Integrative phylogenetic, phylogeographic and morphological characterisation of the Unio crassus species complex reveals cryptic diversity with important conservation implications.

The global decline of freshwater mussels and their crucial ecological services highlight the need to understand their phylogeny, phylogeography and patterns of genetic diversity to guide conservation efforts. Such knowledge is urgently needed for Unio crassus, a highly imperilled species originally widespread throughout Europe and southwest Asia. Recent studies have resurrected several species from synonymy based on mitochondrial data, revealing U. crassus to be a complex of cryptic species. To address long-standing taxonomic uncertainties hindering effective conservation, we integrate morphometric, phylogenetic, and phylogeographic analyses to examine species diversity within the U. crassus complex across its entire range. Phylogenetic analyses were performed using cytochrome c oxidase subunit I (815 specimens from 182 populations) and, for selected specimens, whole mitogenome sequences and Anchored Hybrid Enrichment (AHE) data on âˆ¼ 600 nuclear loci. Mito-nuclear discordance was detected, consistent with mitochondrial DNA gene flow between some species during the Pliocene and Pleistocene. Fossil-calibrated phylogenies based on AHE data support a Mediterranean origin for the U. crassus complex in the Early Miocene. The results of our integrative approach support 12 species in the group: the previously recognised Unio bruguierianus, Unio carneus, Unio crassus, Unio damascensis, Unio ionicus, Unio sesirmensis, and Unio tumidiformis, and the reinstatement of five nominal taxa: Unio desectusstat. rev., Unio gontieriistat. rev., Unio mardinensisstat. rev., Unio nanusstat. rev., and Unio vicariusstat. rev. Morphometric analyses of shell contours reveal important morphospace overlaps among these species, highlighting cryptic, but geographically structured, diversity. The distribution, taxonomy, phylogeography, and conservation of each species are succinctly described.

Effect of an educational booklet for prevention and treatment of foot musculoskeletal dysfunctions in people with diabetic neuropathy: the FOotCAre (FOCA) trial II, a study protocol of a randomized controlled trial.

BACKGROUND: This study is a part of a series of two clinical trials. We consider diabetic polyneuropathy (DPN), a common chronic and progressive complication of diabetes mellitus that has several impacts on individuals' foot health and quality of life. Based on the current trends of self-monitoring and self-care, providing a tool with foot-related exercises and educational care may help patients to avoid or reduce the musculoskeletal complications resulting from DPN, improving autonomous performance in daily living tasks. The aim of this trial is to evaluate the effects of an educational booklet for foot care and foot muscle strengthening on DPN symptoms and severity, clinical outcomes, and gait biomechanics in patients with DPN. METHODS/DESIGN: The FOotCAre (FOCA) trial II study has been designed as a single-blind, two-parallel-arm randomized controlled trial. It will include 48 patients with DPN who will be randomly allocated to a control (recommended foot care by international consensus with no foot exercises) group or an intervention (foot-related exercises using an educational booklet three times/week at home for 8 weeks) group. Participants from both groups will be assessed at baseline, after 8 weeks, and at 16 weeks for follow-up. The primary outcomes are the DPN symptoms and severity, and the secondary outcomes are foot-ankle kinematics, gait kinetics, plantar pressure distribution during gait, tactile and vibratory sensitivities, foot strength, functional balance, and foot health and functionality. DISCUSSION: The booklet is a management tool that allows users to be autonomous in their treatment by choosing how and where to perform the exercises. This allows the patients to perform the exercises regularly as a continuous habit for foot care and health, which is an important element in the management of the diabetic foot. As the booklet focuses on specific foot-ankle exercises, we expect that it will improve the clinical aspects of DPN and produce beneficial biomechanical changes during gait, becoming a powerful self-management tool that can be easily implemented to improve the performance of daily living tasks. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04008745. Registered on 2 July 2019.

Study protocol for a randomized controlled trial on the effect of the Diabetic Foot Guidance System (SOPeD) for the prevention and treatment of foot musculoskeletal dysfunctions in people with diabetic neuropathy: the FOotCAre (FOCA) trial I.

BACKGROUND: This study is part of a series of two clinical trials. Taking into account the various musculoskeletal alterations of the foot and ankle in people with diabetic peripheral neuropathy (DPN) and the need for self-care to avoid more serious dysfunctions and complications, a self-manageable exercise protocol that focuses on strengthening the foot muscles is presented as a potentially effective preventive method for foot and gait complications. The aim of this trial is to investigate the effect of a customized rehabilitation technology, the Diabetic Foot Guidance System (SOPeD), on DPN status, functional outcomes and gait biomechanics in people with DPN. METHODS/DESIGN: Footcare (FOCA) trial I is a randomized, controlled and parallel two-arm trial with blind assessment. A total of 62 patients with DPN will be allocated into either a control group (recommended foot care by international consensus with no foot exercises) or an intervention group (who will perform exercises through SOPeD at home three times a week for 12 weeks). The exercise program will be customized throughout its course by a perceived effort scale reported by the participant after completion of each exercise. The participants will be assessed at three different times (baseline, completion at 12 weeks, and follow-up at 24 weeks) for all outcomes. The primary outcomes will be DPN symptoms and severity classification. The secondary outcomes will be foot-ankle kinematics and kinetic and plantar pressure distribution during gait, tactile and vibration sensitivities, foot health and functionality, foot strength, and functional balance. DISCUSSION: As there is no evidence about the efficacy of rehabilitation technology in reducing DPN symptoms and severity or improving biomechanical, clinical, and functional outcomes for people with DPN, this research can contribute substantially to clarifying the therapeutic merits of software interventions. We hope that the use of our application for people with DPN complications will reduce or attenuate the deficits caused by DPN. This rehabilitation technology is freely available, and we intend to introduce it into the public health system in Brazil after demonstrating its effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04011267. Registered on 8 July 2019.

