Inter-annual and spatial climatic variability have led to a balance between local fluctuating selection and wide-range directional selection in a perennial grass species.

BACKGROUND AND AIMS: The persistence of a plant population under a specific local climatic regime requires phenotypic adaptation with underlying particular combinations of alleles at adaptive loci. The level of allele diversity at adaptive loci within a natural plant population conditions its potential to evolve, notably towards adaptation to a change in climate. Investigating the environmental factors that contribute to the maintenance of adaptive diversity in populations is thus worthwhile. Within-population allele diversity at adaptive loci can be partly driven by the mean climate at the population site but also by its temporal variability. METHODS: The effects of climate temporal mean and variability on within-population allele diversity at putatively adaptive quantitative trait loci (QTLs) were evaluated using 385 natural populations of Lolium perenne (perennial ryegrass) collected right across Europe. For seven adaptive traits related to reproductive phenology and vegetative potential growth seasonality, the average within-population allele diversity at major QTLs (HeA) was computed. KEY RESULTS: Significant relationships were found between HeA of these traits and the temporal mean and variability of the local climate. These relationships were consistent with functional ecology theory. CONCLUSIONS: Results indicated that temporal variability of local climate has likely led to fluctuating directional selection, which has contributed to the maintenance of allele diversity at adaptive loci and thus potential for further adaptation.

[A long distance between home and hospital does not bother ambulatory surgery for ureteroscopy in French Guyana]. / Une grande distance entre le domicile et l'hôpital ne contre-indique pas l'ambulatoire pour urétéroscopie en Guyane française.

INTRODUCTION: French Guyana is 83,500 km2 wide (equivalent to 1/6 of France). Communes are distant. Public urology is set in Kourou only. These particularities led to develop ambulatory urological surgery including for patients living far away from the reference centre. We report our experience with patient ureteroscopy (URS). MATERIAL: The study is retrospective (2018-2019), and includes 125 patients. Among these patients, 19.2% live in Kourou, 71.1% live 40 to 100km from the hospital and 9.7% beyond 100km. Every patient had an outpatient procedure for rigid and/or flexible URS to treat stone disease, including in lower calyx [LC] (38.4%). Ambulatory surgery was also proposed to the patients living away with the usual restrictions. Complications, results and switch to conventional hospitalisation (CH) were studied. RESULTS: Mean stone size was 10,5mm (4-30), stone density was 1030 UH (470-1700). The postoperative complication rate was 4%. There were 90.4% 'stone free' patients (85.4% for LC). One patient was rehospitalised within 48hours for acute flank pain and 9 patients had a switch of ambulatory to CH: 6 for discharge too late and 3 for complication (fever and/or pain). Distance between home and hospital was linked neither to complication rate, nor to switch to CH. CONCLUSION: Ambulatory URS is possible without further complications in selected patients living beyond 100km from the hospital, because of a specific organisation and an appropriate training of the caregivers involved in postoperative patient care. LEVEL OF PROOF: 3.

[MRI of the axial skeleton for evaluation of prostate cancer extent in french Guyana]. / IRM du squelette axial pour le bilan du cancer de prostate en Guyane française.

INTRODUCTION: Spread evaluation of Prostate Cancer (PC) in French Guyana is bothered by the lack of bone scintigraphy. The availability of 4 MRI allows to develop alternatives using Axial Skeleton MRI (AS MRI). We report the related results. MATERIAL: AS MRI was done in patients with diagnosis of high risk PC: PSA>=10ng/ml and/or Gleason Score>=7 (predominant Gleason grade 4) and/or clinical T2b and/or T2b/T3 MRI and/or >50% positive biopsies. AS MRI was including spine, pelvis and skull assessement.The results were systematically compared to the clinical, biological and biopsy features. RESULTS: Amongst 163 AS MRI performed, 30 were positive and 133 negative. Of these 133 patients, 60 were submited to radical prostatectomy with or without lymphadenectomy. In these 133 patients with negative AS MRI, median PSA was 11ng/ml (1-51) and 27 (20,3%) had PSA>20ng/ml. In patients with positive AS MRI, only 1 had PSA<20ng/ml and predominant Gleason grade 3. CONCLUSION: Our study shows that AS MRI assessement is especially usefull in patients who are most likely to have bone metastasis that is to say those with PSA>20ng/ml and/or predominant Gleason grade 4. LEVEL OF EVIDENCE: 3.

