BACKGROUNDContinuous glucose monitoring (CGM) provides important information to aid in achieving glycemic targets in people with diabetes. PURPOSEWe performed a meta-analysis of randomized controlled trials (RCTs) comparing CGM with usual care for parameters of glycemic control in both type 1 and type 2 diabetes. DATA SOURCESMany electronic databases were searched for articles published from inception until 30 June 2019. STUDY SELECTIONWe selected RCTs that assessed both changes in HbA 1c and time in target range (TIR), together with time below range (TBR), time above range (TAR), and glucose variability expressed as coefficient of variation (CV). DATA EXTRACTIONData were extracted from each trial by two investigators. DATA SYNTHESISAll results were analyzed by a random effects model to calculate the weighted mean difference (WMD) with the 95% CI. We identified 15 RCTs, lasting 12-36 weeks and involving 2,461 patients. Compared with the usual care (overall data), CGM was associated with modest reduction in HbA 1c (WMD 20.17%, 95% CI 20.29 to 20.06, I 2 5 96.2%), increase in TIR (WMD 70.74 min, 95% CI 46.73-94.76, I 2 5 66.3%), and lower TAR, TBR, and CV, with heterogeneity between studies. The increase in TIR was significant and robust independently of diabetes type, method of insulin delivery, and reason for CGM use. In preplanned subgroup analyses, real-time CGM led to the higher improvement in mean HbA 1c (WMD 20.23%, 95% CI 20.36 to 20.10, P < 0.001), TIR (WMD 83.49 min, 95% CI 52.68-114.30, P < 0.001), and TAR, whereas both intermittently scanned CGM and sensor-augmented pump were associated with the greater decline in TBR. LIMITATIONSHeterogeneity was high for most of the study outcomes; all studies were sponsored by industry, had short duration, and used an open-label design. CONCLUSIONSCGM improves glycemic control by expanding TIR and decreasing TBR, TAR, and glucose variability in both type 1 and type 2 diabetes.

Background and Objective Neutropenia, a low absolute neutrophil count (ANC), may be a sign of new‐onset hyperthyroidism. The aim of this systematic review and meta‐analysis was to provide the most reliable estimates of prevalence, degree and response to treatments of neutropenia in the pure hyperthyroidism setting. Methods A comprehensive literature search was performed in PubMed and Scopus databases for retrieving articles in English and non‐English languages reporting ANC values/neutropenic cases at presentation and after therapy in patients with hyperthyroidism. A proportion meta‐analysis was performed with DerSimonian and Laird method (random‐effects model). Pooled data were presented with 95% confidence intervals (95% CI) and displayed in a forest plot. I2 statistic index was used to quantify the heterogeneity among the studies. Sensitivity analyses for the prevalence of neutropenia and the mean of ANC in hyperthyroid patients were performed by excluding the studies without full details. Trim and fill analysis and Egger's linear regression test were carried out to evaluate the publication bias. A two‐sided P‐value of <.05 was regarded as significant for all analyses. The National Heart, Lung and Blood Institute Quality Assessment Tool was used to evaluate the quality of studies included. Results The literature search yielded 1880 studies of which 13 studies were included for systematic review and meta‐analysis. Results of the meta‐analysis demonstrated that the prevalence of neutropenia in newly diagnosed and untreated patients with Graves’ hyperthyroidism was 10% (CI 5%‐19%, I2 88.6%) and summary mean ANC value in neutropenic was 1.4 ± 0.3 × 109/L. In all neutropenic patients under ATD therapy neutropenia resolved, thus without the worsening of the baseline ANC values or the development of agranulocytosis. The sensitivity analyses showed similar results as those of the main analyses. For all outcomes, the publication bias was not statistically significant or not calculable. Conclusions Graves’ disease per se is associated with neutropenia in about 10% of cases. Neutropenia usually appears as a mild to moderate laboratory abnormality with no detectable consequences. Subnormal/mild neutropenia should not be regarded as a contraindication to use ATDs, and clinicians should know that treating hyperthyroidism they have a significant chance to normalize ANC too.

The Mediterranean coastline is a dynamic and complex system which owes its complexity to its past and present vicissitudes, e.g. complex tectonic history, climatic fluctuations, and prolonged coexistence with human activities. A plant species that is widespread in this habitat is the sea daffodil, Pancratium maritimum (Amaryllidaceae), which is a perennial clonal geophyte of the coastal sands of the Mediterranean and neighbouring areas, well adapted to the stressful conditions of sand dune environments. In this study, an integrated approach was used, combining genetic and environmental data with a niche modelling approach, aimed to investigate: (1) the effect of climate change on the geographic range of this species at different times {past (last inter-glacial, LIG; and last glacial maximum, LGM), present (CURR), near-future (FUT)} and (2) the possible influence of environmental variables on the genetic structure of this species in the current period. The genetic results show that 48 sea daffodil populations (867 specimens) display a good genetic diversity in which the marginal populations (i.e. Atlantic Sea populations) present lower values. Recent genetic signature of bottleneck was detected in few populations (8%). The molecular variation was higher within the populations (77%) and two genetic pools were well represented. Comparing the different climatic simulations in time, the global range of this plant increased, and a further extension is foreseen in the near future thanks to projections on the climate of areas currently—more temperate, where our model suggested a forecast for a climate more similar to the Mediterranean coast. A significant positive correlation was observed between the genetic distance and Precipitation of Coldest Quarter variable in current periods. Our analyses support the hypothesis that geomorphology of the Mediterranean coasts, sea currents, and climate have played significant roles in shaping the current genetic structure of the sea daffodil especially during LGM because of strong variation in coastline caused by glaciations.

