Iatrogenic metacarpal fracture after K-wire fixation: A case report and prevention.
Iatrogenic fractures after failed K-wire fixation in the management of a carpometacarpal (CMC) joint fracture-dislocation have not yet been reported (Hsu et al., 2011). We present a case of K-wire-related complication in the management of a CMC joint fracture-dislocation and highlight the importance of planning K-wire placement and minimizing the number of K-wire passes. After beating his hand against a wall, a 22-year-old patient visited our clinic complaining of a swollen and painful wrist. Following our protocol, reduction and K-wire fixation was planned. During these procedures, the resident of our team made several attempts to insert transfixation pins and radiologic finding demonstrated incorrect placement of the K-wire track. The patient visited the outpatient clinic at 5 weeks postoperatively then we removed the K-wires and began mobilization. Two weeks later, the patient came back with acute onset of pain and swelling at the 5th metacarpal area. Stahl and Schwartz reported that 27.8 % of complications related K-wire were due to technical failure and 90 % of technical failure were caused by hospital residents. Well-established guidelines and supervision by a highly experienced surgeon is likely to reduce the rate of technical failure. Multiple passes of the K-wire have resulted in blunting of the K-wire and subsequent heat generation then lead to subsequent loosening and loss of fixation. Preoperative planning, marking the K-wire route, and appropriate K-wire thickness minimize such complications. Patients should be informed that following K-wire removal, the residual holes could be subject to stress risers.


Migratory insertion of the R2P group into a nitrogen-nitrogen bond - a novel type of rearrangement in phosphorus-nitrogen ligand chemistry. 3. The rearrangement of triphosphinohydrazide ligand -N(PPh2)-N(PPh2)2 to triphosphazenide anion {[(Ph2P-N]2PPh2}- in the coordination sphere of divalent cobalt and nickel.
Hydrazine dihydrochloride reacts with 3 equiv of Ph2PCl in tetrahydrofuran in the presence of triethylamine to give tris(diphenylphosphino)hydrazine (1) in 70% yield. Each nitrogen atom in 1 has a trigonal-planar environment according to X-ray analysis. Thermolysis of 1 at 130 degrees C results in the formation of two products: bis(diphenylphosphino)amine and octaphenylcyclotetraphosphazene. The interaction of free ligand 1 with NiBr2 affords a simple adduct [(Ph2P)2N-NH-PPh2]NiBr2, while its anionic (hydrazide) form undergoes rearrangement in a coordination sphere of divalent cobalt and nickel involving migratory insertion of the Ph2P group into a nitrogen-nitrogen bond. The reaction of 1 with cobalt bis(trimethylsilyl)amide, [(Me3Si)2N]2Co, yields the complex of phosphazenide-type (Me3Si)2N-Co[(Ph2PN)2PPh2] (2) in 86% yield. A similar reaction of 1 with nikelocene proceeds with substitution of one Cp ring to form durable 18-electron complex CpNi[(Ph2PN)2PPh2] (3).


Effects of changing reference values on the interpretation of spirometry for rubber workers.
The National Health and Nutrition Assessment Survey (NHANES) is being adopted for interpreting spirometry in occupational examinations. Rubber workers have an elevated risk of respiratory health issues due to industrial exposure, and changes in the equations would affect spirometry monitoring programs. To determine the differences in the use of the Knudson and NHANES III equations in nonsmoking workers in the rubber industry. A cross-sectional study was conducted with 75 nonsmoking workers with occupational exposure to rubber for at least two years. The factory had engineered protection controls and provided respiratory protection to the workers. Spirometry was conducted according to Spirometry Testing in Occupational Health Programs and Standardization of Spirometry: American Thoracic Society/European Respiratory Society. Spirometric prediction differences were present in the restrictive pattern assessment based on forced vital capacity (FVC), in which three individuals (4%) classified as normal according to Knudson presented restrictive disease according to NHANES III; only in the record of one participant was there restrictive disease using both equations. There was an 8% discrepancy for small airway obstruction in which six workers classified as normal using NHANES III were classified as diseased (FEF 25-75 <50%) using the Knudson equation. In the respiratory examination of workers exposed to rubber, the NHANES III equation is better able to detect restrictive diseases than is the Knudson equation; however, the Knudson equation is more sensitive to obstructive patterns.


Impact of Low Birth Weight and Prematurity on Neonatal Raltegravir Pharmacokinetics: Impaact P1097.
HIV treatment of neonates requires identifying appropriate antiretroviral dosing regimens. Our aims were to characterize raltegravir elimination kinetics in low birth weight (LBW) neonates after maternal dosing and to develop a pharmacokinetic model to predict raltegravir plasma concentrations for term and preterm neonates. Mothers living with HIV who received raltegravir during pregnancy and their LBW neonates participated in IMPAACT P1097 study. Up to 6 serial plasma samples were collected from each infant over the first 2 postnatal weeks to characterize raltegravir elimination. Safety laboratory evaluations were obtained, and infants were monitored for 6 weeks for signs of raltegravir toxicity. An integrated maternal-neonatal pharmacokinetic model was developed to predict neonatal raltegravir plasma concentrations. Sixteen mothers and their 18 LBW neonates were enrolled. The median (range) raltegravir elimination half-life was 24.4 (10.1-83) hours (N = 17 neonates). No adverse events related to raltegravir in utero exposure were observed. Pharmacokinetic modeling revealed that raltegravir clearance in full-term LBW neonates was well described by allometric scaling but clearance in preterm LBW neonates was better described using slower clearance maturation kinetics. Simulations suggest receipt of the current dosing recommendations in a 34-week gestation neonate would result in plasma concentrations up to 2.5-fold higher than those observed in full-term LBW infants. Modeling suggests that prematurity reduces raltegravir clearance and a modified raltegravir dosing regimen will be necessary to avoid elevated plasma raltegravir concentrations.


High-resolution sampling of beam-driven plasma wakefields.
Plasma-wakefield accelerators driven by intense particle beams promise to significantly reduce the size of future high-energy facilities. Such applications require particle beams with a well-controlled energy spectrum, which necessitates detailed tailoring of the plasma wakefield. Precise measurements of the effective wakefield structure are therefore essential for optimising the acceleration process. Here we propose and demonstrate such a measurement technique that enables femtosecond-level (15 fs) sampling of longitudinal electric fields of order gigavolts-per-meter (0.8 GV m-1). This method-based on energy collimation of the incoming bunch-made it possible to investigate the effect of beam and plasma parameters on the beam-loaded longitudinally integrated plasma wakefield, showing good agreement with particle-in-cell simulations. These results open the door to high-quality operation of future plasma accelerators through precise control of the acceleration process.


Motor adaptation to real-life external environments using immersive virtual reality: A pilot study.
Virtual reality (VR) has been described as an emerging therapeutic strategy to promote motor adaptation in different populations. The aim of this study was to investigate the effect of virtual environment demands, provided by an immersive VR system, on kinematic and spatio-temporal gait parameters in healthy young participants. Fifteen healthy young participants participated in this experimental study performing, in sequence, a baseline natural walking (NW) block, two different virtual environment walking blocks (snowy and crowded conditions), and a mixed walking block (including NW, snowy, and crowded conditions). Participants' Center-of-Mass (COM) excursion angle, medio-lateral (ML) COM excursion, step length, and walking speed were analyzed for each trial. COM excursion angle and ML-COM excursion increased significantly during the first snowy and crowded VR trials compared to NW trials, while walking speed and step length decreased only for the snowy conditions. COM excursion angle and ML-COM excursion increased significantly from the first to the fourth VR snowy trial and decreased from the first to the fourth VR crowded trial. Participants retained the acquired motor adaptations even after the mixed block. This study showed that kinematic and spatio-temporal gait parameters of young participants changed according to the virtual environment demands provided for each virtual scenario. In addition, all participants showed a consistent gait adaptation process to each virtual environment across the VR trials. The present findings highlight the impact of VR for gait adaptation, suggesting that VR training could modify motor behavior and enhance the motor adaptation process in healthy young participants.


Umbilical cord blood procalcitonin as a risk factor for mortality in very premature infants.
Fetal inflammatory response syndrome is implicated as a cause of fetal or neonatal injury. We analyzed the relationship between the procalcitonin umbilical cord blood level and neonatal outcome. A total of 237 preterms born in a level III perinatal medicine unit of a French university hospital were enrolled in a prospective observational study. Measurement of the procalcitonin umbilical cord blood level was performed at birth. After hospitalization, surviving infants were enrolled in the regional follow-up program. Outcome data were recorded on standardized questionnaires. The main outcome measures were neonatal mortality and impaired functional outcome at 2 years of corrected age. The terciles of procalcitonin levels were calculated. Preterm infants of the third tercile were defined as infants with elevated procalcitonin. Among the 237 infants, 13 (5.5%) died during the neonatal period, 20 (8.4%) were lost to follow-up, and 31 (13.1%) were classified as having an impaired functional outcome. After adjustment, elevated cord blood procalcitonin (>0.33 ng/ml) was significantly associated with an increase in mortality (adjusted odds ratio [aOR] = 8.3 [1.4-48]; p = 0.018), but not with the 2-year impaired functional outcome (aOR = 1.0 [0.4-2.5]; p = 0.93). Elevated umbilical blood cord procalcitonin concentration is an independent risk factor of mortality in preterm infants at less than 33 weeks' gestation.


Colligative properties of anomalous water.
Investigations of the phase behaviour on freezing and subsequent melting and of other properties indicate that anomalous water is a solution containing a fixed amount of relatively involatile material in normal water. There seems to be no need to postulate the existence of a new polymer of water in such solutions. If only water and silica are present, the properties are consistent with those of a silicic acid gel.


Treatment of carpal tunnel syndrome by members of the American Society for Surgery of the Hand: results of a questionnaire.
Carpal tunnel syndrome is one of the most common problems seen by the hand surgeon. In spite of its frequent occurrence there are several aspects of its treatment that remain controversial. A survey of the members of the American Society for Surgery of the Hand determined whether a consensus exists concerning the treatment of carpal tunnel syndrome among surgeons who regularly treat hand problems.


Host range mutants of an influenza A virus.
Temperature-sensitive (ts) mutants of fowl plague virus with a ts-lesion in segment 1 (ts 3, polymerase 1 gene) or segment 2 (ts 90, transport gene) do not form plaques on MDCK cells at the permissive temperature, while the wild type and ts-mutants of other groups are able to do so. This property is correlated with the ts-lesion, since revertants for the ts-lesion of ts 3 and ts 90 again form plaques on MDCK cells. The block on MDCK cells--at least for ts3--may be located in a late function, since viral RNA polymerase and hemagglutinin are formed in almost normal yields. MDCK cells infected with ts 3 or ts 90 exhibit a retarded cytopathic effect at 33 degrees C, but no cytopathic effect at 39 degrees C, at which temperature the infected cells can be passaged and super-infected with the wild type strain. Cells surviving the infection with ts 90 at 33 degrees C sometimes grow out again to a normal monolayer. It is suggested that the spread of virus is inhibited under these conditions.


