Association of chemokine and chemokine receptor polymorphisms with activity degree of IBD in Tunisian patients.
Crohn's disease (CD) and ulcerative colitis (UC) have complex genetic background that is characterised by more than one susceptibility locus. To detect a possible association between the functional polymorphisms of the chemokine receptors CCR5, CCR2 and MCP-1 genes and susceptibility to CD and UC in Tunisian population, polymorphisms of CCR5-delta32, CCR5-59029-A/G, CCR2-V641 and MCP-1-2518-G/A were analysed in 194 Inflammatory bowel disease (IBD) patients and 169 healthy blood donors using PCR-RFLP and PCR-SSP methods. The patients were classified in 126 patients with CD and 68 patients with UC. The genotypic and allelic frequencies of all polymorphisms studied, did not reveal significant differences between patients and conrols and among CD and UC patients. However, analysis of CD patients revealed that those without homozygosous G/G genotype are more frequently in remission compared to those with this genotype (OR: 0.4, 95% CI: [0.174-0.928]; p = 0.03). Also, the frequency of the CCR2-641 muted allele was statistically higher in CD patients in remission disease than those in active form (OR: 0.267 95% CI: [0.09-0.78]; p = 0.01). Adjustment for known covariates factors (age, gender and immunosuppressive regimen) confirmed these univariate findings and revealed that the CCR5-59029-A/G and CCR2-V64I genotype were associated to remission form of CD (OR: 263; 95% CI: [1.01-6.80]; p = 0.047 and OR: 4.64; 95% CI: [1.01-21.31]; p = 0.049 respectively). In conclusion, the present study supports the involvement of chemokine receptor (CCR2 and CCR5) polymorphisms in activity degree of the IBD disease in Tunisian patients.


Glomerular dimensions in spontaneously hypertensive rats: effects of AT1 antagonism.
A reduction in glomerular number and/or size has been implicated in the development of hypertension. This study investigated whether differences in glomerular number and/or size occur during the development of hypertension in the spontaneously hypertensive rat (SHR) and whether angiotensin II is responsible for any glomerular differences. SHR (n=6) and Wistar-Kyoto (WKY) rats (n=6) were administered the angiotensin II type I receptor antagonist TCV-116 from 4 to 10 weeks of age. At 10 weeks of age, the kidneys from these rats and those from untreated SHR (n=6) and WKY rats (n=6) controls were perfusion fixed at physiological pressures and analysed using unbiased stereological techniques. There were no significant differences in glomerular number, glomerular volume or total glomerular volume between SHR and WKY rats. Treatment of SHR with TCV-116 significantly lowered systolic blood pressure but had no significant effect on glomerular number or volume or total glomerular volume. Treatment of WKY rats with TCV-116 reduced systolic blood pressure, body weight, glomerular volume and total glomerular volume; however, total glomerular volume per body weight of treated WKY rats was not significantly different from that of untreated WKY rats. There were no differences in glomerular number or volume in SHR compared with WKY rats at 10 weeks of age. We therefore conclude that glomerular changes are not responsible for the development of hypertension in SHR. Angiotensin II, via the type 1 receptor, does not contribute to glomerular growth during the development of hypertension in the SHR.


Maternal dietary pattern and its association with birthweight in Northern Ethiopia: A hospital-based cross-sectional study.
Birthweight is a useful public health measure of maternal health, nutrition, healthcare delivery, and child morbidity and mortality. Previous research did not focus on dietary patterns but rather on a single or a few foods or nutrients. This study aimed to assess the maternal dietary pattern and its association with birthweight in northern Ethiopia. A hospital-based cross-sectional study was conducted among 373 pregnant mothers in their third trimester of pregnancy who came to attend their routine antenatal care service. The food frequency questionnaire was collected from the previous week, and the birthweight data were collected from the medical records after delivery. Three maternal dietary patterns were identified; dietary pattern includes eggs, milk, milk products, and certain fruits and roots. Dietary pattern 2 includes certain vegetables, green leafy vegetables, vitamin A-rich vegetables, pulses such as beans, peas, and chickpeas, and drinks like coffee, tea, and soda. Dietary pattern 3 includes meat, nuts, and grains such as teff, corn, wheat, and white flour. Dietary pattern 1 (β = 52.45, p = .03) and dietary pattern 2 (β = 66.76, p = .01), residency (β = 287.08, p < .001), a mid-upper-arm circumference of 21-23 cm (β = 187.10, p = .02), a mid-upper-arm circumference of >23 cm (β = 272, p = .01), and gestational age at delivery (β = 12.58, p = .004) were the factors significantly associated with increased birthweight. The maternal dietary pattern has a significant association with birthweight. The focus should be given to maternal dietary patterns to prevent suboptimal and high birthweight.


The Link between Right and Left Ventricular Systolic Performance at Rest and after Stress: Insights Into the Mechanism.
Right ventricular (RV) systolic performance is more difficult for evaluation compared to the left ventricle (LV). Despite differences in structure, RV myocardial fibers are in continuity with those of LV. The aim is assessment of the effects of LV wall motion abnormalities (WMA) on RV systolic function at rest and after stress. Fifty nine subjects, 15 with LV-WMA underwent dobuatmine stress echocardiography (DSE) studies using the usual protocol. Measurement of tricuspid annular plane systolic excursion (TAPSE), velocity (TASV), mitral annular plane systolic excursion (MAPSE) and velocity (MASV), were performed before and immediately after DSE studies. TAPSE was lower, in those with LV-WMA than in those without, both at rest 20.5 ± 4.8 mm versus 24.9 ± 4.7 mm, P = 0.015 and after DSE studies, 21.5 ± 5.6 mm versus 27.65 ± 5.7 mm, P = 0.005. DSE studies did not change TAPSE significantly in the presence of LV-WMA. TASV at rest in those with LV-WMA was 16.5 ± 2.7 cm/sec and similar to that in those without, 17.6 ± 3 cm/sec. In both groups the velocity increased after DSE studies, 23.25 ± 7.5 cm/sec, P = 0.01 with LV-WMA, and 27.5 ± 6 cm/sec, P = 0.0005, without LV-WMA. Despite similar TASV at rest, the TAPSE/TASV ratio, indicating duration of shortening, was lower (124 ± 21 msec) in subjects with of LV-WMA, than in those without (145 ± 27 msec), P = 0.0065, implying increased after load for RV longitudinal shortening in the presence of LV-WMA. TAPSE is lower at rest and after DSE studies in subjects with LV-WMA than in subjects without; however, DSE studies increase TPASE only in the absence of LV-WMA. TASV increases after DSE studies and is similar at rest in both groups with or without LV-WMA. It seems that LV-WMA increases after load to RV longitudinal motion.


[«Diabetes Drugs» without Diabetes: SGLT-2 Inhibitors].
No other class of drugs has caused as much of a stir in the last decade as sodium-glucose linked transporter 2 inhibitors (SGLT-2i) or gliflozines. At the latest since the SGLT-2i originally developed as a diabetes mellitus drug unexpectedly also showed protective effects for heart and kidney in pivotal studies, they are now the talk of the town. Although the cellular and molecular mechanisms have not yet been clarified in all details, they have revolutionized therapeutic approaches for diabetes mellitus, heart failure independent of left ventricular ejection fraction, and nephropathies based on positive data available. The purpose of this article is to review the effects and postulated mechanisms of action of SGLT-2 inhibitors, particularly in heart failure and renal failure, and to outline their potential risks and side effects.


A comparative intervention trial on fish sauce fortified with NaFe-EDTA and FeSO4+citrate in iron deficiency anemic school children in Kampot, Cambodia.
Inhabitants of agrarian villages of rural Cambodia suffer from high prevalences of iron deficiency and anemia in the context of a monotonous diet. To compare the efficacy and safety of placebo Khmer fish sauce to that of 10 mL of fish sauce containing 10 mg of iron, added to daily school meals either as NaFe-EDTA or as FeSO4+ citrate. 140 students aged 6-21 years were enrolled in a double-blinded, placebo-controlled intervention trial. They were randomly allocated to one of three treatment groups, and followed for 21 weeks during which 114 school meals seasoned with 10 mL of fish sauce were consumed by each participant. Changes in the concentrations of hemoglobin (hb), serum ferritin (SF), and C-reactive protein (CRP) and in body weight and standing height were determined. Prevalences of vomiting, diarrhea, and acute respiratory infections were monitored weekly. Both iron-fortified fish sauces increased hb and SF concentrations significantly as compared to placebo. No significant differences were observed between FeSO4+citrate and NaFe-EDTA fortification, regarding mitigation of iron-deficiency anemia (IDA) or regarding CRP, growth, infections, or side-effects. Iron-fortified Khmer fish sauce added to Khmer food is a suitable vehicle for iron fortification in children and adolescents. FeSO4+citrate and NaFe-EDTA show equivalent efficacy and safety.


Subunit interactions of native and ADP-ribosylated alpha 39 and alpha 41, two guanine nucleotide-binding proteins from bovine cerebral cortex.
Bovine cerebral cortex contains two major substrates for ADP-ribosylation by pertussis toxin: a 39-kDa protein, alpha 39, and a 41-kDa protein, alpha 41 (Neer, E. J., Lok, J. M., and Wolf, L. G. (1984) J. Biol. Chem. 259, 14222-14229). Both of these proteins bind guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) with a similar affinity (Kd = 30 +/- 10 nM for alpha 39, Kd = 32 +/- 14 nM for alpha 41). Both proteins associate with a beta X gamma subunit made up of a 36-kDa beta component and a 6-kDa gamma component. We have previously shown that the beta X gamma unit is required for pertussis toxin-catalyzed ADP-ribosylation (Neer et al. (1984)). By measuring the amount of beta X gamma required for maximal incorporation of ADP-ribose, we now find that the EC50 for beta X gamma in this reaction is 3 +/- 1 times lower for alpha 41 than for alpha 39. ADP-ribosylation by pertussis toxin does not prevent dissociation of alpha 41 X beta X gamma or alpha 39 X beta X gamma by GTP gamma S. GTP gamma S decreases the sedimentation coefficient of ADP-ribosylated alpha 41 from 4.2 S to 3.0 S and the sedimentation coefficient of ADP-ribosylated alpha 39 from 4.3 S to 2.9 S. The conclusion that GTP gamma S dissociates both ADP-ribosylated heterotrimers was confirmed by the observation that GTP gamma S blocks precipitation of ADP-ribosylated alpha 39 or alpha 41 by anti-beta antibody. Neither alpha 41 X beta X gamma nor alpha 39 X beta X gamma is dissociated by GTP whether or not the proteins are ADP-ribosylated. The observation that alpha 41 more readily associates with beta X gamma than does alpha 39 may explain our earlier observation that alpha 41 is more readily ADP-ribosylated than alpha 39. In most intact membranes, only a 41-kDa ADP-ribosylated protein is seen. However, alpha 39 is also present in most tissues since we can detect it with anti-alpha 39 antibody. The functional consequences of pertussis toxin treatment may depend on whether one or both proteins are ADP-ribosylated. This in turn may depend on the ratio of alpha 41 and alpha 39 to beta X gamma in a given tissue.


