Thromboelastography clot strength profiles and effect of systemic anticoagulation in COVID-19 acute respiratory distress syndrome: a prospective, observational study.

OBJECTIVE: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection may yield a hypercoagulable state with fibrinolysis impairment. We conducted a single-center observational study with the aim of analyzing the coagulation patterns of intensive care unit (ICU) COVID-19 patients with both standard laboratory and viscoelastic tests. The presence of coagulopathy at the onset of the infection and after seven days of systemic anticoagulant therapy was investigated. PATIENTS AND METHODS: Forty consecutive SARS-CoV-2 patients, admitted to the ICU of a University hospital in Italy between 29th February and 30th March 2020 were enrolled in the study, providing they fulfilled the acute respiratory distress syndrome criteria. They received full-dose anticoagulation, including Enoxaparin 0.5 mg·kg-1 subcutaneously twice a day, unfractionated Heparin 7500 units subcutaneously three times daily, or low-intensity Heparin infusion. Thromboelastographic (TEG) and laboratory parameters were measured at admission and after seven days. RESULTS: At baseline, patients showed elevated fibrinogen activity [rTEG-Ang 80.5° (78.7 to 81.5); TEG-ACT 78.5 sec (69.2 to 87.9)] and an increase in the maximum amplitude of clot strength [FF-MA 42.2 mm (30.9 to 49.2)]. No alterations in time of the enzymatic phase of coagulation [CKH-K and CKH-R, 1.1 min (0.85 to 1.3) and 6.6 min (5.2 to 7.5), respectively] were observed. Absent lysis of the clot at 30 minutes (LY30) was observed in all the studied population. Standard coagulation parameters were within the physiological range: [INR 1.09 (1.01 to 1.20), aPTT 34.5 sec (29.7 to 42.2), antithrombin 97.5% (89.5 to 115)]. However, plasma fibrinogen [512.5 mg·dl-1 (303.5 to 605)], and D-dimer levels [1752.5 ng·ml-1 (698.5 to 4434.5)], were persistently increased above the reference range. After seven days of full-dose anticoagulation, average TEG parameters were not different from baseline (rTEG-Ang p = 0.13, TEG-ACT p = 0.58, FF-MA p = 0.24, CK-R p = 0.19, CKH-R p  = 0.35), and a persistent increase in white blood cell count, platelet count and D-dimer was observed (white blood cell count p < 0.01, neutrophil count p = 0.02, lymphocyte count p < 0.01, platelet count p = 0.13 < 0.01, D-dimer levels p= 0.02). CONCLUSIONS: SARS-CoV-2 patients with acute respiratory distress syndrome show elevated fibrinogen activity, high D-dimer levels and maximum amplitude of clot strength. Platelet count, fibrinogen, and standard coagulation tests do not indicate a disseminated intravascular coagulation. At seven days, thromboelastographic abnormalities persist despite full-dose anticoagulation.

Quantitative analysis of backscattered electron (BSE) contrast using low voltage scanning electron microscopy (LVSEM) and its application to Al0.22Ga0.78N/GaN layers.

A novel method to quantify and predict the material contrast using Backscattered Electron (BSE) imaging in Scanning Electron Microscopy (SEM) is presented while using low primary electron beam energies (Ep). In this study, the parameters for BSE imaging in Low Voltage Scanning Electron Microscopy (LVSEM) are optimized for the layer system Al0.22Ga0.78N/GaN, which is typically used in High Electron Mobility Transistors (HEMTs). The layers are imaged at high resolution and the compounds are identified based on the quantitative BSE material contrast between Al0.22Ga0.78N and GaN. The quantification process described in this study is based on an analytical description that predicts the material contrast using a function that correlates the effective backscattering coefficient (η) with the atomic number Z.

The quality of dietary intake methodology and reporting in child and adolescent obesity intervention trials: a systematic review.