Acute effects of human growth hormone on zinc, copper, calcium and magnesium metabolism in normal subjects.

The acute effects of human growth hormone (hGH) on the metabolism of zinc, copper, calcium and magnesium ions was studied. Seven normal subjects were perfused iv with doses of 0.2 or 1.0 mg hGH over a period of 60 min. An increase in plasma zinc, calcium and magnesium, and a decrease in plasma copper levels was noted for the 0.2 mg dose, and these effects were reversed for the 1.0 mg dose although no urine changes occurred. Plasma mobilization of these ions appears to be related to their roles as essential physiological modulators for the action of hGH.

Metabolic effects of glucagon on plasma and urine zinc, copper, calcium and magnesium levels.

The present study determines the effect of glucagon on the behavior of zinc, copper, calcium and magnesium ions in human plasma and urine. Five normal adults were submitted to intravenous infusion of 2.0 mg glucagon over a period of 120 min. A decrease in plasma magnesium and copper was observed with no significant change in urine ion concentrations. We related plasma magnesium mobilization to glucagon, and copper mobilization to plasma variation in free fatty acids and albumin.

The effect of the anticonvulsants phenobarbital and diphenylhydantoin on intestinal absorption of calcium.

The effect of anticonvulsant drugs (phenobarbital and diphenylhydantoin) on the metabolic balance of calcium and on its intestinal absorption, as measured by an in situ intraluminal perfusion method, was studied in rats. The administration of these drugs produced: (a) an increase of the fecal excretion of calcium,. (b) a decrease of the intestinal absorption of calcium (45Ca). Both effects were more intense in rats treated with phenobarbital. There is evidence to suggest that the anticonvulsant drugs affect the intestinal mechanism of active transport of calcium.

The effect of low-dose naloxone infusion on plasma ACTH and LH in patients with Cushing's and Addison's diseases.

The ACTH, cortisol and LH responses to low dose (0.8 mg/h) naloxone 90 min infusion were investigated in seven patients with untreated Cushing's disease, six patients with Addison's disease and four control subjects. Naloxone had no effects on ACTH hypersecretion or normal ACTH levels. These data confirm that naloxone cannot provide additional diagnostic or therapeutic approaches in ACTH hypersecretion syndromes, mainly in Cushing's disease. The mean percentage LH levels did not significantly change during low dose naloxone in controls or patients with Cushing's and Addison's diseases. This suggests that increased endogenous opioid peptides in these diseases may not modify the LH responses to low dose of naloxone. However, since three of five adults with Cushing's disease had increased LH levels during naloxone, further studies may be indicated.

HLA antigens and lymphocytes in proliferative vitreoretinopathy.

An immunohistopathological study was performed on 33 epiretinal membrane specimens obtained during vitreoretinal surgery from patients with rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy (PVR). Immunofluorescence and immunoperoxidase methods were used to detect major histocompatibility complex or HLA antigens and immunocompetent cells, and to identify the cellular and the extracellular component of the proliferative tissue. The following antigens were detected in epiretinal membranes: cytokeratin in 18 (of 18 cases studied for this antigen), glial fibrillary acidic protein in 20 (of 20), vimentin in 20 (of 20), actin in 16 (of 18), fibronectin in 20 (of 20), macrophage CD68 in 16 (of 18), leukocyte common antigen in 12 (of 18), T-cell CD45R in 13 (of 22), HLA-ABC in 27 (of 33), HLA-DR in all the 33 membranes and HLA-DR alpha chain in 32 of 33 membranes. We observed the presence of macrophages and of an activated T-cell population in PVR membranes. HLA-DR antigen expression was found on pigmented and nonpigmented epithelial cells and on mononuclear cells in all epiretinal membranes. The HLA-DR expression on retinal pigmented epithelial cells could play a role in triggering a local immune response in PVR. These findings suggest the involvement of immunological phenomena and probable interactions between the immune system and peptide growth factors.

Pubertal maturation of the lh stimulatory response to clomiphene citrate in congenital virilizing adrenal hyperplasia.

To determine the LH release response to clomiphene citrate in children with virilizing congenital adrenal hyperplasia (CAH), we examined six patients with glucocorticoid-treated virilizing CAH, five girls and one boy, chonological age (CA) 4 years 2 months-15 years 9 months and bone age (BA) range 8-18 years. All the patients but one, were treated with nocturnal dexamethasone. Their ages at the onset of treatment ranged from 2 years 6 months to 13 years 8 months. An additional boy (CA = 4 years 3 months and BA = 7-8 years) was studied 10 days after removal of a virilizing adrenal adenoma. Clomiphene citrate (3mg/kg/day) was administered orally in two doses/day for 8 days. Venous blood was collected on days 0, 4, 6 and 8. Two patients were also studied in consecutive years. In three patients no increase was noted over the basal levels of LH, but in the others LH rose during clomiphene administration. In two patients studied in consecutive years, there was detectable shift of LH release pattern. The basal LH levels and the sum of responses (day 4, 6 and 8) to clomiphene citrate and particularly their decimal logarithms were statistically significantly correlated with their respective BA. These results confirm that previous prolonged exposure to elevated concentrations of adrenal sex steroids, in children with treated virilizing CAH, may induce precocious maturation of the hypothalamic pubertal mechanism of LH secretion. This maturation was closely correlated with the degree of skeletal maturation.