Morphological and molecular phylogenetic characterization of Sarcocystis kani sp. nov. and other novel, closely related Sarcocystis spp. infecting small mammals and colubrid snakes in Asia.

We investigated the morphology and phylogenetic relationships of novel and previously recognized Sarcocystis spp. infecting small mammals and colubrid snakes in Asia. The nuclear 18S rRNA and mitochondrial cox1 of Sarcocystis sp.1 from mangrove snakes (Boiga dendrophila) in Thailand and Sarcocystis sp.2 from a ricefield rat (Rattus argentiventer) in Sumatra were partially sequenced. Sporocysts of Sarcocystis sp.1 induced development of sarcocysts in experimentally infected rats, which showed a unique ultrastructure that was observed previously by S.P. Kan in rats from Malaysia; therefore, we describe this species as Sarcocystis kani sp. nov. Its integration into the 18S rRNA phylogeny of Sarcocystis spp. cycling between small mammals and colubrid snakes helped clarify relationships among the so-called S. zuoi-complex of molecularly cryptic species: Sarcocystis kani sp. nov., S. sp.2, S. attenuati, S. scandentiborneensis, and S. zuoi were all included in this clade. Tree topology was resolved into dichotomies congruent with the morphological disparities between the taxa. However, cox1 gene sequencing (including newly sequenced S. singaporensis and S. zamani) revealed that Sarcocystis kani, S. attenuati, and S. scandentiborneensis were identical suggesting a recent, common ancestry. To identify other distinctive features, lineage-specific molecular patterns within both genes were examined revealing that all 18S rRNA sequences of the S. zuoi - complex possess a unique, 7-nt long motif in helix 38 of domain V7 that was different in S. clethrionomyelaphis which branched off basally from the complex. Three-dimensional homology modelling of COX1 protein structure identified amino acid substitutions within the barcode area specific for the S. zuoi-complex and substantial divergence in structurally important amino acids between Sarcocystis species of snakes as definitive hosts and other lineages of the Sarcocystidae. We discuss the utility of selected genes for species delimitation of the Sarcocystis spp. under investigation, which probably evolved during recent radiations of their intermediate and definitive hosts.

Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease.

BACKGROUND: IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. METHODS: We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m 2 at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. RESULTS: We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m 2 in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m 2 . Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. CONCLUSIONS: IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease.

Clonal hematopoiesis with DNMT3A and PPM1D mutations impairs regeneration in autologous stem cell transplant recipients.

Clonal hematopoiesis (CH) is an age-related condition driven by stem and progenitor cells harboring recurrent mutations linked to myeloid neoplasms. Currently, potential effects on hematopoiesis, stem cell function and regenerative potential under stress conditions are unknown. We performed targeted DNA sequencing of 457 hematopoietic stem cell grafts collected for autologous stem cell transplantation (ASCT) in myeloma patients and correlated our findings with high-dimensional longitudinal clinical and laboratory data (26,510 data points for blood cell counts/serum values in 25 days around transplantation). We detected CHrelated mutations in 152 patients (33.3%). Since many patients (n=54) harbored multiple CH mutations in one or more genes, we applied a non-negative matrix factorization (NMF) clustering algorithm to identify genes that are commonly co-mutated in an unbiased approach. Patients with CH were assigned to one of three clusters (C1-C3) and compared to patients without CH (C0) in a gene specific manner. To study the dynamics of blood cell regeneration following ASCT, we developed a time-dependent linear mixed effect model to validate differences in blood cell count trajectories amongst different clusters. The results demonstrated that C2, composed of patients with DNMT3A and PPM1D single and co-mutated CH, correlated with reduced stem cell yields and delayed platelet count recovery following ASCT. Also, the benefit of maintenance therapy was particularly strong in C2 patients. Taken together, these data indicate an impaired regenerative potential of hematopoietic stem cell grafts harboring CH with DNMT3A and PPM1D mutations.

Integrating trauma-informed services in out-of-school time programs to mitigate the impact of community gun violence on youth mental health.