[Epidemiology of prostate cancer (PCa) in French Guyana (FG) - Preliminary results]. / Épidémiologie du cancer de la prostate en Guyane française ­ Données préliminaires.

INTRODUCTION: Epidemiology of prostate cancer (PCa) in French Guyana (FG) is not well documented yet. It differs from the reported one in French West Indies due to a younger population, less exposed to agricultural pesticides with also much lower level of medical information and care. MATERIAL: The incidence and mortality rates available in the regional register of cancers are reported for the period 2010-2014. The characteristics of 242 consecutive prostate biopsy series performed between 2017 January and 2019 October for abnormal digital rectal examination (DRE) and/or PSA>4ng/mL are also described. RESULTS: PCa incidence in FG is 94.4°/°°°° and specific mortality 16.9°/°°°°. Among the biopsies, 77.7% (188/242) are positive with a mean PSA of 72.6ng/mL (1-4000) at a mean age of 66years (50-89), 34% (64/188) with an abnormal DRE, 12.3% (23/188) with a PSA>50ng/mL and 28.2% (53/188) with a Gleason score≥8. CONCLUSION: In spite of young population, less exposure to environmental risk factors and high rate of racial mixing, the early PCa diagnosis is still a challenge in FG. The observed incidence and mortality rates suggest underestimation of PCa cases and too late specific care what is also suggested by adverse pathological and biological characteristics of the tumors at the time of diagnosis. LEVEL OF EVIDENCE: 3.

Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial†.

BACKGROUND: This randomized phase II-III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC). PATIENTS AND METHODS: Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle. RESULTS: In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers. CONCLUSION: Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.

[Bilateral and recurrent facial palsy due to lymphoma: a case report]. / Paralysie faciale périphérique à bascule et lymphome: à propos d'un cas.

OBJECTIVE: To discuss about management of facial paralysis reccurence and to highlight the ENT's important role in the diagnosis of systemic diseases. MATERIAL AND METHODS: This article presents a case report about a controlateral facial palsy recurrence, two months later in a fifty-two year's old woman. This cranial nerves involvement was due to non-Hodgkin lymphoma with neuro-meningeal spreading. The first palsy had completely recovered with steroids. The early recurrence of the palsy and the lymph nodes areas exam lead to the diagnosis. The patient was treated by chemotherapy with good neuromeningeal diffusion. The facial score rapidly improved, according to facial electromyography results. DISCUSSION: Specific biological and radiological explorations are usually carried out in recurrent facial palsy. Complete clinical examination and cerebrospinal fluid study are useful in this case. Moreover it should be preferable to do these explorations before steroid therapy. A diffuse meningeal enhancement on the MRI can complete sometimes clinical and biological data. CONCLUSION: Cranial nerves involvement is sometimes one of the first symptoms of neuro-meningeal lymphoma. Facial palsy reccurence has to conduce ENT pratician to do more specific explorations, of which CSF analysis is required.

Effect of interleukin-1beta on transforming growth factor-beta and bone morphogenetic protein-2 expression in human periodontal ligament and alveolar bone cells in culture: modulation by avocado and soybean unsaponifiables.

