On the pharmacological phenocopying of memory mutations inDrosophila: Alkylxanthines accelerate memory decay

Theophylline and 3-isobutyl-1-methylxanthine, two cyclic nucleotide phosphodiesterase inhibitors, when fed to wild-typeDrosophila adults, cause the rapid decay of learning index after training in a shock-odor learning paradigm. The drugs practically do not affect the olfactory acuity of flies, hence they influence the learning/memory process itself. The time courses of memory decay resemble those of the memory mutantsrutabaga andamnesiac and, to a lesser extent,dunce ² anddunce ^M11. Theophylline further deteriorates the learning performance ofdunce ^M11. Biochemical characterization of the inhibition of the two major phosphodiesterase isoenzymes inDrosophila by theophylline predicts only a slight inhibition of these enzymesin vivo, in accordance with the unchanged level of cAMP in wild-type fly heads during drug feeding. 8-Phenyltheophylline, an adenosine receptor antagonist in mammals, slightly retards memory decay in the wild-type. It is suggested that alkylxanthines induce memory decay inDrosophila by interfering with cAMP dynamics at more than one point of its metabolism.This work was supported by Grants OTKA and OKKFT Tt to P.F.     

Effects of estrogen and medroxyprogesterone acetate on subpopulations of triglyceride-rich lipoproteins and high-density lipoproteins

Hormonal replacement therapy (HRT) in postmenopausal women has been shown to increase both triglyceride (TG) and high-density lipoprotein (HDL) cholesterol levels. To better understand the effects of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA), the 2 most commonly prescribed hormones in HRT, on the different subpopulations of TG-rich and HDL lipoproteins, we conducted a placebo-controlled, double-blind, randomized, crossover study consisting of 3 different phases in 14 postmenopausal women. The 3 phases, each 8-week long, included: (1) placebo, (2) CEE 0.625 mg/d, and (3) CEE 0.625 mg/d and MPA 2.5 mg/d. Slight and statistically nonsignificant elevations in TG levels were observed during the CEE treatment. While very-low-density lipoprotein (VLDL) cholesterol levels were not significantly affected by CEE and CEE + MPA, both HRT treatments lowered remnant lipoprotein (RLP) cholesterol (-14% and -37%, respectively). Compared with placebo, CEE caused a significant increase in HDL, HDL(2), apolipoprotein (apo) A-I, LpAI, alpha1, and prealpha1 levels (12%, 27%, 17%, 26%, 60%, and 102%, respectively). The combination therapy blunted the CEE effect on all HDL parameters, resulting in HDL, HDL(2), and LpAI levels being no longer significantly different from placebo. Apo A-I levels and alpha1, and prealpha1 levels were still significantly higher than placebo (+11%, +50%, and +112%, respectively). These results indicate that HRT has beneficial effects on RLP levels and that, while the estrogen component of HRT has a beneficial effect on the HDL subpopulations mostly associated with coronary heart disease (CHD) protection, MPA partially inhibits this effect.     

Olfactory jump reflex habituation in Drosophila and effects of classical conditioning mutations

Habituation is a nonassociative learning mechanism, in which an initial response toward repeated stimuli gradually wanes. This is amongst the simplest and most widespread forms of behavioral plasticity. So far, neither the underlying molecular mechanisms nor the precise neural networks of habituation are well understood. We have developed a novel paradigm to quantify habituation of the olfactory jump reflex in Drosophila. We present data demonstrating several behavioral properties of this phenomenon, generally observed in other species. We also show that the dunce and rutabaga memory mutants behave abnormally in this assay, suggesting that this assay might be used in behavioral screens for new mutants with defects in this simpler form of behavioral plasticity.     

