Forest stratification shapes allometry and flight morphology of tropical butterflies.

Studies of altitudinal and latitudinal gradients have identified links between the evolution of insect flight morphology, landscape structure and microclimate. Although lowland tropical rainforests offer steeper shifts in conditions between the canopy and the understorey, this vertical gradient has received far less attention. Butterflies, because of their great phenotypic plasticity, are excellent models to study selection pressures that mould flight morphology. We examined data collected over 5 years on 64 Nymphalidae butterflies in the Ecuadorian Chocó rainforest. We used phylogenetic methods to control for similarity resulting from common ancestry, and explore the relationships between species stratification and flight morphology. We hypothesized that species should show morphological adaptations related to differing micro-environments, associated with canopy and understorey. We found that butterfly species living in each stratum presented significantly different allometric slopes. Furthermore, a preference for the canopy was significantly associated with low wing area to thoracic volume ratios and high wing aspect ratios, but not with the relative distance to the wing centroid, consistent with extended use of fast flapping flight for canopy butterflies and slow gliding for the understorey. Our results suggest that microclimate differences in vertical gradients are a key factor in generating morphological diversity in flying insects.

Chlamydia trachomatis regulates growth and development in response to host cell fatty acid availability in the absence of lipid droplets.

Chlamydia trachomatis (Ct) is a Gram-negative obligate intracellular pathogen of humans that causes significant morbidity from sexually transmitted and ocular diseases globally. Ct acquires host fatty acids (FA) to meet the metabolic and growth requirements of the organism. Lipid droplets (LDs) are storehouses of FAs in host cells and have been proposed to be a source of FAs for the parasitophorous vacuole, termed inclusion, in which Ct replicates. Previously, cells devoid of LDs were shown to produce reduced infectious progeny at 24 hr postinfection (hpi). Here, although we also found reduced progeny at 24 hpi, there were significantly more progeny at 48 hpi in the absence of LDs compared to the control wild-type (WT) cells. These findings were confirmed using transmission electron microscopy where cells without LDs were shown to have significantly more metabolically active reticulate bodies at 24 hpi and significantly more infectious but metabolically inert elementary bodies at 48 hpi than WT cells. Furthermore, by measuring basal oxygen consumption rates (OCR) using extracellular flux analysis, Ct infected cells without LDs had higher OCRs at 24 hpi than cells with LDs, confirming ongoing metabolic activity in the absence of LDs. Although the FA oleic acid is a major source of phospholipids for Ct and stimulates LD synthesis, treatment with oleic acid, but not other FAs, enhanced growth and led to an increase in basal OCR in both LD depleted and WT cells, indicating that FA transport to the inclusion is not affected by the loss of LDs. Our results show that Ct regulates inclusion metabolic activity and growth in response to host FA availability in the absence of LDs.

Non-albuminuric renal disease among subjects with advanced stages of chronic kidney failure related to type 2 diabetes mellitus.

Urinary albumin excretion has been consistently found to be normal in a significant number of subjects with early stages of diabetic kidney disease. This study was aimed to estimate the prevalence and characteristics of non-albuminuric chronic kidney disease associated with type 2 diabetes mellitus among subjects who reach advanced stages of renal failure. Study population was composed of incident patients with advanced chronic kidney disease (glomerular filtration rate <30 mL/min) related to type 2 diabetes in a tertiary hospital from Gran Canaria (Spain) during a period of 2 years. Subjects were classified as normoalbuminuric (urinary albumin-to-creatine ratio [UACR] <30 mg/g), microalbuminuric (UACR ≥30 and <300 mg/g), or proteinuric (UACR ≥300 mg/g). Of 78 eligible patients, 21.8% had normoalbuminuria, 20.5% had microalbuminuria, and 57.7% had proteinuria. Individuals with normoalbuminuria were mostly women and had a lower prevalence of smoking and polyneuropathy than subjects with microalbuminuria or proteinuria. They also presented greater measures of body mass index and waist circumference, higher values of total and LDL cholesterol, and lower values of HbA1c and serum creatinine than subjects with microalbuminuria or proteinuria. Multivariate analysis demonstrated that female sex (positively) and HbA1c and polyneuropathy (negatively) were independently associated with absence of albuminuria. In conclusion, around 20% of subjects with diabetes-related advanced chronic kidney disease, characteristically women, have normal urinary albumin excretion. HbA1c and polyneuropathy are inversely related to this non-albuminuric form of nephropathy.

