Search

PurposeData on myopia progression during its entire course are scarce. The aim of this study is to investigate myopia progression in Europeans as a function of age and degree of myopia from first prescription to final refractive error.MethodsThe Drentse Refractive Error and Myopia Study assessed data from a branch of opticians in the Netherlands from 1985 onwards in a retrospective study. First pair of glasses prescribed was defined as a spherical equivalent of refraction (SER) ≤−0.5 D to ≥−3.0 D. Subjects with prescriptions at an interval of at least 1 year were included in the analysis.ResultsA total of 2555 persons (57.3% female) met the inclusion criteria. Those with first prescription before the age of 10 years showed the strongest progression (−0.50 D; IQR: −0.75 to −0.19) and a significantly (pConclusionOur trajectories of the natural course of myopia progression may serve as a guide for myopia management in European children. SER at 10 years is an important prognostic indicator and will help determine treatment intensity.

The brown marmorated stink bug (BMSB), Halyomorpha halys, has caused significant agricultural damage to numerous hosts, so agricultural producers seek to limit its spread. Where established, BMSB can also cause substantial urban and commercial disturbance, as overwintering adults may seek refuge inside dwellings, covered spaces, vehicles, and consignments. Phytosanitary authorities are most concerned with the importation of 'hitchhiking' adults in this refugia, with certain countries requiring a quarantine treatment to mitigate risk. This study explores fumigation with ethyl formate, applied as 16.7% by mass dilution in carbon dioxide, for control of adult BMSB.The induction of diapause, to simulate overwintering physiology, resulted in 2- and 3-fold increases in the tolerance of adults toward this ethyl formate fumigation at 10 ± 0.5 °C (The toxicity of ethyl formate in this mixture can be distinct for different physiological states of the same life stage, as evidenced by a ca. 3-fold increase in the Haber's z parameter for adult BMSB when in diapause. Respective to the physiological state of adults, this study identifies how the applied dose and/or treatment duration can be modulated (i.e. tuned) to ensure adequate toxicological efficacy toward BMSB infesting hosts or refuge at temperatures ca.10 °C. Published 2022. This article is a U.S. Government work and is in the public domain in the USA.

The correct time for harvesting is a key factor contributing to the production of high-quality maize seeds. We conducted field experiments to harvest seeds at 11 developmental stages for 3 years, to investigate seed vigor traits in three early maturity maize varieties and two late maturity varieties in one location.Significant correlations (r = 0.72 ~ 0.89) were found among six seed-related traits: standard germination (SG), accelerated aging germination (AAG), cold test germination (CTG), hundred-seed weight (HSW), seed moisture content (SMC), and ≥ 10 °C accumulated temperature from pollination to harvest (AT10). Analysis of variance showed that harvest stage, year, and variety had significant effects on all traits, and harvest stage displayed the greatest effect. The responses of SG, AAG, CTG, HSW and SMC to harvest stage fitted quadratic models, and AT10 fitted a linear model. From the quadratic models, an ideal harvest time (IHT, the final date to reach maximum SG, AAG, and CTG) could be calculated for each variety. The three early maturity varieties reached their IHT at 54.94-58.44 days after pollination (DAP); the two later maturity varieties reached IHT several days later (at 59.87-59.90 DAP). The early maturity varieties consistently required less AT10 to reach the IHT than the later maturity varieties. However, all of the varieties reached the IHT at similar SMC levels of about 35%.The later maturity varieties reached the IHT at later DAPs when they acquired more AT10 than the early maturity varieties but both reached it at similar SMC levels. © 2022 Society of Chemical Industry.

Our objective was to systematically evaluate the efficacy and safety of intravenous (IV) iron therapy for treating anaemia in critically ill adults (16 years) admitted to intensive care or high dependency units. We excluded quasi-RCTs and other not truly randomised trials. We searched 7 electronic databases (including CENTRAL, MEDLINE, and Embase) using a pre-defined search strategy from inception to June 14, 2021. One reviewer screened, extracted, and analysed data, with verification by a second reviewer of all decisions. We used Cochrane risk of bias (ROB) 1 and GRADE to assess the certainty of the evidence. We reported 3 comparisons across 1198 patients, in 8 RCTs: (1) IV iron vs control (7 RCTs, 748 participants); our primary outcome (hemoglobin (Hb) concentration at 10 to 30 days) was reported in 7 of the 8 included trials. There was evidence of an effect (very-low certainty) in favour of IV iron over control in the main comparison only (6 RCTs, n = 528, mean difference (MD) 0.52g/dL [95%CI 0.23, 0.81], P = .0005). For the remaining outcomes there was no evidence of an effect in either direction (low certainty of evidence for Hb concentration at10 days; very-low certainty of evidence for hospital duration, ICU duration, hospital readmission, infection, mortality; HRQoL outcomes were not GRADED). (2) IV iron + subcutaneous erythropoietin (EPO) vs control (2 RCTs, 104 participants); reported outcomes showed no evidence of effect in either direction, based on very-low certainty evidence (Hb concentration at 10-30 days, and10 days, infection, mortality). (3) Hepcidin-guided treatment with IV iron or iron+ EPO vs standard care (1 RCT, 399 participants) reported evidence of an effect in favour of the intervention for 90-day mortality (low certainty of evidence), but no other group differences for the reported outcomes (low certainty evidence for Hb concentration at 10-30 days, hospital duration; HRQoL was not GRADED). The evidence across all comparisons was downgraded for high and unclear ROB for lack of blinding, incomplete outcome data, baseline imbalance, and imprecision around the estimate (wide CIs and small sample size). In conclusion, the current evidence continues to support further investigation into the role for iron therapy in increasing Hb in critically ill patients. Recent, small, trials have begun to focus on patient-centred outcomes but a large, well conducted, and adequately powered trial is needed to inform clinical practice.