Community gun violence disproportionately impacts youth in low-income urban neighborhoods. Integrating trauma-informed mental health care in community-based out-of-school time (OST) programs is an innovative method of service delivery for these youth. This article provides justification for integrating evidence-based, trauma-informed services in OST programs within communities characterized by high rates of violent crime to minimize the impact of violence exposure on youth mental health. We describe the initial feasibility of a model program, the Violence Intervention and Prevention (VIP) Initiative, implemented in a small city in southeastern Pennsylvania. Within the first six months of the VIP Initiative, 95 community residents (90% under age 18; 51% Hispanic) received intervention services, primarily through single-session and short-term weekly group intervention in OST programs, and 80% of OST youth development staff participated in at least one trauma-informed professional development training. Recommendations to enhance and expand the delivery of trauma-informed services in the novel setting of OST programs are provided.

Comparison of left ventricular deformation abnormalities by echocardiography with cardiac magnetic resonance imaging in patients with acute myocarditis and preserved left ventricular ejection fraction.

Purpose: Cardiac magnetic resonance imaging (cMRI) represents the gold standard to detect myocarditis. Left ventricular (LV) deformation imaging provides additional diagnostic options presumably exceeding conventional transthoracic echocardiography (TTE). The present study aimed to analyze the feasibility to detect myocarditis in patients (pts) with preserved LV ejection fraction (LVEF) by TTE compared to cMRI. It has been hypothesized that the number of pathological findings by deformation imaging correspond to findings in cMRI. Methods and results: Between January 2018 and February 2020 102 pts with acute myocarditis according to the modified Lake Louise criteria and early gadolinium enhancement (EGE) by cMRI were identified at the department of cardiology at the University Hospital Leipzig. Twenty-six pts were included in this retrospective comparative study based on specific selection criteria. Twelve pts with normal cMRI served as a control group. LV deformation was analyzed by global and regional longitudinal strain (GLS, rLS), global and regional circumferential and radial strain (GCS, rCS, GRS, rRS), and LV rotation (including layer strain analysis). All parameters were compared to findings of edema, inflammation, and fibrosis by cMRI according to Lake Louise criteria. All pts with acute myocarditis diagnosed by cMRI showed pathological findings in TTE. Especially rCS and LV rotation analyzed by regional layer strain exhibit a high concordance with pathological findings in cMRI. In controls no LV deformation abnormalities were documented. Mean values of GLS, GRS, and GCS were not significantly different between pts with acute myocarditis and controls. Conclusion: This retrospective analysis documents the feasibility of detecting regional deformation abnormalities by echocardiography in patients with acute myocarditis confirmed by cMRI. The detection of pathological findings due to myocarditis requires the determination of regional deformation parameters, particularly rCS and LV rotation. The assessment of global strain values does not appear to be of critical value.

Proteogenomics refines the molecular classification of chronic lymphocytic leukemia.

Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic-based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterize the proteome and transcriptome alongside genetic and ex-vivo drug response profiling in a clinically annotated CLL discovery cohort (n = 68). Unsupervised clustering of the proteome data reveals six subgroups. Five of these proteomic groups are associated with genetic features, while one group is only detectable at the proteome level. This new group is characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). Classifiers developed to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n = 165, n = 169) confirm that ASB-CLL comprises about 20% of CLL patients. The inferior overall survival in ASB-CLL is also independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling.

Echocardiographic characteristics of patients with SARS-CoV-2 infection.