BACKGROUND: In periodontal disease, interleukin-1beta (IL-1beta) is responsible for the matrix breakdown through excessive production of degrading enzymes by periodontal ligament fibroblasts and osteoblasts. Transforming growth factor-beta (TGF-beta) plays an important role in tissue regeneration as one of the factors capable of counteracting IL-1beta effects. In this study, we investigated the in vitro effect of avocado and soya unsaponifiables (ASU) on the expression of TGF-beta1, TGF-beta2, and bone morphogenetic protein-2 (BMP-2) by human periodontal ligament (HPL) and human alveolar bone (HAB) cells in the presence of IL-1beta. METHODS: HPL and HAB cells were incubated for 48 hours with ASU (10 microg/ml) in the presence or absence of IL-1beta (10 ng/ml). The steady-state levels of TGF-beta1, TGF-beta2, and BMP-2 mRNAs were determined by Northern blot or reverse transcription-polymerase chain reaction (RT-PCR). The amounts of TGF-beta1 and TGF-beta2 proteins were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The data indicated that IL-1beta strongly decreases the expression of TGF-beta1 and TGF-beta2 by HPL cells. ASU were capable of opposing the cytokine effect. In HAB cells, TGF-beta1 and BMP-2 mRNA levels were downregulated by the cytokine. ASU were found to reverse the IL-1beta-inhibiting effect. In contrast, the cytokine stimulated the production of TGF-beta2 in alveolar bone cells, with no significant effect of ASU. CONCLUSIONS: The results indicate that the IL-1beta-driven erosive effect in periodontitis could be enhanced by a decreased expression of members of the TGF-beta family. The ASU stimulation of TGF-beta1, TGF-beta2, and BMP-2 expression may explain their promoting effects in the treatment of periodontal disorders, at least partly. These findings support the hypothesis that ASU could exert a preventive action on the deleterious effects exerted by IL-1beta in periodontal diseases.

Phenotypic Plasticity and Selection: Nonexclusive Mechanisms of Adaptation.

Selection and plasticity are two mechanisms that allow the adaptation of a population to a changing environment. Interaction between these nonexclusive mechanisms must be considered if we are to understand population survival. This review discusses the ways in which plasticity and selection can interact, based on a review of the literature on selection and phenotypic plasticity in the evolution of populations. The link between selection and phenotypic plasticity is analysed at the level of the individual. Plasticity can affect an individual's response to selection and so may modify the end result of genetic diversity evolution at population level. Genetic diversity increases the ability of populations or communities to adapt to new environmental conditions. Adaptive plasticity increases individual fitness. However this effect must be viewed from the perspective of the costs of plasticity, although these are not easy to estimate. It is becoming necessary to engage in new experimental research to demonstrate the combined effects of selection and plasticity for adaptation and their consequences on the evolution of genetic diversity.

Congestive heart failure in dialysis patients.

To determine the prevalence of congestive heart failure in dialysis patients and the disorders with which it is associated, 85% of 153 nondiabetic patients who were undergoing maintenance dialysis had echocardiography and gated cardiac scan. Ten percent (n = 15) had congestive heart failure, 53% (n = 8) of whom had dilated cardiomyopathy, and 47% (n = 7) had hypertrophic hyperkinetic cardiomyopathy. Ischemic heart disease was an additional independent risk factor for congestive heart failure. Significantly more of those patients with dilated cardiomyopathy were smokers and none were hypertensive, whereas all those patients with hypertrophic cardiomyopathy were hypertensive. The prevalence of hypertrophic hyperkinetic disease was 11%, of dilated cardiomyopathy 18%, and of symptomatic ischemic heart disease 18%. We concluded that congestive heart failure in dialysis patients is associated not only with dilated cardiomyopathy but also with hypertrophic cardiomyopathy, a disease that requires echocardiography for diagnosis and that has different risk factors and management.

[Sinuso-nasal sarcoidosis]. / Les localisations naso-sinusiennes de la sarcoïdose.

