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We used data from a Fracture Liaison Service to compare the mean T-scores of obese and non-obese patients after a recent fragility fracture. After adjusting for age, sex, and diabetes mellitus, T-score values were significantly higher at all measurement sites in obese patients, with a mean difference of 1 SD., Purpose: This study aimed to compare the mean T-scores of obese and non-obese patients after recent fragility fractures., Methods: Over a period of 5 and a half years, from January 2016 to May 2021, patients from a fracture liaison service were identified and their demographic characteristics, osteoporosis risk factors, BMD T-scores, and fracture sites were compared between obese (BMI ≥ 30 kg/m 2 ) and non-obese (19 kg/m 2  < BMI < 30 kg/m 2 ) patients., Results: A total of 712 patients were included (80.1% women; mean age 73.8 ± 11.3 years). Sixteen % had type 2 diabetes mellitus and 80% had a major osteoporotic fracture (MOF). 135 patients were obese and 577 non-obese, with obese patients younger (p < 0.001) and more frequently female (p = 0.03). Obese patients presented with fewer hip fractures (10% vs. 21%, p = 0.003) and more proximal humerus fractures (16% vs. 7%, p < 0.001) than non-obese patients. After adjusting for age, sex, and diabetes mellitus, BMD T-score values were significantly higher at all measurement sites (lumbar spine, total hip, and femoral neck) in obese patients than in non-obese patients for all types of fractures, with a mean difference of 1 standard deviation (p < 0.001 for all comparisons). The same results were observed in the population limited to MOF., Conclusions: Given the crucial role of BMD T-score in determining the need for anti-osteoporotic medication following fragility fractures, it is reasonable to question the existing T-score thresholds in obese patients., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Objectives: Early confirmation of the diagnosis of connective tissue diseases (CTD) is important, as prolonged disease activity can result in irreversible organ damage. Although antinuclear antibodies (ANAs) have been shown to precede the diagnosis of SLE, this has not been investigated in large cohorts for other CTDs. In this study, we investigated whether the presence of antinuclear autoantibodies in undiagnosed patients suspected of having CTDs is predictive of development of a future CTD., Methods: We screened the Electronic Health Records of a cohort of 1030 patients, who were tested for ANAs and their specificity in 2013/2014, to evaluate whether new CTD diagnoses had been recorded by a clinician between the original blood draw date and 2020. We compared the prevalence of ANAs in patients who developed a new CTD diagnosis during follow-up with patients with similar symptoms at baseline who did not receive a subsequent CTD diagnosis and with patients with an established CTD at baseline., Results: Sixteen out of 1030 patients had developed a new CTD in the studied time period. The mean time period between baseline blood draw and subsequent CTD diagnosis of these patients was approximately 2.3 years. Eleven out of 16 (69%) newly diagnosed patients had positive ANA screening tests, compared to 54% of patients with a CTD diagnosis at baseline (p=ns) and 30% of symptomatic undiagnosed patients (p<0.001). This resulted in a positive predictive value (PPV) of 7% and a negative predictive value (NPV) of 98% for the development of a new CTD in undiagnosed symptomatic patients. For specific ANAs associated with the suspected CTD, the PPV was 12%, with a NPV of 98%., Conclusions: Progression to a CTD diagnosis is rare in undiagnosed patients. Undiagnosed patients with symptoms associated with a CTD who progress to a CTD more often have ANAs than patients with similar symptoms who do not progress to a CTD. ANA testing can be used to more stringently select patients who should remain in follow-up.