Clinical pharmacology of dilevalol (II). The pharmacokinetic, pharmacodynamic, and tolerance studies of dilevalol during repeated administration in healthy subjects.
Dilevalol (50 mg) was given orally twice daily for eight days in six healthy subjects. All parameters were obtained following 1st (on day 1) and 15th (on day 8) dosages. Blood samples for plasma drug concentrations were taken for a 12-hour (after 1st dosage) or a 24-hour (after 15th dosage) post-drug period. Blood pressure (BP) as well as heart rate (HR) at supine position, during 50 degrees tilting and during a submaximal exercise were measured after each dosage. The mean time to maximum concentration (tmax) was faster, and the mean area under the plasma concentration-time curve (AUC) was greater after 15th dosage than following 1st dosage. No significant differences were observed in the maximum plasma concentration (Cmax), the distribution half-life (t 1/2 alpha) or the elimination half-life (t 1/2 beta) between the two dosages. BP at supine position as well as during 50 degrees tilting decreased significantly after each dosage, and did not differ between 1st and 15th dosages. Postural changes in BP or HR during 50 degrees tilting were not induced following 1st or 15th dosage. The suppressing effects (%R) on an increase in HR during a submaximal exercise were significantly larger after 15th dosage than after 1st dosage. A significant correlation was observed between plasma dilevalol concentration and %R in HR. These data indicate that the hypotensive effect of dilevalol is not altered during the repeated administration of the drug for 8 days. However, the beta-blocking activity of dilevalol might be enhanced during the repeated dosages, which is, in part, attributed to dosage-dependent elevation in plasma drug concentrations.


Cell population kinetics of Kupffer cells during the onset of fibrosis in rat liver by chronic carbon tetrachloride administration.
The cell population kinetics of Kupffer cells (KCs) were investigated during the induction of fibrosis in rat liver by carbon tetrachloride. KCs, characterized microscopically by their specific peroxidase pattern, increased in number during the first 24 h after CCl4 injection. After repeated injections of the toxin the number of KCs increased logarithmically. After 9 weeks of CCl4 treatment, the KC population reached a new steady state with a 2.6-times-higher cell number than in control animals. Local KC proliferation was demonstrated by the metaphase arrest technique using vinblastine. It was calculated that at 24 h and at 72 h after one injection of CCl4, local proliferation did not account for the entire growth of the population. This means that, in addition to local proliferation of KCs, an influx of mononuclear phagocytes into the liver sinusoids occurred.


Prediction of height using ulna length in African-Caribbean children.
Standing height is an essential anthropometric measurement in pediatrics. In children unable to stand upright, measurement of ulna to predict standing height is recommended, but height prediction equations based on the ulna have not been established in children of African ancestry. We hypothesized that such equations would result in lower predicted height compared to using equations derived from non-African children. We measured prospectively standing height and both ulna in 358 African-Caribbean children without bone deformity or muscle disease, referred to two pulmonary function test laboratories. Interobserver variability was low for standing height (n = 54) and ulna measurement (n = 51) (mean biases [95%CI]: -0.02 [-0.99; 0.95] and 0.05 [-0.91; 1.01] cm, respectively), as well as inter-ulna variability (n = 352; mean bias 0.03 95%CI [-0.66; 0.73] cm). We used the mean value of 247 bilateral ulna measurements to calculate prediction equations using a generalized linear model including age, sex, ulna length, and geographic origin group, the latter showing no influence on the model. In the validation population of 107 children, the median difference [inter-quartile range] between standing height and ulna-predicted height was -0.4 [-2.7; 1.0] cm. Of 260 reliable baseline spirometry, there was a strong concordance between bronchial obstruction diagnosis established using standing height or ulna-predicted height (kappa coefficient: 0.85 [0.77; 0.94]) with only 11 (4.3%) children misclassified. The ulna predicted height calculated from African-Caribbean prediction equations resulted in a smaller height than the height calculated using equations derived from non-African children.


Some necessary and sufficient conditions for containment of second-order multi-agent systems with intermittent sampled data.
This paper comes up with two novel sampled data containment control protocols with intermittent communication for second-order multi-agent systems, where the intermittent communication is periodic. For the protocols with or without time delay, two necessary and sufficient conditions are obtained. In both cases, containment control can be implemented, where each follower can eventually reach the convex hull made up of multiple leaders. In particular, for the protocol with time delay, depending on the size of the time delay, two different conditions are obtained to achieve containment. More interestingly, the result that the smaller the time delay is, the easier it is to calculate the interval of the appropriate sampling period has been found. At last, the correctness of the theoretical results is verified by several simulations.


The influence of spontaneous accelerations of fetal heart rate on umbilical artery velocity waveforms.
For clinical interpretation of Doppler waveforms, it is important to establish the extent to which fetal heart rate changes affect the umbilical artery velocity waveform. Umbilical artery waveforms were measured with continuous wave ultrasonography during spontaneous accelerations of the fetal heart rate in 20 uncomplicated, near-term pregnancies. On average, an acceleration of 20 beats/min of fetal heart rate within an individual was associated with a reduction in the systolic/diastolic velocity ratio of 0.25. There was, however, considerable variability in the response, and in six patients the systolic/diastolic ratio actually increased with heart rate. We conclude that fetal heart accelerations within the normal range cause only small and variable changes in the systolic/diastolic ratio.


Effects of acetylation and guanidination on alkaline conformations of chymotrypsin.
Guanidination leads to stabilization of several globular proteins, including bovine chymotrypsinogen, as determined by hydrogen isotope exchange (P. Cupo, W. El-Deiry, P.L. Whitney, and W.M. Awad, Jr. (1980) J. Biol. Chem. 255, 10828-10833). The present study examined the binding of proflavin to guanidinated, acetylated, and native chymotrypsins in order to compare conformational flexibilities. The order of decreasing alkaline stabilities of the catalytically active conformations of the different delta-chymotrypsin forms was guanidinated, native, and acetylated proteins; delta-chymotrypsin showed greater stability than alpha-chymotrypsin. In each case removal of calcium reduced the amount of the catalytically active conformation. The alkaline pH dependence for the decrease of the catalytically active conformation of guanidinated alpha-chymotrypsin could not be attributed to the titration of a single group, indicating that the alpha-amino group of isoleucine-16 is not the sole feature regulating the conformational transition for this derivative. At neutral pH values delta-chymotrypsin exists completely in an active conformation and the percentage of alpha-chymotrypsin in this form is only slightly lower. These differences from earlier results are possibly due to differences in buffers, calcium ion concentrations, and ionic strength. The rate of inactivation of guanidinated delta-chymotrypsin with methyl acetimidate was much lower than the corresponding rate for the native enzyme. This suggests that guanidination increases enzyme stability which in turn leads to a reduced accessibility of the alpha-amino group of isoleucine-16.


Glycation Inhibition of Bovine Serum Albumin by Extracts of Momordica charantia L. using Spectroscopic and Computational Methods.
Momordica charantia (M. charantia) has been used in traditional medicine for the management of complications associated with diabetes mellitus. Several phytochemicals with different pharmacological properties have been previously identified from the botanical; however, the mechanisms of actions of this plant vis-à-vis inhibition of non-enzymatic protein glycation are not known. This study aimed at understanding the putative mechanisms underlying the antiglycation properties of M. charantia extracts experimental and theoretical approaches. The antiglycation properties of the plant were evaluated by studying the inhibitory actions of methanol and aqueous extracts on glucose-induced glycation of Bovine Serum Albumin (BSA) and protein aggregation. The mode of binding of identified phenolics of the botanical with BSA, amyloid beta-peptide (1-42) and 3D amyloid beta (1-42) fibrils were also investigated. The in vitro experimental properties of the extracts showed that the extracts could prevent inductions of protein glycation and protein folding. The molecular docking analyses revealed that phenolics had better binding affinities with chlorogenic acid showing the highest binding score (-7.13±0.04 kcal/mol) towards BSA than glucose and their respective interactions with BSA could prevent glucose-induced protein aggregation. Consequently, the results of this study provide insight into the probable mechanisms of actions of the extracts of M. charantia against the inhibition of advanced glycation end products formation.


Endometrial glandular haemosiderosis in homozygous beta-thalassaemia.
Female patients with beta-thalassaemia major usually suffer from hypogonadotropic hypogonadism associated with amenorrhea, anovulation and infertility, attributed to the deposition of haemosiderin in the pituitary gland as well as in the ovaries. Pregnancies are rare and, with few exceptions, occur mainly in patients with beta-thalassaemia intermedia. Our study presents histopathological evidence that deposition of haemosiderin occurs in the endometrial glandular epithelium of 3 patients with beta-thalassaemia major. This deposition is mainly evident in the apical part of these cells above the nuclei, and should be taken into consideration as a contributing factor to the infertility in these patients by altering endometrial receptivity for implantation. In 2 patients who received effective iron chelating treatment with desferrioxamine the endometrial haemosiderin deposits either disappeared (patient C.R.), or were significantly reduced (patient G.L.).


Complications of concurrent lithium and electroconvulsive therapy: a review of clinical material and theoretical considerations.
Several anecdotal reports and two retrospective chart reviews have examined complications of concurrent lithium and electroconvulsive treatment. Discussions have generally been contradictory or confusing. This article reviews the literature and particularly emphasizes theoretical considerations and mechanisms, concluding (A) that lithium may act synergistically with neuromuscular blockers, but the effect is not clinically significant, and (B) that repeated electroconvulsive seizures may cause a toxic delirium in patients concurrently taking lithium.