Impaired family functioning has been associated with obesity in children and adolescents, but few longitudinal studies exist. We examined whether family functioning from early to mid-childhood is associated with overweight and obesity in later childhood and adolescence.We examined data from the Quebec Longitudinal Study of Child Development (QLSCD), a birth cohort (N = 2120), collected between 1998 and 2011. Parent-reported family functioning was assessed at 4 time points between ages 0.5 and 8 years using the McMaster Family Assessment Device with established cut-offs for impaired family functioning. Participants were classified as having experienced: 1) early-childhood impaired functioning, 2) mid-childhood impaired functioning, 3) both early and mid-childhood impaired functioning, or 4) always healthy family functioning. Overweight and obesity were determined at 10- and 13-years using WHO criteria. Covariate adjusted multinomial logistic regressions were fitted to the data to examine associations between longitudinal family functioning groups (using the always healthy functioning as reference category) and the likelihood of having overweight and obesity (vs normal weight) at ages 10 (n = 1251) and 13 years (n = 1226).In the 10- and 13-year sub-samples, respectively 10.2% and 12.5% of participants had experienced both early and mid-childhood impaired family functioning. Participants in this group had an increased likelihood of having obesity (vs normal weight) at age 10 years [OR = 2.63 (95% CI: 1.36; 5.08)] and at age 13 years [OR = 1.94 (95% CI: 0.99; 3.80] compared to those in the always healthy functioning group. No associations were found for other family functioning categories or for overweight status.Approximately one in ten children experienced impaired family functioning throughout early and mid-childhood. Findings suggest a link between impaired functioning across childhood and the development of obesity at 10 years of age and possibly at 13 years of age.

BackgroundIn high-resource settings, postponing the interruption of cardiopulmonary resuscitation from 10 to 20 min after birth has been recently suggested, but data from low-resource settings are lacking. We investigated the outcome of newborns with Apgar scores of 0–1 at 10 min of resuscitative efforts in a low-resource setting.MethodsThis observational substudy from the NeoSupra trial included all 49 late preterm/full-term newborns with Apgar scores of 0–1 at 10 min of resuscitation. The study was carried out at Mulago National Referral Hospital (Kampala, Uganda) between May 2018 and August 2019. Outcome measures were mortality and hypoxic-ischaemic encephalopathy in the first week of life. All resuscitations were video recorded and daily reviewed by trial researchers.ResultsMedian duration of resuscitation was 32 min (IQR 17–37). Advanced resuscitation was provided to 21/49 neonates (43%). Overall, 48 neonates (98%) died within 2 days of life (44 in the delivery room, three on the first day and one on the second day) and one survived at 1 week with severe hypoxic-ischaemic encephalopathy.ConclusionOur study adds information from a low-resource setting to the recent evidence from high-resource settings about prolonging the resuscitation in infants with Apgar scores of 0–1 at 10 min. The vast majority died in the delivery room despite prolonged resuscitative efforts. We confirm that duration of resuscitation should be tailored to the setting, while the focus in low-resource settings should be improving the quality of antenatal and immediately after birth care.

To tackle growing antibiotic resistance (AR) and hospital-acquired infections (HAIs), novel antimicrobials are warranted that are effective against HAIs and safer for human use. We hypothesize that small 5 nm size positively charged nanoparticles could specifically target bacterial cell wall and adherent fimbriae expression, serving as the next generation antibacterial agent. Herein we show highly positively charged, 5 nm amino-functionalized silver nanoparticles (NH2–AgNPs) were bactericidal; highly negatively charged, 45 nm citrate-functionalized AgNPs (Citrate–AgNPs) were nontoxic; and Ag+ ions were bacteriostatic forming honeycomb-like potentially resistant phenotype, at 10 µg Ag/mL in E. coli. Further, adherent fimbriae were expressed with Citrate–AgNPs (0.5–10 µg/mL), whereas NH2–AgNPs (0.5–10 µg/mL) or Ag+ ions (only at 10 µg/mL) inhibited fimbriae expression. Our results also showed no lipid peroxidation in human lung epithelial and dermal fibroblast cells upon NH2–AgNPs treatments, suggesting NH2–AgNPs as a biocompatible antibacterial candidate. Potent bactericidal effects demonstrated by biocompatible NH2–AgNPs and the lack of toxicity of Citrate–AgNPs lend credence to the hypothesis that small size, positively charged AgNPs may serve as a next-generation antibacterial agent, potentially addressing the rising HAIs and patient health and safety.