Nanostructural Influence on Optical and Thermal Properties of Butterfly Wing Scales Across Forest Vertical Strata.

Butterfly wing scales feature complex nanostructures that influence wing coloration and various mechanical and optical properties. This configuration plays a key role in ecological interactions, flight conditions, and thermoregulation, facilitated by interactions with environmental electromagnetic energy. In tropical forests, butterflies occupy distinct vertical habitats, experiencing significant light and temperature variations. While wing nanostructures have been widely studied, their variation across different vertical flight preferences remains underexplored. This study investigates the wing nanostructures of 12 tropical butterfly species from the Nymphalidae family, focusing on their optical, morphological, and thermal properties across different forest strata. We analyzed the optical response through diffuse reflectance in the UV, Vis, and NIR ranges, correlating these findings with nanostructural configuration and thermal stability using thermogravimetric analysis (TGA). Our results reveal a significant correlation between flight stratification and wing optical responses, alongside distinct nanostructural features within each stratum. This study demonstrates the variability in butterfly wing nanostructures along the vertical stratification of the forest to cope with environmental conditions, raising new questions for future research on eco-evolutionary flight and thermal adaptations. Additionally, this underscores the importance of understanding how these structural adaptations influence butterfly interactions with their environment and their evolutionary success across different forest strata.

Flexible tethering of primase and DNA Pol α in the eukaryotic primosome.

The Pol α/primase complex or primosome is the primase/polymerase complex that initiates nucleic acid synthesis during eukaryotic replication. Within the primosome, the primase synthesizes short RNA primers that undergo limited extension by Pol α. The resulting RNA-DNA primers are utilized by Pol δ and Pol ε for processive elongation on the lagging and leading strands, respectively. Despite its importance, the mechanism of RNA-DNA primer synthesis remains poorly understood. Here, we describe a structural model of the yeast primosome based on electron microscopy and functional studies. The 3D architecture of the primosome reveals an asymmetric, dumbbell-shaped particle. The catalytic centers of primase and Pol α reside in separate lobes of high relative mobility. The flexible tethering of the primosome lobes increases the efficiency of primer transfer between primase and Pol α. The physical organization of the primosome suggests that a concerted mechanism of primer hand-off between primase and Pol α would involve coordinated movements of the primosome lobes. The first three-dimensional map of the eukaryotic primosome at 25 Å resolution provides an essential structural template for understanding initiation of eukaryotic replication.

Evolution of Quality of Life and Treatment Adherence after One Year of Intermittent Bladder Catheterisation in Functional Urology Unit Patients.

OBJECTIVE: To determine patient difficulties and concerns when performing IBC (Intermittent Bladder Catheterisation), as well as the evolution of adherence, quality of life, and emotional state of patients one year after starting IBC. METHOD: A prospective, observational, multicentre study conducted in 20 Spanish hospitals with a one-year follow-up. Data sources were patient records and the King's Health Questionnaire on quality of life, the Mini-Mental State Examination (MMSE), and the Hospital Anxiety and Depression Scale (HADS). Perceived adherence was measured using the ICAS (Intermittent Catheterization Adherence Scale) and perceived difficulties with IBC were assessed using the ICDQ (Intermittent Catheterization Difficulty Questionnaire). For data analysis, descriptive and bivariate statistics were performed for paired data at three points in time (T1: one month, T2: three months, T3: one year). RESULTS: A total of 134 subjects initially participated in the study (T0), becoming 104 subjects at T1, 91 at T2, and 88 at T3, with a mean age of 39 years (standard deviation = 22.16 years). Actual IBC adherence ranged from 84.8% at T1 to 84.1% at T3. After one year of follow-up, a statistically significant improvement in quality of life (p ≤ 0.05) was observed in all dimensions with the exception of personal relationships. However, there were no changes in the levels of anxiety (p = 0.190) or depression (p = 0.682) at T3 compared to T0. CONCLUSIONS: Patients requiring IBC exhibit good treatment adherence, with a significant proportion of them performing self-catheterisation. After one year of IBC, a significant improvement in quality of life was noted, albeit with a significant impact on their daily lives and their personal and social relationships. Patient support programmes could be implemented to improve their ability to cope with difficulties and thus enhance both their quality of life and the maintenance of their adherence.