BACKGROUND: Myocardial involvement induced by SARS-CoV-2 infection might be important for long-term prognosis. The aim of this observational study was to characterize the myocardial effects during SARS-CoV-2 infections by echocardiography. RESULTS AND METHODS: An extended echocardiographic image acquisition protocol was performed in 18 patients with SARS-CoV-2 infection assessing LV longitudinal, radial, and circumferential deformation including rotation, twist, and untwisting. Furthermore, LV deformation was analyzed in an age-matched control group of healthy individuals (n = 20). The most prevalent finding was a reduced longitudinal strain observed predominantly in more than one basal LV segment (n = 10/14 patients, 71%). This pattern reminded of a "reverse tako-tsubo" morphology that is not typical for other viral myocarditis. Additional findings included a biphasic pattern with maximum post-systolic or negative regional radial strain predominantly basal (n = 5/14 patients, 36%); the absence or dispersion of basal LV rotation (n = 6/14 patients, 43%); a reduced or positive regional circumferential strain in more than one segment (n = 7/14 patients, 50%); a net rotation showing late post-systolic twist or biphasic pattern (n = 8/14 patients, 57%); a net rotation showing polyphasic pattern and/or higher maximum net values during diastole (n = 8/14 patients, 57%). CONCLUSION: Myocardial involvement due to SARS-CoV-2-infection was highly prevalent in the present cohort-even in patients with mild symptoms. It appears to be characterized by specific speckle tracking deformation abnormalities in the basal LV segments. These data set the stage to prospectively test whether these parameters are helpful for risk stratification and for the long-term follow-up of these patients.

Author Correction: Antigenic cross-reactivity between Schistosoma mansoni and allergenic invertebrates putatively due to shared glycanic epitopes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Antigenic cross-reactivity between Schistosoma mansoni and allergenic invertebrates putatively due to shared glycanic epitopes.

Previous studies have shown that rabbit IgG antibodies against Schistosoma mansoni egg antigens (SmSEA) cross-react with allergens in natural rubber latex, peanuts and grass and tree pollens. Here we describe antigenic molecules that cross-react with rabbit anti-S. mansoni IgG antibodies in extracts of the house dust mite (HDM) Dermatophagoides farinae, the Australian cockroach (ACR) Periplaneta australasiae and in the venom of the honey bee Apis mellifera (HBV). Tandem mass spectrometry identified the cross-reactive allergens as Der f 15 in HDM, two homologues of the Periplaneta americana cockroach allergen Cr-PI/Per a 3 in ACR and two isoforms of the allergen Api m 1 (phospholipase A2: PLA2) in HBV. Cross-reactive rabbit anti-SmSEA IgG antibodies eluted from the three invertebrate allergens reacted with S. mansoni egg antigens and variably with schistosome cercarial and worm antigens. Treatment of the electroblotted allergens with sodium metaperiodate abrogated most of the cross-reactivity of the rabbit anti-SmSEA antibodies, suggesting it was due to cross-reactive carbohydrate determinants (CCDs). Furthermore, analyses of the allergens' amino acid sequences indicated that they had potential for both N- and O-linked glycosylation. A potential role for the CCDs shared by the schistosome and invertebrates in inducing an allergy-protective effect, as proposed by the hygiene hypothesis, is discussed.

Choice perseveration in value-based decision making: The impact of inter-trial interval and mood.

In a series of decisions, people tend to show choice perseveration, that is, they repeat their choices. This choice perseveration is assumed to emerge due to residual activity from the previous decision. Here, we use a computational model with attractor dynamics to describe this process and to predict how choice perseveration can be modulated. We derive two qualitative predictions: Choice perseveration should decrease under longer (vs. shorter) inter-trial intervals and positive (vs. negative) mood. We test these predictions in a dynamic decision task where we modulate decisions across trials via sequentially manipulated reward options. Our findings replicate our previous study in showing choice perseveration in value-based decision making. Furthermore, choice perseveration decreased with increasing inter-trial interval as predicted by the model. However, we did not find clear evidence supporting mood effects on choice perseveration. We discuss how integrating decision process dynamics by the means of applying the neural attractor model can increase our understanding of the evolution of decision outcomes and therefore complement the psychophysical perspective on decision making.

Variables linked to hepatitis B vaccination success in non-dialyzed chronic kidney disease patients: Use of a bayesian model.

