.

BACKGROUND: In Europe, surveillance and monitoring of pediatric tuberculosis (TB) remains important, particularly in the light of migration in recent years. The aim of the study was to evaluate incidence rates of childhood TB and detailed diagnostic pathways and treatment. METHODS: Data were collected through the Swiss Pediatric Surveillance Unit (SPSU) from December 2013 to November 2019. Monthly -notifications are obtained from the 33 pediatric hospitals in the SPSU, and a detailed questionnaire was sent out upon notification. Inclusion criteria were children and adolescents aged up to 15 years with culture- or molecular-confirmed TB disease or for whom a treatment with ≥3 antimycobacterial drugs had been initiated. Data were compared with age-matched notification data from the Swiss Federal Office of Public Health (FOPH). RESULTS: Of the 172 cases notified to SPSU, a detailed questionnaire was returned for 161 (93%) children, of which 139 met the inclusion criteria. Reasons for exclusion were age >15 years, double reporting, and not fulfilling the criteria for TB disease. During the same time period, 172 pediatric TB cases were reported to the FOPH, resulting in an incidence of 2.1 per 100,000, ranging from 1.4 to 2.8 per year, without a clear trend over time. In the 64 (46.0%) foreign-born children, incidence rates were higher and peaked in 2016, with 13.7 per 100,000 (p = 0.018). The median interval between arrival in Switzerland and TB diagnosis was 5 (IQR 1-21) months, and 80% were diagnosed within 24 months of arrival. In 58% of the cases, TB disease was confirmed by culture or molecular assays. Age >10 years, presence of fever, or weight loss were independent factors associated with confirmed TB. CONCLUSION: The annual pediatric TB incidence rate only varied among foreign-born children and was highest in 2016 when refugee influx peaked in Europe. Importantly, most foreign-born children with TB were diagnosed within 2 years after arrival in Switzerland. Thus, the early period after arrival in Switzerland is associated with a higher risk of TB disease in children, and this should be considered for screening guidance in refugees.

Changes in the prevalence of self-reported sexually transmitted bacterial infections from 2010 and 2017 in two large European samples of men having sex with men-is it time to re-evaluate STI-screening as a control strategy?

BACKGROUND/OBJECTIVES: Many European countries reported increased numbers of syphilis, gonorrhoea and chlamydia diagnoses among men who have sex with men (MSM) in recent years. Behaviour changes and increased testing are thought to drive these increases. METHODS: In 2010 and 2017, two large online surveys for MSM in Europe (EMIS-2010, EMIS-2017) collected self-reported data on STI diagnoses in the previous 12 months, diagnostic procedures, STI symptoms when testing, number of sexual partners, and sexual behaviours such as condom use during the last intercourse with a non-steady partner in 46 European countries. Multivariate regression models were used to analyse factors associated with diagnoses of syphilis, gonorrhoea/chlamydia, and respective diagnoses classified as symptomatic and asymptomatic. If applicable, they included country-level screening rates. RESULTS: Questions on STI diagnoses and sexual behaviours were answered by 156,018 (2010) and 125,837 (2017) participants. Between 2010 and 2017, overall diagnoses with gonorrhoea/chlamydia and syphilis increased by 76% and 83% across countries. Increases were more pronounced for asymptomatic compared to symptomatic infections. The proportion of respondents screened and the frequency of screening grew considerably. Condomless anal intercourse with the last non-steady partner rose by 62%; self-reported partner numbers grew. Increased syphilis diagnoses were largely explained by behavioural changes (including more frequent screening). Gonorrhoea/chlamydia increases were mainly explained by more screening and a change in testing performance. A country variable representing the proportion of men screened for asymptomatic infection was positively associated with reporting symptomatic gonorrhoea/chlamydia, but not syphilis. DISCUSSION/CONCLUSION: The positive association of country-level screening rates with the proportion of symptomatic infections with gonorrhoea/chlamydia may indicate a paradoxical effect of screening on incidence of symptomatic infections. Treatment of asymptomatic men might render them more susceptible to new infections, while spontaneous clearance may result in reduced susceptibility. Before expanding screening programmes, evidence of the effects of screening and treatment is warranted.

Specific decorations of 17-hydroxygeranyllinalool diterpene glycosides solve the autotoxicity problem of chemical defense in Nicotiana attenuata.