Arthrodesis of finger joints by dynamic external compression using dorsoventral Kirschner wires and rubber bands.
A new method is presented for arthrodesis of small joints in the hand. In this method Kirschner wires are inserted dorsoventrally through the phalanges on either side of the joint, and the external ends bent into hooks. Longitudinal compression is achieved by connecting these hooks with rubber bands. This technique gives a solid and painless immobilization in a proper position, and the latter can be corrected easily when necessary. We arthrodesed 46 joints in 39 patients by this method in 1975 and 1976. The fusion time was 4 to 6 weeks, and the method produced a good bony arthrodesis in 42 of the 46 fingers.


Evaluation of the effectiveness of macaíba palm seed kernel (Acrocomia intumescens drude) on anxiolytic activity, memory preservation and oxidative stress in the brain of dyslipidemic rats.
Macaíba palm seed kernel is a source of lipids and phenolic compounds. The objective of this study was to evaluate the effects of macaíba palm seed kernel on anxiety, memory, and oxidative stress in the brain of health and dyslipidemic rats. Forty rats were used, divided into 4 groups (n = 10 each): control (CONT), dyslipidemic (DG), kernel (KG), and Dyslipidemic kernel (DKG). Dyslipidemia was induced using a high fat emulsion for 14 days before treatment. KG and DKG received 1000 mg/kg of macaíba palm seed kernel per gavage for 28 days. After treatment, anxiety tests were carried out using the Open Field Test (OFT), Elevated Plus Maze (EPM), and the Object Recognition Test (ORT) to assess memory. In the animals' brain tissue, levels of malondialdehyde (MDA) and total glutathione (GSH) were quantified to determine oxidative stress. The data were treated with Two Way ANOVA followed by Tukey (p <0.05). Results demonstrated that the animals treated with kernel realized more rearing. DG and KG groomed less compared with CONT and DKG compared with all groups in OFT. KG spent more time in aversive open arms compared with CONT and DKG compared with all groups in EPM. Only DKG spent more time in the central area in EMP. KG and DKG showed a reduction in the exploration rate and MDA values (p <0.05). Data showed that macaíba palm seed kernel consumption induced anxiolytic-like behaviour and decreased lipids peroxidation in rats' brains. On the other hand, this consumption by healthy and dyslipidemic animals compromises memory.


Molecular hydrogen: prospective treatment strategy of kidney damage after cardiac surgery.
Cardiac surgery-associated acute kidney injury is a common post-operative complication, mostly due to increasing oxidative stress. Recently, molecular hydrogen (H2 gas) has also been applied to cardiac surgery due to its ability to reduce oxidative stress. We evaluated the potential effect of H2 application on the kidney in an in vivo model of simulated heart transplantation. Pigs underwent cardiac surgery within 3 h while connected to extracorporeal circulation (ECC) and subsequent 60 min of spontaneous reperfusion of the heart. We used two experimental groups: T-pigs after transplantation and TH-pigs after transplantation treated with 4% H2 mixed with air during inhalation of anesthesia and throughout oxygenation of blood in ECC. The levels of creatinine, urea and phosphorus were measured in plasma. Renal tissue samples were analyzed by Western blot method for protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap-1), and superoxide dismutase (SOD1). After cardiac surgery, selected plasma biomarkers were elevated. However, H2 therapy was followed by the normalization of all these parameters. Our results suggest activation of Nrf2/Keap1 pathway as well as increased SOD1 protein expression in the group treated with H2. The administration of H2 had a protective effect on the kidneys of pigs after cardiac surgery, especially in terms of normalization of plasma biomarkers to control levels.


Planned wedge size compared to achieved advancement in dogs undergoing the modified Maquet procedure.
To evaluate the patellar ligament to tibial plateau angle (PL-TPA) and amount of achieved advancement in dogs that underwent the modified Maquet procedure; compare wedge sizes recommended using two different planning techniques (Orthomed and modified tibial tuberosity advancement); and evaluate anatomical factors that predict the wedge size required to obtain a 90° PL-TPA. Pre- and postoperative radiographs of dogs that had a modified Maquet procedure performed were evaluated for the following: calculated wedge size using two different planning techniques, the actual wedge size used, the achieved tibial tuberosity advancement, and the changes in PL-TPA. Anatomical measurements of the tibia were evaluated and correlated with the actual wedge size. Of the 38 modified Maquet procedures identified, 53% (n = 20) had a PL-TPA of 90° ± 5°. Actual achieved advancement of the tibial tuberosity was 30% less than the wedge size used. Changes in PL-TPA and tibial width persisted at eight weeks postoperatively without loss of advancement. The two planning techniques did not result in a significantly different selection of wedge size. Current planning techniques for the modified Maquet procedure result in under-advancement of the tibial tuberosity. Both measurement techniques evaluated do not result in appropriate advancement.


Management of severe neonatal respiratory distress due to vertical transmission of severe acute respiratory syndrome coronavirus 2: a case report.
Neonates with severe acute respiratory syndrome coronavirus 2 infection are usually asymptomatic or have mild to moderate symptoms. Acute respiratory distress syndrome due to severe acute respiratory syndrome coronavirus 2 with respiratory insufficiency is rare. Therefore, information about the best intensive care strategy for neonates requiring mechanical ventilation is lacking. We report a neonatal case of severe acute respiratory distress syndrome, probably due to vertical transmission of severe acute respiratory syndrome coronavirus 2, complicated by Staphylococcus aureus sepsis. We aim to inform pediatric providers on the clinical course and acute management considerations in coronavirus disease-related neonatal acute respiratory distress syndrome. A late preterm (gestational age 36 0/7 weeks) Caucasian girl was born from a severe acute respiratory syndrome coronavirus 2-positive mother and tested positive for severe acute respiratory syndrome coronavirus 2 at 19 hours after birth. She developed acute respiratory distress syndrome requiring intensive care admission and mechanical ventilation. The clinical course was complicated by S. aureus pneumonia and bacteremia. Multimodal management included well-established interventions for respiratory distress syndrome such as surfactant therapy, high-frequency oscillatory ventilation, and inhaled nitric oxide, combined with therapies extrapolated from adult care for severe acute respiratory syndrome coronavirus 2 patients such as dexamethasone, coronavirus disease 2019-specific immunoglobins, and prophylactic low-molecular-weight heparin. The neonate was successfully weaned from the ventilator and improved clinically. This case shows a rare but serious neonatal severe acute respiratory syndrome coronavirus 2 infection, leading to severe acute respiratory distress syndrome. Because of limited therapy guidelines for neonates, we suggest multimodal management with awareness of the possibility of S. aureus coinfection, to treat this age group successful.


Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity.
NK1R antagonists, investigated for the treatment of several pathologies, have shown encouraging results in the treatment of several cancers. In the present study, we report on the synthesis of carbohydrate-based NK1R antagonists and their evaluation as anticancer agents against a wide range of cancer cells. All of the prepared compounds, derived from either d-galactose or l-arabinose, have shown high affinity and NK1R antagonistic activity with a broad-spectrum anticancer activity and an important selectivity, comparable to Cisplatin. This strategy has allowed us to identify the galactosyl derivative 14α, as an interesting hit exhibiting significant NK1R antagonist effect (kinact 0.209 ± 0.103 μM) and high binding affinity for NK1R (IC50 = 50.4 nM, Ki = 22.4 nM by measuring the displacement of [125I] SP from NK1R). Interestingly, this galactosyl derivative has shown marked selective cytotoxic activity against 12 different types of cancer cell lines.


Secondary bacterial infection in Ghanaian patients with scabies.
From 110 patients with secondarily infected scabies lesions, 105 bacteria consisting of 66 aerobes and 39 anaerobes were isolated. A mixture of aerobic and anaerobic bacteria was present in 15 (13.6%). The predominant aerobic and anaerobic bacteria were staphylococcous aureus 39.1% and pepostreptococcus spp. 14.2% respectively. Organisms that resided in the mucus membranes close to or in contact with the lesions predominated in those infections. Most organisms were recovered from the finger and buttock lesions. These organisms were mainly staph. aureus, beta-haemolytic streptococci group. A and peptostreptococcus. More than 80% of staph. aureus isolated were resistant to penicillin. Less than 20% of the anaerobes were resistant to penicillin. The enteric Gram-negative, E. coli and Klebsiella spp. showed 100% sensitivity to Amoxycilin/clavulanic acid and gentamicin. Pseudomonas spp. were only susceptible to gentamicin, Amoxycillin/clavulanic acid proved to be the most active therapeutic agent in in vitro against the isolated microorganisms.


Microbiology and immunology of autism spectrum disorders.
Both generic and environmental factors are likely to contribute to the pathogenesis of neurodevelopmental disorders. Even in heritable disorders of high penetrance, variability in timing of onset or severity of disease indicate a role for modifying principles. Investigation in animal models of the consequences of interactions between host response genes and microbes, toxins, and other environmental agents in a temporal context may elucidate the pathophysiology of a wide spectrum of chronic diseases. Here we review the evidence that infectious and immune factors may contribute to the pathogenesis of neurodevelopmental disorders, describe an animal model of neurodevelopmental disorders based upon viral infection, identify processes by which neural circuitry may be compromised, and outline plans for translational research in animal models and prospective human birth cohorts.


The relationship between debrisoquine oxidation phenotype and the pharmacokinetics and pharmacodynamics of propranolol.
The pharmacokinetics and pharmacodynamics of propranolol (80 mg by mouth) were studied in seven extensive and four poor metabolisers of debrisoquine. Evidence for impairment of the 4'-hydroxylation of propranolol was found in poor metabolisers. However, no significant difference was detected in the oral clearance of unchanged drug between the two groups of debrisoquine oxidation phenotypes. Poor metabolisers of debrisoquine did not experience more intense or more prolonged beta-adrenoceptor blockade than extensive metabolisers of debrisoquine.