BACKGROUND: Hepatitis B vaccination is recommended for chronic kidney disease (CKD) patients before starting dialysis. We performed an analyis aimed to describe the clinical and biological parameters related to the success of vaccination in CKD patients before starting dialysis. METHODS: We extracted data of 170 non-dialyzed patients who were offered hepatitis B vaccination from a register. They received a first vaccination of 40µg followed by boosters after one, two and six months. Patients were considered protected if their hepatitis B antibody level was >10IU/L, three months apart. A logistic regression and a Bayesian model were used to describe the relationships between variables and the success of vaccination. RESULTS: Vaccination protected 50.6% of the patients. Model adjustment to the data was higher using the Bayesian model compared to the logistic regression (with area under the ROC curve of 0.955±0.007 vs 0.775±0.066 respectively). The Bayesian model's robustness studied using a 10 fold cross validation showed a percentage of misclassified subjects of 12.4±1.8%, a sensitivity of 87.7±0.3%, a specificity of 87.5±0.3%, a positive predictive value of 87.8±0.3% and negative predictive value of 87.4±0.2%. As classified by the Bayesian model, the variables most related to successful vaccination were, in descending order: age, eGFR, protidemia, albuminemia, cause of renal failure, gender, previous vaccination and weight. CONCLUSION: The Bayesian network confirmed that both kidney function and nutritional status of patients are important factors to explain the success of vaccination against hepatitis B in CKD patients before dialysis. For research purposes, before an external validation, the network can be used online at www.hed.cc/?s=Bhepatitis&n=ReseauhepatiteBsup10.neta.

[Impact of the adjunction of boiled-egg during the chronic hemodialysis session on the nutrition state]. / Impact du renforcement de la prise en charge nutritionnelle du patient en hémodialyse chronique par ajout d'œufs durs en collation.

Denutrition for chronic hemodialysed patients is common and severe, often the first step of many complication and comorbidities. This work was aimed to study the impact of the adjunction of hard-boiled egg during six months, at the time of the hemodialysis session, if the classic nutritional support with oral nutritional supplements and intradialytic parenteral nutrition has failed. Required criteria were: Albuminemia, prealbuminemia and Moreau and Gaudry's score. Thirty-six patients have been included. During the six months, the following nutritional parameters have improved: Moreau and Gaudry's score decreased of 0.27, C reactive protein of 9.44 mg/L. Albuminemia improved of 3.53 g/L in average, pre-albuminemia of 0.2 g/L, and normalized Protein catabolic rate of 0.01 g/kg/day. Half of the patients were successful to stop the intradialytic parenteral nutrition. Protein adjunction with hard-boiled egg during chronic hemodialysis session, on top of the classic dietetic support has improved nutritional patient status.

Examination of Sarcocystis spp. of giant snakes from Australia and Southeast Asia confirms presence of a known pathogen - Sarcocystis nesbitti.

We examined Sarcocystis spp. in giant snakes from the Indo-Australian Archipelago and Australia using a combination of morphological (size of sporocyst) and molecular analyses. We amplified by PCR nuclear 18S rDNA from single sporocysts in order to detect mixed infections and unequivocally assign the retrieved sequences to the corresponding parasite stage. Sarcocystis infection was generally high across the study area, with 78 (68%) of 115 examined pythons being infected by one or more Sarcocystis spp. Among 18 randomly chosen, sporocyst-positive samples (11 from Southeast Asia, 7 from Northern Australia) the only Sarcocystis species detected in Southeast Asian snakes was S. singaporensis (in reticulated pythons), which was absent from all Australian samples. We distinguished three different Sarcocystis spp. in the Australian sample set; two were excreted by scrub pythons and one by the spotted python. The sequence of the latter is an undescribed species phylogenetically related to S. lacertae. Of the two Sarcocystis species found in scrub pythons, one showed an 18S rRNA gene sequence similar to S. zamani, which is described from Australia for the first time. The second sequence was identical/similar to that of S. nesbitti, a known human pathogen that was held responsible for outbreaks of disease among tourists in Malaysia. The potential presence of S. nesbitti in Australia challenges the current hypothesis of a snake-primate life cycle, and would have implications for human health in the region. Further molecular and biological characterizations are required to confirm species identity and determine whether or not the Australian isolate has the same zoonotic potential as its Malaysian counterpart. Finally, the absence of S. nesbitti in samples from reticulated pythons (which were reported to be definitive hosts), coupled with our phylogenetic analyses, suggest that alternative snake hosts may be responsible for transmitting this parasite in Malaysia.