Assessing dietary intake is important in evaluating childhood obesity intervention effectiveness. The purpose of this review was to evaluate the dietary intake methods and reporting in intervention studies that included a dietary component to treat overweight or obese children. A systematic review of studies published in the English language, between 1985 and August 2010 in health databases. The search identified 2,295 papers, of which 335 were retrieved and 31 met the inclusion criteria. Twenty-three studies reported energy intake as an outcome measure, 20 reported macronutrient intakes and 10 studies reported food intake outcomes. The most common dietary method employed was the food diary (n = 13), followed by 24-h recall (n = 5), food frequency questionnaire (FFQ) (n = 4) and dietary questionnaire (n = 4). The quality of the dietary intake methods reporting was rated as 'poor' in 15 studies (52%) and only 3 were rated as 'excellent'. The reporting quality of FFQs tended to be higher than food diaries/recalls. Deficiencies in the quality of dietary intake methods reporting in child obesity studies were identified. Use of a dietary intake methods reporting checklist is recommended. This will enable the quality of dietary intake results to be evaluated, and an increased ability to replicate study methodology by other researchers.

Describing weight status and fitness in a community sample of children attending after-school programming.

Although the body of research on public-health aspects of after-school programs is growing, little is known with regard to physical fitness levels of attending children. The purpose of this study was to describe the health-related fitness in a community sample (N.=826) of under-served children attending after-school programming. Health-related fitness was assessed via Fitnessgram(R) and body mass index. In this population, numerous children failed to meet national standards for the push-up (54%), curl-up (24%) and pacer (47%) tests. Many of those failing to meet national standards were unable to perform a single push-up (32%), or curl-up (12%), and over half (51%) of the children were overweight or obese. Significant differences by race/ethnicity, gender, and weight status emerged for some fitness measures. Based on these data, fitness aspects beyond weight status should be considered when designing PA programs for children, especially those in communities of underserved youth.

The effect of condoms in sexually explicit narratives on male sexual arousal.

Research into why people choose not to use condoms despite a growing AIDS epidemic has tapped the attitude that the use of condoms somehow interferes with the progression of the sexual act or lessens sexual pleasure. The current study investigated the effects on male sexual arousal of condom use described in sexually explicit audiotaped narratives. The sexual arousal of 14 male university students was measured physiologically by penile plethysmography and by self-report using a within-subjects design. Subjects listened to 10 audiotaped scripts, half of which included the use of a condom and half of which did not. No significant differences in either physiological or subjective arousal data were found between conditions.

PIP: It has been speculated that some people who choose not to use condoms in the context of a growing AIDS pandemic do so because condom use interferes with the progression of the sexual act or lessens sexual pleasure. 14 male students in undergraduate psychology courses at the University of North Dakota volunteered to listen to sexually explicit audiotaped narratives in a study of male sexual arousal in the context of condom use. 20 audio scripts based upon 10 sexually explicit scenarios were used in the study. Each approximately two-minute long script depicted sexual interactions culminating in sexual intercourse between an adult male and an adult female. Ten scripts depicted scenarios involving no condom use. Modified versions of these scripts included condom use, thereby comprising the other 10 scenarios. The scripts were recorded on standard audiotapes by an adult female not connected with the study. Each volunteer was placed alone in a room furnished with only a reclining chair, a pair of stereo headphones, and a Likert scale mounted on a wall four feet from the chair. The young men were told how to apply and calibrate the Parks Medical Electronics, Inc. model 240-A mercury-in-rubber strain gauge plethysmograph, a device capable of measuring slight changes in penile circumference. Each subject then alternately heard 10 randomly selected scripts, half involving condom use and half not. Physiological data on penile response while listening to the tapes were collected via Advanced CODAS software and stored individually for each subject on a Gateway computer. Each subject also reported upon his sexual arousal. No significant differences were observed in physiologically and subjectively assessed patterns of male sexual arousal between the condom-present and condom-absent conditions. The brief description of putting on a condom within a sexually explicit audiotaped narrative had neither detrimental nor enhancing effects upon male sexual arousal. That condoms and condom use truly have no effect upon male sexual arousal is, however, only one of many possible explanations for these findings.