Objective: In young patients, the discoid lateral meniscus (DLM) usually becomes symptomatic at the time of peripheral rim instability of a complete discoid form. However, little is known about the natural history of meniscal instability. The aim was to detect hidden forms of presentation of instability using the history and clinical mechanical symptoms of instability., Methods: Retrospective study of 114 paediatric knees treated for DLM. A new clinical grading system for instability (stable, locked, snapping, blocked and unblocked knees) was defined and studied in combination with MRI and arthroscopic findings., Results: One hundred seven DLMs (94%) showed instability due to edge detachment. Fifteen (13%) knees were stable (grade 0), 2 (2%) were grade 1, 57 (50%) were grade 2, 35 (31%) were grade 3 and 5 (4%) were grade 4. The cause of grade 3 was an extension deficit (26/35) or flexion deficit (9/35). Grade 1 or 2 correlated with limited detachment, unlike grade 3 or 4. The grade of instability never decreased, but rather increased in many knees during the natural history of DLM., Conclusion: A new presentation of DLM is presented: episodic locking phenomenon and blocked knee with flexion deficit. Clinicians should be wary of pseudo-improvement with the recovery of mobility after a period of the blocked knee, which may be due to a progression towards the ultimate degree of instability. Clinical grading of instability has clarified the natural history of DLM-associated tearing., Level of Evidence: III., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Wireworms (Coleoptera: Elateridae) are economically significant pests of potatoes (Solanum tuberosum), damaging the marketable portion of the crop by feeding and tunneling into tubers. While conventional potato growers use the few registered synthetic insecticides to control wireworms, certified organic growers are left with less options due to the limited effectiveness of the available insecticides. Biologically derived pesticides provide an additional alternative for both systems. Certain gram-negative proteobacteria, such as Burkholderia spp., possess insecticidal compounds. However, very little is known about their efficacy on wireworms. From 2018 to 2021, we conducted experiments in Virginia to assess the efficacy of a Burkholderia spp.-based commercial pesticide, Majestene, as a wireworm control in potatoes. In a lab experiment, soil drench application of this insecticide at a rate of 66 g a.i. per 1 liter resulted in 30% wireworm mortality and significantly reduced wireworm feeding damage on potato tubers. In the field, in-furrow applications of Burkholderia spp. at a rate of 17.66 kg a.i. per ha significantly reduced wireworm damage to tubers in 2 of 7 field experiments conducted. By comparison, the commercial standard insecticide, bifenthrin, significantly reduced tuber damage in 3 of the 7 field experiments. Our study demonstrates the prospect for proteobacteria-derived insecticides for control of wireworms and potentially other soil-dwelling insects. In conclusion, findings present growers with another option to combat wireworm pressure, especially in organic systems., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We describe a case of healthcare-associated bloodstream infection due to Mycobacterium fortuitum . Whole-genome sequencing showed that the same strain was isolated from the shared shower water of the unit. Nontuberculous mycobacteria frequently contaminate hospital water networks. Preventative actions are needed to reduce the exposure risk for immunocompromised patients.

Overwintering success is an important determinant of arthropod populations that must be considered as climate change continues to influence the spatiotemporal population dynamics of agricultural pests. Using a long-term monitoring database and biologically relevant overwintering zones, we modeled the annual and seasonal population dynamics of a common pest, Helicoverpa zea (Boddie), based on three overwintering suitability zones throughout North America using four decades of soil temperatures: the southern range (able to persist through winter), transitional zone (uncertain overwintering survivorship), and northern limits (unable to survive winter). Our model indicates H. zea population dynamics are hierarchically structured with continental-level effects that are partitioned into three geographic zones. Seasonal populations were initially detected in the southern range, where they experienced multiple large population peaks. All three zones experienced a final peak between late July (southern range) and mid-August to mid-September (transitional zone and northern limits). The southern range expanded by 3% since 1981 and is projected to increase by twofold by 2099 but the areas of other zones are expected to decrease in the future. These changes suggest larger populations may persist at higher latitudes in the future due to reduced low-temperature lethal events during winter. Because H. zea is a highly migratory pest, predicting when populations accumulate in one region can inform synchronous or lagged population development in other regions. We show the value of combining long-term datasets, remotely sensed data, and laboratory findings to inform forecasting of insect pests.

Glycoclusters displaying synthetic fragments of the O-specific polysaccharide (OSP) of Vibrio cholerae O1 serotype Inaba on a carbohydrate platform were prepared by Cu(i)-catalysed azide alkyne cycloaddition (CuAAC, click chemistry). The clusters were subsequently conjugated to BSA via squaric acid chemistry. Their immunoreactivity was compared with those of similar conventional conjugates, i.e. made from single oligosaccharides presented in non cluster form, using plasma of patients recovering from cholera. The results showed that the conjugates were displayed in immunologically relevant manners and that the immunoreactivity of hexasaccharide-cluster conjugates was similar to that of a conjugate displaying OSP isolated from wild type V. cholerae, further supporting the immunologic relevance of antigens made from synthetic oligosaccharides.