Structural and functional characterization of an influenza virus RNA polymerase-genomic RNA complex.

The replication and transcription of influenza A virus are carried out by ribonucleoproteins (RNPs) containing each genomic RNA segment associated with nucleoprotein monomers and the heterotrimeric polymerase complex. These RNPs are responsible for virus transcription and replication in the infected cell nucleus. Here we have expressed, purified, and analyzed, structurally and functionally, for the first time, polymerase-RNA template complexes obtained after replication in vivo. These complexes were generated by the cotransfection of plasmids expressing the polymerase subunits and a genomic plasmid expressing a minimal template of positive or negative polarity. Their generation in vivo was strictly dependent on the polymerase activity; they contained mainly negative-polarity viral RNA (vRNA) and could transcribe and replicate in vitro. The three-dimensional structure of the monomeric polymerase-vRNA complexes was similar to that of the RNP-associated polymerase and distinct from that of the polymerase devoid of template. These results suggest that the interaction with the template is sufficient to induce a significant conformation switch in the polymerase complex.

Vascular calcification and 25-hydroxyvitamin D levels in non-dialysis patients with chronic kidney disease stages 4 and 5.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death among chronic kidney disease (CKD) patients. Vascular calcification is highly prevalent in this population and is an independent predictor of cardiovascular mortality. Vascular calcification in uraemic patients is known to be an active and regulated process subject to the action of many promoting and inhibitory factors. The role of vitamin D in this process remains controversial. We evaluated the relationship between serum levels of 25-hydroxyvitamin D (25(OH)D) and vascular calcification evaluated by plain X-ray images, in predialysis patients with CKD stages 4 and 5. METHODS: We performed a cross-sectional study with 210 CKD patients stages 4 and 5 managed at our predialysis unit. Patients were 63.5 ± 13 years of age, 60.5% males, 64.8% diabetics and 47.1% with a history of CVD. Plain X-ray images of pelvis, hands and lateral lumbar spine from all subjects were studied for calculation of semiquantitative vascular calcification scores as described by Adragao and Kauppila. RESULTS: We found a high prevalence of vascular calcification in our population. Adragao scores revealed only 47 patients (22.4%) without vascular calcification and 120 (57.1%) with scores higher than 3. Kauppila scores revealed only 29 patients (13.8%) without aortic calcifications and 114 patients (54.3%) with scores higher than 7. Higher vascular calcification scores were related to older age, diabetes, history of CVD and lower levels of 25(OH)D. Only 18.5% of patients had adequate levels of 25(OH)D (> 30 ng/mL), 53.7% of them had insufficient levels (15-30 ng/mL) and 27.8% had deficient levels (< 15 ng/mL). Multivariate analysis showed that age, diabetes and CVD were directly associated and 25(OH)D levels were inversely associated with vascular calcifications. CONCLUSIONS: Our results show an independent and negative association between serum levels of 25(OH)D and vascular calcification. Further and larger prospective studies are needed to clarify the possible role of vitamin D deficiency in the development of vascular calcification in CKD patients.

Quality of Life and Autonomy in Patients with Intermittent Bladder Catheterization Trained by Specialized Nurses.

