Aetiology and management of extrahepatic portal vein obstruction in children: King's College Hospital experience.
To study a single-centre experience of the management of extrahepatic portal vein obstruction (EHPVO) in children during the last 3 decades. The medical records of 108 children (67 male, median age 4.75 years, range = 1 day-16.3 years) presenting with EHPVO between 1979 and 2005 were reviewed retrospectively. Extended prothrombotic screening performed in 30 patients revealed low protein C activity (6 patients), low free protein S (2), and a positive lupus anticoagulant (1); factor V Leiden mutations and the JAK2V617F mutation were not identified. Associated congenital anomalies were found in 26 of the 108 children (24%). Clinical presentation included splenomegaly in 98 (91%) and ascites in 3 (3%). Elevation of liver enzymes and prolonged international normalized ratio were seen in 13 (12%) and 14 (13%) children, respectively. Haematological parameters of hypersplenism were present in 13 (12%). Bleeding occurred in 83 (77%) patients with a median age of 4.58 (0.02-16.37) years. On first endoscopy, oesophageal varices were present in 92 patients; of those subjects, 70 (76%) received sclerotherapy, 5 (5%) had band ligation, and 16 (17%) received both. Complications of endoscopy occurred in 34 (37%) patients: oesophageal ulcers in 16, oesophageal stricture in 10, both in 7, and erosive gastritis in 1. Seventeen (16%) children underwent shunt surgery for uncontrolled bleeding at a median age of 9.7 (5.2-23.7) years. The aetiology of EHPVO in the majority of patients remains unknown. Sclerotherapy and banding are effective treatments for bleeding varices with good long-term outcome. Procoagulant state is an infrequent cause of EHPVO in children.


Molecular genetics of ornithine decarboxylase in human tumor cells.
As the molecular biology of mammalian ornithine decarboxylase is coming of age, more and more interesting features of this unique protein are being uncovered. Ornithine decarboxylase belongs to those 20 or so enzymes or binding proteins, the genes for which are easily amplified under suitable selection pressure. This also applies to the human enzyme. Gene amplification of ornithine decarboxylase is not the only means to acquire resistance to inhibitors of the enzyme, as its overproduction can occur through an enhanced transcription or even through a more efficient translation of normal mRNA amounts. The resistance in human tumors can likewise be acquired by activating other enzymes, such as arginase. In contrast to the multigene family in mouse, it appears that in the human genome only two ornithine decarboxylase genes are present mapping to the chromosomes 2 and 7. Out of these, at least the sequences in the short arm of chromosome 2 are transcriptionally active and amplifiable. Human ornithine decarboxylase also belongs to those proteins which show a positive correlation between gene hypomethylation and expression. The genes of human ornithine decarboxylase are methylated to varying extents and distinct hypomethylation is seen in certain malignant cells, most notably human lymphatic leukemia cells. The human ornithine decarboxylase gene is easily transferrable into other mammalian cells in which it is efficiently expressed. Some indirect evidence seems to indicate that overproduction of ornithine decarboxylase may confer a growth advantage to mammalian cells. A further piece of information suggesting an important role for the enzyme is the fact that the structure of the ornithine decarboxylase gene is extremely well conserved during evolution. This does not apply only to the coding region but also to the overall organization of the gene itself.


The development of language-like communication without a language model.
Deaf children who are unable to acquire oral language naturally and who are not exposed to a standard manual language can spontaneously develop a structured sign system that has many of the properties of natural spoken language. This communication system appears to be largely the invention of the child himself rather than of the caretakers.


Allosteric modulation of muscarinic acetylcholine receptors.
Five subtypes of muscarinic acetylcholine receptors have been identified in mammalian tissues, but the selectivity of ligands that are active at these receptors is low. It is possible, however, that selective compounds may be developed by targeting their allosteric site(s). Important new insights into the mechanism of allosteric control of muscarinic receptors have been obtained recently in investigations of the allosteric effects of neuromuscular blockers, and competition between ligands for the allosteric binding site has now been demonstrated. It is now apparent that the binding site for most allosteric ligands is close to the binding site for acetylcholine but that it is located at a more extracellular position. Stanislav Tucek and Jan Proska discuss the pharmacological implications of ligand interaction at these two sites and the therapeutic possibilities.


Untypically mild phenotype of a patient suffering from Sanfilippo syndrome B with the c.638C>T/c.889C>T (p.Pro213Leu/p.Arg297Ter) mutations in the NAGLU gene.
Sanfilippo syndrome B (or mucopolysaccharidosis type IIIB [MPS IIIB]) is a severe inherited metabolic disorder caused by mutations in the NAGLU gene, encoding α-N-acetylglucosaminidase. Dysfunction of this enzyme results in impaired degradation of heparan sulfate, one of glycosaminoglycans, and accumulation of this complex carbohydrate in lysosomes. Severe symptoms occurring in this disease are related to progressive neurodegeneration and include extreme hyperactivity, sleeping problems, aggressive-like behavior, reduced fear, and progressive mental and cognitive deterioration. No cure is currently available for Sanfilippo disease. Clinical characterization of the patient's symptoms has been performed. Biochemical analyses included glycosaminoglycan level determination and measurement of α-N-acetylglucosaminidase activity. Molecular analyses included exome sequencing and detailed analysis of the NAGLU gene. Psychological tests included assessment of attention, communication and behavior. We describe a patient with an untypically mild phenotype, who was diagnosed at the age of 13 years. Many cognitive, communication, and motoric functions were preserved in this patient, contrary to vast majority of those suffering from MPS IIIB. The patient is a compound heterozygote (c.638C>T/c.889C>T) in the NAGLU gene, and relatively high residual activity (about 25%) of α-N-acetylglucosaminidase was measured in serum (while no activity of this enzyme could be detected in dry blood spot). We suggest that the mild phenotype might arise from the partially preserved function of the mutant enzyme (p.Pro213Leu), suggesting the genotype-phenotype correlation in this case.


Age-dependent increases of DNA adducts (I-compounds) in human and rat brain DNA.
Brain DNA from 20 humans ranging in age from neonatal to 100 years was analyzed by the nuclease P1-enhanced version of the 32P-postlabeling assay for bulky covalently modified nucleotides. A reproducible pattern of three 32P-labeled spots was obtained by thin-layer chromatography followed by autoradiography. Two of these spots increased with age (Mann-Whitney U-test; P < 0.001; comparison of ages < or = 60 years and ages > 60 years). Thus, these spots met the definition of I-compounds. Rat brain DNA exhibited the same two I-spots, whose intensities also increased with animal age (1, 4, and 10 months). In humans, considerable individual variation of brain I-compound levels was observed, especially at ages > 60 years, presumably reflecting environmental, life-style, or genetic factors. This variation was not noted for brain DNA of laboratory rats. Thus, human brain DNA undergoes progressive covalent modifications with aging.


The use of folding patterns in the prediction of protein topologies.
We proved previously that the distribution of formation energies which may be associated with the predicted secondary structures (or nuclei) is specific of the folding process (Busetta, B. 1986, Biochim. Biophys. Acta 870, 327-338). We developed a new predictive algorithm for protein topologies, based on the search of standard 'folding patterns'. In another manner, the strongest predicted nuclei are used to propose a fast sequence-alignment process which is efficient for distantly related proteins.


Changes in cholinesterase activity of muscle after crushing the sciatic nerve of rats.
The subcellular distribution of cholinesterase (ChE) was studied in the gastrocnemius muscle of rats after strong or weak nerve crushing. The ChE activities of muscle were decreased to a greater extent by strong crushing than by weak crushing. In particular, the ChE activity of the fraction containing sarcoplasmic reticulum was most greatly decreased. These results suggest that the change in the ChE activity of the microsomal fraction most finely reflects the strength of nerve crushing.


The postnatal development of functional properties of central vestibular neurons in the rat.
The postnatal development of the responses of rat central vestibular neurons to horizontal angular acceleration was studied in the time and frequency domain. The resting discharge was very low and irregular during the first postnatal days, increased gradually and became more regular throughout the first month and reached adult values approximately by the end of the first month. The relative distribution of type I and type II units was the same in all age groups. Threshold for frequency increase to angular acceleration and sensitivity of unit responses became lower and higher, respectively, as time elapsed after birth. Adult values were reached approximately by the end of the first month. There was a slight tendency towards shorter time constants and smaller phase lags in one-month-old animals when compared with the younger animals. The results are discussed in conjunction with similar work performed in vestibular afferents and correlated with known morphological and behavioral studies.


[Sex education and education for family life in adolescents].
A program of education of college girls and boys between 14--18 years of age for sexual and family life is going on in the Hungarian secondary school. There are 20 lectures within 4 years. The goal and the subjects of the lectures specially designed for each semester are outlined by the author.