Neonatal Intensive Care Unit Nurses' Perceptions and Knowledge of Newborn Individualized Developmental Care and Assessment Program: A Multicenter Study.
The newborn individualized developmental care and assessment program (NIDCAP) is a new multifaceted approach, which is developmentally and functionally supportive of health especially in premature newborns at the neonatal intensive care unit (NICU). This study is designed for assessing the knowledge and perception of nurses as the most important members of the multidisciplinary team of NIDCAP about this program. This cross-sectional study was conducted on 120 nurses working in the NICUs of Alzahra, Taleghani, and Children hospitals affiliated to the educational and treatment centers of Tabriz University of Medical Sciences as well as 29 Bahman Hospital affiliated to Tabriz Social Security Organization in 2016 using census sampling method. Three questionnaires were employed to collect demographic data and to explore the nurses' perceptions and knowledge of the NIDCAP program. Findings of the study indicated that the mean (SD) nurses' knowledge and perception scores for NIDCAP were 71.83 (1.64) and 76.80 (0.79), respectively. In the terms of knowledge, significant differences were found with regard to being married (t = -2.39, p < 0.019), having an MSc degree (t = -2.14, p = 0.034), and employment experience (t = -3.38, p = 0.001). However, there was no significant relationship between perception and demographic variables (p > 0.05), nor was there any significant relationship between perception and knowledge (p = 0.275). The results of this study showed that the majority of nurses participating in the study had high knowledge about NIDCAP.


Psychiatric symptoms in the elderly in a primary care practice.
During a 15-month period in a rural group medical practice 1063 patients of four general internists completed a 49-item version of the Hopkins Symptom Check List (HSCL). This version of the HSCL measured symptoms of depression, anxiety, phobic anxiety, hostility, and interpersonal sensitivity. In comparison to younger groups, the elderly patients reported decreased symptomatology on all HSCL scales except the phobic anxiety scale. These differences could be due to a reporting effect, selective migration or mortality, a cohort effect, or they could reflect a true age effect, the view favored by the authors.


Price differentials of tobacco products: A cross-sectional analysis of 79 countries from the six WHO regions.
Increased taxation is one of the most effective tobacco control measures. Price differentials across tobacco product types may undermine the effectiveness of taxation policies by providing the option to switch to cheaper products rather than to quit. The aim of this study was to use commercial data to compare prices and price differentials of both cigarette and non-cigarette products across countries from all geographical regions. We analyzed 6920 price data points (i.e. product brands) from Euromonitor Passport 2016 for 12 types of tobacco products across 79 countries from the six WHO regions: Africa (n=5), Eastern Mediterranean (n=6), Europe (n=39), the Americas (n=15), South-East Asia (n=3), and Western Pacific (n=12). For each product and country, a price differential was computed as the percentage of minimum price to the median. Median cigarette prices (US$) were highest in Western Pacific countries (4.00; range: 0.80-16.20) and European countries (3.80; range: 0.80-14.00), but lowest in African countries (2.00; range: 0.80-2.20). The medians of cigarette price differentials were largest in the Eastern Mediterranean (48.33%) and African regions (50.00%), but smallest in Europe (82.35%). Pipe tobacco and fine-cut tobacco were generally less expensive than cigarettes while cigars were the most expensive. However, there were wide variations in prices and price differentials across regions and tobacco products. We found substantial variations in prices and price differentials between countries and world regions across tobacco products, likely reflecting differences in taxation policies and structures. Findings identify types of tobacco products in specific geographical regions where price differentials are highest, thereby highlighting areas where taxation policies need improvement, for example through implementing specific excise taxes.


Influence of estrogen treatment on hepatic cystathionine synthase and cystathionase of female rats fed varying levels of vitamin B-6.
Diets containing 8, 4, 2, or 0 mg vitamin B-6/kg were fed to intact, female rats designated high-, medium-, low-, and deficient-diet groups, respectively. After receiving the diets for 2 weeks, each group was subdivided so as to receive scheduled subcutaneous injections of corn oil with or without estradiol benzoate (Es and NoEs rats, respectively). In experiment 1, rats were fed ad libitum and injections given daily for 2 weeks. In experiment 2, rats were pair-fed and injections given every other day for 3 weeks. Es injections contained 10 microgram and 20 microgram of estradiol benzoate in experiments 1 and 2, respectively. Hepatic cysthionine synthase (CStase) and cystathionase (CNase) activities were determined both with and without exogenous pyridoxal-5-phosphate (stimulated and basal activities, respectively). Regardless of estradiol treatment, the deficient-diet decreased food intake, weight gain, and the basal and stimulated activities of both enzymes with the exception of stimulated CNase activity in Es rats. Estradiol reduced stimulated CNase activity in the medium- and high-diet groups in experiment 1. In experiment 2, estradiol reduced basal CNase activity of all diet groups and reduced stimulated CNase of low- and high-diet groups. It had little effect on CStase activity.


Effects of Curcumin and Boric Acid Against Neurodegenerative Damage Induced by Amyloid Beta (1-42).
Synaptosomes are used as an ex vivo model in the investigation of neuronal transmission and neurodegenerative processes. In this study, we aimed to determine the protective effects of boric acid (BA) and curcumin, which have antioxidant and anti-inflammatory properties, on Aβ1-42 induced neurodegenerative damage. Synaptosomes obtained from the rat cerebral cortex were divided into five groups: control, 10 μM Aβ1-42, 10 μM Aβ1-42 + 25 mM BA, 10 μM Aβ1-42 + 10 μM curcumin, and 10 μM Aβ1-42 + 25 mM BA+10 μM curcumin. Synaptosomes treated with Aβ1-42 caused a significant decline in synaptophysin levels and increase in malondialdehyde (MDA) levels, acetylcholinesterase (AChE) activities, DNA fragmentation values, and nitric oxide (NO) levels compared with the control group (P < 0.01). Synaptosomes treated with BA showed a significant reduction in MDA and NO levels against Aβ1-42 exposure (P < 0.01). In addition, curcumin treatment has been found to cause a significant reduction in AChE activities and MDA levels in synaptosomes (P < 0.05). Co-administration of BA and curcumin on synaptosomes exposed to Aβ1-42 resulted in a significant decrease in DNA fragmentation values, MDA levels, and AChE activities. Curcumin and BA + curcumin combination showed an enhancement in synaptophysin levels of Aβ1-42-induced synaptosomes (P < 0.01). The results showed that BA and curcumin had protective effects on rat brain synaptosomes against Aβ1-42 exposure. BA and curcumin treatment can have abilities to prevent the alterations of the cholinergic system and inhibit oxidative stress in the cerebral cortex synapses of Aβ1-42 exposed.


Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6.
Mitochondrial-derived peptides are encoded by mitochondrial DNA but have biological activity outside mitochondria. Eight of these are encoded by sequences within the mitochondrial 12S and 16S ribosomal genes: humanin, MOTS-c, and the six SHLP peptides, SHLP1-SHLP6. These peptides have various effects in cell culture and animal models, affecting neuroprotection, insulin sensitivity, and apoptosis, and some are secreted, potentially having extracellular signaling roles. However, except for humanin, their importance in normal cell function is unknown. To gauge their importance, their coding sequences in vertebrates have been analyzed for synonymous codon bias. Because they lie in RNA genes, such bias should only occur if their amino acids have been conserved to maintain biological function. Humanin and SHLP6 show strong synonymous codon bias and sequence conservation. In contrast, SHLP1, SHLP2, SHLP3, and SHLP5 show no significant bias and are poorly conserved. MOTS-c and SHLP4 also lack significant bias, but contain highly conserved N-terminal regions, and their biological importance cannot be ruled out. An additional potential mitochondrial-derived peptide sequence was discovered preceding SHLP2, named SHLP2b, which also contains a highly conserved N-terminal region with synonymous codon bias.


Distribution of actin filaments in human malignant keratinocytes.
Distribution of actin filaments in human malignant keratinocytes was examined by immunofluorescence staining. The primary cultures were obtained from a squamous cell carcinoma, a basal cell carcinoma, and Bowen's disease. Rhodamine-phalloidin staining revealed that actin filaments were occasionally organized to form stress fibers, many short bundles with a ripple appearance, and regular arrays of actin patches. Some of these structures appeared in untransformed keratinocytes as a result of a brief exposure to a tumor promotor, TPA. These findings suggest that regulation of actin functions is involved in neoplastic processes from the very early stages and that alteration is persistent in neoplastic cells.


The heritability of gestational age in a two-million member cohort: implications for spontaneous preterm birth.
Preterm birth (PTB), defined as birth prior to a gestational age (GA) of 37 completed weeks, affects more than 10% of births worldwide. PTB is the leading cause of neonatal mortality and is associated with a broad spectrum of lifelong morbidity in survivors. The etiology of spontaneous PTB (SPTB) is complex and has an important genetic component. Previous studies have compared monozygotic and dizygotic twin mothers and their families to estimate the heritability of SPTB, but these approaches cannot separate the relative contributions of the maternal and the fetal genomes to GA or SPTB. Using the Utah Population Database, we assessed the heritability of GA in more than 2 million post-1945 Utah births, the largest familial GA dataset ever assembled. We estimated a narrow-sense heritability of 13.3% for GA and a broad-sense heritability of 24.5%. A maternal effect (which includes the effect of the maternal genome) accounts for 15.2% of the variance of GA, and the remaining 60.3% is contributed by individual environmental effects. Given the relatively low heritability of GA and SPTB in the general population, multiplex SPTB pedigrees are likely to provide more power for gene detection than will samples of unrelated individuals. Furthermore, nongenetic factors provide important targets for therapeutic intervention.


5-hydroxytryptophol in human cerebrospinal fluid: conjugation, concentration gradient, relationship to 5-hydroxyindoleacetic acid, and influence of hereditary factors.
The serotonin metabolite 5-hydroxytryptophol was studied in human cerebrospinal fluid. A minor fraction (approximately 13%) was found in conjugated form from which it was liberated by treatment with sulphatase containing beta-glucuronidase activity. A concentration gradient of 5-hydroxytryptophol concentration was shown on lumbar tapping and the concentration in ventricular CSF was about 2.5 times higher than that in lumbar CSF. 5-Hydroxytryptophol and 5-hydroxyindoleacetic acid concentrations were significantly correlated in healthy, psychotic, and depressed subjects, but not in alcoholics. 5-Hydroxytryptophol concentrations in CSF of psychotic and depressed subjects were not different from those of healthy controls (4.22 pmol/ml +/- 0.15, SEM). In healthy subjects, hereditary factors seemed to have little influence on the CSF level of 5-hydroxytryptophol.