Chronic manipulation of dietary salt modulates renal physiology and kidney dopamine receptor subtypes: functional and autoradiographic studies.

1. Compared to rats maintained on the normal NaCl (0.33%) diet, animals maintained on the low NaCl (0%) diet for 4 weeks exhibited increased plasma aldosterone and chloride and decreased urinary sodium excretion. 2. Rats maintained on the high NaCl (8%) diet for 4 weeks showed increased systolic blood pressure, water intake, urine volume, sodium and dopamine excretion and decreased plasma aldosterone and glomerular filtration rate. 3. Administration of SCH 23390 (10 mg/kg, po), but not domperidone to the high salt diet rats attenuated the diuretic effect, indicating the involvement of DA1 rather than DA2 receptors. The dopamine decarboxylase inhibitor, carbidopa (30 mg/kg, i.p.), also reduced the high salt-induced diuresis. 4. Kidney sections from rats fed the low NaCl diet showed a 63-100% decrease (P < 0.001-0.02) in cortical and medullary DA1 and DA2 binding sites, while rats fed the high NaCl diet demonstrated only a 70% decrease (P < 0.01-0.02) in cortical DA1 binding, without affecting DA2 binding. 5. These data indicate that chronic modification of dietary salt profoundly affects the sodium, water and dopamine excretion and leads to selective modulation of renal dopamine receptor subtypes.

Quantitative autoradiography demonstrates selective modulation of rat brain regional dopamine (D1 and D2) receptor subtypes after chronic manipulation of dietary salt.

The effects of chronic dietary sodium chloride (NaCl) consumption on renal function and brain dopamine receptors were studied in adult, male normotensive rats. Compared to rats maintained on the normal NaCl (0.33%) diet, animals maintained on the low NaCl (0%) diet for 4 weeks exhibited significant increases in plasma aldosterone, chloride and changes in urinary electrolyte excretion. In contrast, rats maintained on the high NaCl (8%) diet for 4 weeks demonstrated significant increases in urine volume and urinary sodium, chloride and dopamine excretions and water intake. Rats fed the high NaCl diet displayed a 42-59% decrease (p < 0.001-0.05) in D1 binding in the nucleus accumbens (NA), olfactory tubercle (OT) and the striatum (STM), without any effects on D2 binding in these brain regions. Rats maintained on the low NaCl diet also demonstrated decreased D1 binding in the ventral (24%, p < 0.02) and lateral (29%, p < 0.01) STM, but not in the OT, NA, entopeduncular nucleus and substantia nigra. Rats fed low or high NaCl diets exhibited a 35-180% increase (p < 0.01-0.05) in D2 binding in several mid-brain areas (e.g. hypothalamus, thalamus and hippocampus) and hindbrain regions (e.g. superior colliculus and nucleus tractus solitarius) without affecting the D1 binding. These data indicate that chronic modification of dietary salt intake profoundly affects the renal handling of sodium/water excretion and leads to selective up- and/or down-regulation of DA receptor subtypes in different areas of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

A pharmacological comparison of [3H]GBR12935 binding to rodent striatal and kidney homogenates: binding to dopamine transporters?