Fatty acid hydroxylation in rat kidney cortex microsomes.
Rat kidney microsomes have been found to catalyze the hydroxylation of medium-chained fatty acids to the omega- and (omego-1)-hydroxy derivatives. This reaction, which requires NADPH and molecular oxygen, is a function of monooxygenase system present in the kidney microsomes, containing NADPH-cytochrome c reductase and cytochrome P-450K. NADH is about half as effective as an electron donor as NADPH and there is an additive effect in the presence of both nucleotides. Cytochrome P-450K absorbs light maximally at 452-3 nm, when it is reduced and bound to carbon monoxide. The extinction coefficient of this complex is 91 mM(-1) cm(-1). Electrons from NADPH are transferred to cytochrome P-450K via the NADPH-cytochrome c reductase. The reduction rate of cytochrome P-450K is stimulated by added fatty acids and the reduction kinetics reveal the presence of endogenous substrates bound to cytochrome P-450K. Both cytochrome P-450K concentration and fatty acid hydroxylation activity in kidney microsomes are increased by starvation. On the other hand, phenobarbital treatment of the rats has no effect on either the hemoprotein or the overall hydroxylation reaction and 3,4-benzpyrene administration induces a new species of cytochrome P-450K not involved in fatty acid hydroxylation. Cytochrome P-450K shows, in contrast to liver P-450, high substrate specificity. The only substances forming enzyme-substrate complexes with cytochrome P-450K are the medium-chained fatty acids and certain derivatives of these acids. The chemical requirements for substrate binding include a carbon chain of medium length and at the end of the chain a carbonyl group and a free electron pair on a neighbouring atom. The distance between the binding site for the carbonyl group and the active oxygen is suggested to be in the order of 16 A. This distance fixes the ratio of omega- and (omega-1)-hydroxylated products formed from a certain fatty acid by the single species of cytochrome P-450K involved. The membrane microenvironment seems also to be of importance for the substrate specificity of cytochrome P-450K, since removal of the cytochrome from the membrane lowers its binding specificity to some extent. A comparison between the liver and kidney cytochrome P-450 systems suggests that the kidney cytochrome P-450K system is specialized for fatty acid hydroxylation.


Multipolar passive cloaking by nonradiating anapole excitation.
In this paper, we demonstrate the relation between cloaking effect and its nonradiating state by considering the destructive multipolar interaction between near-field scattering by bare object and surrounding coating located in its proximity. This cloaking effect is underpinned by anapole mode excitation and it occurs as destructive interference between the electric dipole moment, generated by a bare object (here a central metallic scatterer) and the toroidal moment, formed inside the cloak (a surrounding cluster of dielectric cylinders). Numerical results show how a cloaking effect based on the formation of the anapole mode can lead to an overall nonradiating metamolecule with all-dielectric materials in the coating region.


Macroporous natural capsules extracted from Phoenix dactylifera L. spore and their application in oral drugs delivery.
Macroporous natural sporopollenin exine capsules (SEC) were extracted from date palm (Phoenix dactylifera L.) and coated by natural polymer composite (carboxymethyl cellulose with epichlorohydrin). The polymer coated exine capsules (PCEC) were used in in-vitro investigations for controlled delivery of paracetamol. SEC, PCEC, and drugs loaded capsules (PCEC-PAR) were characterized by scanning electron microscope (SEM), surface area (BET), Fourier-transform infrared (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The length of SEC was found to be 20-20.5 μm, and the pore sized was 50-135 nm, as measured using SEM. The studies revealed that maximum loading of the drug was at pH 6.0 (97.2%, with 50 mg mL(-1)). The results indicate that by increasing the pH from 1.4 to 7.4, the cumulative release rates of paracetamol in physiological buffer solution (PBS) is more than two times as in simulated gastric fluid (SGF). In addition, the in-vitro toxicity of PCEC against Caco-2 cells was tested by the 3-[4,5-dimethylthiazole-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay, and the results revealed that PCEC are biocompatible materials. The overall results encourage further studies on the clinical use of PCEC as drug carriers.


Echocardiographic prevalence of rheumatic heart disease in Indian school children using World Heart Federation criteria - A multi site extension of RHEUMATIC study (the e-RHEUMATIC study).
Rheumatic heart disease (RHD) continues to be major public health burden in developing world. Echocardiographic screening in school children has shown that subclinical RHD cases are several times more than clinical cases. Recent reports have used World Heart Federation (WHF) criteria. Objective of present study was to determine RHD prevalence using WHF criteria in Indian children. Children (5-15years) from randomly selected schools across four sites were included. After focused clinical evaluation, echocardiography was performed using WHF criteria in all children. Images/loops of abnormal cases were analyzed independently by an additional experienced cardiologist. Children with murmur and confirmatory echocardiography were categorized 'clinical RHD'; those with abnormal echocardiography alone were labeled 'subclinical RHD'. Among 16,294 children included, mean age was 10.8 ± 2.9years; 55.1% were males; 11,405 (70%) were from rural areas and 3978 (24.4%) were from government schools. We detected RHD by echocardiography in 125 children [prevalence: 7.7/1000 (95% CI 6.3, 9.0)]. Borderline RHD was present in 93 children (5.7/1000, 95% CI 4.6, 6.9), definite RHD in 32 (2/1000, 95% CI 1.2, 2.6), and clinical RHD in six [0.36/1000, 95% CI: 0.1-0.7]. On univariate analysis, older age, female gender, and higher waist circumference were associated while on multivariate analysis, older age (OR 1.18, 95% CI: 1.09, 1.26) and female gender (OR 1.61, 95% CI: 1.13, 2.3) were associated with RHD. RHD prevalence varies in different parts of India. Echocardiographic prevalence is several times higher than clinical and underscores importance of echocardiographic screening in community.


Glycemic Variability in Patients with Type 2 Diabetes Mellitus (T2DM): The Role of Melatonin in a Crossover, Double-Blind, Placebo-Controlled, Randomized Study.
Glycemic variability in patients with type 2 diabetes mellitus (T2DM) may be associated with chronic complications of the disease. Melatonin is a hormone that plays a crucial role in biological rhythms. Previous studies have indicated that individuals with T2DM often exhibit reduced melatonin production. In this study, our objective was to investigate whether nighttime melatonin supplementation could mitigate glycemic variability in these patients. Crossover, double-blind, placebo-controlled, randomized study. A total of 30 patients were enrolled in this study. The study included 15 participants who followed the intervention sequence of placebo (7 days)-washout (7 days)-melatonin (3 mg) (7 days), and another 15 participants who followed the sequence of melatonin (3 mg) (7 days)-washout (7 days)-placebo (7 days). During the final three days of the first and third weeks, the participants measured their pre- and postprandial capillary blood glucose levels. This study was reported according to the CONSORT 2010 statement: extension to randomized crossover trials. There was a significant absolute difference in the breakfast blood glucose levels (p = 0.016) on Day 7. The use of melatonin determined a greater positive variation between pre- and postprandial glycemia than the placebo. The difference in glycemic amplitude between post-dinner Day 6 and pre-breakfast Day 7 was also significantly higher in the melatonin group (p = 0.032). Melatonin increased glycemic variability in individuals with type 2 diabetes mellitus (T2DM). These results can be attributed to the residual daytime effects of melatonin, prospective proximal effects, and damage to the prospective distal effects of exogenous melatonin. Therefore, caution should be exercised when administering melatonin supplementation to patients with T2DM, taking into consideration factors such as dosage, duration of use and genetic considerations.


SIRT2 and FOXO3a expressions in the cerebral cortex and hippocampus of young and aged male rats: antioxidant and anti-apoptotic effects of melatonin.
Melatonin has antioxidant, anti-apoptotic and anti-aging effects in the brain. Sirtuin2 (SIRT2) accumulates in the central nervous system with aging, and its inhibition appears to be protective in aging and aging-related neurodegenerative diseases. Forkhead Box-class O3a (FOXO3a) transcription factor is one of the main targets of SIRT2, and SIRT2-mediated FOXO3a deacetylation is closely related to aging, oxidative stress, and apoptosis. This study aimed to investigate the effects of melatonin on SIRT2 and FOXO3a expressions in the cerebral cortex and hippocampus of aged rats. Young (3 months, n = 18) and aged (22 months, n = 18) male Wistar rats were divided into control (4% DMSO-PBS, sc, for 21 days), melatonin (10 mg/kg, sc, for 21 days) and salermide (1 mM; 25 μl/100 g bw, ip, for 21 days) groups. SIRT2, FOXO3a, Bcl-2, Bax and Bim expressions in the cerebral cortex and hippocampus were demonstrated by Western blotting. SIRT2 and FOXO3a protein levels were also measured by a sandwich ELISA method. Oxidative stress index (OSI) was calculated by measuring total oxidant status (TOS) and total antioxidant status (TAS). Aging increased SIRT2, FOXO3a, Bim (only in the cerebral cortex), Bax (only in the hippocampus), TOS, and OSI, while decreasing Bcl-2, Bcl-2/Bax and TAS in both brain regions. Melatonin decreased SIRT2, FOXO3a, oxidative stress parameters and pro-apoptotic proteins, while increasing TAS, Bcl-2 and Bcl-2/Bax, more specifically in the hippocampus of the aged brain. Our results indicate that inhibition of SIRT2 and FOXO3a expressions appears to be involved in the protective effects of melatonin in the hippocampus of aged rats.


Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy.
Effective immunosuppression is an essential pre-requisite for successful organ transplantation and improvements in outcome after transplantation have to a large extent been dependent on developments in immunosuppressive therapy. Here we provide an overview of the different immunosuppressive agents currently used in solid organ transplantation. A historical perspective on the development of immunosuppression for organ transplantation is followed by a review of the individual agents, with a focus on their mechanism of action and efficacy. Steroids, anti-proliferative agents (azathioprine and mycophenolate), calcineurin inhibitors (cyclosporine and tacrolimus) and TOR inhibitors (sirolimus and everolimus) are discussed along with both polyclonal and monoclonal antibody preparations. Many of the key clinical trials that underpin current clinical usage of these agents are described and side-effects of the different agents are highlighted. Finally, a number of newer agents still in various stages of clinical development are briefly considered.


Spinal epidural cavernous haemangioma: a case report and review of literature.
A case report of purely epidural cavernous haemangioma with MRI appearance and pathological features. To present a rare case of extradural mass with differential diagnosis. Delhi, India. A 55-year-old man presented with progressive weakness and diminished sensation in both lower limbs. MRI demonstrated a pure extradural mass with no bony invasion. Histopathology of the lesion revealed a typical cavernous haemangioma. The patient showed significant improvement after surgery. Radiological presentation could be confusing in a purely epidural cavernous haemangioma. Awareness of the characteristics of the lesion will facilitate diagnosis and treatment of the lesion.


Etoposide-resistant human colon and lung adenocarcinoma cell lines exhibit sensitivity to homoharringtonine.
Human colon (HCT116/VP48) and lung (A549B/VP29) adenocarcinoma cell lines selected for resistance to etoposide exhibited modified patterns of multi-drug resistance (MDR) that included a differential sensitivity to other DNA topoisomerase II inhibitors and to the plant alkaloids homoharringtonine, vinblastine, and vincristine. The resistance and cross-resistance drug phenotype of the A549B/VP29 cell line was different from that of the HCT116/VP48 cell line. The HCT116/VP48 cell line was 50-fold resistant to etoposide and 30-fold resistant to teniposide. The degree of resistance to other DNA topoisomerase II inhibitors was of a lower magnitude: Adriamycin, 9-fold; daunomycin, 3-fold; 4'-[(9-acridinyl)-amino]-methanesulfone-m-anisidide (m-AMSA), 3-fold; and actinomycin D, 6-fold. The HCT 116/VP48 cell line exhibited a 7-fold resistance to vincristine and a 2-fold resistance to vinblastine but was sensitive to homo-harringtonine. The A549B/VP29 cell line was 5-fold resistant to etoposide and 2-fold resistant to teniposide. The A549B/VP29 cell line exhibited a 2-fold resistance to Adriamycin but was sensitive to daunomycin and showed a 3-fold resistance to m-AMSA. This cell line was sensitive to actinomycin D. The A549B/VP29 cell line was 2-fold resistant to vinblastine and sensitive to homoharringtonine. Both cell lines (HCT116/VP48 and A549/VP29) exhibited no amplification of the human mdr1 DNA sequence, the 4.3-kb P-glycoprotein transcript, or the membrane P-glycoprotein. The sensitivity of cells exhibiting an MDR phenotype not mediated by P-glycoprotein suggests a potential use for homoharringtonine in treating tumors with this type of drug resistance.


Natural human chimeras: A review.
The term chimera has been borrowed from Greek mythology and has a long history of use in biology and genetics. A chimera is an organism whose cells are derived from two or more zygotes. Recipients of tissue and organ transplants are artificial chimeras. This review concerns natural human chimeras. The first human chimera was reported in 1953. Natural chimeras can arise in various ways. Fetal and maternal cells can cross the placental barrier so that both mother and child may become microchimeras. Two zygotes can fuse together during an early embryonic stage to form a fusion chimera. Most chimeras remain undetected, especially if both zygotes are of the same genetic sex. Many are discovered accidently, for example, during a routine blood group test. Even sex-discordant chimeras can have a normal male or female phenotype. Only 28 of the 50 individuals with a 46,XX/46,XY karyotype were either true hermaphrodites or had ambiguous genitalia. Blood chimeras are formed by blood transfusion between dizygotic twins via the shared placenta and are more common than was once assumed. In marmoset monkey twins the exchange via the placenta is not limited to blood but can involve other tissues, including germ cells. To date there are no examples in humans of twin chimeras involving germ cells. If human chimeras are more common than hitherto thought there could be many medical, social, forensic, and legal implications. More multidisciplinary research is required for a better understanding of this fascinating subject.


A topographic study of Helicobacter pylori density, distribution and associated gastritis.
The topographic distribution and density of Helicobacter pylori and associated gastritis in the stomach were studied in order to determine which biopsy sites are likely to provide the maximum yield so as to reduce the fallacious results due to sampling error. Fifty patients with upper gastrointestinal symptoms were studied. Eleven gastric biopsies from predetermined sites were obtained and subjected to ultra-rapid urease test, imprint cytology and histology. Haematoxylin and eosin stain was used for defining gastritis and other associated histopathological details. Loeffler's methylene blue stain was used to confirm the presence of H. pylori in imprint smears and histological sections. All 50 patients had H. pylori infection and evidence of chronic gastritis at one or more of the 11 biopsy sites. Maximum and minimum percentage positivity were observed at A3 (antral lesser curvature) and B4 (corpus greater curvature), respectively. Various sites in decreasing order of percentage positivity were A3 > A2 > A1 > A4 > B3 > B1 > A5 > B6 > B5 > B2 > B4. Among the biopsies obtained from the corpus, B3 (corpus lesser curvature) was the site with maximum positivity. A3 and B4 had a statistically significant difference in percentage positivity (P < 0.0001) for H. pylori and gastritis. The maximum and minimum density scores of H. pylori and gastritis were found in A3 and the B4, respectively. A3 had a significantly higher (P < 0.0001) mean density score than any other site in the stomach. The difference in the grading of H. pylori between A3 and B3 (sites of maximum positivity in antrum and corpus) was statistically significant (P < 0.0001). A statistically significant (P < 0.001) positive correlation between increasing grades of H. pylori and gastritis was observed at the site of maximum density. Eighty per cent of the patients had antral predominant gastritis and in 82%, H. pylori was predominantly observed in antral biopsies. It is concluded that two biopsies taken from A3 are sufficient for confirmation of presence of H. pylori and associated gastritis for initiation of treatment. However, additional biopsies from B3 will help in deciding the topographic pattern of gastritis.


Proteins at polysaccharide-based biointerfaces: A comparative study of QCM-D and electrokinetic measurements.
Controlling protein adsorption on biomaterial surfaces requires a thorough understanding of interfacial phenomena. Proteins adhering after implantation influence successful biointegration. Deciphering adsorption mechanisms at biointerfaces is crucial and of high interest. Here, a combination of time-resolved in situ electrokinetic measurements and quartz crystal microbalance with dissipation monitoring (QCM-D) was employed to understand the adsorption phenomena of blood proteins at thin layers of polysaccharide-based biointerfaces. Adsorption kinetics of bovine serum albumin (BSA), fibrinogen (Fg), and γ-globulin (γG) was studied on polydimethylsiloxane (PDMS) coatings functionalised with chitosan-surfactant complex and hyaluronic acid. The functionalised surfaces show a suppressed protein affinity compared to hydrophobic PDMS. Fg exhibits peculiar adsorption behaviour on PDMS, stemming from the highly oriented end-on adsorption with freely moving α chains. BSA demonstrates arbitrary surface orientation, while γG shows preferential surface orientation on PDMS, exposing a higher density of cationic moieties. The combination of the mentioned techniques proved beneficial for the investigation of interactions, orientations, and changes at biointerfaces in real-time. The approach is versatile and promising where research on surfaces and interfaces is in high demand.


Acid-secretory effects of pentagastrin, histamine, urecholine, DBcAMP, and cBMP in isolated stomachs of fed and fasted rats.
Pentagastrin, histamine, urecholine, DBcAMP, and cGMP were all potent stimulants of acid secretion in the isolated stomach of the fed rat. With the exception of histamine and cGMP, all of these compounds were inactive when the stomach of the fasted rat was used. Pentagastrin was most effective when given on the serosal surface while histamine was equally potent whether it was added to the mucosal or serosal surface of the isolated stomach. The test would appear to be a relatively simply, but effective system for studying the basic mechanisms of action of several important secretagogues in the rat.