Cytocompatible in situ cross-linking of degradable LbL films based on thiol-exchange reaction.
Formation of both mechanically durable and programmably degradable layer-by-layer (LbL) films in a biocompatible fashion has potential applications in cell therapy, tissue engineering, and drug-delivery systems, where the films are interfaced with living cells. In this work, we developed a simple but versatile method for generating in situ cross-linked and responsively degradable LbL films, based on the thiol-exchange reaction, under highly cytocompatible conditions (aqueous solution at pH 7.4 and room temperature). The cytocompatibility of the processes was confirmed by coating individual yeast cells with the cross-linked LbL films and breaking the films on demand, while maintaining the cell viability. In addition, the processes were applied to the controlled release of an anticancer drug in the HeLa cells.


Effects of statin therapy on vascular dysfunction.
Dyslipidemia and vascular inflammation play critical roles in the onset of acute coronary syndromes including myocardial infarction. Recent advances in cardiovascular medicine demonstrate that lipid-lowering therapy by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) prevents acute coronary complications, probably by limiting inflammation in atheroma. Although a number of studies have suggested various effects of statins on vascular dysfunction independent of lipid lowering, the clinical benefits of such effects are not established as yet.


Plk1 phosphorylation of CAP-H2 triggers chromosome condensation by condensin II at the early phase of mitosis.
Condensin complexes play crucial roles in chromosome condensation that is a fundamental process to establish the "rod-like" shape of chromosome structure in mitosis. Failure of the chromosome assembly causes chromosome segregation errors and subsequent genomic instability. However, a molecular mechanism that controls condensin function for the chromosomal organization has not been fully understood. Here, we show that the abundance of CAP-H2, one of the condensin II subunits, is fluctuated during the cell cycle in accordance with Plk1 kinase activity. Inhibition of Plk1 leads to Cdc20-mediated degradation of CAP-H2 in mitosis. Plk1 phosphorylation of CAP-H2 at Ser288 is required for the accumulation of CAP-H2 and accurate chromosomal condensation during prophase. These findings suggest that Plk1 phosphorylation regulates condensin II function by modulating CAP-H2 expression levels to facilitate proper mitotic chromosome organization.


Fine structure of the mouse portal vein in relation to its peristaltic movement.
The hepatic portal vein has been known to make a spontaneous peristaltic movement in some mammals, including the mouse and rat. To investigate the fine structure of the portal vein in relation to its physiological characteristics, we observed the mouse portal vein by using various histological techniques including conventional light microscopy, videomicroscopy, transmission and scanning electron microscopy, and real-time confocal laser scanning microscopy. The mouse hepatic portal vein was provided with a spiral fold which was produced by the inner layer, i.e. the endothelium and smooth muscles of the wall protruding into the lumen. Longitudinal smooth muscle cells spanned the interval of the fold, like a spirally arranged palisade around the vessel wall. The longitudinal muscle fibers ended at the spiral fold, being partly connected with a network of irregularly shaped smooth muscle cells. This network, hitherto unknown, was recognized to be restricted to the fold in distribution and characterized by numerous gap junctions connecting the muscle cells. Real-time confocal laser scanning microscopy using a Ca2+ sensitive fluorescent dye revealed that a transient and periodic increase in Ca2+ concentration occurred in the longitudinal smooth muscle cells and was transmitted spirally from the intestinal to the hepatic side. These findings indicate that, during the peristaltic movement, the contraction of smooth muscle cells is transmitted along the longitudinal smooth muscles of the portal vein wall toward the liver, presumably controlled by the network of the irregularly-shaped smooth muscle cells in the fold of the portal vein. Light microscopic observation in some specimens indicated an occurrence of cardiac muscle cells outside the smooth muscle layer. Restricted to the site of the porta hepatis in distribution, their involvement in the peristaltic contraction of the portal vein seemed unlikely.


Cesarean section and intraoperative surgical complications.
The incidence of surgical complications associated with cesarean section (CS) was studied prospectively in 1319 patients undergoing CS during the years 1978, 1979 and 1980 (18% of all deliveries). The overall complication rate was 11.6% (9.5% patients with minor complications and 2.1% with major complications). The complication rate for emergency operations was 18.9% and for elective CS, 4.2%--a highly significant difference. (p less than 0.001). Six risk factors were associated with the occurrence of surgical complications in emergency cases: Station of the presenting part of the fetus in relation to the spinal plane (p less than 0.001), labor prior to surgery (p less than 0.001), low gestational age (less than 32 weeks) (p less than 0.001), rupture of fetal membranes (with labor) prior to surgery (p less than 0.01), previous CS (p less than 0.01), and skill of the operator (p less than 0.05). However, no such risk factors were found in the elective group. The clinical relevance of these findings is summarized in two conclusions. Firstly, the proportion of emergency operations needs to be reduced, either in favor of elective procedures, or by allowing more patients to give birth by the vaginal route. Secondly, emergency CS requires great skill on the part of the surgeon, and should therefore not be entrusted to young, inexperienced obstetricians.


Lateral thoracic artery as recipient vessel for head and neck free flap reconstruction in the vessel depleted neck: A case report.
Vessel depleted necks present a challenge to identifying suitable recipient vessels for microvascular head and neck reconstruction. Many alternative recipient vessels have been described. The purpose of this report is to describe the feasibility of using the lateral thoracic artery as a recipient vessel for head and neck free flap reconstruction in vessel depleted necks. In this report we describe surgery for a 62 year old male with osteoradionecrosis of the right mandibular body in which we performed right segmental mandibulectomy with free fibular flap reconstruction in a vessel depleted neck. We used the lateral thoracic artery which was ~10 cm in length. It provided good reach to the neck, proper blood flow, and acceptable vessel diameter of ~1.5 mm at 6 cm above the clavicle. The patient had an uncomplicated postoperative course and the flap was viable and well healed at 2 months follow-up. The lateral thoracic artery could be considered as one of the options for recipient vessels for microvascular reconstruction in patients with vessel depleted necks.


Effect of nociception level index-guided intra-operative analgesia on early postoperative pain and opioid consumption: a systematic review and meta-analysis.
Acute postoperative pain remains a critical treatment priority and has prompted a search for technologies and techniques to assist with intra-operative analgesic monitoring and management. Anaesthetists traditionally rely on clinical judgement to guide intra-operative analgesia, but several emerging technologies such as the nociception level index herald the possibility of routine intra-operative analgesia monitoring. However, the impact of devices like nociception level index on postoperative outcomes has not been proven. We undertook a systematic review and meta-analysis of articles which compared nociception level index-guided analgesia to standard care. The primary outcomes were pain intensity and opioid consumption during the first 60-120 min after surgery. Secondary outcomes were the incidence of postoperative nausea and vomiting and duration of stay in the post-anaesthesia care unit. Ten studies, collectively including 662 patients and published between 2019 and 2023, met inclusion criteria for both the qualitative systematic review and quantitative meta-analysis. Risk of methodological bias was generally low or unclear, and six studies reported a significant conflict of interest relevant to their findings. Our meta-analysis was performed using a random-effects model. It found statistically significant benefits of nociception level index-guided analgesia for early postoperative pain (mean (95%CI) difference -0.46 (-0.88 to -0.03) on an 11-point scale, p = 0.03), and opioid requirement (mean (95%CI) difference -1.04 (-1.94 to -0.15) mg intravenous morphine equivalent, p = 0.02). Our meta-analysis of the current literature finds that nociception level index-guided analgesia statistically significantly reduces reported postoperative pain intensity and opioid consumption but fails to show clinically relevant outcomes. We found no evidence that nociception level index-guided analgesia affected postoperative nausea and vomiting nor duration of stay in the post-anaesthesia care unit.


Comparative Study on Feature Selection in Protein Structure and Function Prediction.
Many effective methods extract and fuse different protein features to study the relationship between protein sequence, structure, and function, but different methods have preferences in solving the research of protein structure and function, which requires selecting valuable and contributing features to design more effective prediction methods. This work mainly focused on the feature selection methods in the study of protein structure and function, and systematically compared and analyzed the efficiency of different feature selection methods in the prediction of protein structures, protein disorders, protein molecular chaperones, and protein solubility. The results show that the feature selection method based on nonlinear SVM performs best in protein structure prediction, protein solubility prediction, protein molecular chaperone prediction, and protein solubility prediction. After selection, the accuracy of features is improved by 13.16% ~71%, especially the Kmer features and PSSM features of proteins.


[Structure of an O-specific polysaccharide of Proteus mirabilis 03, containing N-(2-hydroxyethyl)-D-alanine].
O-Specific polysaccharide, obtained by mild acid degradation of the Proteus mirabilis 03 lipopolysaccharide, was dephosphorylated with 48% HF to give a linear polysaccharide and an amino acid, N-(2-hydroxyethyl)-D-alanine. The structure of the polysaccharide was determined by methylation, the Smith degradation and computer-assisted analysis of the 13C NMR spectra of original and dephosphorylated polymers and oligomers. The structure of the amino acid was elucidated by using 1H and 13C NMR spectroscopy and mass spectrometry (applied to the acetylated methyl ester derivative), optical rotation and CD spectrum data and comparison with the synthetic sample. The repeating unit of P. mirabilis 03 O-specific polysaccharide is shown to have the following structure: (formula; see text)


The promise of targeted proteomics for quantitative network biology.
Proteomics is a powerful tool for obtaining information on a large number of proteins with regard to their expression levels, interactions with other molecules, and posttranslational modifications. Whereas nontargeted, discovery proteomics uncovers differences in the proteomic landscape under different conditions, targeted proteomics has been developed to overcome the limitations of this approach with regard to quantitation. In addition to technical advances in instruments and informatics tools, the advent of the synthetic proteome composed of synthetic peptides or recombinant proteins has advanced the adoption of targeted proteomics across a wide range of research fields. Targeted proteomics can now be applied to measurement of the dynamics of any proteins of interest under a variety of conditions as well as to estimation of the absolute abundance or stoichiometry of proteins in a given network. Multiplexed targeted proteomics assays of high reproducibility and accuracy can provide insight at the quantitative level into entire networks that govern biological phenomena or diseases. Such assays will establish a new paradigm for data-driven science.