Phase I study of the tolerability and pharmacokinetics of palifermin in children undergoing allogeneic hematopoietic stem cell transplantation.
The maximum tolerated dose of palifermin, a keratinocyte growth factor, in children is not known, and its pharmacokinetics in this population has not been well studied. This is a phase I study of palifermin was designed to evaluate its tolerability at doses of 40, 60, and 90 μg/kg/day in children age 2-18 years of age, receiving a myeloablative preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT). In each cohort, palifermin was given for 3 consecutive days before the preparative regimen and for 3 days after the stem cell infusion. Twelve patients were enrolled. Palifermin 90 μg/kg/day was tolerated in 6 patients without dose-limiting toxicity. All patients had at least 1 adverse event, mostly National Cancer Institute grade 1 or 2 severity. Skin rash, grade 2 or lower, was the most common adverse event, seen in 67% of patients. Only 3 patients (25%) had mucositis. The area under the concentration-time curve increased proportionally to the dose, and approximately 97% of palifermin exposure occurred in the first 24 hours after administration. Palifermin clearance increased linearly with body weight, supporting dosing by body weight. The mean clearance was 1893 mL/hour/kg, and it did not change significantly between administration of the first and last doses (P = .80). The mean elimination half-life was 4.6 hours. Our data show that palifermin was tolerated at a dose of 90 μg/kg/day, and exhibits linear pharmacokinetics in children undergoing allogeneic HSCT.


[Blood transfusion on battlefield. The Kabul hospital experience].
Blood transfusion is an aspect of medical care on the battlefield. French assets include: red blood cell units (RBCu), lyophilized plasma (PLYO), fresh whole blood (FWB) but neither fresh-frozen plasma (FFP) nor platelets. French transfusion strategy in military operations follows the evolution of knowledge and resources. We describe the characteristics of the transfusion at the military hospital in Kabul. Retrospective study of records of patients transfused between October 2010 to December 2011 conducted in Kabul from transfusion register. Variables studied were: patient characteristics, biology at admission, type and amount of transfusion products, evolution. One hundred and twenty-six patients were transfused: 49 military (39%) which 22 French soldier (17%), most of time afghan (n=97; 77%), mean age at 24 years old (3-66). Two hundred and seventy-three RBCu from France were transfused and 350 unused were destroyed. Conditions leading to a transfusion were: 76 war wounds (60%), 21 trauma (17%) and 29 other (23%). In the first 24 hours, patients received in mean: two RBCu (0-12), one unit of FWB (0-18) and two PLYO (0-14). PLYO/RBCu ratio was 1/1.6. A massive transfusion (more than 10 RBCu) concerned 9% of patients. Twenty-seven percent of patients received FWB. We note 17 dead people (13.5%). The use of the FWB and PLYO in substitution of FFP and platelets can provide cares of high quality in a logistically constrained context while controlling costs.


Serum troponin T concentrations in two strains of commercial broiler chickens aged one to 56 days.
Troponin T is a specific and sensitive serological indicator of acute myocardial infarction in human patients. The concentration of serum troponin T was measured by an ELISA technique in two strains of healthy commercial broiler chickens (Cobb 500 and Ross I) aged between one and 56 days. The concentrations of cardiac-derived troponin T in day-old Cobb and Ross chicks were 5.74 and 8.35 ng ml-1, respectively, and much higher than in 14-day-old chicks. Between 21 and 56 days, the values were consistently lower than the mean troponin T concentration of 0.20 ng ml-1 reported previously in a group of healthy 30-day-old broilers. All the other heart measurements, including the arterial pressure index, were within normal limits. The high troponin T concentrations after hatching are probably due to an embryonic isoform that rapidly becomes replaced by an adult isoform by three weeks of age. The data suggest that in healthy birds, there is an inverse relationship between troponin T concentrations and age.


Inhibition of HIV-1 reverse transcriptase by pyridinone derivatives. Potency, binding characteristics, and effect of template sequence.
The inhibition of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase by pyridinone compounds has been investigated using as templates synthetic RNA with sequences based on the HIV-1 genome sequence. In reactions catalyzed by the enzyme that incorporated more than one nucleotide per primer, inhibition by a representative pyridinone inhibitor, 3-[2-(1,3-benzoxazol-2-yl)ethyl]-5-ethyl-6-methyl-pyridin-2(1H)one (L-696,229), was noncompetitive against deoxynucleotide triphosphate. For reactions that incorporated one deoxynucleotide per primer, IC50 values ranged from 20 to 200 nM, depending on the position of incorporation of the incoming deoxynucleotide base on the template. Inhibition of synthesis on a set of four templates differing only at the template base complementary to the incoming nucleotide had similar IC50 values. These results demonstrate that inhibitory potency is dependent on the primary structure of the template and that inhibitory potency is largely independent of the identity of the incoming nucleotide base. The inhibition of HIV-1 reverse transcription by L-696,229 also displayed slow-binding characteristics. The slow-binding aspect was exploited to gauge the interaction between inhibitor and enzyme. By titrating the reduction in the extent of the burst of synthesis observed in a reaction incorporating dideoxythymidine monophosphate into poly(rA)-oligo(dT)18, the apparent equilibrium constant for dissociation of the reverse transcriptase-L-696,229 complex was estimated to be 400 nM.


One year treatment with low dose methotrexate in rheumatoid arthritis: effect on class specific rheumatoid factors.
We evaluated the effect of a one-year treatment of low dose methotrexate (MTX) on class specific rheumatoid factors in 27 patients with rheumatoid arthritis (RA). Enzyme-linked immunosorbent assay (ELISA) showed after 6 and 12 months a significant reduction of IgM-RF, IgA-RF and IgG-RF levels from the baseline values. During MTX treatment, changes of each RF isotype were not correlated with any other isotype and its corresponding immunoglobulin changes. Moreover, immunological changes were not related to the improvement of clinical parameters. Our results showed that low dose MTX can specifically affect levels of RF isotypes, which are involved in the immune pathogenesis of RA.


Multifunctional phototheranostic nanoplatform based on polydopamine-manganese dioxide-IR780 iodide for effective magnetic resonance imaging-guided synergistic photodynamic/photothermal therapy.
Multifunctional phototheranostics combining diagnostic and therapeutic modalities may provide a revolutionary opportunity for cancer treatment. As a promising tumor phototheranostic molecule, IR780 iodide (IR780) shows excellent photodynamic and photothermal performance under near-infrared laser irradiation; however, its hydrophobicity and instability limit its further use in organisms. This work demonstrates the design and development of a multifunctional nanoplatform (PMIDA, referring to polydopamine (PDA)-manganese dioxide (MnO2)-IR780) for imaging-guided phototherapy. The good biocompatibility of PDA greatly improves the water solubility and photostability of IR780, and its excellent photothermal properties make PMIDA a dual photothermal therapy (PTT). MnO2-induced generation of oxygen in the tumor microenvironment improves the hypoxia effect and photodynamic therapy (PDT) of IR780. Moreover, Mn2+ serves as a decent T1-weighted magnetic resonance imaging (MRI) probe to guide treatment. Notably, in relevant cellular assays, PMIDA shows high photodynamic and photothermal effects contributing to the final therapeutic effect. The MRI-guided PDT/PTT synergistic therapy effect in vivo is demonstrated by precise tumor diagnosis and complete tumor elimination outcomes. Based on these experiments, PMIDA nanoparticles display promising effects in facilitating intravenous injection of IR780 and achieving magnetic resonance imaging (MRI)-guided phototheranostic efficacy for tumor treatment.


Mammillary body abnormalities and cognitive outcomes in children cooled for neonatal encephalopathy.
To evaluate mammillary body abnormalities in school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (cases) and matched controls, and associations with cognitive outcome, hippocampal volume, and diffusivity in the mammillothalamic tract (MTT) and fornix. Mammillary body abnormalities were scored from T1-weighted magnetic resonance imaging (MRI) in 32 cases and 35 controls (median age [interquartile range] 7 years [6 years 7 months-7 years 7 months] and 7 years 4 months [6 years 7 months-7 years 7 months] respectively). Cognition was assessed using the Wechsler Intelligence Scale for Children, Fourth Edition. Hippocampal volume (normalized by total brain volume) was measured from T1-weighted MRI. Radial diffusivity and fractional anisotropy were measured in the MTT and fornix, from diffusion-weighted MRI using deterministic tractography. More cases than controls had mammillary body abnormalities (34% vs 0%; p < 0.001). Cases with abnormal mammillary bodies had lower processing speed (p = 0.016) and full-scale IQ (p = 0.028) than cases without abnormal mammillary bodies, and lower scores than controls in all cognitive domains (p < 0.05). Cases with abnormal mammillary bodies had smaller hippocampi (left p = 0.016; right p = 0.004) and increased radial diffusivity in the right MTT (p = 0.004) compared with cases without mammillary body abnormalities. Cooled children with mammillary body abnormalities at school-age have reduced cognitive scores, smaller hippocampi, and altered MTT microstructure compared with those without mammillary body abnormalities, and matched controls. Cooled children are at higher risk of mammillary body abnormalities than controls. Abnormal mammillary bodies are associated with reduced cognitive scores and smaller hippocampi. Abnormal mammillary bodies are associated with altered mammillothalamic tract diffusivity.


Development of 4πβ(LS)-γ digital coincidence counting system at NIM.
A new 4πβ(LS)-γ digital coincidence counting (DCC) system has been developed at NIM. The system equipped with a triple-to-double coincidence ratio (TDCR) counter in the β-channel and a NaI(Tl) scintillation detector in the γ-channel. A dedicated DCC software was designed for off-line implementation of 4πβ(LS)-γ coincidence counting method. The software consists of three modules: software-based circuits module, dead-time and resolving-time correction module and efficiency extrapolation module, respectively. The performance of the newly developed 4πβ(LS)-γ DCC system was demonstrated by a comparison measurement of Co-60 solution with the conventional 4πβ(PC)-γ DCC system.


Inheritance of wild and truncated DAT alleles from grand-parents: Opposite transgenerational consequences on the behavioral phenotype in adolescent DAT heterozygous rats.
Dopamine plays important roles in implicit memory and motivation of behavior. Environmental inputs can produce transgenerational epigenetic changes. This concept also includes the uterus: experimentally, we sought to create hyper-dopaminergic uterine conditions through ineffective dopamine-transporter (DAT) protein, obtained by inserting a stop-codon into the SLC6A3 gene. By crossing WT-dam with KO-sire (or vice-versa), we obtained a 100% DAT-heterozygous (HET) offspring with known derivation of the wild allele: MAT rats are offspring of WT-female and KO-male; PAT rats are offspring of KO-female and WT-male. We reconstructed inheritance of alleles, by crossing PAT-male with MAT-female or vice-versa, obtaining GIX (PAT-male with MAT-female) and DIX (MAT-male with PAT-female) rats (such offspring present specular paths in allele inheritance from grandparents). We conducted three experiments: first, we assessed maternal behaviour (four epigenotypes: WT, MAT, PAT and WHZ=HET-pups fostered-to-a WT-dam); in the second, we analysed sleep-wake cycles of GIX and DIX epigenotypes with their WIT siblings as controls; in the third, we explored the impact of WT or MAT mother on WT or HET pups. MAT-dams (with GIX-pups) express excessive licking/grooming. However, in the mere presence of "sick" epigenotype, PAT-dams (with DIX-pups) and also WHZ (i.e., WT-dams but with HET-pups) expressed greater nest-building care towards the offspring, compared to "true-wild" litters (WT-dams with WT-pups). In Exp. 2 at adolescence, GIX epigenotype showed locomotor hyperactivity during late waking-phase, while DIX epigenotype exhibited pronounced hypoactivity compared to controls. In Exp. 3, we confirmed that HET adolescent pups receiving cares from a MAT-dam may develop additional hyperactivity when awake, but additional hypoactivity during rest-hours. Thus, behavioral changes observed in DAT-heterozygous offspring have opposite courses based on of DAT-allele inheritance from a grandparent through the sire or the dam. In conclusion, behavioural changes in the offspring have antithetic courses with respect to inheritance of DAT-allele via sperm or egg.