[Compliance and leaflet's reading, which link and which media? Results from a French population with chronic kidney disease]. / Observance et lecture des notices, quel lien et quels médias ? Résultats d'une population avec maladie rénale chronique.

Leaflets inside drug boxes are complex and often poorly understood. Patients consulting in nephrology are mostly old and often suffer from multiple comorbidities. As so, they are often subject to various contra-indications and drug interactions. This paper aims to evaluate if patients actually read leaflets or other medical information on others medias such as Internet and whether this could, potentially, interfere with their observance. Results showed that leaflets were read by 65.1% of patients, leading to 12% of withdrawal or not taking drugs. Furthermore, compliance to medical guidance was deemed e-read by 65.1% of patients, leading to 12% of withdrawal or not taken drugs. Furthermore, this study showed no clear profile for non-compliant patients. Even the youngest patients (under 50 years old) have had a good compliance, with not more withdrawal or not taking pills. Nonetheless, youngest patients used more often to consult alternative medias and did not read much of the leaflets' information. Patients who were reading leaflets however, tended to search further information on other medias. This situation would create new challenges in health care, as it seems that data available on new medias are not systematically validated or adapted to the needs of the patients.

Oral antidiabetics use among diabetic type 2 patients with chronic kidney disease. Do nephrologists take account of recommendations?

BACKGROUND: There is an increasing prevalence of diabetes type 2 and chronic kidney disease, challenging appropriate prescribing of oral anti-diabetic drugs (OADs). METHODS: We have described the practice patterns of 13 nephrologists in 4 centers, in a cohort of 301 consecutive adult type 2 diabetic patients. Among oral anti-diabetic prescriptions, we have detailed drugs dosage for each subject, with 3 different formulae for estimating glomerular filtration rate (GFR) and its adequation according to the latest ERBP recommendations (2015). As individuals were mostly obese in this work, we also compare adequacy rates using both standard indexed CKD-EPI formula and CKD-EPI formula de-indexed from body surface area. RESULTS: Using the CKD-EPI formula as the reference method for estimating GFR, 53.5% of patients were outside the recommendations, mostly for metformin (30% of the whole cohort) and for sitagliptin (17.9% of the whole cohort). With Cockcroft and Gault formula, 38.2% of persons were outside recommendations and 45.9% (p<0.001) with CKD-EPI de-indexed. Among individuals consulting a nephrologist for the first time (n=90), 61.1% were outside recommendations (p=0.1). Among those persons under diabetologist supervision (n=103), 63.1% were outside recommendations (p=0.09), and were taking significantly more often metformin and insulin. CONCLUSION: We have found a substantial number of inadequate OAD prescriptions in type 2 diabetic patients with chronic kidney disease. The proportion of individuals outside guidelines was strongly affected by the method used for estimating GFR and by the type of practice, i.e., specialists versus general practitioners.

[Emergency vascular access conversion to native arterio veinous fistula: a prospective study of 37 hemodialysis patients in Rwanda]. / Conversion des abords vasculaires d'urgence pour hémodialyse en fistules natives au Rwanda : à propos de 37 cas.

UNLABELLED: Chronic hemodialysis in Rwanda is relatively recent and most of patients are treated with catheters. SUMMARY: Thirty-seven patients who require chronic hemodialysis with catheters were evaluated during a 3-years period in order to facilitate the creation of a permanent vascular access for hemodialysis (AVF). Patient selection were made during a multi-disciplinary consultation. The sex-ratio was 1.5 and the main cause of the nephropathy was arterial hypertension. RESULTS: Thirty-one patients benefited from the creation of an arterioveinous fistula. All of the interventions were performed using local or loco-regional anesthesia. Sixty percent of these AVF were radio-cephalic, 35.4% were humero-cephalic. Sixty-four percent of the operations were performed on ambulatory patients, with a primary function for 90% of them. CONCLUSION: This work proves the feasibility of the creation of AVF in Rwanda, thus allowing to preclude the various complications that arise with the prolonged use of a catheter. This experience was made possible by the pooling of the resources of 4 of Rwanda's leading hospitals. In an early future, the development of vascular surgery will assure the permanence of this care.