Oligosaccharides equipped with amine-containing linkers can be conjugated to carrier proteins using squaric acid chemistry. In a two-step process, a squarate derivative of such oligosaccharide is formed first, which is followed by its reaction with a protein carrier. Monitoring of the conjugation reaction is achieved by SELDI-TOF-MS or MALDI-TOF-MS. This experimentally simple procedure yields desired glycoconjugates in high yields and with reproducible hapten-protein ratios.

Background: The limitations of conventional sperm analyses have highlighted the need for additional means of evaluating sperm quality., Methods: In a study of a cohort of 245 men with known conventional sperm parameters, one-dimensional PAGE was used to monitor protein content and quality in samples from individual ejaculates., Results: The sperm protein content varied markedly from sample to another, especially in the high-molecular-weight range. The intensity of the 80-110 kDa bands was correlated with progressive motility ( r  = 0.15, p  = 0.015 ) and was significantly higher ( p  = 0.0367) in the group of men with conventional parameters above the World Health Organization's 2010 reference values than in the group with at least one subnormal parameter (i.e. semen volume, sperm concentration, sperm count per ejaculate, progressive motility, proportion of normal forms or multiple anomaly index below the lower reference value). Using mass spectrometry, the 80-110 kDa bands were found to correspond primarily to three proteins from the flagellum's fibrous sheath: A-kinase anchor protein 4, A-kinase anchor protein 3, and spermatogenic cell-specific type 1 hexokinase., Conclusion: One-dimensional PAGE constitutes a simple, rapid, reliable, inexpensive method for analyzing proteins associated with sperm motility in individual human ejaculates., Competing Interests: Human ejaculates were obtained (following the provision of written, informed consent) from the Assisted Reproduction Unit at Lille University Medical Center (Lille, France). All the donors (age range: 30–37) had consented to use of the ejaculates for research purposes. Furthermore, the study protocol was approved by the local investigational review board (Comité de Protection des Personnes Nord Ouest IV, Lille, France; reference HP 16/53). The study was conducted in accordance with Lille University Medical Center’s regulations on clinical research.Not applicable.BL, MV and SN are co-founders of SPQI, a spin-off company involved in biomarker research in male infertility. JF, SJ, SN and MV are cited as inventors on a patent application (Patent EP13306212.5).Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Transgenic crops containing the bacterium Bacillus thuringiensis (Bt) genes reduce pests and insecticide usage, promote biocontrol services, and economically benefit growers. Area-wide Bt adoption suppresses pests regionally, with declines expanding beyond the planted Bt crops into other non-Bt crop fields. However, the offsite benefits to growers of other crops from such regional suppression remain uncertain. With data spanning 1976-2016, we demonstrate that vegetable growers benefit via decreased crop damage and insecticide applications in relation to pest suppression in the Mid-Atlantic United States. We provide evidence for the regional suppression of Ostrinia nubilalis (Hübner), European corn borer, and Helicoverpa zea (Boddie), corn earworm, populations in association with widespread Bt maize adoption (1996-2016) and decreased economic levels for injury in vegetable crops [peppers ( Capsicum annuum L.), green beans ( Phaseolus vulgaris L.), and sweet corn ( Zea mays L., convar. saccharata )] compared with the pre-Bt period (1976-1995). Moth populations of both species significantly declined in association with widespread Bt maize (field corn) adoption, even as increased temperatures buffered the population reduction. We show marked decreases in the number of recommended insecticidal applications, insecticides applied, and O. nubilalis damage in vegetable crops in association with widespread Bt maize adoption. These offsite benefits to vegetable growers in the agricultural landscape have not been previously documented, and the positive impacts identified here expand on the reported ecological effects of Bt adoption. Our results also underscore the need to account for offsite economic benefits of pest suppression, in addition to the direct economic benefits of Bt crops., Competing Interests: Conflict of interest statement: The European corn borer damage data for this study were derived from control plots of pesticide efficacy trials that were part of other unrelated studies funded by various organizations and companies including DuPont Pioneer, Dow AgroSciences, Monsanto, Bayer CropScience, and Syngenta. The pesticide efficacy trials were unrelated to this study, and these companies did not provide funding to support this work, but may be affected financially by publication of this paper and have funded other work by G.P.D., T.P.K., K.H., J.W., and W.D.H.