OBJECTIVES: Sinonasal sarcoidosis is unusual and may be misdiagnosed. We describe the characteristic clinical presentation observed in three patients treated in our institution and define the complementary explorations leading to diagnosis. Basis for treatment is also developed. PATIENTS AND METHODS: Among one hundred and one patients treated for sarcoidosis between 1983 and 2003 in three department of RD Hospital, three had histologically proved sinonasal sarcoidosis. These three cases were retrospectively analyzed and compared with the literature. RESULTS: All patients complained of chronic rhinosinusitis without improvement under usual treatment. Computed tomography showed usual aspects of chronic rhinosinusitis. The diagnosis was finally based on the biopsy of the nasal mucosa. Even if sarcoidosis had been already diagnosed, the main point was the delay between ENT symptoms and diagnosis because all clinical presentations and radiological aspects were aspecific. CONCLUSION: This case report underlines the difficulty to diagnose sinonasal sarcoidosis. When a patient is treated for sarcoidosis, sinonasal localization of the disease must be suggested in the event of chronic rhinosinusitis. On the other hand, sarcoidosis must be suggested and specific complementary examination must be performed in the event of chronic rhinosinusitis without improvement under usual treatment. ENT biopsy remains the main argument for diagnosis.

Cloning, sequence and expression of the gene encoding the malolactic enzyme from Lactococcus lactis.

Many lactic acid bacteria can carry out malolactic fermentation. This secondary fermentation is mediated by the NAD- and Mn(2+)-dependent malolactic enzyme, which catalyses the decarboxylation of L-malate to L-lactate. The gene we call mleS, coding for malolactic enzyme, was isolated from Lactococcus lactis. The mleS gene consists of one open reading frame capable of coding for a protein with a calculated molecular mass of 59 kDa. The amino acid sequence of the predicted MleS gene product is homologous to the sequences of different malic enzymes. Bacterial and yeast cells expressing the malolactic gene convert L-malate to L-lactate.

Metabolic analysis of S. cerevisiae strains engineered for malolactic fermentation.

A complete malolactic fermentation was achieved using Saccharomyces cerevisiae strains coexpressing the genes mleS and mae1 coding for the Lactococcus lactis malolactic enzyme and the Schizosaccharomyces pombe malate permease under the control of yeast promoters. The expression level of mae1 greatly influences the kinetics of the reaction by controlling the rate of malate uptake meanwhile a high expression level of mleS induces a partial consumption of malate derived from glucose by the malolactic enzyme. A strain expressing several copies of mae1 and one copy of mleS degrades 3 g/l of malate almost exclusively through the malolactic pathway in 4 days under enological conditions, without metabolic side effects.

Hyperapobetalipoproteinemia: the major dyslipoproteinemia in patients with chronic renal failure treated with chronic ambulatory peritoneal dialysis.

In the present study, plasma cholesterol, triglyceride, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, and the major protein in LDL, apoB, were measured in 28 patients with chronic renal failure treated with hemodialysis and in 28 patients with chronic renal failure treated with chronic ambulatory peritoneal dialysis (CAPD). Elevated plasma triglycerides and reduced HDL cholesterol were frequent in both the hemodialysis and CAPD patients. However LDL levels were significantly higher in the CAPD patients as evident both by LDL cholesterol and LDL apoB. Even so, only one of the CAPD patients was hypercholesterolemic whereas 14 (or 50%) had hyperapobetalipoproteinemia (HyperapoB). Insulin-dependent diabetes was more frequent in the CAPD group but only 2 of the 9 insulin-dependent diabetics in this group had HyperapoB, and therefore, diabetes mellitus cannot account for the difference between the 2 groups. Thus HyperapoB appears to be a prevalent dyslipoproteinemia in CAPD patients and as such might be another factor which places CAPD patients at particularly increased risk of atherosclerosis.

Hydroxychloroquine treatment of hypercalcemia in a patient with sarcoidosis undergoing hemodialysis.