A spinner knob attached to the steering wheel enables one-handed driving. However, changes in steering performance and muscle activity of the upper extremity based on the differences in the position of the knob are unknown.To quantify changes in steering performance and their muscle activity according to the position of the knob.Twenty right-handed healthy men with a mean age of 30.9 years participated in the study. Steering operation (reaction time, accuracy, right-left balance and adaptability) as assessed by steering with both hands and left one-handed driving with the spinner knob at three positions (8, 10, and 12 o'clock) were evaluated using a driving simulator. Muscle activities of the left anterior deltoid, biceps brachii and long head of the triceps brachii during the simulated tasks were also recorded using a wireless surface electromyography.Muscle activity while steering with the knob at 8 o'clock was significantly lower than with the knob at 10 or 12 o'clock, and was equivalent to the steering performance and muscle activity when driving with both hands. On the other hand, muscle activity while driving with the knob at 10 o'clock was significantly higher than with the knob in the other positions.The present study provides basic data for determining the position of the spinner knob attached to the steering wheel when driving one-handed with the non-dominant left hand. Positioning of the knob at 8 o'clock can be recommended on the basis of steering performance and lower muscle activities.IMPLICATIONS FOR REHABILITATIONThe safe driving of an automobile requires the driver to have an adequate range of motion and advanced voluntary motor control of the upper and lower extremities.When steering with the bilateral hands becomes difficult and driving with one-hand is required, it is necessary to attach a spinner knob on the steering wheel.This study provides objective and valuable information for clinicians and therapists to determine the optimum position of the spinner knob.

Many mammalian species use photoperiod as a predictive cue to time seasonal reproduction. In addition, metabolic effects on the reproductive axis may also influence seasonal timing, especially in female small, short-lived mammals. To get a better understanding of how annual cycling environmental cues impact reproductive function and plasticity in small, short-lived herbivores with different geographic origins, we investigated the mechanisms underlying integration of temperature in the photoperiodic-axis regulating female reproduction in a Northern vole species (tundra vole, Microtus oeconomus) and in a Southern vole species (common vole, Microtus arvalis). We show that photoperiod and temperature interact to determine appropriate physiological responses; there is species-dependent annual variation in the sensitivity to temperature for reproductive organ development. In common voles, temperature can overrule photoperiodical spring-programmed responses, with reproductive organ mass being higher at 10°C than at 21°C, whereas in autumn they are less sensitive to temperature. These findings are in line with our census data, showing an earlier onset of spring reproduction in cold springs, while reproductive offset in autumn is synchronized to photoperiod. The reproductive organs of tundra voles were relatively insensitive to temperature, whereas hypothalamic gene expression was generally upregulated at 10°C. Thus, both vole species use photoperiod, whereas only common voles use temperature as a cue to control spring reproduction, which indicates species-specific reproductive strategies. Due to global warming, spring reproduction in common voles will be delayed, perhaps resulting in shorter breeding seasons and thus declining populations, as observed throughout Europe.

Aim: Despite males typically exhibiting greater muscle strength and fatigability than females, it remains unclear if there are sex-based differences in neuromuscular recruitment strategies e.g. recruitment and modulation of motor unit firing rate (MU FR) at normalized forces and during progressive increases in force. Methods: The study includes 29 healthy male and 31 healthy female participants (18-35years). Intramuscular electromyography (iEMG) was used to record individual motor unit potentials (MUPs) and near-fibre MUPs from the vastus lateralis (VL) during 10% and 25% maximum isometric voluntary contractions (MVC), and spike-triggered averaging was used to obtain motor unit number estimates (MUNE) of the VL. Results: Males exhibited greater muscle strength (P

Cardiovascular disease (CVD) is the leading cause of death in women. The risk of CVD increases in women after menopause. The aim was to study how sleep parameters and cardiovascular risk factors in 46-year-old women predict future carotid intima-media thickness (IMT) 10 years after.Prospective study of 92 healthy women, aged 46 years, were studied at baseline and at 10-year follow-up. Polysomnography for sleep and breathing; blood samples for cholesterol, glucose and follicle stimulating hormone; blood pressure (BP), weight and height measurements; questionnaires for background variables and vasomotor symptoms were carried out at both time points. Carotid ultrasound was scanned for IMT at 10-year follow-up.After adjusting for conventional risk factors, apnea-hypopnea index (AHI) during rapid-eye-movement (REM) sleep was the only parameter at baseline that predicted IMT 10 years after (IMT mean: β 81.4 [95% CI, 14.0-148.8]; IMT max: β 104.7 [95% CI, 15.4-194.1]). At 10-year follow-up, higher arousal index (IMT mean: β 55.6 [95% CI, 19.5-91.8]; IMT max β 59.9 [95% CI, 11.4-108.4]) and lower vasomotor symptoms (IMT max: β -60.5 [95% CI, -119.0 to -2.0]) were associated with concurrent higher IMT. The conventional risk factors at baseline did not associate with future IMT but 10 years after higher concurrent HbA1c (IMT mean: β 11.0 [95% CI, 3.4-18.5]; IMT max β 14.0 [95% CI, 4.1-23.8]) and systolic BP (IMT mean: β 2.4 [95% CI, 1.1-3.7]; IMT max: β 2.7 [95% CI, 1.03 to 4.53]) were associated with higher IMT.In healthy 46-year-old women, AHI during REM sleep predicted IMT 10 years after. The conventional risk factors (HbA1c and BP) only associated with the concurrent IMT at 10-year follow-up.