Intermittent bladder catheterization (IBC) involves regular urine draining using a catheter, which is removed immediately after urinary elimination. It allows for the patient's urological health to be managed and their renal function to be preserved, and it promotes autonomy. Compliance with the prescribed number of daily catheterizations, which must be conducted by the patient, and infection prevention measures are crucial. To identify the patients requiring IBC, and to determine their adherence (whether they followed the prescribed guidelines and their difficulty in carrying out the procedure, as well as to assess how the IBC influences their quality of life and state of mind after receiving self-care training from a specialized nurse), we carried out a prospective, multicenter observational study in 24 Spanish hospitals with one month of monitoring and a sample of 99 patients. The sources of information were the patients' clinical records, the King's Health Questionnaire, the Mini-Mental State Examination (MMSE), and the hospital anxiety and depression scale (HADS). Descriptive and bivariate statistics were used to analyses the paired data. After recruitment (n = 99), 79 patients completed the questionnaire at a mean age of 35.2 years (SD = 20.5 years). In total, 53.5% (53) of the sample consisted of men and 32.3% (32) had neurological damage as the reason for prescription; 67% (67.7) performed self-catheterization and 86.7% adhered to the IBC. After one month of monitoring, a statistically significant improvement in quality of life was observed in all criteria, with the exception of personal relationships (p < 0.005), as well as an improvement in anxiety and depression levels (p < 0.001). Patients who require IBC show good adherence to the IBC with a significant percentage of self-catheterization. After one month of IBC, a significant improvement in the patients' quality of life and mood was observed. These results could be attributed to adequate patient training and adequate personalization of the IBC materials by the specialized nurses.

Conformational rearrangements upon Syk auto-phosphorylation.

Syk is a cytoplasmic tyrosine kinase that is activated after recruitment to immune receptors, triggering the phopshorylation of downstream targets. The kinase activity of Syk is controlled by an auto-inhibited conformation consisting of a regulatory region that contains two N-terminal Src homology 2 (SH2) domains inhibiting the catalytic activity of the kinase domain located at the C-terminus. The atomic structure of the related Zap-70 kinase and an electron microscopy (EM) model of Syk have revealed the structural mechanism of this auto-inhibition based on the formation of a compact conformation sustained by interactions between the regulatory and catalytic domains. On the other hand, the structural basis of Syk activation is not fully understood due to the lack of a 3D structure of full-length Syk in an active conformation. Here, we have used single-particle electron microscopy to analyse the conformational changes taking place in an activated form of Syk induced by auto-phosphorylation. The conformation of phosphorylated Syk is reminiscent of the compact structure of the inhibited protein but significant conformational changes are observed in the regulatory region. These rearrangements could be sufficient to disrupt the inhibitory interactions, contributing to Syk activation. These results suggest that the regulation of the activation of Syk might be modulated by subtle changes in the positioning of the regulatory domains rather than a full opening mechanism as proposed for the Src kinases.

[25 hydroxyvitamin D levels and cardiovascular risk in a cohort of patients with advanced chronic kidney disease]. / Niveles de 25 hidroxivitamina D y riesgo cardiovascular en una cohorte de pacientes con enfermedad renal crónica avanzada.

BACKGROUND: Decreased 25 hydroxyvitamin D serum levels have been related to an increase in cardiovascular morbility and mortality in both general population and chronic kidney disease patients. The aim of this study was to evaluate the relationship between 25 hydroxyvitamin D serum level, cardiovascular risk factors and previous established cardiovascular disease in a group of patients with advanced chronic kidney disease. MATERIAL AND METHODS: We performed a cross-sectional observational study in a cohort of 171 stage 4 and 5 chronic kidney disease outpatients seen in our predialysis clinic, mean age 64.16 +/- 13 years, 59.6% were men, 64.3% had diabetes, 47.3% had obesity, 46.8% had previous cardiovascular disease. 25 hydroxyvitamin D and 1-25 dihydroxyvitamin D were measured, we also determined other routine biochemical parameters. All subjects underwent an echocardiogram and 24 hours ambulatory blood pressure monitoring was also performed. RESULTS: Mean 25 hydroxyvitamin D levels were 22.1 +/- 13 ng/mL, only 18.7% of the patients had adequate levels, levels were insufficient in 58.5% of the patients and deficient in 22.8% of them. Low 25 hydroxyvitamin D levels were significantly related with age, diabetes, female gender, obesity, MDRD glomerular filtration rate and previous cardiovascular disease. Pulse pressure was the Ambulatory Blood Pressure Monitoring parameter that was better correlated with 25 hydroxyvitamin D levels. We could not find any association between vitamin D levels and other bone and mineral metabolism parameters. No relationship was seen between low vitamin D levels and left ventricular hypertrophy. On multivariate analysis lower levels of 25 hydroxyvitamin D were independently associated with female gender, previous cardiovascular disease, MDRD4-GFR and higher pulse pressure. CONCLUSIONS: Our study confirm a high prevalence of 25 hydroxyvitamin D insufficiency and deficiency in advanced chronic kidney disease patients, this was associated with the presence of cardiovascular risk markers and previous established cardiovascular disease. However we could not see any relationship with left ventricular hypertrophy which is a known predictor of future cardiovascular events in this population.