Advancing Clinical Trials to Streamline Drug Development.
The last decade in oncology has been marked by the identification of numerous new potential cancer targets and even more agents designed to inhibit them. The matrix of new targets, new agents, and the companion diagnostics required to identify the right patient for the right drug has created a major challenge for the clinical trial process. This has been compounded by the addition of new immunomodulators targeting the host immune system rather than the tumor. Recognizing the need for new approaches, industry, investigators, and regulators have responded to this challenge. New clinical trial designs are being evaluated to incorporate the genomic sequence data being obtained almost routinely after cancer diagnosis. New dose-finding approaches are being proposed to identify the maximum effective dose rather than the maximum tolerated dose. The FDA is involved in the drug approval process from points early in development and has accepted registration quality data from expansion cohorts in support of drug approval. Despite progress on several fronts, many challenges remain, including the lack of predictability of preclinical data for clinical results and phase II data for phase III results, an infrastructure that can be an obstacle to clinical trial development and implementation, and the increasing use of contracted clinical research organizations that limit a fit-for-purpose approach to clinical trial execution. Perhaps most challenging and important of all are the difficulties with clinical trial accrual that can prevent study completion. Both the innovations and the challenges highlight the important role of process in progress in clinical oncology.


Phenotypic and functional characterization of human suppressor T-cell clones: II. Activation by Mycobacterium leprae presented by HLA-DR molecules to alpha beta T-cell receptors.
We have been studying human T-cell clones that suppress anti-mycobacterial T-cell responses but not T-cell responses to an unrelated antigen or mitogen. In the present paper we report our studies on the activation requirements of these suppressor-T-cell clones. The suppressor-T-cell clones could proliferate and produce interferon-gamma upon stimulation with Mycobacterium leprae and other mycobacteria but not with unrelated antigens or autologous T cells. Both suppressor and nonsuppressor clones react to a 36-kDa antigen of M. leprae. Thus far, we have not been able to demonstrate whether they see the same or different epitopes. The antigen-driven proliferation of suppressor-T-cell clones was, however, significantly lower than that observed for T-cell clones that did not mediate suppression. The proliferation of suppressor-T-cell clones to M. leprae antigens could be blocked by monoclonal antibodies to HLA-DR, alpha beta T-cell receptor, interleukin-2 receptor, and, in the case of CD4-positive suppressor-T-cell clones, anti-CD4 monoclonal antibodies. DR restriction of the antigen presentation to these suppressor-T-cell clones was shown in mixing experiments using antigen-presenting cells as mononuclear cells from family members and unrelated individuals. These experiments also indicated that apart from regular DR-restriction a hitherto unknown factor may be required for presentation to or activation of suppressor-T-cell clones that is present in the family members and unrelated individuals with the same ethnic and geographic background but absent in DR/Dw-matched healthy Dutch individuals.


Wandering spleen as a cause of acute abdomen: a case report.
We report a case of acute abdomen due to torsion of the long vascular pedicle of a wandering spleen, displaced in the abdominal cavity, and caused by partial infarction of the spleen. The 46-year-old patient presented to the casualty department with piercing abdominal pain, fever, vomiting, leukocytosis, thrombocytopenia, and a palpable mass in the mesogastric region. US and CT scan revealed the presence of a mass compatible with an ectopic spleen in the mesohypogastric region, featuring necrotic-haemorrhagic areas, a long, contorted vascular pedicle twisted on its axis, and an empty splenic space. We performed an emergency laparoscopic splenectomy. Conservative surgery (splenopexy) could not be done because of the severe impairment of the vascular supply to the organ. Nowadays, conservative surgery is preferred in cases without vascular impairment, especially in children, by creating an omental or synthetic pouch after fixing the organ in the splenic space.


Folding single-stranded DNA to form the smallest 3D DNA triangular prism.
The smallest DNA 3D object, a triangular prism with only one turn on each edge, was constructed from a single-stranded DNA. We confirmed its structure using scanning tunneling microscopy. This work proves that single-stranded DNA can escape from kinetic traps to form stable topology.


Biomimetic on-chip assay reveals the anti-metastatic potential of a novel thienopyrimidine compound in triple-negative breast cancer cell lines.
Introduction: This study presents a microfluidic tumor microenvironment (TME) model for evaluating the anti-metastatic efficacy of a novel thienopyrimidines analog with anti-cancer properties utilizing an existing commercial platform. The microfluidic device consists of a tissue compartment flanked by vascular channels, allowing for the co-culture of multiple cell types and providing a wide range of culturing conditions in one device. Methods: Human metastatic, drug-resistant triple-negative breast cancer (TNBC) cells (SUM159PTX) and primary human umbilical vein endothelial cells (HUVEC) were used to model the TME. A dynamic perfusion scheme was employed to facilitate EC physiological function and lumen formation. Results: The measured permeability of the EC barrier was comparable to observed microvessels permeability in vivo. The TNBC cells formed a 3D tumor, and co-culture with HUVEC negatively impacted EC barrier integrity. The microfluidic TME was then used to model the intravenous route of drug delivery. Paclitaxel (PTX) and a novel non-apoptotic agent TPH104c were introduced via the vascular channels and successfully reached the TNBC tumor, resulting in both time and concentration-dependent tumor growth inhibition. PTX treatment significantly reduced EC barrier integrity, highlighting the adverse effects of PTX on vascular ECs. TPH104c preserved EC barrier integrity and prevented TNBC intravasation. Discussion: In conclusion, this study demonstrates the potential of microfluidics for studying complex biological processes in a controlled environment and evaluating the efficacy and toxicity of chemotherapeutic agents in more physiologically relevant conditions. This model can be a valuable tool for screening potential anticancer drugs and developing personalized cancer treatment strategies.


Curcumin and neurodegenerative diseases: a perspective.
Curcumin, a dietary polyphenol found in the curry spice turmeric, possesses potent antioxidant and anti-inflammatory properties and an ability to modulate multiple targets implicated in the pathogenesis of chronic illness. Curcumin has shown therapeutic potential for neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). This article highlights the background and epidemiological evidence of curcumin's health benefits and its pharmacodynamic and pharmacokinetic profile. Curcumin's ability to counteract oxidative stress and inflammation and its capacity to modulate several molecular targets is reviewed. We highlight the neuroprotective properties of curcumin including pre-clinical evidence for its pharmacological effects in experimental models of AD and PD. The bioavailability and safety of curcumin, the development of semi-synthetic curcuminoids as well as novel formulations of curcumin are addressed. Curcumin possesses therapeutic potential in the amelioration of a host of neurodegenerative ailments as evidenced by its antioxidant, anti-inflammatory and anti-protein aggregation effects. However, issues such as limited bioavailability and a paucity of clinical studies examining its therapeutic effectiveness in illnesses such as AD and PD currently limit its therapeutic outreach. Considerable effort will be required to adapt curcumin as a neuroprotective agent to be used in the treatment of AD, PD and other neurodegenerative diseases.


[Endoscopic subfascial vein dissection].
Endoscopic subfascial dissection is an effective method for the interruption of incompetent perforating veins. From 15th October to 15th December of 1995 11 patients underwent endoscopic subfascial sectioning. It is the first time to apply this procedure in Hungary. A venous ulcer was found in 5 patients. Endoscopic sectioning supplemented by extensive fasciotomy, without any substantial complication. The method is recommended due to its reduced invasiveness and fair results.


A time series study of the effectiveness and costs of EPSDT outreach in Maine.
Maine's Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) program provides outreach and case management services through written agreements with 13 community-based agencies. These agencies are reimbursed on a cost-related basis for contacting new and re-eligible Medicaid families to inform them about EPSDT services and to enroll children in the program. Since October 1979, local agency outreach workers have attempted to inform 95 percent of the eligible families in their own homes. Effectiveness was measured by comparing the percentages of families informed with the 95 percent Federal requirement. Concurrently, but separately, agency costs were monitored. The authors undertook a study to determine the unit costs of informing families for 4 years and to relate those costs to the percentages of families informed. Using a single group time series design combined with a cost-effectiveness model, both effectiveness and efficiency were examined. The percentage of families informed increased 7.8 percent from State Fiscal Year (SFY) 1980 through SFY 84. The percent of increase per year, however, has decreased from 3.42 percent to 1.29 percent. The statewide informing unit cost decreased from $51.19 to $45.34 during the same time period. Examination of individual agency unit costs indicates that the difference between the lowest and highest agency unit cost is becoming greater each year. This study has reaffirmed the authors' belief that personal contact with families increases the likelihood of enrolling children in the program; less than 3 percent of the families informed of EPSDT services declined them. The study also indicates that changes in program procedures, reimbursement, or both, are needed to increase further the effectiveness and efficiency of this aspect of the program.


Polar silica-based stationary phases. Part I - Singly and doubly layered sorbents consisting of TRIS-silica and chondroitin sulfate A-TRIS-silica for hydrophilic interaction liquid chromatography.
Two polar silica bonded stationary phases were prepared by first functionalizing the silica surface with γ-glycidoxypropyltrimethoxysilane, which was then reacted with TRIS to yield a polyhydroxy surface that also has secondary amine functionalities. This step produced the singly layered TRIS-silica column, a cationic hydrophilic column. The TRIS-silica surface was further coated with a layer of chondroitin sulfate A (CSA) yielding the doubly layered hydrophilic CSA-TRIS-silica column. The adsorbed CSA layer provided enhanced hydrophilicity and multi-mode interactions with polar solutes leading to different retention behavior and selectivity compared to the singly layered TRIS-silica column. The anionic sulfate and carboxylate groups in the CSA coating are electrostatically attracted by the cationic TRIS-silica surface yielding a relatively stable physically anchored CSA layer under HILIC elution conditions. The CSA-TRIS-silica column exhibited dual cationic and anionic character with mobile phases at pH ∼3.0 and pH > 4.5, respectively. When comparing solute retention observed on both columns under identical elution conditions, the k values of neutral and cationic solutes were significantly higher on the more hydrophilic doubly layered CSA-TRIS-silica column whereas anionic solutes showed lower k values due to the electrostatic repulsion from the CSA layer.