The native diploid tobacco Nicotiana attenuata produces abundant, potent anti-herbivore defense metabolites known as 17-hydroxygeranyllinalool diterpene glycosides (HGL-DTGs) whose glycosylation and malonylation biosynthetic steps are regulated by jasmonate signaling. To characterize the biosynthetic pathway of HGL-DTGs, we conducted a genome-wide analysis of uridine diphosphate glycosyltransferases (UGTs) and identified 107 family-1 UGT members. The transcript levels of three UGTs were highly correlated with the transcript levels two key HGL-DTG biosynthetic genes: geranylgeranyl diphosphate synthase (NaGGPPS) and geranyllinalool synthase (NaGLS). NaGLS's role in HGL-DTG biosynthesis was confirmed by virus-induced gene silencing. Silencing the Uridine diphosphate (UDP)-rhamnosyltransferase gene UGT91T1 demonstrated its role in the rhamnosylation of HGL-DTGs. In vitro enzyme assays revealed that UGT74P3 and UGT74P4 use UDP-glucose for the glucosylation of 17-hydroxygeranyllinalool (17-HGL) to lyciumoside I. Plants with stable silencing of UGT74P3 and UGT74P5 were severely developmentally deformed, pointing to a phytotoxic effect of the aglycone. The application of synthetic 17-HGL and silencing of the UGTs in HGL-DTG-free plants confirmed this phytotoxic effect. Feeding assays with tobacco hornworm (Manduca sexta) larvae revealed the defensive functions of the glucosylation and rhamnosylation steps in HGL-DTG biosynthesis. Glucosylation of 17-HGL is therefore a critical step that contributes to the resulting metabolites' defensive function and solves the autotoxicity problem of this potent chemical defense.

Lateral unicompartmental knee arthroplasty is a safe procedure for post-traumatic osteoarthritis after lateral tibial plateau fracture: a case-control study at 10-year follow-up.

PURPOSE: Very few studies focus on lateral unicompartmental arthroplasty (LUKA) in the setting of post-traumatic osteoarthritis (PTOA). The hypothesis of our study is that LUKA is an effective procedure for isolated lateral PTOA with similar outcomes to non-traumatic LUKA. METHODS: Between 1990 and 2016, eighteen LUKA performed for isolated lateral tibiofemoral osteoarthritis secondary to tibial plateau fracture were retrospectively reviewed (post-traumatic group) and matched with a control group of thirty-six LUKA performed for non-traumatic OA. Clinical (International Knee Score), radiological outcomes and revision rate were compared between the two groups with a minimum follow-up of three years. RESULTS: With a mean follow-up of 10.1 years, postoperative IKS scores were similar between the two groups (IKS Knee: 89.1 (control) versus 85 (p = 0.03) and IKS Function: 85.9 (control) versus 77.9 (n.s.). Clinical improvement was greater for the post-traumatic group. No difference was observed with regard to revision rate (3/18 (16.7%) cases in the post-traumatic group and 7/36 (19.4%) in the control group, n.s.) or polyethylene wear per year between the two groups. The revision free-survival rate was 64.8% for the post-traumatic group and 58.8% for the control group at 22-year follow-up (n.s.). CONCLUSION: LUKA is an effective procedure at long-term for patients suffering from isolated lateral PTOA with similar clinical and radiographic results compared to LUKA performed for non-traumatic OA and without increased risk of revision or prosthetic wear. LEVEL OF EVIDENCE: IV.

Why Reintervention After Total Knee Arthroplasty Fails? A Consecutive Cohort of 1170 Surgeries.

BACKGROUND: The aim of this study was to analyze why contemporary reintervention after total knee arthroplasty (RiTKA) fails. METHODS: Between January 2006 and December 2010, from a multicenter cohort of 1170 RiTKAs, we assessed all failures of RiTKA requiring additional surgery. All indications for the index reintervention were included. The minimum follow-up period was 3 years. RESULTS: A total of 192 (16.4%) patients required additional surgery after RiTKA (re-reintervention). The mean follow-up period was 7.7 years. Mean age was 69.2 years. The mean time to re-reintervention was 9.6 months with 90.1% of rTKA failure occurring within the first two years. Infection was the main cause of new surgery after RiTKA (47.9%; n = 92/192). Other causes included extensor mechanism pathology (14.6%), stiffness (13.5%), pain (6.8%), aseptic loosening (5.2%), laxity (5.2%), periprosthetic fracture (3.6%), and wound pathology (3.1%). In four groups, the main indication for re-reintervention was recurrence of the pathology leading to the first reintervention: RiTKA for infection (59/355, 16.6%, P < .05), stiffness (18/174, 10.3%, P < .05), extensor mechanism failure (9/167, 5.4%, P < .05), and RiTKA for pain (4/137, 2.9%, P = .003). Global survival curve analysis found 87.9% survivorship without re-reintervention at one year and 83% at eight years. CONCLUSION: Contemporary RiTKA failures mainly occur in the first two postoperative years. Infection is the main cause of failure in RiTKA. Recurrence of the initial pathology occurs in four groups of RiTKA and is the main indication for re-reintervention in these groups; infection (16.6%), stiffness (10.3%), extensor mechanism failure (5.4%), and pain (2.9%).

Opening wedge high tibial osteotomy allows better outcomes than unicompartmental knee arthroplasty in patients expecting to return to impact sports.