The phylogenetics and biogeography of Pancratium (Amaryllidaceae) were investigated, with a focus on the Mediterranean and adjacent areas, with the aim of contributing new information towards a better understanding of the evolutionary history of the genus and the taxonomic placement of P. linosae and P. hirtum. To address these questions, we sequenced four plastid DNA markers: the ndhF and rbcL genes, the trnL(UAA)–trnF(GAA) intergenic spacer and the trnL(UAA) intron, analysing them using parsimony, likelihood and Bayesian approaches. The results show that the relationships among the majority of the species are resolved; however, the relationships of one of the major clades of the genus are unresolved compared with the others. The phylogenetic and the dispersal–vicariance analyses show that Pancratium appears as a well‐structured group with interesting patterns of speciation. Notably, P. arabicum and P. linosae fall within the P. maritimum complex. In addition, P. hirtum is identical, in terms of plastid DNA sequences, to the P. trianthum accessions. The results provide new insights and help to formulate new working hypotheses for evolutionary biology of the genus. © 2012 The Linnean Society of London, Botanical Journal of the Linnean Society, 2012, 170, 12–28.

Our investigation aims to understand the genetic structure and evolutionary history of Petagnaea gussonei, an ancient and endangered species belonging to the Saniculoideae subfamily (Apiaceae). It is paleoendemic to Sicily, with a small number of populations in the Nebrodi Mountains. A\ud total of seven chloroplast microsatellite repeat loci and 12 AFLP primer combinations were used to screen 115 individuals\ud corresponding to 17 populations. The ratio of seed to pollen flow was also calculated using the modified Ennos equation. A relatively high level of genetic diversity was detected with AFLPs (e.g., 0.045\H\0.278), and a moderate variation was also found using cpSSRs (0\Hk\0.667). Two different haplotypes (B and W) were\ud identified, with five populations being monomorphic for haplotype B. There was no genetic differentiation on the basis\ud of haplotypic frequency (GST) and similarity (RST), and no phylogeographic structure was detected among the populations. AFLP values also confirmed that the populations are\ud not very genetically differentiated. The principal component analysis based on pairwise genetic differences showed three\ud groupings without a geographical correlation. The AMOVA analysis indicates that theamount of variation is higher within\ud populations (82 %) than among populations (18 %). Results of the pollen flow/seed flow ratio indicated positive values for\ud each population, indicating that gene flow by seed is not more efficient than by pollen. Instead, the total pollen/seed flow for all population presents a negative value, suggesting that pollen dispersal does not appear to be more effective over the\ud long range for gene flow than seed dispersal. This differentiation level supports the hypothesis that the fragmentation and isolation of the residual populations is in progress. This\ud phenomenon is due not only to post-ice age climate changes, but also to direct and indirect anthropic actions

Context Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a severe chronic illness which reduces the quality of life. A potential role of neuroendocrine autoimmune dysfunction has been hypothesized. Objective To investigate the occurrence of anti-pituitary (APA) and anti-hypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunctions in ME/CSF patients. Design, Setting, Patients and Other Participants This is a case-control study conducted in University Hospital setting (Stanford, Naples). Thirty women with ME/CSF (Group 1) diagnosed according to Fukuda, Canadian, and IOM criteria, at Stanford University, were enrolled and compared with 25 age-matched healthy controls. Main Outcome Measures APA and AHA were detected by immunofluorescence; moreover, we investigated hormonal secretions of anterior pituitary and respective target glands and plasma and urinary osmolality. Both APA and AHA titers were assessed and the prevalence of pituitary hormone deficiencies was also investigated. Results Patients in Group 1 showed a high prevalence of AHA (33%) and APA (56%) and a significant lower levels of ACTH/cortisol, and GH peak/IGF1 vs controls (all AHA/APA negative). Patients in Group 1A (13 patients positive at high titers, ≥1:32) showed ACTH/cortisol and GH peak/ IGF1 levels significantly lower and more severe forms of ME/CFS with respect to patients in Group 1B (7 positive at middle/low titers,1:16-1:8) and 1C (10 Ab negative patients). Conclusions Both AHA and/or APA at high titers associated with hypothalamic/pituitary dysfunction suggest that hypothalamic/pituitary autoimmunity may play an important role in the manifestations of ME/CFS, especially in its more severe forms.

Pancratium maritimum L. (Amaryllidaceae) is a bulbous perennial plant growing on coastal sands of Mediterranean, Black and Caspian seas as well as on part of European coasts of Atlantic Ocean. The excess of flowers sampling, urbanization and tourism put serious threats to the species, resulting in a significant decrease of its populations. In order to investigate its conservation genetics, we developed and characterized microsatellite markers in P. maritimum. Twenty-one microsatellite loci were isolated using the SSRpatchwork protocol. The average number of alleles per locus was 4.4. Polymorphic information content value ranged from 0 to 0.75 with an average of 0.39. Eleven loci showed significant departures from Hardy–Weinberg equilibrium

Hybridization and introgression events between lineages ancestral to modern central and eastern North American Platanus species occurred. Plastid haplotypes and qualitative and quantitative SNP genotyping provide information critical for understanding the complex history of Mexican Platanus. Compared with the usual molecular techniques of sub-cloning, sequencing and genotyping, real-time PCR assay is a quick and sensitive technique for analysing complex evolutionary patterns.