New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking.
Phenolic acids (caffeic-, ferulic and p-coumaric acid) are widely distributed in the plant kingdom and exhibit broad spectrum of biological activities, including antimicrobial activity. The goal of this paper is the synthesis of some caffeic acid derivatives selected based on computer-aided predictions and evaluate their in vitro antimicrobial properties against Gram positive and Gram negative bacteria and also a series of fungi. In silico prediction of biological activity was used to identify the most promising structures for synthesis and biological testing, and the putative mechanisms of their antimicrobial action. The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was studied using microdilution method. Twelve tested compounds have shown good antibacterial activity. Five out of twelve tested compounds appeared to be more active than the reference drugs ampicillin and streptomycin. Despite that all compounds exhibited good activity against all bacteria tested, the sensitivity of bacteria towards compounds in general was different. The evaluation of antifungal activity revealed that all compounds were more active than ketoconazole, while seven compounds (2, 3, 4, 5, 7, 8 and 12) appeared to be more active than bifonazole. Docking results indicate that gyrase inhibition is the putative mechanism of antibacterial action while the inhibition of 14α-demethylase may be responsible for antifungal action. Prediction of cytotoxicity by PROTOX showed that compounds are not toxic (LD50 1000-2000 mg/kg). Thirteen compounds, from which six are new ones, were synthesized, and twelve compounds were tested for antimicrobial activity. The studied compounds appeared to be promising potent and non-toxic antimicrobials, which could be considered as leads for new pharmaceutical agents.


[Respiratory infections outside the hospital. DIRA study].
Most visits to the primary care center are for infection and particularly respiratory tract infection. Antimicrobial administration for these clinical processes is common and these agents are often used to treat viral infections. La Fundación para el Estudio de la Infección (Foundation for the Study of Infection) designed the DIRA (Día de la Infección Respiratoria del Adulto, Adult Respiratory Infection Day) Project to investigate and assess the impact of this problem. The study design consisted of one-day cross sections with the participation of 720 physicians belonging to Primary Health Care Centers from the 17 Autonomic Regions of Spain, establishing a one-day cross section every three months for one year. Epidemiologic, clinical and therapeutic factors were evaluated. The total number of visits attended was 72 929, and 14 426 patients had infectious processes (43.9%). Among these, 9145 (63.4%) had a respiratory infection. The mean age of the patients was 44.6 years and 34.1% had an underlying condition. Common cold was the most frequent diagnosis. Antibiotics were prescribed in 53.2% of patients. Results were compared to those of a previous study. Infection in general and respiratory infection in particular is frequently attended in primary care. Antibiotics are widely used in our setting and self-medication is common.


Activation of nociceptin/orphanin FQ receptors inhibits contextual fear memory reconsolidation.
Several neuropeptidergic systems act as modulators of cognitive performances. Among them, nociceptin, an opioid-like peptide also known as orphanin FQ (N/OFQ), has recently gained attention. Stimulation of its receptor, the N/OFQ opioid receptor (NOP), which is expressed in brain regions involved in emotion, memory and stress response, has inhibitory effects on the acquisition and/or consolidation of spatial and emotional memory in rodents. Recently, N/OFQ was also proposed to be linked to the pathogenesis of Post-Traumatic Stress Disorder in humans. However, until now the effect of the activation of the N/OFQ-NOP system on already consolidated memory, such as during retrieval and reconsolidation phases, has never been explored. In the present study, we investigated the consequences of systemic injection of NOP agonists or i.c.v. injection of the N/OFQ peptide on the retrieval and the reconsolidation of contextual fear memory in mice. We demonstrate that the activation of the N/OFQ system impairs the reconsolidation of context-dependent but not cue-dependent aversive memories. We also show that this amnestic effect is associated with decreased c-Fos expression in the hippocampus and amygdala. Our data thus provide the first evidence that the NOP receptor could be targeted during the reconsolidation process to weaken maladaptive memories. The N/OFQ-NOP system might constitute in the future an interesting pharmacological target for interfering with so-called "pathological memories", in particular those involving maladaptive contextual memories.


NMR studies of ultrafast intramolecular proton tautomerism in crystalline and amorphous n,n'-diphenyl-6-aminofulvene-1-aldimine: solid-state, kinetic isotope, and tunneling effects.
Using solid-state NMR spectroscopy, we have detected and characterized ultrafast intramolecular proton tautomerism in the N-H-N hydrogen bonds of solid N, N'-diphenyl-6-aminofulvene-1-aldimine ( I) on the microsecond-to-picosecond time scale. (15)N cross-polarization magic-angle-spinning NMR experiments using (1)H decoupling performed on polycrystalline I- (15)N 2 and the related compound N-phenyl- N'-(1,3,4-triazole)-6-aminofulvene-1-aldimine ( II) provided information about the thermodynamics of the tautomeric processes. We found that II forms only a single tautomer but that the gas-phase degeneracy of the two tautomers of I is lifted by solid-state interactions. Rate constants, including H/D kinetic isotope effects (KIEs), on the microsecond-to-picosecond time scale were obtained by measuring and analyzing the longitudinal (15)N and (2)H relaxation times of I- (15)N 2, I- (15)N 2- d 10, and I- (15)N 2- d 1 over a wide temperature range. In addition to the microcrystalline modification, a novel amorphous modification of I was found and studied. In this modification, proton transfer is much faster than in the crystalline form. For both modifications, we observed large H/D KIEs that were temperature-dependent at high temperatures and temperature-independent at low temperatures. These findings are interpreted in terms of a simple quasiclassical tunneling model proposed by Bell and modified by Limbach. We obtained evidence that a reorganization energy is necessary in order to compress the N-H-N hydrogen bond and achieve a molecular configuration in which the barrier for H transfer is reduced and tunneling or an over-barrier reaction can occur.


Preferential expression of OVOL1 in inner root sheath of hair, sebaceous gland, eccrine duct and their neoplasms in human skin.
OVOL1 is an important transcription factor for epidermal keratinization, which suppresses proliferation and switches on the differentiation of keratinocytes. A recent genome-wide association study has revealed that OVOL1 is one of the genes associated with susceptibility to atopic dermatitis. Although it is known to be expressed in murine skin and hair follicles, no investigations have focused on its localization in human skin. In the present study, we thus immunolocalized the expression of OVOL1 in normal and diseased human skin. In normal human skin, OVOL1 was preferentially expressed in the suprabasal layer of the epidermis, inner root sheath of hair, mature sebocytes and the ductal portion of the eccrine glands. Compared to this, no remarkable change in the expression of OVOL1 was observed among inflammatory skin diseases. The expression of OVOL1 was evident in eccrine poroma and hidradenoma. Moreover, it was overexpressed in Bowen's disease and sebaceous adenoma, in sharp contrast to its downregulation in their more malignant counterparts, squamous cell carcinoma and sebaceous carcinoma. OVOL1 may play an important role in human skin morphogenesis and tumorigenesis.


Assembly-disassembly of actin bundles in starfish oocytes: an analysis of actin-associated proteins in the isolated cortex.
One rapid response of starfish oocytes to the maturation-inducing hormone, 1-methyladenine (1-MA), is the formation of transient actin-filled spikes on the cell surface. The presence and distribution of G- and F-actin and several actin-associated proteins were examined in cortices isolated from oocytes before, during, and after spike formation by using antibodies and the F-actin-specific stain, NBD-phallacidin. Before 1-MA addition, staining with antiactin and NBD-phallacidin indicates that most of the actin in the cortex is either G-actin or oligomeric actin, but rather little is F-actin. Application of the hormone results in the conversion and redistribution of this cortical actin into large bundles of F-actin which form the cores of spikes. When the spikes recede, F-actin disappears, and the amount of all forms of actin bound in the cortex appears to decrease. Antibodies to sea urchin egg myosin, fascin and a 220-kDa protein were used to examine these actin-associated proteins during the times that the organization of actin changes. Myosin and the 220-kDa protein are bound to the cortex and uniformly distributed before 1-MA application while fascin appears to be unbound. When spikes appear after 1-MA addition, fascin and the 220-kDa protein are localized coincidently with the spikes, whereas myosin remains uniformly distributed throughout the cortex and is excluded from the spikes. After spike resorption, fascin and the 220-kDa protein appear to lose their cortical binding while myosin retains its localization unchanged. These results indicate that actin, fascin and the 220-kDa protein undergo major organizational changes in the cortex in response to 1-MA.


[Laser and corneal surgery: topography and preoperative evaluation].
The purpose of preoperative clinical examination is to determine accurately the refraction under cycloplegia. Operative techniques and protocols are chosen in relation to the degree of ametropia. Computer assisted videokeratography allows early keratoconus detection and gives reference quantitative datas for analysing postoperative changes.


Exercise stress testing in recently abstinent chronic cocaine abusers.
We compared treadmill exercise stress testing (EST) in 28 medically screened, chronic cocaine users with the cardiovascular effects of an IV cocaine challenge (25 mg or 50 mg). All subjects had a clinically normal EST and echocardiography (except 2 subjects had septal wall hypokinesis). The EST produced significantly greater increases in heart rate and rate-pressure product than did the cocaine challenges. These findings suggest that EST may not provide additional diagnostic information in medically screened cocaine users. EST may cause more cardiac work (indicated by heart rate and blood pressure) than intravenous cocaine (at the doses in this study).


Comparison of Cleaning Efficacy of Different Rotary Files in Primary Teeth-An In vitro Study.
The aim of the present study was to comparatively assess the cleansing efficiency of dissimilar rotary files in deciduous teeth. Forty-five deciduous anterior teeth that had been subjected to extraction were chosen for this research. The teeth were included if they had a minimum of 2/3rd undamaged root portions. Coronal entrée was completed using round diamond burs. All 45 samples were allocated at random to one of the following three groups: Group I: Control group in which the radicular canal was not subjected to any form of instrumentation, Group II: The radicular canal was subjected to instrumentation employing rotary ProTaper files, Group III: The radicular canal was subjected to instrumentation with rotary MTwo files. The samples were subjected to immersion in a succession of diluted ethyl alcohols to permit dehydration: With a change of solution every eight hours, the first 16 hours were spent in 70% alcohol, followed by eight hours in 80% alcohol, eight hours in 95% alcohol, and eight hours in 100% alcohol. The samples thus subjected to dehydration were cleared by immersion in methyl salicylate for six hours. Under a stereomicroscope with a 10x magnification, the root canals were examined by a person who was blinded to the groups in order to look for any traces of ink in the coronal, middle, and apical third of the canals. In the control group, greater residual remains were present in the apical 3rd at 2.16 ± 0.08 followed by the coronal 3rd at 2.02 ± 0.14, and then in the middle 3rd at 1.88 ± 0.10. While using the ProTaper files, greater residual remains were present in the middle portion at 1.68 ± 0.16, followed by the coronal third at 0.94 ± 0.09, then the apical third at 0.98 ± 0.22. Greater residual remains were again noted with the MTwo files in the mid-portion at 1.44 ± 0.18, followed by the coronal part at 0.86 ± 0.10 and then the apical part at 0.82 ± 0.04. Differences among these groups were statistically significant with a P value < 0.001. The present study concluded that either of the file types used exhibited reasonably lower remnant score values in the apical third versus the middle/coronal thirds. Nonetheless, MTwo type files delineated superior capacity at removing debris versus the ProTaper file types at the apical level.