[Fulminant acute kidney injury after cholecystectomy in a 45-year-old female patient].
A cholecystectomy was carried out on a 45-year-old female patient with fever, myalgia and right upper abdominal pain because of a suspected cholecystitis. Postoperatively acute kidney injury occurred. A comprehensive medical history taken later revealed a presumed occupational contact to rodents. Serological testing detected a recent infection with Dobrava-Belgrade hantavirus. The kidney function normalized with supportive therapeutic measures. Hantavirus infection should be considered in the differential diagnosis of acute kidney injury combined with fever, myalgia and abdominal pain.


Partial attenuation of dentate granule cell evoked activity by the alternative substrates, lactate and pyruvate: evidence for a postsynaptic action.
Granule cell field potentials were evoked by stimulation of the perforant path of superfused hippocampal slices. Replacing the glucose in the superfusion medium with pyruvate (10 mM) or lactate (10 mM) attenuated the field potentials, significant decreases occurring in both the population spike and the population EPSP. Usually, a new steady state level of evoked activity was established which could be maintained for at least 20 min. Input-output analyses (EPSP vs stimulus strength, population spike vs EPSP) were performed using variable stimulus strengths on slices superfused with control or test media (under steady state conditions). At higher stimulus strengths the rate of rise of population EPSP was significantly lower for a given stimulus strength when pyruvate or lactate replaced glucose. However, the threshold stimulus intensity required to evoke a population EPSP was the same under all conditions. EPSP/population spike relationships were also analyzed under control and test conditions. Pyruvate, but not lactate, increased the threshold EPSP required to generate a population spike. Neither substrate significantly affected the incremental change in EPSP associated with a given increase in the population spike. It is argued that lactate and pyruvate attenuate granule cell evoked activity solely by postsynaptic actions. Lactate and pyruvate both appear to affect the summation of EPSPs; pyruvate may also affect the process of granule cell discharge.


Materials and device design for advanced phototherapy systems.
Phototherapy has recently emerged as a promising solution for cancer treatment due to its multifunctionality and minimal invasiveness. Notwithstanding the limited penetration depth of light through skin, the ability of photopharmaceutical device systems to deliver light to desired lesions is important. The device system deploys advanced biocompatible materials and fabrication technologies for electronics, and eventually enables more efficient phototherapy. In this review, we focus on diverse optical electronics to illuminate the lesion site with light. Then, moving on to the phototherapy, we highlight photo-thermal therapy with light absorbing materials, photo-activated chemotherapy with light sensitive materials, and photo-dynamic therapy using photosensitizers. Furthermore, we introduce a drug delivery system that can deliver these photopharmaceutical agents spatiotemporally to the tumor site. To this end, we provide a general overview of materials and devices for phototherapy and discuss critical issues and pending limitations of such phototherapy.


Fabrication of CdS Frame-in-Cage Particles for Efficient Photocatalytic Hydrogen Generation under Visible-Light Irradiation.
The design of advanced structures for semiconductor photocatalysts is an effective approach to enhance their performance toward solar-to-chemical energy conversion. Hollow and frame-like structures show advantageous features for photocatalytic reactions with enlarged surface area, shortened charge-transfer distance, promoted light-absorption ability, and enhanced mass-transfer capability. Here, a facile two-step sulfidation strategy is developed to fabricate unique CdS frame-in-cage particles for photocatalytic hydrogen generation. Cd-based Prussian blue analog (Cd-PBA) cubes are first converted to Cd-PBA cube-in-CdS cage particles, which are further transformed to CdS frame-in-cage particles. Benefiting from the novel frame-in-cage structure, the obtained CdS photocatalyst exhibits high activity under visible-light irradiation with the hydrogen generation rate of 13.6 mmol h-1 g-1 , which is much enhanced compared with those of the CdS cubes and cages.


Pain assessment by patients and nurses, and nurses' notes on it, in early acute myocardial infarction. Part I.
Pain is a multi-dimensional phenomenon unique to each individual. Most of the research to date on acute pain has focused on oncology, medical and surgical patients. This pilot study was designed to explore the issues of pain assessment by patients and nurses in acute myocardial infarction, and the nurses' subsequent documentation of the pain assessment. Three research instruments were chosen to elicit the information required: A demographic questionnaire was constructed to elicit relevant data on patients and nurses. The Short Form McGill Pain Questionnaire (SFMPQ) was used to measure the quality and quantity of the patient's pain as perceived by the patient and nurse in a myocardial infarction situation. The Chart Audit Information Form (CAIF) was chosen to extract specific information from the nursing notes on the pain experience as recorded by the nurse. A convenience sample of patients comprised 10 males and 5 females. The nursing population comprised a convenience sample of 8 registered nurses holding a recognised coronary care course certificate. The pilot study was conducted in a coronary care unit (CCU) in a large teaching hospital in Dublin, Ireland. The data generated from the SFMPQ and the CAIF were coded prior to computerisation. Descriptive statistics were used to analyse the data. The findings of this pilot study indicated that nurses underestimated the patient's pain in 46% of myocardial infarction situations and overestimated in 13% of them. Furthermore, results indicated that while the majority of nurses documented location and verbal statements of pain, the documentation of quality, intensity and duration of pain was inadequate.(ABSTRACT TRUNCATED AT 250 WORDS)


Unusual gold(I)-catalyzed isomerization of 3-hydroxylated 1,5-enynes: highly substrate-dependent reaction manifolds.
[reaction: see text] The gold(I) isomerization of diversely substituted 3-hydroxylated enynes has led to the discovery of three new unreported skeletal rearrangements furnishing structures such as alkylidene-cyclopentenes, cyclohexadienes or alpha,beta-unsaturated aldehydes under very mild conditions.


Intrinsic vasoactive intestinal polypeptide (VIP)-containing neurons in the baroreceptor nucleus of the solitary tract in rat.
Vasoactive intestinal polypeptide (VIP)-immunoreactive cell bodies, dendrites and nerve terminals in the nucleus of the solitary tract have been identified with electron microscopic immunocytochemistry in rats. The relatively high concentration of VIP in this nucleus, which corresponds to the primary baroreceptor center, was depleted only insignificantly by uni- or bilateral transection of the solitary tract, which eliminates peripheral neuronal (via glossopharyngeal and vagal nerves) input to the nucleus. Both immunocytochemical and biochemical data suggest that the majority of VIP in the nucleus of the solitary tract is present in intrinsic neurons.


Novel non-MRI imaging techniques for primary diagnosis of prostate cancer: micro-ultrasound, contrast-enhanced ultrasound, elastography, multiparametric ultrasound, and PSMA PET/CT.
Multiparametric magnetic resonance imaging (mpMRI) provides enhanced diagnostic accuracy in the detection of prostate cancer, but is not devoid of limitations. Given the recent evolution of non-MRI imaging techniques, this critical review of the literature aimed at summarizing the available evidence on ultrasound-based and nuclear medicine imaging technologies in the initial diagnosis of PCa. Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies examining their diagnostic performance in the primary diagnosis of PCa, weighted against a histological confirmation of PCa diagnosis, using a free-text protocol. Retrospective and prospective studies, both comparative and non-comparative, systematic reviews (SR) and meta-analysis (MA) were included. Based on authors' expert opinion, studies were selected, data extracted, and results qualitatively described. Micro-ultrasound (micro-US) appears as an appealing diagnostic strategy given its high accuracy in detection of PCa, apparently non-inferior to mpMRI. The use of multiparametric US (mpUS) likely gives an advantage in terms of effectiveness coming from the combination of different modalities, especially when certain modalities are combined. Prostate-specific membrane antigen (PSMA) PET/CT may represent a whole-body, one-step approach for appropriate diagnosis and staging of PCa. The direct relationship between lesions avidity of radiotracers and histopathologic and prognostic features, and its valid diagnostic performance represents appealing characteristics. However, intrinsic limits of each of these techniques exist and further research is needed before definitively considering them reliable tools for accurate PCa diagnosis. Other novel technologies, such as elastography and multiparametric US, currently relies on a limited number of studies, and therefore evidence about them remains preliminary. Evidence on the role of non-MRI imaging options in the primary diagnosis of PCa is steadily building up. This testifies a growing interest towards novel technologies that might allow overcoming some of the limitations of current gold standard MRI imaging.


Acute temperature change modulates the response of ICa to adrenergic stimulation in fish cardiomyocytes.
The purpose of this study was to investigate how the endogenous catecholamine adrenaline protects sarcolemmal Ca(2+) flux through the L-type Ca(2+) channel (I(Ca)) during acute exposure to cold in the fish heart. We examined the response of I(Ca) to adrenergic stimulation at three temperatures (7 degrees, 14 degrees, and 21 degrees C) in atrial myocytes isolated from rainbow trout acclimated to 14 degrees C. We found that I(Ca) amplitude varied directly with test temperature and was increased by adrenergic stimulation (AD; 5 nM and 1 microM) at all temperatures. However, I(Ca) was significantly more sensitive to adrenergic stimulation at the coldest test temperature. In fact, at 7 degrees C in the absence of AD, I(Ca) was extremely low. The addition of 1 microM AD increased peak I(Ca) 7.2-fold at 7 degrees C, 2.6-fold at 14 degrees C, and 1.6-fold at 21 degrees C and ameliorated the temperature-dependent difference in Ca(2+) influx across the cell membrane. We suggest that this increased adrenergic sensitivity is a critical compensatory mechanism that allows the rainbow trout heart to maintain contractility during acute exposure to cold temperatures. In particular, the tonic level of adrenergic stimulation provided by circulating plasma catecholamines (i.e., in the nM concentration range) may be crucial for effective excitation-contraction coupling in the cold cardiomyocyte.