PURPOSE: Prior studies have compared unicompartmental knee arthroplasty (UKA) with high tibial osteotomy (HTO) suggesting that both procedures had good functional outcomes. But none had established the superiority of one of the two procedures for patients with high expectation including return to impact sport. The aim of this study was to compare functional outcomes and ability to return to impact sport of active patients defined with a pre-arthritis University of California and Los Angeles activity (UCLA) score > 8, after UKA or HTO procedures. METHODS: A retrospective review of patients with a pre-arthritis UCLA score > 8 operated between January 2014 and September 2017 has identified 91 patients with open-wedge HTO and 117 patients with UKA. A matching process based on age (± 3 years) and gender allowed to include 50 patients in each group for comparative analysis. Patient reported outcomes included Knee Osteoarthritis Outcomes Score (KOOS), UCLA Score, Knee Society Score (KSS) and time to return to sport or previous professional activities at 3, 6, 12 and 24 months following surgery. RESULTS: Mean time to return to sport activities or previous professional activities were significantly lower for the HTO group than for UKA group [respectively, 4.9 ± 2.2 months for HTO group vs 5.8 ± 6.2 months for UKA group (p = 0.006) and 3 ± 3 months for HTO group vs 4 ± 3 months for UKA group (p = 0.006)]. At 24-month follow-up, UCLA score, KOOS Sports Sub-score and KSS activity score were significantly higher for HTO group than for UKA group (Δ: 2 CI 95% (1.3-2.5 points) p < 0.0001, (Δ: 10.9 CI 95% (2.9-18.9 points) p = 0.04 and Δ: 7.8 CI 95% (2.4-13.4 points) p = 0.006, respectively) and 31 patients (62%) were practicing impact sport in the HTO group versus 14 (28%) in the UKA group (odd-ratio 4.2 CI 95% (1.8-9.7) p < 0.0001). CONCLUSION: HTO offers statistically significant quicker return to sport activities and previous professional activities with a higher rate of patients able to practice impact activity (62% for HTO vs 28% for UKA) and better sports related functional scores at two years after surgery compared to UKA. LEVEL OF EVIDENCE: III retrospective case-control study.

'Break the Chains 2015' community-based HIV prevention campaign for men who have sex with men in Switzerland: non-randomised evaluation and cost analysis.

OBJECTIVES: To study the implementation, effects and costs of Break the Chains, a community-based HIV prevention campaign for men who have sex with men (MSM) in Switzerland, from March to May 2015, which aimed to reduce early HIV transmission by promoting the campaign message to adopt short-term risk reduction followed by HIV testing. DESIGN: Non-randomised evaluation and cost analysis. SETTING: Gay venues in 11 of 26 cantons in Switzerland and national online media campaign. PARTICIPANTS: MSM in online surveys (precampaign n=834, postcampaign n=688) or attending HIV testing centres (n=885); campaign managers (n=9); and campaign staff (n=38) or further intermediaries (n=80) in an online survey. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the proportion of MSM at risk of HIV acquisition or transmission who adhered to the campaign message. Secondary outcomes were postcampaign test uptake, knowledge about HIV primary infection and sense of belonging to the gay community. RESULTS: Campaign staff estimated that they contacted 17 145 MSM in 11 cantons. Among 688 respondents to the postcampaign survey, 311 (45.2%) were categorised as MSM at risk. Of 402/688 (58.5%) MSM who had heard about Break the Chains 2015, MSM categorised as being at risk were less likely to report adherence to the campaign message than MSM not at risk (adjusted OR 0.24; 95% CI 0.14 to 0.42). Twenty per cent of MSM with a defined risk of HIV acquisition or transmission who adopted risk reduction declared having done so because of the campaign. Costs for one MSM at risk to adhere to the campaign message were estimated at USD purchasing power parity 36-55. The number of HIV tests in the month after the campaign was twice the monthly average. CONCLUSION: Break the Chains increased HIV testing, implying that community-based campaigns are useful HIV prevention strategies for MSM. Additional interventions are needed to reach MSM at the highest risk of infection more effectively.

Clusters of Sexual Behavior in Human Immunodeficiency Virus-positive Men Who Have Sex With Men Reveal Highly Dissimilar Time Trends.

BACKGROUND: Separately addressing specific groups of people who share patterns of behavioral change might increase the impact of behavioral interventions to prevent transmission of sexually transmitted infections. We propose a method based on machine learning to assist the identification of such groups among men who have sex with men (MSM). METHODS: By means of unsupervised learning, we inferred "behavioral clusters" based on the recognition of similarities and differences in longitudinal patterns of condomless anal intercourse with nonsteady partners (nsCAI) in the HIV Cohort Study over the last 18 years. We then used supervised learning to investigate whether sociodemographic variables could predict cluster membership. RESULTS: We identified 4 behavioral clusters. The largest behavioral cluster (cluster 1) contained 53% of the study population and displayed the most stable behavior. Cluster 3 (17% of the study population) displayed consistently increasing nsCAI. Sociodemographic variables were predictive for both of these clusters. The other 2 clusters displayed more drastic changes: nsCAI frequency in cluster 2 (20% of the study population) was initially similar to that in cluster 3 but accelerated in 2010. Cluster 4 (10% of the study population) had significantly lower estimates of nsCAI than all other clusters until 2017, when it increased drastically, reaching 85% by the end of the study period. CONCLUSIONS: We identified highly dissimilar behavioral patterns across behavioral clusters, including drastic, atypical changes. The patterns suggest that the overall increase in the frequency of nsCAI is largely attributable to 2 clusters, accounting for a third of the population.