RNA Polymerase II Read-Through Promotes Expression of Neighboring Genes in SAL1-PAP-XRN Retrograde Signaling.
In plants, the molecular function(s) of the nucleus-localized 5'-3' EXORIBONUCLEASES (XRNs) are unclear; however, their activity is reported to have a significant effect on gene expression and SAL1-mediated retrograde signaling. Using parallel analysis of RNA ends, we documented a dramatic increase in uncapped RNA substrates of the XRNs in both sal1 and xrn2xrn3 mutants. We found that a major consequence of reducing SAL1 or XRN activity was RNA Polymerase II 3' read-through. This occurred at 72% of expressed genes, demonstrating a major genome-wide role for the XRN-torpedo model of transcription termination in Arabidopsis (Arabidopsis thaliana). Read-through is speculated to have a negative effect on transcript abundance; however, we did not observe this. Rather, we identified a strong association between read-through and increased transcript abundance of tandemly orientated downstream genes, strongly correlated with the proximity (less than 1,000 bp) and expression of the upstream gene. We observed read-through in the proximity of 903 genes up-regulated in the sal1-8 retrograde signaling mutant; thus, this phenomenon may account directly for up to 23% of genes up-regulated in sal1-8 Using APX2 and AT5G43770 as exemplars, we genetically uncoupled read-through loci from downstream genes to validate the principle of read-through-mediated mRNA regulation, providing one mechanism by which an ostensibly posttranscriptional exoribonuclease that targets uncapped RNAs could modulate gene expression.


Voluntary lung function screening to reveal new COPD cases in southern Italy.
Underdiagnosis of COPD is a relevant issue, and most frequently involves patients at early stages of the disease. Physicians do not routinely recommend smokers to undergo spirometry, unless they are symptomatic. To investigate the effectiveness of voluntary lung function screening in bringing to light patients with previously unknown COPD and to evaluate the relationships among symptoms, smoking status, and airway obstruction. A voluntary screening study for COPD was conducted during two editions of the annual Fiera del Levante (2014 and 2015), an international trade fair in Bari. Subjects were eligible for the study if they fulfilled the following inclusion criteria: age ≥35 years, smoker/ex-smoker ≥5 pack-years (PYs), or at least one chronic respiratory symptom (cough, sputum production, shortness of breath, and wheezing). A free post-β2-agonist spirometry test was performed by trained physicians for each participant using portable spirometers. Post-β2-agonist forced expiratory volume in 1 second (FEV1):forced vital capacity ratio <0.7 was chosen to establish the diagnosis of COPD. Sensitivity, specificity, and negative and positive predictive values (NPVs and PPVs) of symptoms for the presence of obstruction were calculated. A total of 1,920 individuals were eligible for the study; 188 subjects (9.8%) met COPD criteria. There was a 10.4% prevalence of COPD in subjects with one or more symptoms who had never smoked or smoked ≤5 PYs. Among COPD patients, prevalence of symptoms increased in the presence of FEV1 <80%. COPD smokers were more symptomatic than smokers without COPD. Sensitivity and specificity in all subjects with one or more symptoms were 87% and 32%, respectively, whereas in smoker subgroups, sensitivity and specificity were 71% and 41% (≥5 PYs) and 74% and 35% (≥10 PYs), respectively. In all subjects, the presence of at least one symptom was associated with a low PPV for COPD of 11%, but a very high NPV (96%). These data did not change if the analysis was limited to smokers. Voluntary public lung function screening programs in Italy are effective, and may detect a large number of undiagnosed subjects with COPD in early stages. In our population, COPD symptoms had low specificity and PPV, even considering smokers only.


The association of serum anti-ribosomal P antibody with clinical and serological disorders in systemic lupus erythematosus: a systematic review and meta-analysis.
Anti-ribosomal P (anti-P) antibody is a serological specific marker of systemic lupus erythematosus (SLE). The aim of this study is to investigate the association of this antibody with clinical and serological disorders in SLE. All relevant literature was retrieved from PubMed, EMBASE, Web of Science and CNKI databases. The qualities of these studies were evaluated using a modified version of the Newcastle-Ottawa scale. The associations of anti-P antibody with clinical and serological disorders were determined by the pooled odds ratio (OR) and the confidence interval (CI) calculated using meta-analysis with the Mantel-Haenszel method. Sixteen cohort studies with 2355 patients were included in this study. Malar rash, oral ulcer and photosensitivity were strongly associated with serum anti-P antibody, with OR (95% CI) values of 2.05 (1.42-2.92), 1.49 (1.05-2.13) and 1.44 (1.08-1.91), respectively. Arthritis and renal involvement were not associated with anti-P antibody, whereas a high heterogeneity was observed due to ethnicity and publication bias, respectively. Neuropsychiatric SLE (NPSLE), hepatic involvement, anti-dsDNA, anti-Sm and anti-cardiolipin antibodies (aCL) were observed more frequently in anti-P positive patients than in negative patients. Studies on hepatic involvement showed a low precision with substantially broad CI (2.56-11.2). A high heterogeneity presented among studies on NPSLE, anti-Sm and aCL. Anti-P antibody is significantly associated with malar rash, oral ulcer, photosensitivity and serum anti-dsDNA antibody, and potentially associated with NPSLE, hepatic damage, serum anti-Sm and aCL.


Whole body heat exposure modulates acute glucose metabolism.
Exercise modulates glucose tolerance and homeostasis in both healthy and diabetic individuals. Heat stress is a fundamental element of exercise. The acute glycemic response and alterations in glucose clearance following whole body passive heat stress in the absence of muscle activity has yet to be examined in humans. Knowledge of this relationship may prove useful, particularly in populations with compromised glucoregulation from reduced activity. To determine insulin/glucose levels before and after an acute bout of heat stress in healthy, lean individuals and examine the effects of whole body heat stress (WBHS) and exercise on acute glucose tolerance in an expanded cohort. Ten subjects (24.1 ± 0.7 years) participated in a randomized control/WBHS session (up to 30 minutes at 73 °C) with fasting glucose (FG) and insulin drawn at baseline, immediately after and 30 minutes post heat stress. In the follow-up experiment, 20 anthropometrically diverse subjects (24.6 ± 2.1 years) underwent an oral glucose tolerance test (OGTT) under the conditions above. FG levels rose 10% immediately following heat stress (8.6 (±5.6) mg/dl, p < .01) and returned to near baseline levels 30 minutes following WBHS. Insulin release showed its greatest increase at 30 minutes post WBHS (2.7 ± 3.5) uU/ml p < .05). WBHS resulted in a decrease in glucose uptake [AUC increased 8.2% (1430.6 ± 1957.03) mg/dl (p = .005)], particularly in nonlean individuals. WBHS modulates physiologic markers of metabolism. An acute bout of WBHS increases glucose and insulin levels in healthy individual and decreases glucose uptake in response to a glucose challenge, particularly those who are non-lean.


Odd couple: The unexpected partnership of glucocorticoid hormones and cysteinyl-leukotrienes in the extrinsic regulation of murine bone-marrow eosinopoiesis.
Granulopoiesis in murine bone-marrow is regulated by both intrinsic and extrinsic factors (including hormones, drugs, inflammatory mediators and cytokines). Eosinophils, a minor subpopulation of circulating leukocytes, which remains better understood in its contributions to tissue injury in allergic disease than in its presumably beneficial actions in host defense, provide a striking example of joint regulation of granulopoiesis within murine bone-marrow by all of these classes of extrinsic factors. We first described the upregulation of eosinopoiesis in bone-marrow of allergen-sensitized mice following airway allergen challenge. Over the last decade, we were able to show a critical role for endogenous glucocorticoid hormones and cytokines in mediating this phenomenon through modification of cytokine effects, thereby supporting a positive association between stress hormones and allergic reactions. We have further shown that cysteinyl-leukotrienes (CysLT), a major proinflammatory class of lipid mediators, generated through the 5-lipoxygenase pathway, upregulate bone-marrow eosinopoiesis in vivo and in vitro. CysLT mediate the positive effects of drugs (indomethacin and aspirin) and of proallergic cytokines (eotaxin/CCL11 and interleukin-13) on in vitro eosinopoiesis. While these actions of endogenous GC and CysLT might seem unrelated and even antagonistic, we demonstrated a critical partnership of these mediators in vivo, shedding light on mechanisms linking stress to allergy: GC are required for CysLT-mediated upregulation of bone-marrow eosinopoiesis in vivo, but also attenuate subsequent ex vivo responses to CysLT. GC and CysLT therefore work together to induce eosinophilia, but through subtle regulatory mechanisms also limit the magnitude of subsequent bone-marrow responses to allergen.


Antifungal activity of Gracilaria corticata methanol extract against Trichophyton mentagrophytes, Microsporum canis, and Microsporum gypseum on rat dermatophytosis models.
Dermatophytosis is one of the most prevalent zoonotic diseases. Increased resistance of dermatophytosis-causing pathogens against antidermatophytic agents highlights the need for alternative medicine with higher efficiency and lower side effects. In the present study, the in vitro antifungal activities of different concentrations of Gracilaria corticata methanol extract against Trichophyton mentagrophytes, Microsporum canis, and Microsporum gypseum were assessed and their efficacy was evaluated in rat dermatophytosis models. The broth microdilution and well diffusion methods were used to determine the in vitro antidermatophytic activity. The in vivo study was carried out using 40 dermatophytosis-infected adults male Wistar rats. The animals were divided into 4 groups (5% and 10% G. corticata ointment, terbinafine, and Vaseline) and treated with ointment until complete recovery. The percentage of wound closure was calculated for each group. The results revealed that G. corticata methanol extract was effective to varying extents against the tested dermatophytes. The highest inhibitory activity of G. corticata was found against T. mentagrophytes with minimum inhibitory concentration and minimum fungicidal concentration values of 4 and 9 µg mL-1, respectively. The in vivo experiment revealed that 10% G. corticata ointment significantly accelerated skin lesions reduction and completely cured M. gypseum, T. mentagrophytes, and M. canis infections after 19, 25, and 38 days, respectively. The methanol extract of G. corticata exhibited significant antifungal activity in vitro and in vivo, suggesting that it could be used as an alternative to antidermatophytic therapy in a dose-dependent manner.