Thirty-Day Post-Discharge Outcomes Following COVID-19 Infection

BackgroundThe clinical course of COVID-19 includes multiple disease phases. Data describing post-hospital discharge outcomes may provide insight into disease course. Studies describing post-hospitalization outcomes of adults following COVID-19 infection are limited to electronic medical record review, which may underestimate the incidence of outcomes.ObjectiveTo determine 30-day post-hospitalization outcomes following COVID-19 infection.DesignRetrospective cohort studySettingQuaternary referral hospital and community hospital in New York City.ParticipantsCOVID-19 infected patients discharged alive from the emergency department (ED) or hospital between March 3 and May 15, 2020.MeasurementOutcomes included return to an ED, re-hospitalization, and mortality within 30 days of hospital discharge.ResultsThirty-day follow-up data were successfully collected on 94.6% of eligible patients. Among 1344 patients, 16.5% returned to an ED, 9.8% were re-hospitalized, and 2.4% died. Among patients who returned to the ED, 50.0% (108/216) went to a different hospital from the hospital of the index presentation, and 61.1% (132/216) of those who returned were re-hospitalized. In Cox models adjusted for variables selected using the lasso method, age (HR 1.01 per year [95% CI 1.00–1.02]), diabetes (1.54 [1.06–2.23]), and the need for inpatient dialysis (3.78 [2.23–6.43]) during the index presentation were independently associated with a higher re-hospitalization rate. Older age (HR 1.08 [1.05–1.11]) and Asian race (2.89 [1.27–6.61]) were significantly associated with mortality.ConclusionsAmong patients discharged alive following their index presentation for COVID-19, risk for returning to a hospital within 30 days of discharge was substantial. These patients merit close post-discharge follow-up to optimize outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06924-0.KEY WORDS: COVID-19, mortality, re-admission, discharge     

Airway and tissue mechanics in anesthetized paralyzed children

To estimate the mechanical properties of the airways and respiratory tissues, respiratory system impedance (Zrs) was measured with low-frequency forced oscillations in 26 anesthetized, paralyzed children (aged 3 months-10 years) undergoing surgical correction of congenital heart diseases. Zrs was determined from the signals of tracheal flow and pressure between 0.4-12 Hz before surgery at zero mean transrespiratory pressure. The pulmonary (Z(L)) and chest wall (Z(W)) components of Zrs were also determined in 5 children by measuring esophageal pressure. A model containing frequency-independent resistance (R) and inertance (I), and coefficients of tissue-damping (G) and elastance (H), was fitted to the Zrs, Z(L), and Z(W) spectra. The total respiratory parameters normalized to body weights were 82.2 +/- 8.5 (SE) hPa x sec x l(-1) x kg, 0.152 +/- 0.05 hPa x sec(2) x l(-1) x kg, 293.8 +/- 20.0 hPa. l(-1) x kg, and 1,583 +/- 65.5 hPa x l(-1) x kg, for R, I, G, and H, respectively. The measurements of Z(L) and Z(W) revealed the dominance of the lungs in R (91 +/- 4.3%) and I (109 +/- 16%), and the major contribution of the lung parenchyma to G (61 +/- 7.3%) and H (66 +/- 7.4%) of the total respiratory system. It is concluded that anesthesia-paralysis provides an ideal condition for the measurement of low-frequency forced oscillatory impedance and its partitioning into airway and tissue components in mechanically ventilated children. The separation of pulmonary and chest wall mechanics demonstrates that airway properties can be estimated appropriately from Zrs data, while the chest wall may damp the changes in parenchymal properties.     

Reverse LISS plating for intertrochanteric Hip Fractures in elderly patients

Background  

Fractures of the intertrochanteric hip are common and the treatment of unstable fractures generally requires an operative approach. In elderly patients, osteoporosis makes internal fixation problematic and frequently contributes to failed fixation and poor clinical results. We have attempted to apply the Less Invasive Stabilization System (LISS) in reverse position for the repair of intertrochanteric hip fractures in elderly patients with osteoporotic bones. A retrospective review is presented of the cases of 28 elderly patients with stable and unstable fractures of the intertrochanteric hip treated using the reverse LISS.     

Changes in cardiovascular risk factors after renal transplantation

Authors examined the serum concentration of creatinine, uric acid, homocysteine, cystatine C, total cholesterol and triglyceride in 115 male and 77 female patients six months after the transplantation. The change of the BMI (Body Mass Index) was studied, fat and water body weight was determined by bioelectrical impedance analysis, and the ratio of intra- and extracellular volume was calculated. Both creatinine and cystatine C levels decreased significantly compared to the levels before the transplantation (p < 0.001) because of the good renal function, and there was a good correlation between creatinine, cystatine C and homocysteine levels (r = 0.5315 in females, r = 0.3189 in males). Elevated BMI (36.49%) and hypercholesterolaemia along with moderate hyperhomocysteinaemia was found in a considerable part of the patients. Increase in body weight was confirmed by the increase in fat body weight and volume determined by bioelectrical impedance analysis. In patients with adequate compliance the ratio of intra- and extracellular volume was between 1.67 and 1.79. Blood pressure values showed frequently the non-dipper phenomenon despite appropriate antihypertensive therapy, and negative diurnal index was found with high nocturnal blood pressure levels. The mean blood pressure was 148/81 +/- 13.2/4.8 mmHg in males and 133/84 +/- 15.3/9.8 mmHg in females. Authors enhance the importance of regular monitoring of cardiovascular risk factors in the prevention of cardiovascular complications.     