Mesenchymal stromal cells (MSC) are nonhematopoietic cells that can be isolated from several adult and fetal tissues. MSC present specific features as the capacity to support hematopoiesis and to regulate immune response. Thus, the use of MSC as a cell therapeutic product in the field of immune-hematology is of great importance. In this review, we focused on human MSC and discussed their immune-hematologic properties and their translation toward therapeutic clinical applications. Thus, these features hold great promise for cell-based therapy and are of important relevance for the field.

Background: Obesity in infertile women increases the costs of fertility treatments, reduces their effectiveness and increases significantly the risks of many complications of pregnancy and for the newborn. Studies suggest that even a modest loss of 5-10 % of body weight can restore ovulation. However, there are gaps in knowledge regarding the benefits and cost-effectiveness of a lifestyle modification program targeting obese infertile women and integrated into the fertility clinics. This study will evaluate clinical outcomes and costs of a transferable interdisciplinary lifestyle intervention, before and during pregnancy, in obese infertile women. We hypothesize that the intervention will: 1) improve fertility, efficacy of fertility treatments, and health of mothers and their children; and 2) reduce the cost per live birth, including costs of fertility treatments and pregnancy outcomes., Methods/design: Obese infertile women (age: 18-40 years; BMI ≥30 kg/m(2) or ≥27 kg/m(2) with polycystic ovary syndrome) will be randomised to either a lifestyle intervention followed by standard fertility treatments after 6 months if no conception has been achieved (intervention group) or standard fertility treatments only (control group). The intervention and/or follow-up will last for a maximum of 18 months or up to the end of pregnancy. Evaluation visits will be planned every 6 months where different outcome measures will be assessed. The primary outcome will be live-birth rates at 18 months. The secondary outcomes will be sub-divided into four categories: lifestyle and anthropometric, fertility, pregnancy complications, and neonatal outcomes. Outcomes and costs will be also compared to similar women seen in three fertility clinics across Canada. Qualitative data will also be collected from both professionals and obese infertile women., Discussion: This study will generate new knowledge about the implementation, impacts and costs of a lifestyle management program in obese infertile women. This information will be relevant for decision-makers and health care professionals, and should be generalizable to North American fertility clinics., Trial Registration: ClinicalTrials.gov NCT01483612. Registered 25 November 2011.

Urine metabolomic profiling can identify biochemical alterations resulting from various injuries affecting the graft outcome after renal transplantation. Here, we aimed to describe in depth the metabolite content of urines of renal transplant patients and to link it with the major injury factors acting at critical stages following transplantation. Morning urine samples were prospectively collected from 38 kidney transplant patients at 7 days (D7), 3 months (M3) and 12 months (M12) after transplantation. Twenty-five patients were treated with tacrolimus (Tac) and thirteen patients with cyclosporine (CsA). (1)H-NMR (proton nuclear magnetic resonance) and gas chromatography-mass spectrometry (GC-MS) were used to examine the overall metabolomic signature of each sample. Multivariate analysis was performed to study the changes in the metabolic profile over time and their dependency on the type of calcineurin inhibitor (CNI) administered to patients. Biological pathways affected by transplantation were identified using a metabolomics pathway analysis (MetPA) web-tool. The metabolic profile of urine samples clearly varied with time. Markers of medullary injury, tubule cell oxidative metabolism and impaired tubular reabsorption or secretion were present at D7. Differences in metabolic profiles became less marked as time passed on, urine content being quite similar at M3 and M12. The metabolite profile tended to differ between patients receiving Tac and those receiving CsA but no clear discriminating profiles can be found. The combination of (1)H-NMR and GC-MS for the analysis of urine metabolomic profiles is a very useful method to study patho-physiological alterations in kidney transplant patients over time.