One of the key components that affects soil productiveness, plant growth, and crop quality is fertilization. The effect of fertilizer, both organic and chemical, on the extremely acidic (pH 4.10) sandy loam soil chemical properties, yield, and quality of white mugwort grown were evaluated in this study. The field experiment arranged in a randomized complete block design, with four replications was conducted in Prachin Buri province, Thailand. There were six treatments, no fertilization (control), chemical fertilizer (25-7-7 + 46-0-0) applied at 187.50 (66.56 N:6.77 P2O5:6.77 K2O kg ha-1) kg ha-1 and applied at 375.00 (133.12 N:13.13 P2O5:13.13 K2O kg ha-1) kg ha-1, chicken manure applied at 3.36, 6.72, and 10.08 t ha-1. After harvesting, application of chicken manure tended to increase soil organic matter compared to the control, however, the application of chemical fertilizer did not show the same effect. The fresh weight of white mugwort increased with the rise in both fertilizer levels. Chicken manure application at 10.08 t ha-1 produced the highest fresh weight at all times. The level of accumulated nitrate was significantly greater when fertilizer rates increased. In addition, the total phenolic content of the white mugwort fertilized with chicken manure was higher than that fertilized with chemical fertilizer. However, there was no association between the DPPH radical scavenging capacity at harvesting times and different fertilization. Based on the results, chicken manure applied at 10.08 t ha-1 gave the best yield and higher total phenolic content of white mugwort, which was probably due to the improved soil organic matter.

ObjectiveThis study was undertaken to determine whether the vertical parasagittal approach or the lateral peri-insular/peri-Sylvian approach to hemispheric surgery is the superior technique in achieving long-term seizure freedom.MethodsWe conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri-insular/peri-Sylvian, or lateral trans-Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time-to-eventmethod andcalculated using the Kaplan-Meier survival method.ResultsData for 672 participants across 23 centers were collected on the specific hemispherotomy approach. Of these, 72 (10.7%) underwent vertical parasagittalhemispherotomy and 600 (89.3%) underwent lateral peri-insular/peri-Sylvian or trans-Sylvian hemispherotomy. Seizure freedom was obtained in 62.4% (95% confidence interval [CI]=53.5%-70.2%) of the entire cohort at 10-year follow-up. Seizure freedom was 88.8% (95% CI=78.9%-94.3%) at 1-year follow-up and persisted at 85.5% (95% CI=74.7%-92.0%) across 5- and 10-year follow-up in the vertical subgroup. In contrast, seizure freedom decreased from 89.2% (95% CI=86.3%-91.5%) at 1-year to 72.1% (95% CI=66.9%-76.7%) at 5-year to 57.2% (95% CI=46.6%-66.4%) at 10-year follow-up for the lateral subgroup. Log-rank test found that vertical hemispherotomy was associated with durable seizure-free progression compared to the lateral approach (p=.01). Patients undergoing the lateral hemispherotomy technique had a shorter time-to-seizure recurrence (hazard ratio=2.56, 95% CI=1.08-6.04, p=.03) and increased seizure recurrence odds (odds ratio=3.67, 95% CI=1.05-12.86, p=.04) compared to those undergoing the vertical hemispherotomy technique.SignificanceThis pilot study demonstrated more durable seizure freedom of the vertical technique compared to lateral hemispherotomy techniques. Further studies, such as prospective expertise-based observational studies or arandomized clinical trial, are required to determine whether a vertical approach to hemispheric surgery provides superior long-term seizure outcomes.

Introduction. Hypoparathyroidism after hyroidectomy is treated with oral calcium and vitamin-D supplements. Everyday prolonged use of calcium and vitamin D medications can lead sometimes to hypercalcemia that can cause Akute Kidney Injury (AKI) and Arterial Hypertension. We report on a clinical case of a man patient with postoperative hypoparathyroidism who presented with hypercalcemia, AKI and Chronic Kidney Disease (CKD) as a result of prolonged treatment with Dihydrotachysterol and calcium medications. Сlinical case. A male patient, 59 y.o., 11 years ago underwent total thyroidectomy, since that time was daily medicated with l-thyroxine 125-150 mcg, dihydrotachysterol 15 drops (approx. 0,62 mg), calcium in different forms without monitoring the blood and urine levels. He had high arterial pressure up to 200/120 mm Hg, treated with amlodipine 10 mg daily. After 5 years he took onemonth treatment with non-steroidal antiinflammatory drugs for pain relief because of a rib fracture. That time he underwent first AKI with full recovery. After 5 years a few AKI recurred with hypercalcemia. Dihydrotachysterol and calcium were cancelled, but since that time patient kept on getting non-prescribed Dihydrotachysterol and calcium in the same doses. After 1 year more in relapse series a puncture biopsy of the kidney showed nephrocalcinosis, chronic interstitial nephritis and CKD (С4А3) was diagnosed. The patient was treated successfully by dis-continuation of the above drugs, intravenous fluid administration and enhancement of calcium renal excretion. The patient is currently free of complaints for about 3 months. Сonclusion. It is important for clinicians to monitor calcium and 25-OH-D levels in blood serum during the prolonged treatment with calcium and vitamin D medications to prevent a hypercalcemia that can lead to AKI, CKD and other sever complications.