The Epidemic of COVID-19-Related Erectile Dysfunction: A Scoping Review and Health Care Perspective.
COVID-19 infection is expected to be associated with an increased likelihood of erectile dysfunction (ED). Considering the high transmissibility of COVID-19, ED may be a concerning consequence for a large segment of the population. To (1) summarize existing published evidence for the impact of COVID-19 on the prevalence, severity, treatment, and management of ED; and (2) identify health-related trends in the emerging literature and identify gaps in the existing research literature and make recommendations for future research needs in the area. A scoping literature search was conducted on April 27, 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (Preferred Reporting Items for Systematic Reviews and Meta-Analyses-ScR) checklist was followed. The literature search was performed in PubMed using the terms: COVID-19, erectile, sexual, and dysfunction. A total of 693 publications were screened for relevance. Studies were appraised for their level of evidence based on study design and the rigor of methodology. The evidence that COVID-19 infection causes or impacts ED is compelling. Four topics emerged regarding the nature of the association between COVID-19 and ED: (1) the biological impact of COVID-19 infection on ED; (2) the mental health impact of COVID-19 on ED; (3) the impact of COVID-19 on the management of ED and access to ED treatment; and (4) health disparities and the impact of COVID-19 on ED. Long-term and well-designed studies are needed to clarify the extent of the impact of COVID-19 on ED. The pandemic exposed several vulnerabilities within worldwide healthcare and social systems. COVID-19 has a uniquely harmful impact on men's health and erectile function through biological, mental health, and healthcare access mechanisms. As the pandemic wanes, strategies to identify long-term effects and additional health care support may be needed to adequately mitigate the impact of COVID-19 on men's health. Hsieh T-C, Edwards NC, Bhattacharyya SK, et al.The Epidemic of COVID-19-Related Erectile Dysfunction: A Scoping Review and Health Care Perspective. Sex Med Rev 2022;10:286-310.


Reduced hatchability of Anopheles gambiae s.s eggs in presence of third instar larvae.
We investigated the hatchability rates of freshly laid Anopheles gambiae s.s. eggs in presence of third instars larvae. These experiments were conducted using 30 eggs in larval densities of 20, 60 and 100 larvae in microcosms. These experiments were designed to evaluate the eggs hatchability in habitats with late larvae instars of the same species (experimental) or no larvae at all (control). Freshly laid eggs of An.gambiae s.s. were washed in microcosms containing larvae of third instars in different three densities (20, 60 and 100) and likewise in control microcosms (without larvae). Eggs hatchability was monitored twice daily until no more first instar larvae emerged. The numbers of first instars larvae were recorded daily and lost eggs were considered preyed upon by third instars. The findings of this study showed that egg hatchability was significantly influenced by larval density. The findings of this study suggest that presence of larvae in habitats may significantly reduce hatchability of eggs.


Molecular and cellular correlates of cardiac function in end-stage DCM: a study using speckle tracking echocardiography.
We sought to compare the effects of interstitial fibrosis and myocardial force generation/relaxation elements on left ventricular (LV) function in patients with end-stage dilated cardiomyopathy (DCM). Interstitial fibrosis is common in patients with advanced heart failure. However, the extent to which it affects cardiac function remains unclear. Longitudinal, radial, and circumferential strain; strain rate during systole (SRS) and strain rate during early diastole (SRE); LV volume; LV ejection fraction; mean pulmonary capillary wedge pressure (PCWP); and e' were measured in 20 DCM patients. Myocyte diameter, interstitial fibrosis, messenger ribonucleic acid (mRNA) levels of molecules implicated in fibrosis and function (transforming growth factor beta, titin [TTN] N2B and N2BA isoforms, collagen type I, collagen type III, sarcoplasmic reticulum Ca(2+)-ATPase [SERCA2a], phospholamban [PLB], and protein levels of SERCA2a, phosphorylated PLB, and Smad2/3) were correlated with strain from 4 regions per patient (LV apex, midlateral, septum, and right ventricular free wall) as well as LV global function. In another group of 8 DCM patients, we evaluated LV structure and function before and after LV assist device. Significant correlations were present among ejection fraction, e' velocity, PCWP, LV end-diastolic volume/PCWP ratio, strain, SRS, SRE, and mRNA expression of TTN N2B, N2BA, SERCA2a, PLB, and protein levels of SERCA2a and phosphorylated PLB (r = 0.53 to 0.95, p < 0.05). Weak to no associations were present between strain and interstitial fibrosis and its molecular determinants. In patients with repeat studies, regional strain and SRE best tracked the changes in mRNA expression of TTN isoform N2BA and mRNA and protein expression of SERCA2a. LV systolic and diastolic functions in DCM are primarily associated with myocardial force generation/relaxation elements.


Adrenergic regulation of conduction velocity in cultures of immature cardiomyocytes.
During cardiac maturation, increased exposure of the heart to circulating catecholamines correlates with increased conduction velocity and growth of the heart. We used an in vitro approach to study the underlying mechanisms of adrenergic stimulation induced changes in conduction velocity. By combining functional measurements and molecular techniques, we were able to demonstrate that the increased conduction velocity after beta-adrenergic stimulation is probably not caused by changes in intercellular coupling. Instead, RT-PCR experiments and action potential measurements have shown an increased excitability that may well explain the observed increase in conduction velocity. Apart from being relevant to cardiac maturation, our findings are relevant in the context of stem cells and cardiac repair. Preconditioning of stem cell derived cardiomyocytes may help to enhance electrical maturation of de novo generated cardiomyocytes and consequently reduce their proarrhythmogenic potential. (Neth Heart J 2008;16:106-9.).


Surgeons and social media: The use of twitter hashtags at the Academic Surgical Congress 2015-2019: A cross sectional study.
The use of Twitter hashtags at medical conferences has revolutionized the way healthcare professionals interact and advance their education. We aim to investigate the scope of the Academic Surgical Congress's online reach and engagement through the use of Twitter hashtags #ASC from 2015 to 2019, by analyzing the number of impressions and tweets and retweets. A cross sectional study of Twitter data through Symplur with the following conference hashtags for the Academic Surgical Congress annual meetings for years 2015-2019: #ASC2015, #ASC2016, #ASC2017, #ASC2018, and #ASC2019. Data on tweets, retweets, users, and impressions was reviewed along with information on the top 10 influencers and the most frequently tweeted links. Symplur Signals software was utilized to extract and assimilate data. Statistical Significance was defined as p < 0.05. Twitter engagement metrics significantly increased from 11,400 to 32,100 from 2015 to 2017 (p < 0.05). However, from 2017 to 2019, there was a significant decline in engagement metrics from 32,100 to 26,100 (p < 0.05). Impressions increased significantly from 13,100 in 2015 to 71,800 impressions in 2019 (p < 0.05). Users grew significantly from 1500 in 2015 to peak at 4600 in 2017 before dropping back to 3300 in 2019 (p < 0.05). The most influential organizations during these years were the organizers of the conference: Association for Academic Surgery and the Society of University Surgeons. Conference attendance progressively increased from approximately 1700 in 2016 to about 2100 in 2019 (p < 0.05). Twitter engagement metrics at the Academic Surgical Congress 2015-2019 has fluctuated, while impressions significantly increased through the years indicating the consistent dissemination of conference content.


Community attitudes to the collection and use of identifiable data for health research--is it an invasion of privacy?
To investigate community views on the statutory collection of identifiable data by the Western Australian Birth Defects Registry and the extent to which the use of such data is perceived to be an invasion of privacy, when balanced against the community benefit of three public health scenarios. Cross-sectional, computer-assisted telephone interviewing survey. Six hundred respondents were recruited randomly from the electronic version of the Western Australian telephone directory. Interviews were conducted in August 2006 and the response rate was 78%. Most respondents indicated support for statutory notification of cases (79%) and did not consider the statutory notification of postcodes (85%) and names and addresses (65%) to be an invasion of privacy. Similarly, most (76%) did not consider the receipt of a letter requesting participation in research to be an invasion of privacy. Overall, 55% considered none of these to be an invasion of privacy and only 4% considered all to be an invasion of privacy. Most Western Australians do not consider the statutory inclusion and use of identifiable data by the WA Birth Defects Registry to be an invasion of privacy, to the extent that such data are required for legitimate public health research, would be notified by the registrant's medical practitioner and would be kept confidentially and securely.


[Surgical disconnection of the small intestine as a contribution to plastic surgery].
The limitations of conservative therapy of extreme obesity compel the patient to seek a surgeon. He can do the following: Resect deposits of fat, create a condition of malabsorption by jejunoileostomy or perform a gastric by-pass, which reduces the capacity of the stomach. The gastric by-pass is the method of choice for treating the adipose child. We perform the jejunoileostomy only on patients with more than 100% overweight. With the weight reduction the pathologic metabolism is normalized. A plastic correction of pendant skin is necessary.


[Late dislocation of the left ventricular lead as a cause of clinical and functional worsening during cardiac resynchronization therapy].
Efficacy of cardiac resynchronization therapy (CRT) in heart failure is also related to correct positioning of the left ventricular lead. We report the case of a patient treated by CRT who presented, after 6 years of implantation, rapid clinical and functional worsening due to dislodgment of the left ventricular lead.