Shigella sonnei O-antigen features a zwitterionic disaccharide repeat encompassing two rare monosaccharides. The synthesis of the AB repeat and of trisaccharides ABA' and B'AB, which validates chain elongation at either end, is reported. All targets were synthesized using a postglycosylation oxidation strategy in combination with imidate chemistry. Precursors to residue A were obtained from L-glucose. The AAT (B) donor and acceptor were obtained from D-glucosamine. A one-step Pd(OH)2/C-mediated deprotection provided the propyl glycoside targets.

Harlequin bug, Murgantia histrionica (Hahn) (Hemiptera: Pentatomidae), is a piercing-sucking pest of cole crops, causing cosmetic damage in low populations, while heavy pest pressure can kill plants or entire fields. Field studies were conducted to evaluate a trap crop for control of harlequin bug in collard. Field-cage choice tests found that potential trap crop plant species, mustard (Brassica juncea 'Southern Giant Curled'), rapeseed (B. napus 'Athena'), rapini (B. rapa), and arugula (Eruca satica) attracted more harlequin bugs than collard (B. oleracea 'Champion') and a nonbrassica control, bean (Phaseolus vulgaris'Bronco'). Mustard was the most consistently selected by harlequin bug over collard in choice tests, and was found to be an effective trap crop for reducing feeding injury on collard at two experimental sites. Augmentation of the mustard trap crop with a systemic, neonicotinoid insecticide provided no added control of harlequin bug for the 10 wk duration in the spring season.

Background: Genetically modified mice offer the unique opportunity to gain insight into the pathophysiology of pulmonary arterial hypertension. In mice, right heart catheterization is the only available technique to measure right ventricular systolic pressure (RVSP). However, it is a terminal procedure and does not allow for serial measurements. Our objective was to validate a noninvasive technique to assess RVSP in mice., Methods and Results: Right ventricle catheterization and echocardiography (30-MHz transducer) were simultaneously performed in mice with pulmonary hypertension induced acutely by infusion of a thromboxane analogue, U-46619, or chronically by lung-specific overexpression of interleukin-6. Pulmonary acceleration time (PAT) and ejection time (ET) were measured in the parasternal short-axis view by pulsed-wave Doppler of pulmonary artery flow. Infusion of U-46619 acutely increased RVSP, shortened PAT, and decreased PAT/ET. The pulmonary flow pattern changed from symmetrical at baseline to asymmetrical at higher RVSPs. In wild-type and interleukin-6-overexpressing mice, the PAT correlated linearly with RVSP (r(2)=-0.67, P<0.0001), as did PAT/ET (r(2)=-0.76, P<0.0001). Sensitivity and specificity for detecting high RVSP (>32 mm Hg) were 100% (7/7) and 86% (6/7), respectively, for both indices (cutoff values: PAT, <21 ms; PAT/ET, <39%). Intraobserver and interobserver variability of PAT and PAT/ET were <6%., Conclusions: Right ventricular systolic pressure can be estimated noninvasively in mice. Echocardiography is able to detect acute and chronic increases in RVSP with high sensitivity and specificity as well as to assess the effects of treatment on RVSP. This noninvasive technique may permit the characterization of the evolution of pulmonary arterial hypertension in genetically modified mice.

Idiopathic hypogonadotropic hypogonadism (IHH) is a condition characterized by failure to undergo puberty in the setting of low sex steroids and low gonadotropins. IHH is due to abnormal secretion or action of the master reproductive hormone gonadotropin-releasing hormone (GnRH). Several genes have been found to be mutated in patients with IHH, yet to date no mutations have been identified in the most obvious candidate gene, GNRH1 itself, which encodes the preprohormone that is ultimately processed to produce GnRH. We screened DNA from 310 patients with normosmic IHH (nIHH) and 192 healthy control subjects for sequence changes in GNRH1. In 1 patient with severe congenital nIHH (with micropenis, bilateral cryptorchidism, and absent puberty), a homozygous frameshift mutation that is predicted to disrupt the 3 C-terminal amino acids of the GnRH decapeptide and to produce a premature stop codon was identified. Heterozygous variants not seen in controls were identified in 4 patients with nIHH: 1 nonsynonymous missense mutation in the eighth amino acid of the GnRH decapeptide, 1 nonsense mutation that causes premature termination within the GnRH-associated peptide (GAP), which lies C-terminal to the GnRH decapeptide within the GnRH precursor, and 2 sequence variants that cause nonsynonymous amino-acid substitutions in the signal peptide and in GnRH-associated peptide. Our results establish mutations in GNRH1 as a genetic cause of nIHH.