To evaluate the impact of patients lost to follow-up on outcomes of surgery for adolescent idiopathic scoliosis (AIS) at 10-year postoperative.Preoperative, 2-year, and 5-year postoperative demographic, radiographic, and SRS-22 data from a prospective multi-center registry were compared between patients with a 10-year follow-up visit versus those without. A second analysis utilized variables that were different between the groups, along with SRS scores, in a cohort of patients with preoperative, 2-, 5-, and 10-year postoperative SRS scores (complete cohort) to impute missing 10-year data (imputed cohort) utilizing Markov chain Monte Carlo simulation.250 patients had 10-year follow-up (21%). Those with 10-year follow-up had a greater percentage of patients who underwent anterior procedures (p 0.05). Radiographically, the groups were similar at all three time points. SRS-22 scores demonstrated slightly worse pain and function preoperatively and at 2 year in those lost to follow-up (effect size eta = 0.11-0.12), with no differences at 5 year. Imputed data analysis demonstrated similar trends over time in SRS-22 scores compared to the complete cohort for total score and all domains except pain. There was no significant difference in imputed versus complete 10-year SRS-22 scores (p 0.05).This study identified early differences between patients with 10-year follow-up and those without, though effect sizes were small and non-existent at 5 years. SRS-22 scores at 10 year between the complete and imputed data sets did not differ. Clinically relevant outcomes of the subset who followed-up at 10 year are likely generalizable to the entire eligible AIS population.

Objectives The aim of this study was to explore outcomes in a cohort of dcSSc patients fulfilling eligibility criteria for stem cell transplantation (SCT) studies but receiving standard immunosuppression. Methods From a large single-centre dcSSc cohort (n = 636), patients were identified using the published SCT trials’ inclusion criteria. Patients meeting the trials’ exclusion criteria were excluded. Results Of the 227 eligible patients, 214 met the inclusion criteria for ASTIS (Autologous Stem Cell Transplantation International Scleroderma), 82 for SCOT (Scleroderma: Cyclophosphamide Or Transplantation) and 185 for the UPSIDE (UPfront autologous haematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) trial, and 66 were excluded based on age >65 years, low diffusing capacity of the lungs for carbon monoxide (DLco), pulmonary hypertension or creatinine clearance Conclusion SCT inclusion criteria identify patients with poor outcome despite current best practice treatment. Patients meeting the inclusion criteria for SCT but who would have been excluded from the trials because of age, pulmonary hypertension, poor kidney function or DLco

Illicit drug use is known to be associated with premature mortality. Whether exposure to socioeconomic disadvantage and mental health problems in childhood help to explain this association, is unclear. We analysed data from 11,250 participants in the 1970 British Birth Cohort study. At 10-years of age, socioeconomic disadvantage (parental socioeconomic position, material disadvantage, family disruption) and mental health problems with antisocial behaviour, attention, and anxiety were reported by mothers and teachers. At 30-years of age, study members provided information on their illicit drug use, exposure to socioeconomic disadvantage and mental health problems. At 30-years, 19.2% of participants had used an illicit drug in the past year. Mortality was elevated for eight of the twelve drugs assessed. Family disruption, maternal, and teacher assessments of antisocial behaviour at 10-years were associated with illicit drug use at 30-years. There was, however, very little change in these associations when exposure to childhood socioeconomic disadvantage (% change in hazard ratios [HR] 0-10%) or mental health problems (0.4-11.9%) were added to the sex-adjusted model. Adding exposure to socioeconomic disadvantage (0.8-38.9%) and mental health problems (31.7-74.1%) in adulthood to the sex-adjusted model resulted in marked attenuation in HRs for all drugs. These findings imply that interventions which provide opportunities for education, employment and access to effective mental health treatments in early adulthood may help to reduce mortality among drug users.