Red blood cell distribution width improves the prediction of 28-day mortality for patients with sepsis-induced acute kidney injury: A retrospective analysis from MIMIC-IV database using propensity score matching.
The predictive value of red blood cell distribution width (RDW) for mortality in patients with sepsis-induced acute kidney injury (SI-AKI) remains unclear. The present study aimed to investigate the potential association between RDW at admission and outcomes in patients with SI-AKI. The Medical Information Mart for Intensive Care (MIMIC)-IV (version 2.0) database, released in June of 2022, provides medical data of SI-AKI patients to conduct our related research. Based on propensity score matching (PSM) method, the main risk factors associated with mortality in SI-AKI were evaluated using Cox proportional hazards regression analysis to construct a predictive nomogram. The concordance index (C-index) and decision curve analysis were used to validate the predictive ability and clinical utility of this model. Patients with SI-AKI were classified into the high- and low-RDW groups according to the best cut-off value obtained by calculating the maximum value of the Youden index. A total of 7574 patients with SI-AKI were identified according to the filter criteria. Compared with the low-RDW group, the high-RDW group had higher 28-day (9.49% vs. 31.40%, respectively, P <0.001) and 7-day (3.96% vs. 13.93%, respectively, P <0.001) mortality rates. Patients in the high-RDW group were more prone to AKI progression than those in the low-RDW group (20.80% vs. 13.60%, respectively, P <0.001). Based on matched patients, we developed a nomogram model that included age, white blood cells, RDW, combined hypertension and presence of a malignant tumor, treatment with vasopressor, dialysis, and invasive ventilation, sequential organ failure assessment, and AKI stages. The C-index for predicting the probability of 28-day survival was 0.799. Decision curve analysis revealed that the model with RDW offered greater net benefit than that without RDW. The present findings demonstrated the importance of RDW, which improved the predictive ability of the nomogram model for the probability of survival in patients with SI-AKI.


Automatic Brain Categorization of Discrete Auditory Emotion Expressions.
Seamlessly extracting emotional information from voices is crucial for efficient interpersonal communication. However, it remains unclear how the brain categorizes vocal expressions of emotion beyond the processing of their acoustic features. In our study, we developed a new approach combining electroencephalographic recordings (EEG) in humans with a frequency-tagging paradigm to 'tag' automatic neural responses to specific categories of emotion expressions. Participants were presented with a periodic stream of heterogeneous non-verbal emotional vocalizations belonging to five emotion categories: anger, disgust, fear, happiness and sadness at 2.5 Hz (stimuli length of 350 ms with a 50 ms silent gap between stimuli). Importantly, unknown to the participant, a specific emotion category appeared at a target presentation rate of 0.83 Hz that would elicit an additional response in the EEG spectrum only if the brain discriminates the target emotion category from other emotion categories and generalizes across heterogeneous exemplars of the target emotion category. Stimuli were matched across emotion categories for harmonicity-to-noise ratio, spectral center of gravity and pitch. Additionally, participants were presented with a scrambled version of the stimuli with identical spectral content and periodicity but disrupted intelligibility. Both types of sequences had comparable envelopes and early auditory peripheral processing computed via the simulation of the cochlear response. We observed that in addition to the responses at the general presentation frequency (2.5 Hz) in both intact and scrambled sequences, a greater peak in the EEG spectrum at the target emotion presentation rate (0.83 Hz) and its harmonics emerged in the intact sequence in comparison to the scrambled sequence. The greater response at the target frequency in the intact sequence, together with our stimuli matching procedure, suggest that the categorical brain response elicited by a specific emotion is at least partially independent from the low-level acoustic features of the sounds. Moreover, responses at the fearful and happy vocalizations presentation rates elicited different topographies and different temporal dynamics, suggesting that different discrete emotions are represented differently in the brain. Our paradigm revealed the brain's ability to automatically categorize non-verbal vocal emotion expressions objectively (at a predefined frequency of interest), behavior-free, rapidly (in few minutes of recording time) and robustly (with a high signal-to-noise ratio), making it a useful tool to study vocal emotion processing and auditory categorization in general and in populations where behavioral assessments are more challenging.


[Direct approximation of plasma concentration time curves of 3-diethylstilbestrol monoglucuronide following oral and intravenous administration of fosfestrol].
Drugs undergoing presystemic elimination, enterohepatic recycling and multiple biotransformation show atypical plasma level curves with considerable deviations. The data are approximated by modified exponential functions, whose "intrinsic" properties anticipate the overall behaviour of the experimental data, even in complicated cases. The initial parameter estimates can be calculated directly from the experimental data.


A longitudinal, quality of life study comparing four layer bandaging and superficial venous surgery for the treatment of venous leg ulcers.
To investigate and compare changes in quality of life of patients with venous ulcers undergoing treatment with either four layer bandaging or superficial venous surgery. Fifteen patients with venous ulcers were selected from two treatment groups--either four layer bandaging or superficial venous surgery. Each received a postal questionnaire at pretreatment, four weeks and twelve weeks post treatment. The EuroQol quality of life questionnaire was used along with a disease specific questionnaire devised by the author. Analysis of results was undertaken using validated statistical methods. Department of Vascular Surgery Leicester Royal Infirmary and Fosse Health (NHS) Trust (now the Leicestershire and Rutland Healthcare NHS Trust). To measure changes in quality of life of patients undergoing superficial venous surgery or four layer bandaging. Treatment over the twelve week period resulted in improvements in quality of life for both treatment groups (P = 0.001 for surgery and P = 0.019 for bandaging). No statistical differences in quality of life between the two treatment modalities were found at four and twelve weeks. There was evidence of an improvement in quality of life for both groups following twelve weeks of treatment. Improvements in pain and general quality of life were more marked in the bandaging group. Systems of care that offer rapid improvement to the patient's quality of life and wellbeing must be considered when planning effective leg ulcer management.


Clinicopathological features of five cases of CIC::DUX4 positive sarcomas, including literature review.
According to the recent World Health Organization (WHO) classification, CIC-rearranged sarcomas, including CIC::DUX4-positive sarcomas constitute an aggressive subtype of undifferentiated round cell sarcomas. There is a single study on these tumors from our subcontinent. We present clinicopathological features of 5 additional cases of this tumor entity, including literature review. Thirty-nine undifferentiated round cell sarcomas, excluding Ewing sarcomas (ES), were tested for CIC::DUX4 fusion, including Type I (165 base pair size) and II (230 bp) by reverse transcription-polymerase chain reaction. Twenty-five of those tumors were tested for EWSR1 gene rearrangement, 5 for SS18 and 4 for SS18::SSX fusion, and were negative for those tests. Five tumors (12.8 %) were positive for CIC::DUX4(Type II) fusion. Five CIC:: DUX4-positive sarcomas occurred in 4 males and one female; of 25-43 years of age, in soft tissues, including thigh (n = 2), chest wall (n = 1), iliac region (n = 1) and foot (n = 1). Tumor size varied from 2.2 to 19 cm. Microscopically, the tumors were predominantly composed of nodules and sheets of malignant round to epithelioid cells, including "rhabdoid-like" (n = 2) and spindle-shaped (n = 2) with eosinophilic to vacuolated cytoplasm (4/5), distinct nucleoli (4/5), brisk mitoses, focal myxoid to hyalinised stroma (4/5) and necrosis (5/5). Immunohistochemically, tumor cells were positive for WT1 (5/5), calretinin (3/4), pan-keratin (1/4), CD99/MIC2 ("dot-like" to cytoplasmic membranous) (4/4), while negative for desmin (0/4), S100P (0/4), and NKX2.2 (0/5). INI1/SMARCB1 was retained (3/3). All patients underwent excision with adjuvant radiotherapy and chemotherapy (Ewing sarcoma regimen). A single patient developed recurrence, and 2 developed pulmonary metastasis, including one with brain metastasis. CIC:: DUX4-positive sarcomas are ultra-rare tumors, that mainly occur in the soft tissues and in young adult patients. Histopathologically, these tumors display a wide spectrum, including round to epithelioid cells, variable amount of cytoplasmic vacuolization and myxoid stroma with necrosis. Immunohistochemically, these tumors express WT1 and calretinin. Despite adjuvant therapies, these tumors have dismal outcomes, especially in large-sized tumors. CIC::DUX4-positive sarcomas need to be differentiated from their histopathological mimics, including ES, in view of significant treatment-related implications.


Aortic issues in scoliosis and scoliotic operations.
The spatial relations between the aorta and vertebrae are changing with posture, surgical techniques, and operative maneuvers. "Risky screws" (within 1-3 mm proximity to the aorta or other adjacent tissues) were found in 5.8-15.2% screws. In order to avoid early and later aortic complications secondary to scoliotic operations, careful preoperative metrology of aorto-vertebrae relations is of crucial importance. Compared with patients with idiopathic scoliosis, Marfan-related scoliosis is characterized by faster progression and it is more bracing-resistant due to the particular developmental anomalies in Marfan syndrome, implying the refractory nature of the latter. The present study aims to highlight the clinical impact of preoperative aorto-vertebra metrology in the scoliotic operations.


Mass Deconvolution of Top-Down Mass Spectrometry Datasets by FLASHDeconv.
Mass deconvolution, the determination of proteoform precursor and fragment masses, is crucial for top-down proteomics data analysis. Here we describe the detailed procedure to run FLASHDeconv, an ultrafast, high-quality mass deconvolution tool. Both spectrum- and feature-level deconvolution results are obtainable in various output formats by FLASHDeconv. FLASHDeconv is runnable in different environments such as the command line and OpenMS workflows.


Th1/Th2 balance in preeclampsia.
The syndrome of preeclampsia has previously been ascribed to generalized maternal endothelial dysfunction, poor placentation and excessive maternal inflammatory response. Recent reports suggest that preeclampsia is associated with a Th1 predominant profile and may be considered as a failure of the tolerance system allowing the second physiological trophoblastic invasion. In this review, we discuss that Th1 predominant immunity is closely related to inflammation, endothelial dysfunction and poor placentation.


Emergence of asymmetry in evolution.
We investigate symmetry-breaking bifurcation patterns in evolution in the framework of adaptive dynamics (AD). We define weak and strong symmetry. The former applies for populations where only the simultaneous reflection of all individuals is an invariant transformation. The symmetry is strong in populations where reflection of some, but not all, individuals leaves the situation unchanged. We show that in case of weak symmetry evolutionary branching can lead to the emergence of two asymmetric variants, which are mirror images of each other, and the loss of the symmetric ancestor. We also show that in case of strong symmetry, evolutionary branching can occur into a symmetric and an asymmetric variant, both of which survive. The latter, asymmetric branching differs from the generic branching patterns of AD, which is always symmetric. We discuss biological examples for weak and strong symmetries and a specific model producing the new kind of branching.


Analysis of Knowledge Level and Use of Antiretroviral Pre-Exposure and Post-Exposure Prophylaxis Among MSM - China, 2019-2022.
Men who have sex with men (MSM) in China have a high rate of human immunodeficiency virus (HIV) infection. Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) have been shown to be effective in preventing HIV, which may help to contain the HIV epidemic among MSM. This study found that knowledge and usage of PrEP were low among MSM, indicating that this population is at high risk for HIV infection. Promotion of PrEP and PEP among MSM is necessary to reduce the risk of HIV infection in this population. PrEP and PEP are novel HIV prevention strategies that have been demonstrated to be effective and safe. To further reduce HIV transmission among MSM in China, it is necessary to promote the use of PrEP and PEP.