Effect of Sample Collection (Manual Expression vs. Pumping) and Skimming on the Microbial Profile of Human Milk Using Culture Techniques and Metataxonomic Analysis.

Human milk microbiota is a unique bacterial community playing a relevant role in infant health, but its composition depends on different factors (woman health, lactation stage, and geographical lactation). However, information is lacking regarding some other factors that may affect the bacterial community of human milk. In this study we aimed to study the impact of the sample collection method and the skimming procedure using culture-dependent and culture-independent techniques to study the human milk microbial profile. One set of milk samples was provided by women (n = 10) in two consecutive days; half of the samples were collected the first day by manual expression and the other half on the second day by pumping. The rest of the participants (n = 17) provided milk samples that were fractionated by centrifugation; the bacterial profiles of whole milk and skimmed milk were compared by culture techniques in 10 milk samples, while those of whole milk, fat and skimmed milk were subjected to metataxonomic analysis in seven samples. Globally, the results obtained revealed high interindividual variability but that neither the use of single-use sterile devices to collect the sample nor the skimming procedure have a significant impact of the microbial profile of human samples.

Microbiota of human precolostrum and its potential role as a source of bacteria to the infant mouth.

Human milk represents a source of bacteria for the initial establishment of the oral (and gut) microbiomes in the breastfed infant, however, the origin of bacteria in human milk remains largely unknown. While some evidence points towards a possible endogenous enteromammary route, other authors have suggested that bacteria in human milk are contaminants from the skin or the breastfed infant mouth. In this work 16S rRNA sequencing and bacterial culturing and isolation was performed to analyze the microbiota on maternal precolostrum samples, collected from pregnant women before delivery, and on oral samples collected from the corresponding infants. The structure of both ecosystems demonstrated a high proportion of taxa consistently shared among ecosystems, Streptococcus spp. and Staphylococcus spp. being the most abundant. Whole genome sequencing on those isolates that, belonging to the same species, were isolated from both the maternal and infant samples in the same mother-infant pair, evidenced that in 8 out of 10 pairs both isolates were >99.9% identical at nucleotide level. The presence of typical oral bacteria in precolostrum before contact with the newborn indicates that they are not a contamination from the infant, and suggests that at least some oral bacteria reach the infant's mouth through breastfeeding.

3D structure of Syk kinase determined by single-particle electron microscopy.

The cytoplasmic Syk kinase plays key roles in immune responses and comprises two N-terminal regulatory Src homology 2 (SH2) domains followed by a catalytic region. Atomic structures of these domains have only been solved in isolation. To gain insights into the three-dimensional structure of full-length Syk, we have used single-particle electron microscopy. Syk acquires a closed conformation resembling the inhibited structure of Zap-70, another member of the Syk family. Such configuration suggests an inhibition of the N-terminal domains on its catalytic activity. The phosphotyrosine binding pockets of both SH2 domains are not occluded and they could interact with other phosphoproteins.

The combined effect of pre-transplant triglyceride levels and the type of calcineurin inhibitor in predicting the risk of new onset diabetes after renal transplantation.