Resume Introduction L’hypercalcemie n’est pas un evenement rare et peut engendrer des consequences severes. Ses etiologies principales sont l’hyperparathyroidie primaire et les pathologies neoplasiques. L’etiologie iatrogene par intoxication a la vitamine D est plus rare. Presentation du cas Une femme âgee de 76 ans, d’origine finlandaise, consulte aux urgences pour une douleur thoracique. Son histoire medicale est difficile a preciser en raison de la barriere de la langue et d’une confusion initiale. Elle presente une hypercalcemie severe a 4,14 mmol/L, une insuffisance renale et une arythmie cardiaque compliquee secondairement d’un episode ischemique coronaire. La clinique et la biologie orientent vers la recherche d’une pathologie hematologique et neoplasique. Le diagnostic etiologique iatrogene est permis par l’apport secondaire de precisions sur son histoire medicale. Elle etait traitee pour une hypoparathyroidie post-chirurgicale par dihydrotachysterol, un derive de la vitamine D. L’arret de la substitution, le traitement par hydratation et biphosphonates ont permis la correction rapide de l’hypercalcemie. Discussion L’intoxication au dihydrotachysterol est une etiologie rare d’hypercalcemie. Du fait de sa demi-vie longue, le risque d’hypercalcemie semble plus important qu’avec les autres derives de la vitamine D. Cette molecule, retiree du marche francais en 1982, n’est pas detectee par les dosages de 25 et 1,25 OH vitamine D. Conclusion Nous rapportons ici un cas original d’intoxication au dihydrotachysterol, dont le risque d’hypercalcemie doit etre connu. Le suivi medical rapproche, recommande en cas d’hypoparathyroidie, semble particulierement necessaire en cas de supplementation par cette molecule.

Although several etiological factors contribute to the complexity of the aging process, the ultimate component of macromolecular damage and consequent cell death involves the altered redox balance inclined towards increased ROS production and/or decreased antioxidant protection. Given that, the chronic dihydrotachysterol (DHT) intoxication in rats induce Hutchinson Gilford progeria like syndrome, the present study provides the evidence for altered redox balance as evidenced by alteration in parameters of oxidative stress in blood plasma and erythrocytes including MDA, GSH, FRAP AOPP PMRS, AGEs, AChE and osmotic fragility which substantiate the suitability of the model for aging studies.

As part of our program on synthesis of labeled vitamin D metabolites and analogs, we describe here an efficient and versatile synthetic approach to 28,28,28-trideutero- 25-hydroxydihydrotachysterol

Background.Increased oxidative stress is a major cause of aging and age-related diseases. Erythrocytes serve as good model for aging studies. Dihydrotachysterol is known to induce premature aging feature in rats mimicking Hutchinson-Gilford progeria syndrome.Aim.In the present study, attempts have been made to explore the differential response of young and senescent erythrocytes separated by density gradient centrifugation from accelerated senescence model of rats mimicking Hutchinson-Gilford progeria syndrome and naturally aged rats.Methods.The erythrocytes of naturally aged and progeroid rats were separated into distinct, young and old cells on the basis of their differential densities. The parameters of oxidative stress and membrane transport systems were studied.Discussion and Conclusion.Our study provides evidence that organismal aging negatively affects oxidative stress markers and membrane transport systems in both young and old erythrocytes. This study further substantiates that the changes in progeria model of rats resemble natural aging in terms of erythrocyte senescence.

A 2-year-old, castrated, male, domestic ferret weighing 1.125kg (2.48lb) was presented with a history of vomiting, diarrhea, anorexia, and lethargy of sudden onset. Physical examination revealed dehydration, tachypnea, bradychardia, hypotension, and moderate abdominal pain. As reference values for intact parathyroid hormone in ferrets were not available, samples from 3 clinically healthy males were analyzed. Low ionized calcium in conjunction with low intact parathyroid hormone concentrations are diagnostic for hypoparathyroidism. Based on diagnostic testing, the ferret described in this article was diagnosed with spontaneous primary hypoparathyroidism. Regular oral administration of dihydrotachysterol resulted in a therapeutic regimen to adequately control the hypoparathyroid condition of this ferret patient.

Hypercalcemia is not a rare event and can lead to severe consequences. Its main etiologies are primary hyperparathyroidism and neoplasic conditions. The iatrogenic etiology by vitamin D intoxication is more rarely found.A 76-year-old finish woman comes to the emergency room for chest pain. Her medical history is impossible to specify due to the language barrier and initial confusion. She has severe hypercalcaemia (4.14mmol/L), renal insufficiency, cardiac arrhythmia later complicated by an ischemic cardiac episode. Clinic and biologic examinations initially guided the research towards a hematological and neoplasic pathology. The iatrogenic etiology will be permitted by the contribution of details on its medical history and treatment learnt secondly. She was treated for post-surgical hypoparathyroidism by dihydrotachysterol, a vitamin D derivative. The cessation of substitution, treatment with hydration and biphosphonates allowed the rapid correction of hypercalcemia.Dihydrotachysterol intoxication is a rare etiology of hypercalcemia. Because of the longer half-life of this molecule, the risk of hypercalcemia seems to be greater than with other vitamin D derivatives. This molecule, withdrawn from the French market in 1982, is not detected by the dosage of 25 and 1.25 OH vitamin D.We report an original case of intoxication by dihydrotachysterol. The risk of hypercalcemia encountered with this molecule must be known. The close medical follow-up recommended in case of hypoparathyroidism seems to be particularly necessary in case of supplementation by this molecule.