Improvement of neutropenia and neutrophil dysfunction by granulocyte colony-stimulating factor in a patient with glycogen storage disease type Ib.
Patients with glycogen storage disease type Ib (GSD Ib) suffer from recurrent bacterial infections due to neutropenia and neutrophil dysfunction. To improve the quality of life in a 9-year-old boy with GSD Ib, we subcutaneously administered recombinant human granulocyte colony-stimulating factor (G-CSF). Daily injections of 100 micrograms/m2 of G-CSF significantly increased absolute neutrophil counts and augmented neutrophil mobility. The patient was then treated with 70 and 100 micrograms/m2 of G-CSF daily and twice-weekly. The treatment maintained absolute neutrophil counts at significantly higher levels than those without treatment for 22 months and markedly decreased the frequency of infections and the necessity for hospitalisation. Weekly injections of 70 micrograms/m2 of G-CSF were less efficient. No adverse effects were observed during treatment. These findings indicate that daily and twice-weekly treatment with G-CSF of long duration are safe and effective for patients with GSD Ib. G-CSF may be a useful therapeutic agent in patients with neutrophilic impairment as a consequence of a metabolic disorder.


SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation.
Intestinal fibrosis is a prevalent complication of Crohn's disease (CD), characterized by excessive deposition of extracellular matrix (ECM), and no approved drugs are currently available for its treatment. Sirtuin 4 (SIRT4), a potent anti-fibrosis factor in mitochondria, has an unclear role in intestinal fibrosis. In this study, fibroblasts isolated from biopsies of stenotic ileal mucosa in CD patients were analyzed to identify the most down-regulated protein among SIRT1-7, and SIRT4 was found to be the most affected. Moreover, in vivo and in vitro models of intestinal fibrosis, SIRT4 expression was significantly decreased in a TGF-β dependent manner, and its decrease was negatively associated with disease severity. SIRT4 impeded ECM deposition by inhibiting glutaminolysis, but not glycolysis, and α-ketoglutarate (α-KG) was identified as the key metabolite. Specifically, SIRT4 hinders SIRT5's stabilizing interaction with glutaminase 1 (GLS1), thereby facilitating the degradation of GLS1. KDM6, rather than KDM4, is a potential mediator for α-KG-induced transcription of ECM components, and SIRT4 enhances the enrichment of H3K27me3 on their promotors and enhancers. These findings indicate that the activation of TGF-β signals decreases the expression of SIRT4 in intestinal fibrosis, and SIRT4 can facilitate GLS1 degradation, thereby resisting glutaminolysis and alleviating intestinal fibrosis, providing a novel therapeutic target for intestinal fibrosis.


Recovering ammonium nitrate from the waste of fertilizer production by sulphonic cation exchangers.
Preventing environmental contamination and avoiding economic loss, mass transfer parameters effective kinetic mass transfer coefficient (beta) and effective intraparticle diffusivity (Def) have been determined for designing the recovery of ammonium nitrate from caustic condensate (waste of granular fertilizers production: (NH3 0.211 to 0.003 mol(-1) and NH4NO3 0 to 0.214 mol(-1), pH of 11.1 to 5.3), using sulphonic cation exchangers Purolite C 160 MBH (macroporous) and Purolite SGC 100x10 MBH (gel). On decreasing the concentration of ammonia in influent and increasing that of ammonium nitrate instead, and subsequently, decreasing the pH, the beta value, characterizing mass transfer in the liquid film surrounding the bead, for Purolite C 160 MBH (resistant to shrinking and swelling) increases from 2.4 10(-2) to 8.7 10(-2)s(-1), whereas the Def value varies from 0.18 10(-10) to 0.11 10(-10) m2s(-1). For Purolite SGC 100x10 MBH (shrinking in alkaline and swelling in acidic medium) beta varies from 1.8 10(-2) to 2.8 10(-2)s(-1), although Def increases from 0.1 10(-10) to 0.34 10(-10) m2s(-1), whereas uptake by both cation exchangers decreases. Inside the beads of Purolite SGC 100x10 MBH the diffusion is hindered by shrinking in alkaline medium and promoted by swelling in acidic medium. For Purolite C 160 MBH breakpoint is later, capacity at breakthrough (Eb), capacity at exhaustion (Ee) and efficiency of utilization (lambda) are higher than those for Purolite SGC 100x10 MBH. On the basis of parameters considered Purolite C 160 MBH has been installed for the recovery of ammonium nitrate from caustic condensate in fertilizer production.


Prostaglandins and congeners. 15. Synthesis and bronchodilator activity of dl-11-deoxy-15- or 16-alkylprostaglandins.
The synthesis of dl-11-doxy-15- or 16-alkylprostaglandins by the conjugate addition of appropriately substituted lithium alanate or lithium cuprate reagents to several cyclopentenones is described as is the preparation of the requisite intermediate (E)-1-iodo-1-alkenyl compounds 4, 22, 23, and 31. The bronchodilator activity of these prostaglandin congeners is presented.


Arginine binding motifs: design and synthesis of galactose-derived arginine tweezers as galectin-3 inhibitors.
Anionic O2 derivatives of methyl 3-deoxy-3-(4-methylbenzamido)-1-thio-beta-D-galactopyranoside have been synthesized as inhibitors against galectin-3. The sulfate, H-phosphonate, and benzyl phosphate derivatives showed an increased affinity as compared to the parent unsubstituted galactopyranoside. Modeling revealed arginine-144 being pinched by the C3 benzamide and O2 anionic substituents in that the benzamide stacked face-to-face and the anionic O2 substituent ion-paired with the guanidinium moiety.


Hyperammonemia in azotemic cats.
Hyperammonemia occurs in cats with hepatobiliary and nutritional (cobalamin and arginine deficiency) disorders, and has also been documented in four cats with renal azotemia. We hypothesized that in cats with renal azotemia, fasting hyperammonemia would correlate with indices of worsening kidney function, and would be independent of cobalamin, potassium, systemic inflammation or urinary tract infection (UTI) with urease-producing bacteria. A fasted blood sample was prospectively collected for ammonia and cobalamin analysis from 18 client-owned cats with renal azotemia (creatinine [Cr] ⩾1.6 mg/dl, urine specific gravity <1.030 or documentation of historical chronic kidney disease [CKD]). Correlations between blood ammonia and selected biochemical parameters were analyzed using Pearson's correlation coefficient. Seven castrated males and 11 spayed females with a median age of 12 years (range 4-19 years) were enrolled. Ten of 18 (56%) cats presented for acute kidney injury (AKI) or acute on chronic kidney disease (AoCKD), and 8/18 (44%) presented for progressive CKD. The median Cr was 5.9 mg/dl (range 1.9-24.7 mg/dl). Hyperammonemia was documented in 4/18 (22%) cats, with a median of 95 µmol/dl (range 85-98 µmol/dl), and all four of these cats were classified as AKI/AoCKD. Blood ammonia concentrations had a significant moderate positive correlation between blood urea nitrogen (BUN) (r = 0.645, P = 0.003), Cr (r = 0.578, P = 0.012) and serum phosphorus (r = 0.714, P = 0.0009) but not with cobalamin, potassium or white blood cell count. No cats had UTIs with urease-producing bacteria. A correlation exists between blood ammonia and BUN, Cr and phosphorus in cats with renal azotemia. Future studies are warranted in a larger population of cats to determine the true prevalence, etiology and potential therapeutic effect of medical management of hyperammonemia on long-term prognosis in cats with kidney disease.


Lost medicines: a longer view of the pharmaceutical industry with the potential to reinvigorate discovery.
It is widely understood that the 1962 Kefauver-Harris Amendment to the Food, Drug and Cosmetics Act ushered in the modern regulation of medicines requiring a combination of safety and efficacy. However, fewer appreciate the amendment was applied retroactively to virtually all medicines sold in the USA. For various reasons, many medicines faded into history. Here, we identify and analyze >1600 medicines (including over-the-counter drugs) and their innovators prior to the enactment of Kefauver-Harris. We report 880 of these past medicines are no longer accessible. This project also reveals new insight into the pharmaceutical enterprise, which reveals an industry already mature and beginning to retract before enactment of the legislation. Beyond its historical implications, the recollection of these medicines could offer potential starting points for the future development of much-needed drugs.


High-level Zn and Cd tolerance in Silene paradoxa L. from a moderately Cd- and Zn-contaminated copper mine tailing.
Cadmium and zinc tolerance were examined in populations of Silene paradoxa, one from uncontaminated calcareous soil (CVD) and one from a mine tailing (FC) (Cd<1-15 ppm, Zn 400-1300 ppm, pH 2-6). The mine population exhibited extremely high Zn and Cd tolerance levels, although the degrees of Cd and Zn enrichment relatively low at the population site. Cd and Zn hypertolerance in FC were associated with reduced rates of accumulation of these metals, both in roots and shoots (Cd), or exclusively in shoots (Zn). However, exclusion potentially explained only a minor part of the superior tolerance in FC. Cd hypertolerance in FC was associated with decreased, rather than enhanced phytochelatin accumulation. The remarkably high levels of Cd and Zn hypertolerance in FC might relate to the low soil pH, due to oxidation of sulphide minerals, and the absence of soil organic matter at the FC site.


Vertebral augmentation in osteoporotic fractures.
Osteoporotic vertebral compression fractures result in an enormous medical, social and economic burden to society. Here, we review osteoporotic vertebral compression fractures, focusing on both their diagnosis and the treatment options, particularly vertebral augmentation.


A behavioural approach to retraining bowel function after long-standing constipation and faecal impaction in people with learning disabilities.
The authors describe a behavioural programme--involving prompted toilet-sitting after meals, rewards for appropriate evacuation and increased fibre--for four people with severe learning disabilities. Although treatment times were long, such training resulted in near-normal bowel function. While this behavioural approach does not ignore the biological aspects of the problem, soiling in intellectually disabled people should not be attributed to the handicapping condition alone. Training at an earlier age should be considered.