Hypercalcemia developed in a patient undergoing long-term hemodialysis, and she was found to have noncaseating granulomas on lymph node biopsy. Hydroxychloroquine was administered as therapy for the hypercalcemia. Over 24 weeks of treatment with the drug, concentrations of calcium and 1,25-dihydroxyvitamin D returned to normal. The results demonstrate the capacity of hydroxychloroquine to inhibit the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, and emphasize the efficacy of hydroxychloroquine as an alternate to corticosteroids in the treatment of hypercalcemia of granulomatous disease. Hydroxychloroquine may be preferred when existing skeletal disease, or a predisposition to osteopenia, provides relative contraindications to corticosteroid therapy.

Impact of renal transplantation on uremic cardiomyopathy.

In chronic uremia, cardiomyopathy manifests itself as systolic dysfunction, concentric left ventricular (LV) hypertrophy, or LV dilatation. To determine the impact of renal transplantation on uremic cardiomyopathy, all dialysis patients participating in a long-term cohort study who received a successful renal transplant were followed with echocardiography. The transplanted group comprised 102 of 433 (24%) endstage renal disease (ESRD) patients. They were significantly younger and, on starting ESRD therapy, had significantly less ischemic heart disease and cardiac failure than the overall ESRD cohort. During followup, ischemic heart disease developed in only 1 patient and none experienced cardiac failure. In the 12% (n = 12) of patients with systolic dysfunction before renal transplant, fractional shortening normalized in all patients, increasing from 21.5 +/- 4.6% to 33.5 +/- 5.6% after transplantation. In the 41% (n = 41) with concentric LV hypertrophy before transplantation, the LV mass index improved from 158 +/- 39 g/m2 to 132 +/- 39 g/m2. LV dilatation was present in 32% (n = 32) of patients before transplantation. After transplantation, LV volume fell from 116 +/- 3.1 ml/m2 to 89 +/- 21 ml/m2, and LV mass index in this group fell from 166 +/- 55 g/m2 to 135 +/- 37 g/m2. It was not possible to associate risk factors characteristic of the uremic state with the improvement in cardiac structure and function, although the fall in LV mass was significantly associated with fall in blood pressure. We conclude that correction of the uremic state by renal transplantation leads to normalization of LV contractility in systolic dysfunction, regression of hypertrophy in concentric LV hypertrophy, and improvement of cavity volume in LV dilatation. The degree of improvement suggests that dialysis patients with uremic cardiomyopathy would benefit from renal transplantation.

Glycerol overproduction by engineered saccharomyces cerevisiae wine yeast strains leads to substantial changes in By-product formation and to a stimulation of fermentation rate in stationary phase

Six commercial wine yeast strains and three nonindustrial strains (two laboratory strains and one haploid strain derived from a wine yeast strain) were engineered to produce large amounts of glycerol with a lower ethanol yield. Overexpression of the GPD1 gene, encoding a glycerol-3-phosphate dehydrogenase, resulted in a 1.5- to 2.5-fold increase in glycerol production and a slight decrease in ethanol formation under conditions simulating wine fermentation. All the strains overexpressing GPD1 produced a larger amount of succinate and acetate, with marked differences in the level of these compounds between industrial and nonindustrial engineered strains. Acetoin and 2,3-butanediol formation was enhanced with significant variation between strains and in relation to the level of glycerol produced. Wine strains overproducing glycerol at moderate levels (12 to 18 g/liter) reduced acetoin almost completely to 2,3-butanediol. A lower biomass concentration was attained by GPD1-overexpressing strains, probably due to high acetaldehyde production during the growth phase. Despite the reduction in cell numbers, complete sugar exhaustion was achieved during fermentation in a sugar-rich medium. Surprisingly, the engineered wine yeast strains exhibited a significant increase in the fermentation rate in the stationary phase, which reduced the time of fermentation.

The Kidney Disease Questionnaire: a test for measuring patient knowledge about end-stage renal disease.