3D Carbon Microspheres with a Maze-Like Structure and Large Mesopore Tunnels Built From Rapid Aerosol-Confined Coherent Salt/Surfactant Templating.
Hierarchically porous carbons with tailor-made properties are essential for applications wherein rich active sites and fast mass transfer are required. Herein, a rapid aerosol-confined salt/surfactant templating approach is proposed for synthesizing hierarchically porous carbon microspheres (HPCMs) with a maze-like structure and large mesopore tunnels for high-performance tri-phase catalytic ozonation. The confined assembly in drying microdroplets is crucial for coherent salt (NaCl) and surfactant (F127) dual templating without macroscopic phase separation. The HPCMs possess tunable sizes, a maze-like structure with highly open macropores (0.3-30 µm) templated from NaCl crystal arrays, large intrawall mesopore tunnels (10-45 nm) templated from F127, and rich micropores (surface area >1000 m2 g-1 ) and oxygen heteroatoms originated from NaCl-confined carbonization of phenolic resin. The structure formation mechanism of the HPCMs and several influencing factors on properties are elaborated. The HPCMs exhibit superior performance in gas-liquid-solid tri-phase catalytic ozonation for oxalate degradation, owing to their hierarchical pore structure for fast mass transfer and rich defects and oxygen-containing groups (especially carbonyl) for efficient O3 activation. The reactive oxygen species responsible for oxalate degradation and the influences of several structure parameters on performance are discussed. This work may provide a platform for producing hierarchically porous materials for various applications.


Computer-assisted learning compared with weekly seminars for teaching fundamental electrocardiography to junior medical students.
This study was designed to assess whether a self-study interactive computer program is more effective than weekly seminars for teaching fundamental skills of electrocardiographic interpretation to junior medical students. Forty-two students were assigned to the computer and 41 to the seminar group. A test was given to each participant at the beginning and end of each rotation. The computer group used a computer-assisted learning program, and the seminar group met weekly with a cardiologist to review electrocardiograms. Attendance at a minimum of 80% of the seminars or completion of 80% of the computer-assisted learning program was required for inclusion in the statistical analysis. The mean difference in test scores before and after study was 5.69 for the computer group and 4.36 for the seminar group (P less than .02 by one-tailed t-test). These results indicate that the computer group performed significantly better than the seminar group. We believe this difference to be educationally important.


Miners compensated for pneumoconiosis and glutathione s-transferases M1 and T1 genotypes.
Chronic inhalation of quartz-containing dust produces reversible inflammatory changes in lungs resulting in irreversible fibrotic changes termed pneumoconiosis. Due to the inflammatory process in the lungs, highly reactive substances are released that may be detoxified by glutathione S-transferases. Therefore, 90 hard coal miners with pneumoconiosis as a recognized occupational disease (in Germany: Berufskrankheit BK 4101) were genotyped for glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) according to standard methods. Furthermore, occupational exposure and smoking habits were assessed by questionnaire. Changes in a chest x-ray were classified according to ILO classification 2000. Of the investigated hard coal miners 43% were GSTM1 negative whereas 57% were GSTM1 positive. The arithmetic mean of the age at time of investigation was 74.2 yr (range: 42-87 yr). Seventy-four percent of the hard coal miners reported being ever smokers, while 26% denied smoking. All hard coal miners provided pneumoconiosis-related changes in the chest x-ray. The observed frequency of GSTM1 negative hard coal miners was not different from frequencies reported for general Caucasian populations and in agreement with findings reported for Chinese coal miners. In contrast, in a former study, 16 of 19 German hard coal miners (84%) with urinary bladder cancer displayed a GSTM1 negative genotype. The outcome of this study provides evidence that severely occupationally exposed Caucasian hard coal miners do not present an elevated level of GSTM1 negative individuals.


Removal of the olfactory bulbs modifies the gonadal responses to photoperiod in the lesser mouse lemur (Microcebus murinus).
The sexual activity of the lesser mouse lemur, unlike that of most living primates, is clearly dependent on photoperiod. Males responded to long daylengths (> 12 h light/day) by rapid testicular development and an increase in testosterone levels reaching 65.8 +/- 1.5 ng/ml (n = 12) after 3 wk of inductive photoperiod. Levels were maintained unchanged until 14 wk of exposure to long photoperiod, when spontaneous gonadal regression was observed. Under short daylengths, intact males exhibited regressed gonadal function with low plasma concentrations of testosterone: 5.4 +/- 1 ng/ml. To investigate the effect of olfactory bulb deprivation on gonadal responses to photoperiod, 12 males were bulbectomized (BX) during exposure to either long (n = 8, BX1) or short (n = 4, BX2) daylengths. In both groups of BX males, responses to long or short daylengths were maintained. However, the timing and the amplitude of gonadal responses to photoperiod were modified; BX males underwent a significant delay in testis development and also had reduced testosterone levels (53.3 +/- 2.3 ng/ml and 37.3 +/- 0.9 ng/ml for BX1 and BX2 groups, respectively). Moreover, BX males did not exhibit spontaneous gonadal regression after 14 wk of exposure to long daylengths, indicating that the photorefractory state did not appear, at least under our experimental conditions. In this primate, olfactory bulbs exert an important effect on the neuroendocrinological control of reproductive responsiveness to photoperiod.


Atrial Natriuretic Peptide: A Potential Early Therapy for the Prevention of Multiple Organ Dysfunction Syndrome Following Severe Trauma.
Trauma remains a tremendous medical burden partly because of increased expenditure for the management of multiple organ dysfunction syndrome (MODS) developed during hospital stay. The intestinal barrier injury continues to be a second insult resulting in MODS which currently lacks efficient strategies for prevention. Recent studies have uncovered multi-organ protective benefits of atrial natriuretic peptide (ANP) in cardiovascular disease. However, the role of ANP in the prevention of MODS following severe trauma has not been understood. In our laboratory study, 1-h infusion of exogenous ANP during hemorrhagic shock following severe trauma induced high-level expression of endogenous serum ANP after 24 h, this effect was related to the improved level of functional biomarkers in multiple organs. Such phenomenon has not been found in other laboratories. A thorough literature review consequently was performed to uncover the potential mechanisms, to appraise therapy safety, and to propose uncertainties. In severe trauma, short-term exogenous ANP therapy during hemorrhagic shock may promote sustained endogenous expression of ANP from intestinal epithelium through activating a positive feedback loop mechanism involving phospholipase C-γ1 and reactive oxygen species crosstalk. This feedback loop may prevent MODS through multiple signaling pathways. Administration of ANP during hemorrhagic shock is thought to be safe. Further studies are required to confirm our proposed mechanisms and to investigate the dose, duration, and timing of ANP therapy in severe trauma.


Attenuation of endocrine-exocrine pancreatic communication in type 2 diabetes: pancreatic extracellular matrix ultrastructural abnormalities.
Ultrastructural observations reveal a continuous interstitial matrix connection between the endocrine and exocrine pancreas, which is lost due to fibrosis in rodent models and humans with type 2 diabetes mellitus (T2DM). Widening of the islet-exocrine interface appears to result in loss of desmosomes and adherens junctions between islet and acinar cells and is associated with hypercellularity consisting of pericytes and inflammatory cells in T2DM pancreatic tissue. Organized fibrillar collagen was closely associated with pericytes, which are known to differentiate into myofibroblasts-pancreatic stellate cells. Of importance, some pericyte cellular processes traverse both the connecting islet-exocrine interface and the endoacinar interstitium of the exocrine pancreas. Loss of cellular paracrine communication and extracellular matrix remodeling fibrosis in young animal models and humans may result in a dysfunctional insulino-acinar-ductal-incretin gut hormone axis, resulting in pancreatic insufficiency and glucagon-like peptide deficiency, which are known to exist in prediabetes and overt T2DM in humans.


Movement of the sacroiliac joint during the Active Straight Leg Raise test in patients with long-lasting severe sacroiliac joint pain.
The Active Straight Leg Raise is a functional test used in the assessment of pelvic girdle pain, and has shown to have good validity, reliability and responsiveness. The Active Straight Leg Raise is considered to examine the patients' ability to transfer load through the pelvis. It has been hypothesized that patients with pelvic girdle pain lack the ability to stabilize the pelvic girdle, probably due to instability or increased movement of the sacroiliac joint. This study examines the movement of the sacroiliac joints during the Active Straight Leg Raise in patients with pelvic girdle pain. Tantalum markers were inserted in the dorsal sacrum and ilium of 12 patients with long-lasting pelvic girdle pain scheduled for sacroiliac joint fusion surgery. Two to three weeks later movement of the sacroiliac joints during the Active Straight Leg Raise was measured with radiostereometric analysis. Small movements were detected. There was larger movement of the sacroiliac joint of the rested leg's sacroiliac joint compared to the lifted leg's side. A mean backward rotation of 0.8° and inward tilt of 0.3° were seen in the rested leg's sacroiliac joint. The movements of the sacroiliac joints during the Active Straight Leg Raise are small. There was a small backward rotation of the innominate bone relative to sacrum on the rested leg's side. Our findings contradict an earlier understanding that a forward rotation of the lifted leg's innominate occur while performing the Active Straight Leg Raise.


Congenital chylothorax presenting as hydrops fetalis. A case report.
A case of congenital chylothorax presented as polyhydramnios and massive fetal edema. The diagnosis was suspected prior to delivery on the basis of ultrasonography. Ultrasound was helpful in localizing the fluid for postnatal thoracentesis. Congenital chylothorax is part of the differential diagnosis of nonimmune hydrops fetalis.


Development of host resistance to Fasciola hepatica after the elimination of primary infection with diamphenethide.
We studied the specificity of the individual developmental stages of Fasciola hepatica for evoking immune response of the host to reinfection with this parasite, whereby the primary infection was eliminated by a dose of 150 mg/kg diamphenethide administered in various intervals. In rats we observed a state of hypersensitivity demonstrated by retarded migration and growth of the flukes and the reduction in the number of sexually developed parasites. The changes were most marked, if the elimination of the immunizing infection followed 8-10 weeks after primary infection.