BACKGROUND: Insulin resistance precedes overt diabetes in the general population and hypertriglyceridemia is a reliable marker of the disorder. Thus, patients in the waiting list with hypertriglyceridemia may be at risk for new-onset diabetes after transplantation (NODAT). Objectives. We investigate whether pre-transplant triglyceride (TG) levels are a risk factor for NODAT and whether they exert a combined effect with the type of calcineurin inhibitor (CNI). METHODS: We analysed 314 consecutive non-diabetic recipients [215 cyclosporine A (CsA); 99 tacrolimus (Tacro)] transplanted between 1999 and 2003 with a mean follow-up of 34 months. Outcome was NODAT defined by ADA criteria. RESULTS: NODAT developed in 81 recipients (25.8%). Multivariate analysis which included a propensity score for factors determining CNI allocation showed that age (OR: 1.06; 95% CI: 1.03-1.09), pre-transplant BMI (OR: 1.1; 95% CI: 1.02-1.17),TG levels (OR: 1.3 per 50 mg/dl increment, 95% CI: 1.07-1.6) and treated acute rejection (OR: 4.8, 95% CI: 3-11), but not the type of CNI, were independent risk factors for NODAT. A significant interaction between pre-transplant TG and type of CNI was observed. Using CsA as the reference, the combination of Tacro plus pre-transplant hypertriglyceridemia (>/=200 mg/dl) showed an OR of 3.26 (1.4-7.8) to develop NODAT, contrasting with an OR of 0.75 (0.34-1.6) in Tacro recipients with pre-transplant TG levels <200 mg/dl. CONCLUSION: Pre-transplant hypertriglyceridemia was a risk factor for NODAT only in recipients treated with Tacro; it highlights the importance of pre-transplant insulin resistance in the pathogenesis of NODAT.

Randomized controlled study comparing reduced calcineurin inhibitors exposure versus standard cyclosporine-based immunosuppression.

BACKGROUND: Immunosuppressive regimens based on low doses of cyclosporine A (CsA) or tacrolimus (TAC) may improve short-term outcome after kidney transplantation (KT), but the optimal immunosuppressive protocol is currently unknown. METHODS: This study compared the 24-month efficacy and safety of two immunosuppressive regimens using reduced calcineurin inhibitors (CNIs) exposure with standard dosage of CsA in 240 patients who were randomized into three groups: group A (n=80): Thymoglobulin, CsA (4 mg/kg twice daily) plus azathioprine (1.5 mg/kg once daily); group B (n=80): basiliximab, CsA (2 mg/kg/ twice daily) plus mycophenolate mofetil (MMF; 1 g twice daily); and group C (n=80): basiliximab, TAC (0.05 mg/kg/ twice daily) plus MMF (1 g twice daily). Steroid administration was identical for all groups. RESULTS: A significantly better creatinine clearance at 12 months, estimated by Cockcroft-Gault (57+/-12, 65.2+/-20, 73.5+/-27 ml/min, P=0.044), the Jelliffe-2 (51.5+/-16, 56+/-19, 59.4+/-19 ml/min/1.73 m2, P=0.041) and the Modification of Diet in Renal Disease equations (53+/-17, 58.5+/-20, 61.6+/-22 ml/min/1.73 m2, P=0.035), was observed in group C compared with group A. No significant differences were observed between groups B and C. The incidence of biopsy-proven acute rejection was similar between groups (15%, 13.8%, and 16.3%). In addition, patient and graft survival at 24 months were not different between groups. Adverse effects were similar among groups, but cytomegalovirus infections was significantly higher in group A (41% vs. 20% vs. 25%; P=0.008). CONCLUSIONS: Immunosuppressive regimens with reduced CNI exposure provide similar preservation of renal function compared with standard dose of CsA after KT and do not lead to underimmunosuppression.

Response of ACTH to octreotide in a probable corticotropic adenoma associated with Addison's disease.