'It feels like my metabolism has shut down'. Negotiating interactional roles and epistemic positions in a primary care consultation.
Our aim is to explore the ways in which a patient and a general practitioner (GP) negotiate knowledge claims stemming from different epistemic domains while dealing with a mismatch between experiential and biomedical knowledge during the clinical consultation. We interpret their interaction in relation to the sociocultural context in which their negotiation is embedded and identify factors facilitating their successful negotiation (a medical error is avoided). Based on a narrative analysis of a verbatim transcript of a complete naturally occurring primary care consultation, we explore the moment-to-moment unfolding of talk between the patient and the GP (two women). The patient experiences symptoms of what she interprets as a thyroid condition, and indirectly asks for medication. She presents her case by drawing on experiential knowledge ('it feels like my metabolism has shut down') and biomedical knowledge (while suggesting a diagnosis and a diagnostic test). The GP informs her that her thyroid blood tests are normal and uses biomedical knowledge to explain why she turns down the patient's request. This stages a potential conflict between the patient's embodied experiential knowledge and the doctor's biomedical knowledge. However, during their encounter, the patient and the GP manage to co-construct the patient's illness story and make shared decisions about further actions. The transition from potential conflict to consensus is a result of the mutual efforts of two parties: a patient who persistently claims experiential as well as biomedical knowledge while at the same time deferring to the GP's professional knowledge, and a GP who maintains her epistemic authority while also acknowledging the patient's experiential and biomedical knowledge. Our empirical data are sourced from a data archive and patients were not involved in the design or conduct of the study, but our study is based on a naturally occurring clinical consultation with a patient.


Dynamic electrocardiography and ventricular pauses of 3 seconds and more: etiology and therapeutic implications.
A total of 2350 consecutive Holter recordings revealed that 53 patients had ventricular asystole of 3 seconds or more. The diagnoses based on the longest pauses were: sinus arrest in 19; AV block in 5; slow atrial fibrillation in 29. Symptoms occurred in 45 and were absent in 8 patients. Associated heart disease was present in only 33 cases. A pacemaker was implanted in 7 out of 8 asymptomatic patients. Ventricular asystole of 3 seconds or more is proposed as a definite indication for the implantation of a permanent pacemaker.


Physicians' views of patient-planetary health co-benefit prescribing: a mixed methods systematic review.
Health professionals are increasingly called to become partners in planetary health. Using patient-planetary health (P-PH) co-benefit prescribing framing, we did a mixed methods systematic review to identify barriers and facilitators to adopting P-PH co-benefit prescribing by physicians and mapped these onto the Capability, Opportunity, Motivation, and Behaviour (COM-B) model and Theoretical Domains Framework (TDF). We searched electronic databases from inception until October, 2022, and did a content analysis of the included articles (n=12). Relevant categories were matched to items in the COM-B model and TDF. Nine barriers and eight facilitators were identified. Barriers included an absence of, or little, knowledge of how to change practice and time to implement change; facilitators included having policy statements and guidelines from respected associations. More diverse study designs that include health professionals, patients, and health-care system stakeholders are needed to ensure a more holistic understanding of the individual, system, and policy levers involved in implementing clinical work informed by planetary health.


Osteomesopyknosis. Report of two new cases.
Two inherited cases of osteomesopyknosis are reported. This is an autosomal dominant osteosclerosis described by Maroteaux in 1980; its radiological abnormalities consist of increased density of the vertebral plates, pelvis, and sometimes of the upper part of the femur. Osteomesopyknosis, usually discovered incidentally on radiographic examination, is a mild form of familial osteosclerosis and must be distinguished from osteopetrosis which carries a worse prognosis.


Implantation of a HeartMate 3 in a 13-Year-Old Child with Dilated Cardiomyopathy.
Left ventricular assist device is a well-established therapy in heart failure adults, but less in children. A 13-year-old-boy with severe left ventricular dysfunction did not improve under medical treatment. A HeartMate 3 (HM3) was implanted as a bridge to transplantation. Despite the size limitation, the HM3 shows promising results and our case supports its feasibility in children.


Online use of error-related potentials in healthy users and people with severe motor impairment increases performance of a P300-BCI.
To investigate whether error-related potentials can be used to increase information transfer rate of a P3 brain-computer interface (BCI) in healthy and motor-impaired individuals. Extraction and classification of the error-related potential was performed offline on data recorded from six amyotrophic lateral sclerosis (ALS) patients. An online study with 17 healthy and six motor impaired participants followed, using a modified P3 speller to provide explicit feedback of spelled letters. On recognition of error-related potentials, the interface informed users that the incorrect letter was automatically deleted. The offline cross-validation estimate of P3 speller data of six ALS patients increased bit rate by 0.44 bit/trial. During online copy spelling, the participants increased their bit rate by 0.52 bit/trial with the error correction system (ECS). Some participants performed free spelling and were able to increase their bit rate. Finally, we demonstrated that healthy participants could increase their bit rate by using a classifier pre-trained on other users' data. Error-related potentials as a secondary source of information can be used to increase overall bit rate in a P3 BCI. The method should be made available to any patient using the P3 BCI for communication.


Combination of Gold Nanoparticle-Conjugated Tumor Necrosis Factor-α and Radiation Therapy Results in a Synergistic Antitumor Response in Murine Carcinoma Models.
Although remarkable preclinical antitumor effects have been shown for tumor necrosis factor-α (TNF) alone and combined with radiation, its clinical use has been hindered by systemic dose-limiting toxicities. We investigated the physiological and antitumor effects of radiation therapy combined with the novel nanomedicine CYT-6091, a 27-nm average-diameter polyethylene glycol-TNF-coated gold nanoparticle, which recently passed through phase 1 trials. The physiologic and antitumor effects of single and fractionated radiation combined with CYT-6091 were studied in the murine 4T1 breast carcinoma and SCCVII head and neck tumor squamous cell carcinoma models. In the 4T1 murine breast tumor model, we observed a significant reduction in the tumor interstitial fluid pressure (IFP) 24 hours after CYT-6091 alone and combined with a radiation dose of 12 Gy (P<.05 vs control). In contrast, radiation alone (12 Gy) had a negligible effect on the IFP. In the SCCVII head and neck tumor model, the baseline IFP was not markedly elevated, and little additional change occurred in the IFP after single-dose radiation or combined therapy (P>.05 vs control) despite extensive vascular damage observed. The IFP reduction in the 4T1 model was also associated with marked vascular damage and extravasation of red blood cells into the tumor interstitium. A sustained reduction in tumor cell density was observed in the combined therapy group compared with all other groups (P<.05). Finally, we observed a more than twofold delay in tumor growth when CYT-6091 was combined with a single 20-Gy radiation dose-notably, irrespective of the treatment sequence. Moreover, when hypofractionated radiation (12 Gy × 3) was applied with CYT-6091 treatment, a more than five-fold growth delay was observed in the combined treatment group of both tumor models and determined to be synergistic. Our results have demonstrated that TNF-labeled gold nanoparticles combined with single or fractionated high-dose radiation therapy is effective in reducing IFP and tumor growth and shows promise for clinical translation.


Improvement of physiological parameters of rats subjected to hypercaloric diet, with the use of Pereskia grandifolia (Cactaceae) leaf flour.
The aim of the present study was to investigate the anti-obesity effects of Pereskia grandifolia leaf flour on rats fed a hypercaloric diet. After a hypercaloric diet for 10 weeks, 21 animals were divided into the following groups and were fed the following diets for 4 weeks: control (CH), hypercaloric diet with P. grandifolia flour (PGF) 5%, and hypercaloric diet with PGF 10%. Several measurements were performed including body weight, food consumption, body mass index, Lee index, liver weight, liver and body moisture content, and body and hepatic lipid level. Data were analyzed by Tukey's test at 5% probability. Rats fed PGF diet had decreased food consumption and body weight and showed lower body mass and Lee indices compared to control group. At week 2, weight of the PGF 10% group was statistically lower than the control group (CH). At week 4, the PGF 10% group demonstrated the highest body weight loss compared to the other two groups. There were no significant difference in total lipids and moisture level between the groups; however, rats fed PGF diet had lower hepatic lipids levels than control group and reduced liver weight. This suggests that PGF induced weight loss and decreased hepatic lipid level and may be effective in treating obesity and related metabolic diseases.