Gluteo-vaginal sinus formation complicating posterior intravaginal slingplasty followed by successful IVS removal. A case report and review of the literature.
Posterior intravaginal slingplasty (IVS) is a technique used for the treatment of apical prolapse. Type III meshes have been mostly used with this technique. In this article, a case of bilateral gluteo-vaginal sinus tract formation that complicated a posterior vaginal slingplasty with a type III mesh is presented. At 3 months follow-up, the patient complained for bulking through the vagina, continuous offensive vaginal discharge, and constant pain at the buttocks. She had prolapse recurrence, and there was defective healing at the gluteal entry points of the posterior IVS. Ten months after the initial surgery, she underwent a laparotomic subtotal hysterectomy and sacrocervicopexy with prolene type I mesh. At the same time, the posterior mesh was removed allowing the surgeon to discover communication of the canal of the mesh extending from gluteal incisions to the vagina epithelium. The sinus tract was managed surgically with excision of the surrounding tissues. There was no recurrence or other complications at 2 months follow-up.


[Biomechanical tests of a new scaffold for the cultivation of chondrocytes].
Scaffolds for the cultivation of chondrocytes are of increasing importance. So far, only little is known about their biomechanical properties. The present preliminary study addresses the biomechanical characteristics of a new collagen type I scaffold for the cultivation of chondrocytes. Human chondrocytes were amplified in a monolayer and then cultivated in a 3D-scaffold over a period of up to 6 weeks. The biomechanical tests addressed the properties under uniaxial compression including stiffness and viscoelastic characteristics (creep and retardation). The obtained values were normalized against the thickness of the specimens and expressed as ratios. In addition, we present histological and quantitative PCR results (for collagen type II and aggrecan). The maximum force (or penetration force) revealed its highest values after a period of seven days. At this time the median value was 40 mN/mm. In the following period, a marked drop of the values was observed (19.8 mN/mm). With respect to the creep properties, we did not find any major changes over the period of six weeks. The median values were between 0.24 and 0.29 mm/mm. There were no significant differences between the samples seeded with chondrocytes and those which served as controls. A re-expansion of the samples was found with median values between 0.026 and 0.049 mm/mm (retardation). However, the original thickness was not reached after a period of 30 seconds with relief of the strain. Again, major differences of the values with respect to the duration of cultivation were not observed. Light microscopy revealed collagen type II and proteoglycans only in the pericellular region. In this study not all of the biomechanical properties of the cultivated tissue were investigated. The limitation of the tests to stiffness and viscoelastic properties was reasonable in view of a potential routine use. In addition, it may facilitate a comparison between different matrix systems. In our study, the cultivation of cells within the collagen matrix did not alter the mechanical properties of the scaffold.


[Formation of two systems of conditioned reflexes with random alteration of stimuli].
Two heteromodal systems of secretory positive and inhibitory reflexes were elaborated in non-learned dogs to conditioned stimuli presented according to a four-digit table of random figures; then a third system was elaborated. All the systems were presented with one-day intervals in strict alteration (in a stereotype). It has been shown that the formation of a stereotype out of systems of secretory conditioned reflexes, organized at random, is characterized by an enhanced general functional state (tone) of the brain. A comparison of the results of the present work with previous investigations of simultaneous formation of two heteromodal rhythmical stereotypes leads to the conclusion that the structure of the systems in which the conditioned reflexes are formed is the major factor, not the structure of the reflexes.


Development of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Simultaneous Determination of 40 Drugs of Abuse in Human Urine: Application to Real Cases.
Drugs of abuse are constantly evolving, while new synthetized substances are constantly emerging to avoid regulations. However, traditional drugs such as cocaine and amphetamine are still two of the most consumed drugs in the world. It is important, therefore, to provide suitable multiresidue methods for determining a wide range of drugs for use in toxicological and forensic analyses. The aim of this study is to develop a method for determining several families of drugs of abuse, including classic drugs, new psychoactive substances and some of their metabolites, in urine by liquid chromatography-tandem mass spectrometry. Urine is one of the most common biological matrices used in drug analysis because of its easy collection and a wide window of detection. In this study, we used solid-phase extraction to remove interferences and extract analytes from urine. Four different mixed-mode cation-exchange commercial sorbents were evaluated. The best results, in terms of apparent recoveries, were achieved with one of the strong cationic sorbents, ExtraBond SCX. The method achieved detection limits from 0.003 to 0.500 ng/mL and quantification limits from 0.050 to 1.500 ng/mL, which are suitable for determining these compounds at the usual levels found in the urine of drug users. The applicability of this method was demonstrated by analyzing real urine specimens from women following a detoxification program. Our results showed that the drug most consumed was cocaine, since it was detected in most urine specimens together with its main metabolite, benzoylecgonine. The polyconsumption of drugs from different families was also observed in some urine samples analyzed.


The most used medicinal plants by communities in Mahaboboka, Amboronabo, Mikoboka, Southwestern Madagascar.
This paper reports a study undertaken in three remote communities (Mahaboboka, Amboronabo, Mikoboka), located in Sakaraha, Southwestern Madagascar. Not only villages are far away from sanitary infrastructures and doctors but drugs and consulting fees are unaffordable to villagers. They rely essentially on natural resources for health care as for most of rural areas in Madagascar. This paper aims to document medicinal plants used by communities in Sakaraha and to present the most important plant species used in traditional medicine. Semi - structured interview was conducted within 214 informants in 34 villages of the study area. Different ailments encountered in the site study were classified in various categories. For data analysis, frequency of citation (Fq), Informant Consensus Factor (Fic), Fidelity Level (FL) and Use Value (UV) were assessed to find agreement among informants about the use of plants as remedies. Mann-Whitney, Kruskall-Wallis and Spearman correlation tests were performed to determine use of medicinal plants following social status of informants. A total of 235 medicinal plant species belonging to 198 genera and 75 families were inventoried. The richest families in species used for medicinal purposes were: Fabaceae, Apocynaceae, Rubiaceae, Euphorbiaceae, Asteraceae, and Poaceae. Plant species cited by informants were used to treat 76 various ailments classified in 13 categories. Leaves and leafy twigs were the most used plant parts and decoction was the mostly cited way of preparation of these medicinal plants species. In average, local people cited 6.7 ± 6.03 medicinal taxa among them, Cedrelopsis grevei is the most cited medicinal plants (Fq. 0.28). With Cedrelopsis grevei (UV = 0.48), Henonia scoparia (UV = 0.43) are mostly used species. Leonotis nepetifolia (FL = 96%) and Strychnos henningsii (FL = 92%) are plant species claimed by high percentage of informants to treat the Digestive System Disorder. This study highlighted that medicinal plants used by people from three communities in the Southwestern Madagascar are diverse. These plants species ensure care to all family members including babies, children, mothers and adult people. Through this study, newly reported medicinal plants were identified for further work.


Therapeutic Properties and Biological Benefits of Marine-Derived Anticancer Peptides.
Various organisms exist in the oceanic environment. These marine organisms provide an abundant source of potential medicines. Many marine peptides possess anticancer properties, some of which have been evaluated for treatment of human cancer in clinical trials. Marine anticancer peptides kill cancer cells through different mechanisms, such as apoptosis, disruption of the tubulin-microtubule balance, and inhibition of angiogenesis. Traditional chemotherapeutic agents have side effects and depress immune responses. Thus, the research and development of novel anticancer peptides with low toxicity to normal human cells and mechanisms of action capable of avoiding multi-drug resistance may provide a new method for anticancer treatment. This review provides useful information on the potential of marine anticancer peptides for human therapy.


Response of the Chinese Soft-Shelled Turtle to Acute Heat Stress: Insights From the Systematic Antioxidant Defense.
Understanding the responses of animals to acute heat stress can help to reveal and predict the effect of more frequent extreme hot weather episodes on animal populations and ecosystems in the content of global climate change. Antioxidant defenses can help to protect animals against oxidative stress caused by intense temperature variation. In the present study, systematic antioxidant responses to acute heat stress (Δ15°C and maintained for 12 h) and subsequent recovery were assessed by evaluating gene transcript levels and relative enzyme activities in tissues of Pelodiscus sinensis, a subtropical freshwater turtle. Targets included nuclear factor erythroid 2-related factor 2 (Nrf2, the upstream transcription factor), antioxidant enzymes, and the glutathione (GSH) and ascorbic acid (AA) systems. Results showed three main patterns of expression change among antioxidant genes: (1) gene expression of Mn-superoxide dismutase (Mn-SOD), glutathione peroxidase 4 (GPx 4), and catalase (CAT) increased in response to heat stress or recovery in the liver; (2) transcripts of most genes did not change in brain, liver, and kidney of P. sinensis; and (3) expression of several GST isoforms were affected by heat stress or recovery in brain and kidney. However, relative enzyme activities involved in antioxidant defense were little affected by acute heat stress and recovery, indicating a relatively conservative antioxidant response in P. sinensis. Furthermore, results for malondialdehyde (MDA) levels indicated that acute heat stress and recovery did not cause a net increase in oxidative damage in turtle tissues and, in particular, MDA levels in spleen decreased along with increased splenic ascorbic acid concentration. Overall, the present study revealed a conservative antioxidant response in P. sinensis, which may be indicative of a high basal stress tolerance and relate with adaptation to climate change in freshwater turtles.


Trajectories of Device-Measured Physical Activity During Early Childhood and Its Determinants: Findings From the 2015 Pelotas (Brazil) Birth Cohort Study.
The objective was to describe trajectories of physical activity (PA) measured by accelerometry during early childhood and to test associations with sociodemographic, gestational, maternal, and perinatal determinants. Data from 1798 children from the 2015 Pelotas (Brazil) Birth Cohort were analyzed. PA was measured with wrist accelerometers at 1, 2, and 4 years. PA trajectories were estimated using group-based trajectory modeling, and associations with determinants were tested using Poisson regression with robust variance. Two trajectories were identified: Moderate and high PA, both showing a linear increase in PA in the first years but differing in volume. Girls (prevalence ratio [PR]: 0.91; 95% confidence interval [CI], 0.88-0.94), highly educated mothers (PR: 0.93; 95% CI, 0.88-0.97), and high birth weight children (PR: 0.91; 95% CI, 0.85-0.97) showed less probability of high PA trajectory. Birth order ≥3 (PR: 1.06; 95% CI, 1.01-1.11) was associated with higher likelihood of high PA trajectory. Children showed an increase in PA during the first years, with 2 trajectories that differ in PA levels. Female sex, high maternal schooling, and high birth weight reduced the probability of having a high PA trajectory, while higher birth order increased this probability. These characteristics should be considered when planning PA interventions for children in early childhood.