Binding of [3H]GBR12935 to homogenates of mouse and rat striatum and kidney was studied. [3H]GBR12935 bound to both tissue preparations with high affinity (mouse striatum Kd = 2.4 +/- 0.4 nM, n = 4; mouse kidney Kd = 3.8 +/- 0.9 nM, n = 4), in a saturable (striatal Bmax = 1.5 +/- 0.4 pmol/mg protein; kidney Bmax = 4.9 +/- 0.5 pmol/mg protein) and reversible manner. Saturation experiments revealed the presence of a single class of high affinity binding sites in both tissues of both species. Mouse kidney appeared to possess a greater density of [3H]GBR12935 binding sites than the striatum while the reverse situation prevailed for the rat. Although two dopamine uptake inhibitors, namely GBR12909 and benztropine, displaced [3H]GBR12935 binding from striatal and kidney homogenates with a similar affinity in both tissues of these species, unlabelled mazindol, (+/-)cocaine, nomifensine and amfonelic acid were significantly (P < 0.001-0.02) more potent inhibitors of [3H]GBR12935 binding in the striatum than in the kidney. While the pharmacological profile of [3H]GBR12935 binding in the rodent striatum compared well with that of the dopamine transporter reported previously, the pharmacology in the kidney was considerably different to that in the striatum. GBR12909 (1-30 mg/kg, i.p.), a close analog of GBR12935, induced significant antidiuretic and antinatriuretic effects in spontaneously hypertensive rats. These data suggest that while [3H]GBR12935 labels the dopamine uptake sites in the brain, it does not appear to label similar sites in the kidney. The mechanism of action of GBR12909 on sodium and water excretion remains to be determined.

Renin and angiotensinogen expression during the evolution of diabetes.

The expression of renin and angiotensinogen genes and their proteins were studied during the progression of diabetes using adult BioBreeding spontaneously diabetic rats at 1 day and 2-12 months of diabetes. The number of renin-stained cells per juxtaglomerular apparatus was determined by immunocytochemistry. Initially, at 2 months of diabetes the number of renin-stained cells per juxtaglomerular apparatus increased significantly (p less than 0.0001, 2 months versus resistant groups) and was followed by a decrease in the number and intensity of renin-stained cells after 12 months of diabetes (p = 0.007, 2 months versus 12 months). A significant negative correlation was observed between the number of renin-containing cells and the duration of diabetes (r = 0.99, p = 0.014). Immunoreactive angiotensinogen was restricted to the proximal tubule and appeared increased after 4 and 8 months of diabetes as compared with the 2- and 12-month diabetic groups. Renin messenger RNA (mRNA) levels increased with the onset of diabetes and decreased markedly during chronic diabetes. At 1 day of diabetes, renin mRNA levels were 700% higher than at 12 months of diabetes. Angiotensinogen mRNA levels were unchanged. We conclude that diabetes results in an initial increase in renin gene expression, and as the duration of diabetes lengthens, there is a progressive decrease in renin gene expression and in the number of cells containing renin. These findings suggest that as the duration of diabetes and the age of the animal lengthens, there is a decrease in the number of cells expressing the renin gene.

The early care and feeding of anorexics.

Comparing mothers' reports of early feeding practices in 18 mothers of anorexics and 25 mothers of normal children by means of a questionnaire, we found that the mothers of anorexics introduced solids earlier and used Schedule rather than Demand feedings more frequently. The mothers of anorexics did not treat patients and control siblings differentially. Our study suggests that differences in early feeding and in infant temperament may be operative in the pathogenesis of anorexia nervosa.

Effects of the natural and unnatural isomers and degradation products of enprostil on gastric acid secretion and gastrointestinal motility in the rat.

The gastric antisecretory and gastrointestinal (GI) motility activity of the natural and unnatural allenic isomers and degradation products of enprostil (methyl(+/-)-7-[(1R*,2R*,3R*)-3-hydroxy-2-[(E)-(3R*)-3-hydroxy-4-phenoxy - 1-butenyl]-5-oxocyclopentyl]-4,5-heptadienoate, RS-84135-004) were studied in the rat. The natural R-allenic isomer of enprostil was the most potent antisecretory compound. The 8-iso-enprostil, enprostil free acid, and the 5-acetylene isomer had somewhat less activity while the other compounds were relatively inactive. The natural and unnatural allenic isomers increased intestinal dye transit with the same rank potency as the gastric antisecretory activity. Enprostil, 8-iso-enprostil, prostaglandin A-enprostil and enprostil free acid, all increased intestinal dye transit.

Effects of enprostil on cardiovascular and respiratory parameters in the dog, and on hematologic parameters in the rat, monkey, and human.