Risk of noise-induced hearing loss following exposure to Chinese firecrackers.
Firecrackers produce sound impulses reaching peak levels measured at the ear sometimes in excess of 160 dB when fired at 2 m distance. These sound levels are potentially hazardous to the ear. Current damage risk criteria for impulse sounds show that for 10 impulses the peak levels should not exceed 149 dB(lin,peak) at the ear. The A-weighted, impulse (integration time 35 ms) levels should not exceed 125 dB(A,imp) at the ear for 10 impulses.


Edaravone protects against liver fibrosis progression via decreasing the IL-1β secretion of macrophages.
Edaravone (EDA), a strong novel free radical scavenger, have been demonstrated to exert neurovascular protective effects clinically. Furthermore, EDA can suppress the lung injury, pulmonary fibrosis and skin fibrosis, while the precise effects and mechanisms of EDA on liver injury and fibrosis remain unclear. The effects of EDA on the Thioacetamide (TAA)-induced liver fibrosis were evaluated by sirius red staining, α-SMA immunohistochemistry. The percentages of immune cell subsets were analyzed by flow cytometry. Immunofluorescence assay was performed to identify the fibrotic properties of hepatic stellate cells (HSCs). Western blot and qPCR were used to detect the levels of liver fibrosis-related molecules and IL-1β. EDA displayed a hepatic protective role in TAA-induced chronic liver fibrosis via inhibiting monocyte/macrophages recruitment and IL-1β production of macrophages. Mechanically, EDA inhibited of NF-κB signal pathway and reactive oxygen species (ROS) production in macrophages. Moreover, EDA treatment indirectly suppressed the activation of HSCs by decreasing the IL-1β secretion of macrophages. Together, EDA protects against TAA-induced liver fibrosis via decreasing the IL-1β production of macrophages, thereby providing a feasible solution for clinical treatment of liver fibrosis.


Immunoglobulin G passive transfer from mothers to infants: total IgG, IgG subclasses and specific antipneumococcal IgG in 6-week Malawian infants exposed or unexposed to HIV.
The impaired transplacental passage of IgG from mothers living with HIV to their infants could be one of the causes of the high vulnerability to infections of HIV-exposed uninfected (HEU) infants, but controversial results have been obtained in different settings. The aim of this study was to assess in 6-week old HEU and HIV-unexposed, uninfected (HUU) Malawian infants the total IgG levels, the subclasses profile and the concentrations of global anti-pneumococcal capsular polysaccharide (anti-PCP) IgG and IgG2. Dried blood spots were collected from 80 infants (40 HEU, 40 HUU) and antibodies concentrations determined by nephelometric method (total IgG and subclasses), or using ELISA (anti-PCP total IgG and IgG2). Results are expressed as median levels with IQR, while the proportions of each subclass out of the total IgG are used to describe the subclasses profile. At 6 weeks HEU infants had higher median levels of total IgG and IgG1 and a significantly lower level of IgG2 [0.376 (0.344-0.523) g/l vs 0.485 (0.374-0.781) g/l, p = 0.037] compared to the HUU counterparts. The IgG subclasses distribution confirmed the underrepresentation of IgG2 (IgG2 represented 5.82% of total IgG in HEU and 8.87% in HUU). The anti-PCP IgG and IgG2 levels were significantly lower in HEU infants [8.9 (5.4-15.1) mg/l vs 16.2 (9.61-25.8) mg/l in HUU, p < 0.001, and 2.69 (1.90-4.29) mg/l vs 4.47 (2.96-5.71) mg/l in HUU, p = 0.001, respectively]. Compared to HUU infants, HEU infants have IgG abnormalities mainly represented by low IgG2 levels, suggesting that despite maternal antiretroviral therapy, the mechanisms of IgG transplacental passage continue to be impaired in women living with HIV. HEU infants also showed a significantly lower level of specific anti-PCP IgG, possibly favouring a high vulnerability to S. pneumoniae infection at an age when protection is mostly depending on maternal IgG.


Comparison of an EBV transformed cell line and an EBV hybridoma cell line producing the same human anti-HBs monoclonal antibody.
A stable human-mouse heterohybridoma secreting human anti-HBs monoclonal antibody in continuous culture for 12 months was generated. It grew faster than the parent EBV transformed lymphoblastoid cell line (LCL) but produced the same level of specific antibody. The LCL was positive for the Epstein-Barr Virus Nuclear Antigen (EBNA), human CD 23 and contained a diploid number of human chromosomes. The heterohybridoma was negative for EBNA, CD 23 and mouse Ly-1 mouse, despite retaining a full complement of diploid mouse chromosomes and a limited number of human chromosomes.


Highly Active Small Aminated Quinolinequinones against Drug-Resistant Staphylococcus aureus and Candida albicans.
Two subseries of aminated quinolinequinones (AQQs, AQQ1-16) containing electron-withdrawing group (EWG) or electron-donating group (EDG) in aryl amine moiety were successfully synthesized. Antimicrobial activity assessment indicates that some of the AQQs (AQQ8-10 and AQQ12-14) with an EDG in aryl amine exhibited strong antibacterial activity against Gram-positive bacterial strains, including Staphylococcus aureus (ATCC® 29213) and Enterococcus faecalis (ATCC® 29212). In contrast, AQQ4 with an EWG in aryl amine displayed excellent antifungal activity against fungi Candida albicans (ATCC® 10231) with a MIC value of 1.22 μg/mL. To explore the mode of action, the selected AQQs (AQQ4 and AQQ9) were further evaluated in vitro to determine their antimicrobial activity against each of 20 clinically obtained resistant strains of Gram-positive bacteria by performing antibiofilm activity assay and time-kill curve assay. In addition, in silico studies were carried out to determine the possible mechanism of action observed in vitro. The data obtained from these experiments suggests that these molecules could be used to target pathogens in different modes of growth, such as planktonic and biofilm.


Requested meals versus scheduled meals.
Scheduled meals are considered to be equivalent to those requested by the infant (null hypothesis). In adults, we have found high blood glucose before scheduled meals and low blood glucose after recognition of validated initial hunger. Low preprandial blood glucose is associated with a decrease in energy intake and body weight both in adults who are overtly overweight and in those who are of normal weight with insulin resistance (hidden overweight). In this study, we investigated the validity of the null hypothesis between scheduled and requested meals in 2-year-old infants with chronic nonspecific diarrhea. We trained a "recognizing request" meal pattern in 70 mother-infant pairs. The trained meal pattern consisted of administering food after a first request that we validated by blood glucose measurement in the hospital laboratory. Using a 7-day food diary, mothers reported preprandial blood glucose measurements for their infants three times a day. We assessed mean preprandial blood glucose, daily energy intake, days with diarrhea, blood parameters, and anthropometry before training and 4 months after training, and compared the results with measurements in 73 randomly selected untrained controls. In the trained group, there was a decrease in mean blood glucose from 86.9 ± 9.4 mg/dL to 76.4 ± 6.7 mg/dL (P < 0.0001), as well as a decrease in energy intake and days with diarrhea in comparison with control infants who maintained scheduled meals. Only two of 21 infants who had a mean blood glucose lower than 81.2 mg/dL at recruitment showed a statistically significant decrease in mean blood glucose, whereas 36 of 49 infants above this cutoff level showed a statistically significant decrease after training (Chi-square test, P < 0.0001). Requested meals are associated with low preprandial blood glucose, significantly lower energy intake, and recovery from diarrhea, whereas scheduled meals are associated with high blood glucose, higher energy intake, and persistence of diarrhea. The disparities in blood glucose levels and energy intake disprove the null hypothesis, suggesting the need for a change from scheduled to requested meals early on in food administration, ie, during the neonatal period.


A and B sites doped CaAl12O19: Phase component, energy band, color and photoluminescence tuning, color performance prediction and application for pigments.
The polyacrylamide gel method was used to fabricate the Ca1-xCoxAl12O19, Ca1-xNixAl12O19, CaAl12-xInxO19 and CaAl12-xWxO19 (x = 0-0.5) pigments. The phase compositions, energy bands, color and photoluminescence properties of the pigments can be controlled by adjusting the type and content of doping ions. The color of CaAl12O19 changed from white to blue with the Co2+ ion doping, from white to gray green with the Ni2+ ion doping, and from white to bright white with the In3+ and W6+ ions doping. The genetic algorithm optimized back propagation neural network can predict the color properties of CaAl12O19 based pigments. The application of the pigments shows that they can be used in painting, coating and other fields. The Co2+ and Ni2+ doped CaAl12O19 exhibits high blue emission, while In3+ and W6+ doped CaAl12O19 shows strong green emission and the luminescence is highly dependent on the type and content of dopant ion, phase composition and energy transfer.