Objectives: To validate the use of Real Time PCR, a widely used technique that can detect very low levels of Y chromosomal sequence, and to assess the use of a highly sensitive PCR technique, pyrophosphorolysis-activated polymerisation (PAP), for fetal sex determination using free fetal DNA (ffDNA)., Methods: The fetal sex was determined by Real Time PCR in 58 pregnancies using ffDNA isolated from maternal plasma. In parallel with the Real Time PCR experiments, the presence of Y chromosome sequence was also determined using PAP on 54 isolated ffDNA samples., Results: Both techniques detected Y chromosome sequence at very low levels with 98% specificity and 100% sensitivity (Real Time n = 44, PAP n = 54). Furthermore, the PAP technique was shown to be more robust than the Real Time PCR as none of the samples tested failed to meet the acceptance criteria. Combining the two techniques for male fetal sex detection from maternal blood plasma increases the sensitivity and specificity to 100% in this series., Conclusions: This study shows that both Real Time PCR and PAP can be used for Y chromosome detection on ffDNA. Furthermore, by using PAP in combination with Real Time PCR more reliable early prenatal sexing can be performed using ffDNA.

Objective: To determine which first-line medication is more effective in polycystic ovary syndrome (PCOS) patients for ovulation induction and pregnancy achievement and to verify whether any patient characteristic is associated with a better response to therapy., Design: Observational comparative study., Setting: Fertility clinic., Patient(s): One hundred fifty-four infertile women with oligomenorrhea and hyperandrogenism., Intervention(s): Group 1 (56 patients) received clomiphene citrate (CC) 50 mg from days 5-9 of the cycle. Group 2 (57 patients) received 500 mg of metformin 3 times a day. Group 3 (41 patients) received both medications., Main Outcome Measure(s): Ovulation and pregnancy., Result(s): Patients receiving metformin alone had an increased ovulation rate compared with those receiving CC alone (75.4% vs. 50%). Patients on metformin had similar ovulation rates compared with those in the combination group (75.4% vs. 63.4%). Pregnancy rates were equivalent in the 3 groups. Response to metformin was independent of body weight and dose. Finally, nonsmoking predicted better ovulatory response overall as well as lower fasting glucose for CC and lower androgens for metformin., Conclusion(s): Metformin is better for ovulation induction than CC alone and equivalent for pregnancy achievement. We suggest that metformin can be used first for ovulation induction in patients with PCOS regardless of their weight and insulin levels because of its efficacy and known safety profile.

As yeast cells enter meiosis, chromosomes move from a centromere-clustered (Rabl) to a telomere-clustered (bouquet) configuration and then to states of progressive homolog pairing where telomeres are more dispersed. It is uncertain at which stage of this process sequences commit to recombine with each other. Previous analyses using recombination between dispersed homologous sequences (ectopic recombination) support the view that, on average, homologs are aligned end to end by the time of commitment to recombination. We have undertaken further analyses incorporating new inserts, chromosome rearrangements, an alternate mode of recombination initiation, and mutants that disrupt nuclear structure or telomere metabolism. Our findings support previous conclusions and reveal that distance from the nearest telomere is an important parameter influencing recombination between dispersed sequences. In general, the farther dispersed sequences are from their nearest telomere, the less likely they are to engage in ectopic recombination. Neither the mode of initiating recombination nor the formation of the bouquet appears to affect this relationship. We suggest that aspects of telomere localization and behavior influence the organization and mobility of chromosomes along their entire length, during a critical period of meiosis I prophase that encompasses the homology search.