Changes in calcium metabolism after kidney transplantation

Prospective study was performed to measure the changes in calcium metabolism after kidney transplantation. 139 recipients received calcium substitution (1st group) and 81 patients were treated with alfacalcidol (2nd group). Serum Ca, P, Mg, alkaline phosphatase (AP) and intact PTH levels were determined before transplantation and at 1, 3, 6, 12 and 24 months thereafter in the two groups. Femoral and vertebral bone mineral density was measured with bone densitometer at the same period. The serum Ca level elevated and the serum P concentration decreased significantly in both group. The mean serum Mg and AP concentration changed in the normal range after the transplantation. The intact PTH level decreased significantly in both group at 2 years following transplantation. The intact PTH concentration changed from 17.1 pmol/l to 9.3 pmol/l in the 1st group, and it is decreased from 17.7 pmol/l to 7.9 pmol/l in the 2nd group. Bone densitometry showed osteoporosis in both group. At 12 months and at 24 months after kidney transplantation bone mineral density (BMD) of lumbar spine was 90.8% and 86.9% in the 1st group and 85.3% and 81% in the 2nd group. At the same time BMD of the femoral region was 84.4% and 85.5% in the 1st group and 82.0% and 81.3% in the 2nd group. The BMD did not changed significantly in the 1st compared to the 2nd group. During this period osteonecrosis was diagnosed in 6 patients in the 1st group and in 9 cases in the 2nd group. In conclusion, the serum Ca and P levels were in the normal range after kidney transplantation. The alfacalcidol treatment significantly decreased the intact PTH concentration compared to the calcium substitution. Moderate osteopenia was observed in both groups after the transplantation, despite of the administration of alfacalcidol treatment.     

Hypothyroxinemia of prematurity and infant neurodevelopment: a pilot study

To assess whether hypothyroxinemia has specific effects on neurodevelopment in premature infants, thyroid hormone levels were determined at 2 weeks of life and 40 weeks postconceptional age (PCA), and infants were evaluated at 3 months corrected age using the Bayley Scales of Infant Development and Early Infancy Temperament Questionnaire. Additional attention scales were derived from the factor analysis of relevant Bayley items. Fifteen infants born between 30 and 35 weeks and 21 full-term infants were studied. Results indicated no group differences on the Bayley or derived attention scales, whereas the temperament questionnaire revealed lower sensory thresholds and greater reactivity in the preterm group. The preterm group had normal thyroxine (T4) levels at 2 weeks of age, which declined by 40 weeks PCA for both free T4 (p < .01 for reference value and p < .0001 for gestational age-adjusted value) and total T4 (p < .05 for age-adjusted value). Correlations revealed that higher 40-week PCA free T4 levels were associated with better attentiveness ratings (p < .01 for reference and p < .0001 for gestational-age values) and sustained attention (p < .05) and higher 40-week total T4 with better motor skills (p < .05 for gestational-age value). These findings signify that a mild degree of hypothyroxinemia is evident in preterm infants without neurological risk and predicts subsequently poorer cognitive and motor abilities.     

Skeletal maturation during thyroxine treatment in children with congenital hypothyroidism

Heyerdahl S, Kase BF, Stake G. Skeletal maturation during thyroxine treatment in children with congenital hypothyroidism. Acta Prediatr 1994;83:618–22. Stockholm. ISSN 0803–5253
The aim of this investigation was to study if bone age development (assessed by the Greulich & Pyle atlas) was related to L-thyroxine treatment in 47 children with congenital hypothyroidism, treated early and according to general recommendations. In spite of frequent delay in skeletal maturation at diagnosis, the delay in mean bone age at a mean chronological age of 1.5 years was slight (0.5 months), and 30% of the variation in bone age SD score (SDS) at 1.5 years was accounted for by the dose of L-thyroxine and serum thyroxine during the first year. The children with a bone age within ± 1 SDS had a prescribed mean dose of L-thyroxine per kg body weight from 3 to 12 months of age of 5.4 ± 1.7 pg/kg/day, and their mean serum thyroxine concentration during the first year was 175 ± 29 nmol/l. We conclude that bone age at 1.5 years of age was positively correlated with the dose of L-thyroxine and the serum thyroxine concentration during the first year. This supports the general use of bone age assessments as a complement to other treatment variables in the follow-up of children with congenital hypothyroidism.