Functional dyspepsia is associated with duodenal eosinophilia in an Australian paediatric cohort.
The pathophysiology of functional dyspepsia (FD) remains unknown. Duodenal eosinophil infiltration has been reported. To assess the association between dyspeptic symptoms and duodenal eosinophilia in children undergoing upper gastrointestinal endoscopy. In this retrospective cohort study, children with normal upper endoscopy and routine histology at a single tertiary paediatric centre between 2010 and 2014 were included. FD was defined as epigastric pain or discomfort >2 months without response to acid suppression. Controls presented with nonerosive reflux disease, dysphagia or rumination syndrome. Intramucosal eosinophil counts were compared between the groups using uni- and multivariate regression analyses. Thirty-six cases and 36 nonmatched controls were identified. Atopic history (39% vs. 25%) and psychological comorbidity (53% vs. 39%; both P = 0.2) were frequent in cases and controls. Self-reported nausea (64% vs. 17%; P < 0.0001), lethargy (19% vs. 0%; P = 0.005) and family functional gastrointestinal disorder(FGID) (28% vs. 3%; P = 0.003) were more common in cases than controls. Duodenal eosinophil counts [median (IQR): 151 (118-207) vs. 76 (60-106) per mm2 ; P < 0.001] were significantly higher in cases than controls with >112 eosinophils per mm2 predictive for FD (OR: 33.6, 95% CI: 7.1-159.0; P < 0.001). Duodenal eosinophilia was associated with weight loss (OR: 7.1, 95% CI: 1.1-45.5; P = 0.04). Functional dyspepsia in children is strongly associated with duodenal eosinophilia, in the absence of endoscopic or routine histological findings. Frequent atopic and psychological comorbidity illustrate likely multifactorial mechanisms.


Inhibition of yeast cytochrome P-450 by ammonium metavanadate.
Incubation of diploid D7 strain cells of Saccharomyces cerevisiae (grown in 20% glucose) in the presence of ammonium metavanadate (AMV) led to a decrease in the cytochrome P-450-dependent monooxygenase system (cytochrome P-450 level and 7-ethoxycoumarin O-deethylase). The electrophoretic analysis of microsomal fractions of yeast cells treated with metavanadate revealed a decrease in the intensity of the bands corresponding to a M(r) in the range of 51,000-58,000 Da compared with those observed in controls, i.e., cells grown in 20% glucose. Analysis of the cytochrome P-450 transcript showed that AMV treatment reduced the mRNA level. Our results suggest that AMV inhibits the yeast cytochrome P-450 system by acting at both the pre- and post-transcriptional levels.


Quantitative methods in electroencephalography to access therapeutic response.
Pharmacometrics or Quantitative Pharmacology aims to quantitatively analyze the interaction between drugs and patients whose tripod: pharmacokinetics, pharmacodynamics and disease monitoring to identify variability in drug response. Being the subject of central interest in the training of pharmacists, this work was out with a view to promoting this idea on methods to access the therapeutic response of drugs with central action. This paper discusses quantitative methods (Fast Fourier Transform, Magnitude Square Coherence, Conditional Entropy, Generalised Linear semi-canonical Correlation Analysis, Statistical Parametric Network and Mutual Information Function) used to evaluate the EEG signals obtained after administration regimen of drugs, the main findings and their clinical relevance, pointing it as a contribution to construction of different pharmaceutical practice. Peter Anderer et. al in 2000 showed the effect of 20mg of buspirone in 20 healthy subjects after 1, 2, 4, 6 and 8h after oral ingestion of the drug. The areas of increased power of the theta frequency occurred mainly in the temporo-occipital - parietal region. It has been shown by Sampaio et al., 2007 that the use of bromazepam, which allows the release of GABA (gamma amino butyric acid), an inhibitory neurotransmitter of the central nervous system could theoretically promote dissociation of cortical functional areas, a decrease of functional connectivity, a decrease of cognitive functions by means of smaller coherence (electrophysiological magnitude measured from the EEG by software) values. Ahmad Khodayari-Rostamabad et al. in 2015 talk that such a measure could be a useful clinical tool potentially to assess adverse effects of opioids and hence give rise to treatment guidelines. There was the relation between changes in pain intensity and brain sources (at maximum activity locations) during remifentanil infusion despite its potent analgesic effect. The statement of mathematical and computational aspects in the use of clinical data is frequent and elucidation of these aspects we use PhysioNet https://www.physionet.org/, Clinical Database online supported by the National Institutes of Health (National Institutes of Health of United States of America/NIH-USA) for the acquisition of EEG data and the Matlab program to do the simulations with the methods and thus create opportunities greater understanding.


Prevention and control of HPV infection and HPV-related cancers in Colombia- a meeting report.
The Human Papillomavirus (HPV) Prevention and Control Board is an independent multidisciplinary board of international experts that disseminates relevant information on HPV to a broad array of stakeholders and provides guidance on strategic, technical and policy issues in the implementation of HPV control programs. In response to drastic drop of vaccine coverage following the adverse event crisis in Carmen del Bolivar, Colombia, the HPV Prevention and Control Board in collaboration with the Colombian National Cancer Institute and Colombian League Against Cancer convened a meeting in Bogota, Columbia (November 2018). The goal of the meeting was to bring together national and international group of experts to report the disease burden, epidemiology and surveillance of HPV and HPV-related cancers, to discuss the successes and especially the challenges of HPV vaccination and screening in Colombia, as well as the lessons learnt from neighbouring countries. The meeting provided a platform to confer various stakeholder's perspectives, including the role of the Colombian healthcare system and to catalyse various parts of the public health community in Colombia into effective action. The conclusion of the meeting included following suggestions to strengthen HPV prevention and control: 1) Re-introducing school-based vaccine programs, 2) Integrating primary and secondary prevention programs, 3) Developing an innovative crisis communication plan targeting healthcare workers, teachers and general population, 4) Building trust through efficient and timely communication, 5) Building strong relationship with media to ensure a stable vaccination campaign support, and 6) Promoting empathy among healthcare professionals towards patients to build trust and communicate effectively.


Rectal Cancer: Assessing Response to Neoadjuvant Therapy.
MR imaging plays a crucial role in the post-CRT assessment of rectal cancer; results are used for treatment planning. Radiologists should assess response or progression, possibility of a complete response, risk factors for incomplete resection, and nodal stage. T2-weighted MR imaging with diffusion-weighted imaging yields the best results to identify a complete response, but endoscopy is also very important. Overstaging of transmural and MRF invasion after CRT occur regularly, owing to residual stranding regarded as tumor to err on the safe side. Nodal restaging is a challenge. A structured report format or checklist is recommended.


A twofold tale of one mind: revisiting REC's multi-storey story.
The Radical Enactive/Embodied view of Cognition, or REC, claims that all cognition is a matter of skilled performance. Yet REC also makes a distinction between basic and content-involving cognition, arguing that the development of basic to content-involving cognition involves a kink. It might seem that this distinction leads to problematic gaps in REC's story. We address two such alleged gaps in this paper. First, we identify and reply to the concern that REC leads to an "interface problem", according to which REC has to account for the interaction of two minds co-present in the same cognitive activity. We emphasise how REC's view of content-involving cognition in terms of activities that require particular sociocultural practices can resolve these interface concerns. The second potential problematic gap is that REC creates an unjustified difference in kind between animal and human cognition. In response, we clarify and further explicate REC's notion of content, and argue that this notion allows REC to justifiably mark the distinction between basic and content-involving cognition as a difference in kind. We conclude by pointing out in what sense basic and content-involving cognitive activities are the same, yet different. They are the same because they are all forms of skilled performance, yet different as some forms of skilled performance are genuinely different from other forms.


Administering ziconotide and monitoring patients treated with ziconotide: expert opinions.
Some patients with chronic pain who are intolerant of or refractory to treatment with systemic analgesics may benefit from intrathecal therapy. Ziconotide is the first nonopioid analgesic approved by the United States Food and Drug Administration for intrathecal administration. Several randomized, double-blind, placebo-controlled clinical trials have demonstrated the efficacy and safety of ziconotide. However, the maximum recommended dosing and titration schedule provided in the prescribing information may be too aggressive for some patients, and experience has demonstrated that ziconotide is better tolerated with slower titration to a lower maximum dose. Efficacy can be assessed by an evaluation of changes in pain, functionality, and quality of life. Cognitive adverse events may be subtle; therefore, it is important that health care professionals not only monitor patients for signs and symptoms of cognitive adverse events, but also teach family members how to do the same. Careful patient assessment and monitoring can help optimize the potential benefit from treatment with ziconotide.


Substance P and behavior: opposite effects of N-terminal and C-terminal fragments.
Most of the biological actions of substance P (SP) have been thought to be mediated by the carboxy-terminal portion of the peptide. Some of the behavioral effects produced by exogenous SP exhibit a strikingly different structure-activity relationship. The N-terminal heptapeptide fragment of SP, SP(1-7), inhibits nociceptive, aggressive and grooming behaviors and stimulates investigative motor behavior, but the C-terminal hexapeptide fragment analog pyroglutamyl-SP(7-11) exerts opposite effects. While the C-terminal fragment mimics the effects of administered intact SP on motor behaviors, the N-terminal fragment mimics the effects of intact SP on aggressive and nociceptive behaviors. The significant behavioral effects of SP(1-7) and the consistently opposite behavioral effects of N- and C-terminal fragments are important new findings.