Two studies report on the development of the Kidney Disease Questionnaire (KDQ) as a test for measuring patient knowledge about end-stage renal disease and its treatment. The KDQ is available in a 26-item version or as two parallel 13-item tests. Psychometric evaluations indicate that all versions show high levels of reliability. Initial validity tests are also promising. The KDQ is able to discriminate individuals well informed about kidney disease and its treatment from those who are not so well informed. It is also sensitive to the effects of an experimental education program and to ESRD-related knowledge that is acquired as a result of starting dialysis. Data and issues related to the administration, readability, demographic correlates, and a French translation of the KDQ are also presented and discussed.

Renal involvement in malignant histiocytosis. An immunoperoxidase marker study.

In two patients who had malignant histiocytosis, renal involvement was present at an early stage of their diseases and consisted clinically of proteinuria and renal failure. The associated renal lesion was characterized by a diffuse and global endocapillary hypercellularity of the glomeruli imputable to atypical cells occluding the capillary loops. Immunoglobulins were absent from this lesion. The atypical cells were positively identified by lysozyme immunoperoxidase study as malignant histiocytes. It is suggested that renal biopsy complemented by marker study could play a role in the diagnosis of malignant histiocytosis.

A tale of two homocysteines--and two hemodialysis units.

Pharmacologic doses of folic acid are commonly used to reduce the hyperhomocysteinemia of end-stage renal disease (ESRD). Vitamin B12 acts at the same metabolic locus as folic acid, but information is lacking about the specific effects of high doses of this vitamin on homocysteine levels in renal failure. We therefore compared the plasma homocysteine concentrations of maintenance hemodialysis patients in two McGill University-affiliated urban tertiary-care medical centers that differed in the use of vitamin B12 and folic acid therapy. Patients in the first hemodialysis unit are routinely prescribed high-dose folic acid (HI-F, 6 mg/d), whereas those in the second unit receive high-dose vitamin B12 in the form of a monthly 1-mg intravenous injection, along with conventional oral folic acid (HI-B12, 1 mg/d). Predialysis homocysteine was 23.4 +/- 6.8 micromol/L (mean +/- SD) in the HI-F unit and 18.2 +/- 6.1 micromol/L in the HI-B12 unit (P < .002). Postdialysis homocysteine was 14.5 +/- 4.1 in the HI-F unit and 10.6 +/- 3.4 micromol/L in the HI-B12 unit (P = .0001). Multiple regression analysis indicated that high-dose parenteral vitamin B12 was associated with a lower homocysteine concentration even after controlling for the potential confounders of sex, serum urea, serum creatinine, urea reduction ratio, and plasma cysteine. Because this was a cross-sectional observational study, we cannot exclude the possibility that unidentified factors, rather than the different vitamin therapies, account for the different homocysteine levels in the two units. Careful prospective studies of the homocysteine-lowering effect of high-dose parenteral vitamin B12 in ESRD should be undertaken.

Giant axonal neuropathy: clinical, electrophysiologic, and neuropathologic features in two siblings.

Giant axonal neuropathy is a progressive central-peripheral axonopathy characterized by distention of axons by aggregated neurofilaments. We report two female siblings with giant axonal neuropathy. Both patients developed symptoms of a chronic progressive polyneuropathy at age 3 years. Clinical evidence of central nervous system involvement was present in both cases. Autopsy neuropathologic examination of the older sibling at the age of 11 years revealed numerous giant axons, Rosenthal fibers, and gliosis throughout the brain and spinal cord and typical giant axons in the peripheral nerves. Electrophysiologic studies in the younger sibling indicated brain stem dysfunction, and her sural nerve biopsy revealed enlarged axons packed with neurofilaments. These patients illustrate that neurologic deficits of giant axonal neuropathy result from widespread lesions in the central, as well as peripheral (including autonomic), nervous systems. This occurrence of giant axonal neuropathy in two siblings supports a genetic origin of this disease. This is the first report of autopsy findings in giant axonal neuropathy in an affected sibling.