Hypercalcemia can cause renal dysfunction such as nephrogenic diabetes insipidus (NDI), but the mechanisms underlying hypercalcemia-induced NDI are not well understood. To elucidate the early molecular changes responsible for this disorder, we employed mass spectrometry-based proteomic analysis of inner medullary collecting ducts (IMCD) isolated from parathyroid hormone-treated rats at onset of hypercalcemia-induced NDI. Forty-one proteins, including the water channel aquaporin-2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the downregulated proteins were associated with cytoskeletal protein binding, regulation of actin filament polymerization, and cell-cell junctions. Targeted LC-MS/MS and immunoblot studies confirmed the downregulation of 16 proteins identified in the initial proteomic analysis and in additional experiments using a vitamin D treatment model of hypercalcemia-induced NDI. Evaluation of transcript levels and estimated half-life of the downregulated proteins suggested enhanced protein degradation as the possible regulatory mechanism. Electron microscopy showed defective intercellular junctions and autophagy in the IMCD cells from both vitamin D- and parathyroid hormone-treated rats. A significant increase in the number of autophagosomes was confirmed by immunofluorescence labeling of LC3. Colocalization of LC3 and Lamp1 with aquaporin-2 and other downregulated proteins was found in both models. Immunogold electron microscopy revealed aquaporin-2 in autophagosomes in IMCD cells from both hypercalcemia models. Finally, parathyroid hormone withdrawal reversed the NDI phenotype, accompanied by termination of aquaporin-2 autophagic degradation and normalization of both nonphoshorylated and S256-phosphorylated aquaporin-2 levels. Thus, enhanced autophagic degradation of proteins plays an important role in the initial mechanism of hypercalcemic-induced NDI.

This study aimed to identify factors influencing long-term outcome in complete or partial postoperative hypoparathyroidism (parathyroid hormone ≤10 or10 ng/l, respectively) in medullary thyroid carcinoma (MTC). It was designed as retrospective, long-term follow-up with single-center outpatient visits. Quality of treatment, renal calcification, and function were evaluated. In 33 patients with MTC and postoperative hypoparathyroidism, current medication includes: calcium (73%), calcitriol (73%), alfacalcidol (6%), dihydrotachysterol (3%), and cholecalciferol supplements (21%). Mean hypoparathyroidism duration was 15.9±9.4 years. Initially, 15% of patients received high cholecalciferol dosages. Initial calcium dosages were higher (1 542±1 179 mg/day) than final dosages (1 188 ± 595 mg/day) (p0.05); calcitriol dosages remained constant. Over the median observation period of about 12 years it was found that serum calcium was within the target range (2.0-2.3 mmol/l) in 63% of visits, decreased (2.0 mmol/l) in 20.4%, high-normal (2.4-2.6 mmol/l) in 15.8%, and increased (2.65 mmol/l) in 0.9% of visits. Calcitriol dosages were 0.73±0.22 μg/day and 0.47±0.20 μg/day in patients with complete (n=13) and partial (n=20) hypoparathyroidism, respectively (p=0.008). Renal function decreased slightly during follow-up (eGFR: 102±22 vs. 90±27 ml/min). eGFR was negatively correlated with hypoparathyroidism duration (r=-0.35, p=0.05). Of 9 patients with renal calcification, 5 had received high initial cholecalciferol doses. eGFR was lower in patients with than in those without calcification (77±17 vs. 95±29 ml/min) (p=0.07). At least one tetanic episode occurred in 60.6% of patients, and 9% had repeated tetanic complaints. In conclusion, severity of hypoparathyroidism affects treatment: Partial hypoparathyroidism required lower calcitriol dosages than complete hypoparathyroidism. Renal calcifications occurred more frequently in patients treated initially with high cholecalciferol dosages. Impaired renal function was related to hypoparathyroidism duration and renal calcification.

In the sunnier parts of the world a dietary intake of vitamin D is unnecessary,* but for most of us it is a true vitamin. Its dihydroxylated metabolite 1,25-dihydroxyvitamin D3 (l,25(OH)2D3) is, however, a hormone synthesised in the kidney and borne by the bloodstream to distant target organs (gut, bone, and possibly the parathyroid glands) with a complex feedback mechanism regulating its rate of production.1 None of the other vitamin D metabolites has yet been confidently assigned a hormonal role in man. The unravelling of the interrelationships between vitamin D and its metabolites is one of the triumphs of recent medical research, and the stage has now been reached when treatment with synthetic metabolites of vitamin D is beginning to be available for several disorders. The major functional categories of endocrine disease are all represented among defects in the metabolism of l,25(OH)2D3. Hormone deficiency may occur from failure of tubular cell function; impairment of feedback control may result in subnormal or excessive production; or the disorder may be due to unresponsiveness in the target organs. Physiological considerations?Cholecalciferol (D3) is formed in the skin under the influence of ultraviolet light.2 Its pre cursors remain in situ because they are insoluble in water and

The effect of tumor necrosis factor-alpha (TNF) on cyclooxygenase-2 (COX-2) expression in the renal outer medulla (OM) was determined in a model of dihydrotachysterol (DHT)-induced hypercalcemia. Increases in serum calcium and water intake were observed during ingestion of a DHT-containing diet in both wild type (WT) and TNF deficient mice (TNF(-/-)). Polyuria and a decrease in body weight were observed in response to DHT treatment in WT and TNF(-/-) mice. A transient elevation in urinary TNF was observed in WT mice treated with DHT. Moreover, increased urinary levels of prostaglandin E(2) (PGE(2)) and a corresponding increase in COX-2 expression in the OM were observed in WT mice fed DHT. Increased COX-2 expression was not observed in TNF(-/-) mice fed DHT, and the characteristics of PGE(2) synthesis were distinct from those in WT mice. This study demonstrates that COX-2 expression in the OM, secondary to hypercalemia, is TNF-dependent.