Efficacy and tolerability of methylprednisolone pulse therapy in childhood epilepsies other than infantile spasms.

This retrospective study included 54 children with epilepsy. The treatment consisted of four pulses with single doses of 20 mg/kg/d methylprednisolone (MPR), administered every week on 3 consecutive days. After this initial phase, the intervals between the pulses were increased based on individual factors. MPR pulses were administered exclusively orally in 39 patients and 7.8% of all pulses were applied intravenously. After four pulses, 30 of 54 (56%) patients were responders, according to several clinical and electroencephalography criteria. A response was obtained in 12 of 20 (60%) cases with genetic, 7 of 17 (41%) with structural metabolic, and 11 of 17 (65%) with unknown etiology. Responder rates were 11 of 15 (73%) in patients with continuous spike-waves in slow sleep (CSWS) or Landau-Kleffner syndrome, 2 of 6 in patients with myoclonic astatic epilepsy or Lennox-Gastaut syndrome, and 17 of 31 (55%) in patients with unclassified epilepsies. A response was not correlated with any epilepsy-related clinical factor. The patients received a median of eight MPR pulses (range, 1-52), and the median duration of the therapy was 11 weeks. The response was maintained in 19 of 30 (63%) patients, and 3 of 24 (13%) without initial response became seizure-free (total responder rate at the end of the therapy 22/54 [41%]). The majority of patients experienced adverse effects that were typically mild and transient.

Phenotypic plasticity facilitates resistance to climate change in a highly variable environment.

Increased summer drought will exacerbate the regeneration of many tree species at their lower latitudinal and altitudinal distribution limits. In vulnerable habitats, introduction of more drought-tolerant provenances or species is currently considered to accelerate tree species migration and facilitate forest persistence. Trade-offs between drought adaptation and growth plasticity might, however, limit the effectiveness of assisted migration, especially if introductions focus on provenances or species from different climatic regions. We tested in a common garden experiment the performance of Pinus sylvestris seedlings from the continental Central Alps under increased temperatures and extended spring and/or summer drought, and compared seedling emergence, survival and biomass allocation to that of P. sylvestris and closely related Pinus nigra from a Mediterranean seed source. Soil heating had only minor effects on seedling performance but high spring precipitation doubled the number of continental P. sylvestris seedlings present after the summer drought. At the same time, twice as many seedlings of the Mediterranean than the continental P. sylvestris provenance were present, which was due to both higher emergence and lower mortality under dry conditions. Both P. sylvestris provenances allocated similar amounts of biomass to roots when grown under low summer precipitation. Mediterranean seedlings, however, revealed lower phenotypic plasticity than continental seedlings under high precipitation, which might limit their competitive ability in continental Alpine forests in non-drought years. By contrast, high variability in the response of individual seedlings to summer drought indicates the potential of continental P. sylvestris provenances to adapt to changing environmental conditions.

Role of plasma exchange in the thyroid storm.

Inadequately treated thyroid storm can lead to death. Therapeutic plasma exchange (TPE) is a suggested treatment when conventional treatments fail, but its indication is not well codified. We report our experience through three explicit cases. Three elderly patients were admitted to our hospital for cardiac or neurologic symptoms due to thyroid storm. After initiation of conventional therapy, TPE was performed with clinical and biological improvement. The speed of symptom resolution varies depending on the severity. This technique must be carried out by experienced medical staff as many complications can occur; nevertheless, in our patients with severe comorbidities, no complications occurred. The action of TPE mainly results from plasma removal of cytokines, putative antibodies, and thyroid hormones and their bound proteins. TPE has a transitory effect and thus should be associated with other thyroid blockers. When there are threatening symptoms, TPE should be done early, without waiting for the efficiency of conventional treatment, since it is the fastest method known for the improvement of the clinical condition. We also suggest starting TPE in case of neurologic symptoms because of very slow and incomplete regression. The Burch and Wartofsky score seems to be a helpful tool in establishing the diagnosis of thyroid storm and for deciding on when to initiate TPE.