The effects of enprostil (+/-)-7-[(1R*,2R*,3R*)-3-hydroxy-2-[(E)-(3R*)-3-hydroxy-4-phenoxy-1- butenyl]-5-oxocyclopentyl]-4,5-heptadienoate) were studied on cardiovascular and respiratory parameters in the dog and on hematologic parameters in the rat, monkey, and human. Anesthetized dogs were instrumented to allow measurement of heart rate, systemic blood pressure, respiratory rate or tracheal pressure, and ventricular contractile force after intragastric (i.g.) or intravenous (i.v.) administration of enprostil in the presence or absence of autonomic challenges. The effects of intraduodenal (i.d.) enprostil on arterial and venous PO2, PCO2, and pH; respiratory rate, flow rate, and volume; blood pressure (b.p.); and heart rate were also examined. Enprostil i.v. (0.3-10 micrograms/kg) significantly increased tracheal pressure in a dose-dependent manner, but minimally altered b.p., heart rate, and ventricular contractile force. Enprostil i.v. (1-10 micrograms/kg) significantly inhibited pressor and depressor responses to several autonomic challenge agents at the highest dose level, indicative of a nonspecific inhibitory effect on b.p. responses. Cardiovascular effects of enprostil (1-100 micrograms/kg i.g.) were absent. Enprostil (10-3,000 micrograms/kg i.d.) had no noteworthy effects on respiratory parameters in the dog. Platelet aggregation effects of enprostil were studied in vitro using platelet rich plasma (PRP) from the rat, monkey, and human; whole blood clotting time and prothrombin time after oral enprostil were studied in the rat; and ex vivo effects on platelet activation were studied in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Histidyl proline diketopiperazine (Cyclo [His-Pro]) in eating disorders.

The authors explored the role of Cyclo [His-Pro] (CHP) in 50 adolescents who fulfilled DSM III diagnostic criteria for anorexia nervosa and bulimia. CHP, a relatively new neuro modulator which has a role in inducing satiety, was assayed in serum during routine blood work. CHP levels correlated significantly with weight in restrictor (AN-R) (R = -0.449, P less than 0.05) and bulimic anorexics (AN-B) (R = +0.489, P less than 0.01). There was no significant correlation in normal-weight bulimics (NWB) (R = +0.556, P less than 0.01). It did not correlate with weight in a depressed control group. Longitudinal data on six patients showed a similar relationship between weight, purging and CHP binge/purge activity and/or weight changes of around 2 kilograms correlated with average CHP changes of 42%. Clinical material suggests changes in satiety during CHP changes consistent with a satiety disturbance model of these disorders.

[(1H-imidazol-1-yl)methyl]- and [(3-pyridinyl)methyl]pyrroles as thromboxane synthetase inhibitors.

Several [(1H-imidazol-1-yl)methyl]- and [(3-pyridinyl)methyl] pyrroles were prepared and evaluated in vitro as thromboxane synthetase inhibitors in human platelet aggregation studies. A number of structures, e.g. 10b,f,g,i (respective IC50 values: 1 microM, 50 nM, 42 nM, 44 nM) showed superior in vitro inhibition of TXA2 synthetase when compared to the standard dazoxiben (1). However, it was found that in vitro potency did not translate into nor correlate with in vivo activity when these compounds were evaluated in mice in a collagen-epinephrine-induced pulmonary thromboembolism model. (E)-1-Methyl-2-[(1H-imidazol-1-yl)methyl]-5-(2-carboxyprop-1-enyl) pyrrole (10b) was found to offer protection against collagen-epinephrine-induced mortality in mice, thereby demonstrating that oral administration is an effective route for absorption of this drug. Additional evidence for the oral effectiveness of 10b in lowering serum TXB2 levels was obtained by performing ex vivo radioimmunoassay experiments with rats. A 13-week study of 10b in rats with reduced renal mass was conducted in order to evaluate the role of TXA2 production in hypertension and renal dysfunction. Although serum and urinary TXB2 levels in rats were found to be lowered during this study by 10b, the levels of urinary protein excretion remained comparable to that of the control group.