Zusammenfassung Es wurden licht- und elektronenoptisch morphologische Veranderungen, die bei der unspezifischen Organkalzinose nach Verabreichung von Dihydrotachysterol (DHT) an Ratten auftreten, beschrieben. Dabei traten elektronenoptisch Kalkabscheidungen in den untersuchten Organen sowohl in den interstitiellen Bindegewebsanteilen, als auch in geringerem Ausmas in den Parenchymzellen selbst (Niere, Herz, Lunge, Tunica muscularis des Magens und des Darmes) auf. Die diskreteren Inkrustationen innerhalb der Parenchymzellen hatten vornehmlich Kristallnadel- oder Kristallbuschelform und bevorzugten die Mitochondrienmatrix, wahrend extrazellulare Inkrustationen, gelegen im mehr oder weniger nekrotischen Interstitium, meist einen feinstaubigen, kristallinen oder auch konzentrisch geschichteten drusenartigen Aufbau zeigten. Die C-Zellen der Schilddruse wiesen als hauptsachlichstes Merkmal eine fast vollige Entgranulierung auf. Krankheitsbilder, bei denen extraossare Kalkablagerungen im Vordergrund stehen, die durch toxische Pflanzeninhaltsstoffe, wie sie z. B. in Trisetum flavescens, Solanum malacoxylon und Cestrum diurnum vorkommen, wurden vergleichend diskutiert. Summary Light and electronoptical studies on non-specific calcinosis after administration of dihydrotachysterol (DHT) to rats The morphological changes resulting from giving DHT to rats were examined by the light and electron microscope. Calcium deposits were seen with the EM in the organs examined, both in the interstitial connective tissue and in smaller amounts in the parenchyma itself (kidney, heart, lung, gastric and intestinal tunica muscularis). The more discrete deposits within the parenchyma cells had predominantly the form of crystalline needles or brushes and favoured the mitochondrial matrix, whereas extracellular incrustations, deposited in the more or less necrotic interstitial tissue, took the form mainly of finely granular, crystalline or concentrically layered gland-like structures. The C-cells of the thyroid showed almost complete degranulation as their main feature. Disease pictures in which extra-osseous calcium deposition is a predominant feature, caused by toxic plant substances such as those in Trisetum flavescens, Solanum malacoxylon and Cestrum diurnum, are reviewed for comparison. Resume Recherches en microscopie optique et electronique sur une calcinose organique non specifique apres l'application de dihydrotachysterol (DHT) chez des rats On a decrit des lesions morphologiques apparues au microscope optique et electronique qui se sont manifestees sous forme de calcinose organique non specifique chez des rats qui ont recu du dihydrotachysterol (DHT). Les depots de calcium sont apparus au microscope electronique aussi bien dans les tissus interstitiels des organes examines que dans les cellules du parenchyme dans une proportion plus faible (reins, coeur, poumons, Tunica muscularis de l'estomac et de l'intestin). Les incrustations discretes dans les cellules du parenchyme avaient avant tout la forme d'aiguilles ou d'amas de cristaux et avaient une preference pour la matrice des mitochondries; les incrustations extracellulaires, situees dans un interstice plus ou moins necrose, sont apparues sous la forme de poussieres, de eristaux ou en couches concentrees. Les cellules C dlea glande thyroide montrerent une elimination presque totale des granulations. On a compare l'image pathologique avec des accumulations calcaires extra-osseuses qui apparaissent avec des substances vegetales toxiques telles que Trisetum flavescens, Solanum malacoxylon et Cestrum diurnum. Resumen Estudios foto y electronicoopticos sobre la calcinosis organica inspecifica tras administracion de dihidrotaquisterol (DHT) a ratas Se describen modificaciones morfologicas foto y electronicoopticas, las cuales aparecen en la calcinosis organica inespecifica tras la administracion de DHT a ratas. Asi aparecieron segregaciones calcareas electronicoopticas en los organos examinados tanto en las partes conectivas intersticiales como, en grado algo menor, en las propias celulas parenquimatosas (rinon, corazon, pulmon, tunica muscular del estomago e intestino). Las incrustaciones mas discretas dentro de las celulas parenquimatosas tenian, sobre todo, formas de agujas de cristal o haces cristalinos y preferian la matriz mitocondriaca, mientras que las incrustaciones extracelulares, situadas en el intersticio mas o menos necrotico, ostentaban casi siempre una estructura micropulverulenta, cristalina o incluso en forma de drusa con capas concentricas. Las celulas tiroideas C presentaban como caracteristica mas destacable una desgranulacion casi completa. De forma comparativa, se discutieron los cuadros nosologicos, en los que se hallan en primer plano concreciones calcareas extraoseas, producidas por substancias vegetales toxicas, tales como las contenidas en Trisetum flavescens, Solanum malacoxylon y Cestrum diurnum.