BACKGROUND: Our patient was a 65-year-old woman previously diagnosed with Addison's disease. She presented an empty sella turcica and, at the age of 47, was discovered to have autonomous hypersecretion of adrenocorticotropic hormone (ACTH), suggesting a corticotropic adenoma secondary to Addison's disease, with a lack of response to high levels of dexamethasone. She maintained high ACTH levels despite corticosteroid treatment. METHODS: The patient underwent a CRH stimulation test using an intravenous bolus (100 microg) with samples every 30 minutes for 3 hours and, the day after, an octreotide infusion (0.1 mg/200 cc saline) for 2 hours with measurements every 30 minutes for 3 hours. The following month she received subcutaneous octreotide 0.1 mg tid., and samples were taken every week. RESULTS: Thirty minutes after the corticotropic-releasing-hormone (CRH) stimulation test, baseline ACTH levels (1 063 pg/ml) increased to 1530, the other values lying between 1 020-862. After octreotide infusion, baseline ACTH (1 212 pg/ml) was 946-643-1 630-4 600-1 730 at 30-60-90-120-180 minutes. The following month, with octreotide treatment, serum ACTH levels were 454-768-1233-429 pg/ml each week. DISCUSSION: Octreotide acts mainly on somatostatin type 2 receptors (SSTR2) and has no effect in Cushing's syndrome, although a suppressor effect in some ACTH ectopic hypersecretions and in Nelson's syndrome has been demonstrated. It has been observed that SSTR5 appear more frequently than SSTR2 in corticotropic adenomas and corticosteroids downregulate octreotide sensitivity. CONCLUSIONS: Octreotide did not suppress secretion of ACTH in suspected corticotropic adenoma. Newer somatostatin analogues, acting mainly on SSTR5, may be able to control ACTH hypersecretion in cases such as this.

Impact of metabolic syndrome on graft function and survival after cadaveric renal transplantation.

BACKGROUND: The prevalence and consequences of metabolic syndrome after renal transplantation are not well established. Our aims are to analyze in a historic cohort of consecutive renal transplant recipients without diabetes: (1) the prevalence of metabolic syndrome and its evolution to de novo posttransplantation diabetes mellitus (PTDM), and (2) its impact on graft function and graft and patient survival. METHODS: We studied 230 transplant recipients with stable graft function at 1 year (baseline) and at least 18 months of follow-up (assessment date). Metabolic syndrome is defined using the Adult Treatment Panel III criteria with a slight modification. RESULTS: Metabolic syndrome was present in 22.6% of transplant recipients at baseline, increasing to 37.7% at assessment date. Transplant recipients with metabolic syndrome at baseline more frequently developed PTDM during follow-up than those without metabolic syndrome (P < 0.001). In multiple linear regression analysis, metabolic syndrome was an independent risk factor for decreasing inverse serum creatinine (1/Cr) during follow-up (P = 0.038). In Cox proportional analysis, the hazard ratio for a 30% decrease in 1/Cr over time was 2.6 (95% confidence interval, 1.3 to 5.1; P = 0.005). Graft survival was significantly lower in the metabolic-syndrome group (P = 0.008) and remained significant in multivariate Cox analysis (hazard ratios, 3 to 4.5 in different models). Patient survival also was significantly lower in the metabolic-syndrome group (P = 0.02). CONCLUSION: Metabolic syndrome is a prominent risk factor for PTDM, chronic graft dysfunction, graft loss, and patient death in renal transplant recipients. Because metabolic syndrome is a cluster of modifiable factors, prompt intervention may prevent its consequences.

Chlamydia trachomatis growth and development requires the activity of host Long-chain Acyl-CoA Synthetases (ACSLs).

The obligate-intracellular pathogen Chlamydia trachomatis (Ct) has undergone considerable genome reduction with consequent dependence on host biosynthetic pathways, metabolites and enzymes. Long-chain acyl-CoA synthetases (ACSLs) are key host-cell enzymes that convert fatty acids (FA) into acyl-CoA for use in metabolic pathways. Here, we show that the complete host ACSL family [ACSL1 and ACSL3-6] translocates into the Ct membrane-bound vacuole, termed inclusion, and remains associated with membranes of metabolically active forms of Ct throughout development. We discovered that three different pharmacologic inhibitors of ACSL activity independently impede Ct growth in a dose-dependent fashion. Using an FA competition assay, host ACSLs were found to activate Ct branched-chain FAs, suggesting that one function of the ACSLs is to activate Ct FAs and host FAs (recruited from the cytoplasm) within the inclusion. Because the ACSL inhibitors can deplete lipid droplets (LD), we used a cell line where LD synthesis was switched off to evaluate whether LD deficiency affects Ct growth. In these cells, we found no effect on growth or on translocation of ACSLs into the inclusion. Our findings support an essential role for ACSL activation of host-cell and bacterial FAs within the inclusion to promote Ct growth and development, independent of LDs.

Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

BACKGROUND AND OBJECTIVES: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. METHOD: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. RESULTS: Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. CONCLUSIONS: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.