Virtual scribing within otolaryngology during the COVID-19 pandemic and beyond.
Within otolaryngology, scribes have been utilized as a means of increasing clinic efficiency and easing workload on physicians. During the COVID-19 pandemic, a majority of otolaryngology clinic appointments at academic institutions have been moved to telemedicine in order to limit interpersonal contacts. At the height of the pandemic, our institution has protocolized scribe participation from in-person to remote. Scribes have virtually participated in telemedicine appointments in an effort to facilitate documentation and enhance the patient-physician relationship. Beyond the pandemic, as patients start being evaluated in-person, the risk of contamination and spread through aerosol generating procedures has limited the number of ancillary support staff that can be present in the examination rooms. As such, virtual scribing from a separate location within the clinic has been deemed warranted. This paper documents the protocols on virtual scribing for both telemedicine and a hybrid approach for in-clinic appointments where high-risk procedures are being performed.


Detraining from total body exercise ergometry in individuals with spinal cord injury.
This study was designed to investigate the effects of detraining that occurred during an 8 week period of muscular inactivity following a 12 week training program of artificial computerized functional electrical stimulation cycle ergometry (CFES LE) and arm ergometry. Six spinal cord injured male individuals were followed through an 8 week detraining period that was preceded by a 12 week exercise program including CFES LE and arm ergometry. Maximal graded exercise tests were completed and measurements of peak oxygen consumption (VO2), heart rate (HR), ventilation (VE) workload, and creatine kinase were taken. Testing occurred at initial training (0T), after 12 weeks of training (12T), and after 8 weeks of detraining (DT). After the training program, peak VO2 increased significantly from 0.562 +/- 0.126 (0T) to 1.021 +/- 0.247 l/min (12T, P < 0.05). After DT, peak VO2 decreased to 0.791 +/- 0.216 l/min, which was lower than 12T (P < 0.05), yet higher than 0T (P < 0.05). After DT, peak workoad had decreased from 0.675 +/- 0.203 (12T) to 0.32 +/- 0.203 kp (P < 0.05), which was not different than 0T. Creatine kinase levels were significantly lower both at 12T and DT compared to 0T (P < 0.05). In addition, this training program induced linear increases in both VO2 and HR with workload, which were retained after DT. These increases did not reach statistical significance. however. No apparent relationship existed between these values at baseline. There were no significant differences in submaximal or peak HR of VE between the three testing periods. The results indicate that both peripheral muscular adaptations and central distribution adaptations in SCI individuals are partially maintained following 8 weeks of DT from CFES LE and arm ergometry.


Presence of toxin-antitoxin systems in picocyanobacteria and their ecological implications.
Picocyanobacteria (mainly Synechococcus and Prochlorococcus) contribute significantly to ocean's primary production. Toxin-Antitoxin (TA) systems present in bacteria and archaea are known to regulate cell growth in response to environmental stresses. However, little is known about the presence of TA systems in picocyanobacteria. This study investigated complete genomes of Synechococcus and Prochlorococcus to understand the prevalence of TA systems in picocyanobacteria. Using the TAfinder software, Type II TA systems were predicted in 27 of 33 (81%) Synechococcus strains, but none of 38 Prochlorococcus strains contain TA genes. Synechococcus strains with larger genomes tend to contain more putative type II TA systems. The number of TA pairs varies from 0 to 42 in Synechococcus strains isolated from various environments. A linear correlation between the genome size and the number of putative TA systems in both coastal and freshwater Synechococcus was established. In general, open ocean Synechococcus contain no or few TA systems, while coastal and freshwater Synechococcus contain more TA systems. The type II TA systems inhibit microbial translation via ribonucleases and allow cells to enter the "dormant" stage in adverse environments. Inheritance of TA genes in freshwater and coastal Synechococcus could confer a recoverable persister mechanism important to survive in variable environments.


Efficient and strand-selective in vitro transcription initiation by purified RNA polymerase II from a unique site of the fibroin gene.
Using purified RNA polymerase II and the cloned fibroin gene of supercoiled form, we found a novel in vitro transcription initiation site. An analysis by S1 nuclease mapping showed that the transcripts synthesized by RNA polymerase II purified from three different sources gave primarily a common protection band, the 5' terminus of which was located at a specific site about the nucleotide position +25 of the fibroin gene. Such a transcript was not detected in the in vivo RNA; however, this site-specific transcription revealed a coding-strand selectivity and a high efficiency accounting for nearly 90% of total in vitro RNA synthesis. An analysis using a series of 5' deletion mutants of the fibroin gene indicates that this transcription initiation depends on a unique DNA sequence about the nucleotide position +25, which includes an inverted repeat and a sequence homologous to that around the in vivo initiation site of the fibroin gene.


Double dissociation of learned approach-avoidance conflict processing and spatial pattern separation along the dorsoventral axis of the dentate gyrus.
The ventral portion of the rodent hippocampus (HPC; anterior in primates) has been implicated in the detection and resolution of approach-avoidance conflict, which arises when an organism encounters a stimulus that predicts both positive and negative outcomes. Previous work has found differential regulation of approach-avoidance conflict behavior by the CA3 and CA1 subfields, with inhibition of ventral CA3 increasing approach toward conflicting stimuli and inhibition of the ventral CA1 potentiating avoidance. Here, we sought to extend these findings by investigating the role of the dentate gyrus (DG), the input region of the HPC, in learned approach-avoidance conflict processing in rats. Animals were first trained to acquire three different visuotactile cue-outcome associations in separate arms of a Y-maze (appetitive, aversive, and neutral). Postacquisition, they were administered a "conflict test," in which they were presented with a choice between exploring an arm in which the appetitive and aversive cues were concurrently presented (conflict stimulus), and another arm containing the neutral stimulus. GABAR-mediated inactivation of the ventral DG, but not dorsal DG, potentiated approach behavior toward the conflict stimulus, similar to the effects of ventral CA3 inactivation. In contrast, dorsal DG, but not ventral DG, inactivation was found to impair performance on a metric spatial discrimination task, which is commonly used as a test of pattern separation. The findings of this study demonstrate a robust double dissociation between the ventral and dorsal aspects of the DG, in line with previous reports of functional differences along the longitudinal axis of the HPC.


Disease system analysis: basic disease progression models in degenerative disease.
To describe the disease status of degenerative diseases (i.e., type 2 diabetes mellitus, Parkinson's disease) as function of disease process and treatment effects, a family of disease progression models is introduced. Disease progression is described using a progression rate (Rdp) acting on the synthesis or elimination parameters of the indirect response model. Symptomatic effects act as disease-dependent or -independent effects on the synthesis or elimination parameters. Protective drug effects act as disease dependent or -independent effects on Rdp. Simulations with the ten disease models show distinctly different signature profiles of treatment effects on disease status. Symptomatic effects result in improvement of disease status with a subsequent deterioration. Treatment cessation results in a disease status equal to the situation where treatment had not been applied. Protective effects result in a lasting reduction, or even reversal, of the disease progression rate and the resulting disease status during the treatment period. After cessation of treatment the natural disease course will continue from the disease status at that point. Disease system analysis constitutes a scientific basis for the distinction between symptomatic versus protective drug effects in relation to specific disease processes as well as the identification of the exposure-response relationship during the time-course of disease.


Proteins of the Lectin Pathway of complement activation at the site of injury in subarachnoid hemorrhage compared with peripheral blood.
A subarachnoid hemorrhage (SAH) is a debilitating stroke. Activation of the lectin pathway (LP) of the complement system in SAH patients could worsen the prognosis; however, conflicting results have been reported. This potentially reflects that pathological changes at the site of injury are not reflected in peripheral blood. To measure the concentration of LP proteins in blood from the site of brain injury compared with peripheral blood in SAH patients, and to determine the concentration of LP proteins in cerebrospinal fluid (CSF). We included 11 SAH patients undergoing aneurysm clipping or external ventricular drainage. Blood was collected from the site of injury and from a peripheral artery and/or CSF simultaneously. LP proteins were measured using time-resolved immunofluorometric assays. In all patients, the cerebral blood concentration of mannan-binding lectin, collectin liver-1 and collectin kidney-1, and mannan-associated serine proteases 1 and 2 were lower than in peripheral blood. The LP proteins were almost undetectable in CSF. Lectin pathway protein concentrations measured in peripheral blood do not always reflect changes at the site of injury. For some proteins, more information could be obtained in blood from the site of injury when investigating pathogenic mechanisms.


Fluorescence imaging around the abdomen allows evaluation of gastrointestinal retention of various forms of diet in mice.
The aims of this study were to evaluate gastrointestinal (GI) retention of an ingested meal by fluorescence imaging and compare how retention is affected by differences in the physical characteristics of meals. Mice were given an oral fluorescent indocyanine green (ICG) probe enclosed in a liposome. We evaluated the correlation between abdominal and GI fluorescence signals. ICG was administered to mice treated with atropine, and abdominal fluorescence was observed repeatedly. Mice were continuously given a regular chow or a liquid diet containing a low or high methoxyl (LM or HM)-pectin through a catheter placed in the stomach for 2 d, after which the mice were given ICG. In all studies, the mice's abdominal and GI fluorescence signals were observed with in vivo imaging equipment. The fluorescence intensities (FIs) of the abdomen and the excised GI tract correlated strongly. Attenuation of the abdominal FI was delayed in the atropine-treatment group compared with the non-treated group. The attenuation of abdominal FI 8 to 24 h after ICG administration was significantly weakened in the HM group compared with the regular chow and LM groups. Observing FI attenuation around the abdomen allows for the evaluation of GI tract retention of an ingested meal. Compared with a solid meal, a liquid meal stays longer in the digestive tract, whereas a liquid meal in which the viscosity increases in the stomach is retained like a solid meal.


Identification and functional analysis of m6A in the mammary gland tissues of dairy goats at the early and peak lactation stages.
N6-methyladenosine (m6A) is the most common reversible epigenetic RNA modification in the mRNA of all higher eukaryotic organisms and plays an important role in the regulation of gene expression and cell function. In this study, m6A-modified methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome sequencing (RNA-seq) were used to identify the key genes with m6A modification during mammary gland development and lactation in dairy goats. The results showed that m6A methylation occurred at 3,927 loci, which were significantly enriched in the 3' untranslated region (3'UTR) and the termination codon region. In the early stage and peak stage of lactation, m6A methylation occurred extensively in mammary tissues, and a total of 725 differentially expressed m6A-modified genes were obtained, all negatively correlated with mRNA expression. In addition, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that different methylated genes were mainly involved in the growth and apoptosis of mammary epithelial cells through signaling pathways, such as the mitogen-activated protein kinase (MAPK) and phospholipase D pathways, and then affected the development and lactation of mammary gland. All in all, we identified and analyzed the methylation events related to the development and lactation regulation of mammary gland at the early and peak lactation stages, and provided a theoretical basis to reveal the physiological regulatory system of mammary gland development and lactation in dairy goats.