No increased chromosome breakage in three Bloom's syndrome heterozygotes.
The frequency of chromosome aberrations in the lymphocytes of three established heterozygotes for the Bloom's syndrome gene (ages 67, 57, 46) was compared to that in controls (ages 68, 67, 61, 46, 34). The main part of the study was done on coded slides. No difference was found between the heterozygotes and the control group, except for one control (aged 46) who had a significantly higher number of chromosome aberrations than the others.


Gundersen Flap Removal to Restore Eyesight Without Limbal Transplantation-A Case Report.
To report a case of Gundersen flap removal where the ocular surface was restored without the need for additional limbal stem cell transplantation. We describe a case of 57-year-old man who underwent Gundersen flap for a nonhealing corneal ulcer in right eye 17 years ago. He recently lost eyesight in left eye after blunt trauma. Gundersen flap removal was performed in right eye along with amniotic membrane transplantation. The ocular surface recovered completely after surgery without any evidence of limbal stem cell deficiency. His corrected distance visual acuity improved to 20/60 along with a stable ocular surface, which was maintained till last follow-up of 12 months. A normal ocular surface can be restored after Gundersen flap surgery if removal of limbal epithelium is not performed during the primary procedure. Additional corneal surgery might be required depending on corneal clarity.


Genomics of Alzheimer's disease implicates the innate and adaptive immune systems.
Alzheimer's disease (AD) is a chronic neurodegenerative disease characterised by cognitive impairment, behavioural alteration, and functional decline. Over 130 AD-associated susceptibility loci have been identified by genome-wide association studies (GWAS), while whole genome sequencing (WGS) and whole exome sequencing (WES) studies have identified AD-associated rare variants. These variants are enriched in APOE, TREM2, CR1, CD33, CLU, BIN1, CD2AP, PILRA, SCIMP, PICALM, SORL1, SPI1, RIN3, and more genes. Given that aging is the single largest risk factor for late-onset AD (LOAD), the accumulation of somatic mutations in the brain and blood of AD patients have also been explored. Collectively, these genetic findings implicate the role of innate and adaptive immunity in LOAD pathogenesis and suggest that a systemic failure of cell-mediated amyloid-β (Aβ) clearance contributes to AD onset and progression. AD-associated variants are particularly enriched in myeloid-specific regulatory regions, implying that AD risk variants are likely to perturbate the expression of myeloid-specific AD-associated genes to interfere Aβ clearance. Defective phagocytosis, endocytosis, and autophagy may drive Aβ accumulation, which may be related to naturally-occurring antibodies to Aβ (Nabs-Aβ) produced by adaptive responses. Passive immunisation is providing efficiency in clearing Aβ and slowing cognitive decline, such as aducanumab, donanemab, and lecanemab (ban2401). Causation of AD by impairment of the innate immunity and treatment using the tools of adaptive immunity is emerging as a new paradigm for AD, but immunotherapy that boosts the innate immune functions of myeloid cells is highly expected to modulate disease progression at asymptomatic stage.


Beyond spinal headache: prophylaxis and treatment of low-pressure headache syndromes.
This Evidence-Based Case Management article evaluates and grades the evidence for two anesthesiology-related interventions: prophylaxis after unintentional meningeal puncture and treatment of spontaneous intracranial hypotension (SIH). A search was made of relevant English language clinical studies or reports pertinent to the topic of low-pressure headache, but excluding the treatment of meningeal puncture headache. Thirty-seven case reports, case series, and clinical trials were included to develop the best available evidence-based recommendations for the prophylaxis of unintentional meningeal puncture and for the treatment of SIH. The highest quality randomized controlled trials suggest that prophylactic epidural blood patch (EBP) does not reduce the incidence of headache after unintentional meningeal puncture. The weight of existing literature supports EBP as an initial treatment of SIH, although its effectiveness does not approach that seen when EBP is used to treat meningeal puncture headache.


Intramedullary Canal Injection of Vancomycin- and Tobramycin-loaded Calcium Sulfate: A Novel Technique for the Treatment of Chronic Intramedullary Osteomyelitis.
In this study, we present a detailed surgical technique for treating chronic osteomyelitis (COM) of the intramedullary canal with injectable tobramycin and vancomycin-loaded calcium sulfate (CS). Chronic osteomyelitis of the long bones has been treated using antibiotic-impregnated polymethyl methacrylate (PMMA), which typically requires a second procedure for removal. Removal of the infected intramedullary nail (if any), copious irrigation, canal reaming, and intramedullary canal injection of vancomycin- and tobramycin-loaded calcium sulfate as a single-stage procedure for the treatment of COM of long bones. Intramedullary injection of vancomycin- and tobramycin-loaded CS can be used as a single-stage procedure for the treatment of long bone intramedullary COM. Further studies are necessary to compare the long-term outcomes of antibiotic-coated CS vs other antibiotic carriers for infection eradication. The authors have endeavored to explain the best surgical technique to eradicate long bones COM with injectable tobramycin and vancomycin-loaded CS. Elhessy AH, Rivera JC, Shu HT, et al. Intramedullary Canal Injection of Vancomycin- and Tobramycin-loaded Calcium Sulfate: A Novel Technique for the Treatment of Chronic Intramedullary Osteomyelitis. Strategies Trauma Limb Reconstr 2022;17(2):123-130.


Spontaneous neutrophil apoptosis and regulation of cell survival by granulocyte macrophage-colony stimulating factor.
Polymorphonuclear leukocytes (PMNs or neutrophils) are the most prominent cellular component of the innate immune system in humans and produce an array of potent cytotoxic molecules. It is important that neutrophils undergo constitutive (spontaneous) apoptosis as a mechanism to facilitate normal cell turnover and immune system homeostasis. Conversely, several proinflammatory cytokines, including granulocyte macrophage-colony stimulating factor (GM-CSF), prolong neutrophil survival. The molecular mechanisms that regulate PMN apoptosis or survival remain incompletely defined. To that end, we compared global gene expression in human neutrophils during spontaneous apoptosis with that in cells cultured with human GM-CSF. Genes encoding proteins that inhibit apoptosis, such as myeloid cell leukemia sequence 1, caspase 8 and Fas-associated via death domain-like apoptosis regulator (CFLAR), B cell chronic lymphocytic leukemia/lymphoma 2 (BCL2)/adenovirus E1B 19 kDa-interacting protein 2 (BNIP2), and serum/glucocorticoid-regulated kinase (SGK), were down-regulated coincident with neutrophil apoptosis. In contrast, those encoding apoptosis inhibitor 5, BCL2-like 1, BNIP2, CFLAR, SGK, and tumor necrosis factor alpha-induced protein 8 were up-regulated in PMNs cultured with GM-CSF. Correspondingly, GM-CSF delayed PMN apoptosis (P<0.03), increased cell viability (P<0.03), and prolonged neutrophil phagocytic capacity (P<0.05). Prolonged functional capacity was paralleled by striking up-regulation of proinflammatory genes and proteins, including CD14, CD24, CD66, and human leukocyte antigen-DR. In addition, expression of SGK protein diminished during PMN apoptosis but was restored by culture with GM-CSF, suggesting SGK is involved in leukocyte survival. These studies provide a global view of the molecular events that regulate neutrophil survival and apoptosis.


Platelet-derived growth factor is released into the coronary circulation after coronary spasm.
Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth muscle cells and is implicated in the vascular response to injury and the pathogenesis of atherosclerosis. It is also a potent vasoconstrictor. To examine whether acute myocardial ischemia increases the level of PDGF in the coronary circulation, we measured plasma levels of PDGF in the coronary sinus and the aortic root simultaneously in 14 patients with coronary spastic angina. These measurements were performed before and after the left coronary artery spasm induced by intracoronary injection of acetylcholine, and measurements were also taken in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Eleven patients with chest pain but normal coronary arteries and no coronary spasm served as controls. Plasma PDGF levels increased significantly (P < 0.01) from 274 +/- 28 pg/mL to 364 +/- 27 pg/mL only in coronary sinus after anginal attacks in the patients with coronary spastic angina. However, plasma PDGF levels in coronary sinus remained unchanged after these attacks in the patients with stable exertional angina (from 230 +/- 27 pg/ml to 247 +/- 28 pg/mL) and after intracoronary injection of acetylcholine in the control subjects. Plasma PDGF levels in aortic root remained unchanged in all three patient groups. PDGF is released into the coronary circulation after coronary artery spasm, and this may exacerbate coronary artery spasm.


Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats.
The present study was undertaken to examine the attenuative effect of Piper betle leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in the liver of rats. Pre-oral supplementation of PBE (200 mg/kg BW) treated rats showed the protective efficacy against Cd induced hepatic oxidative stress. Oral administration of Cd (5 mg/kg BW) for four weeks to rats significantly (P > 0.05) elevated the level of serum hepatic markers such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs), oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD) and significantly (P > 0.05) reduced the enzymatic antioxidants viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral supplementation of PBE (200 mg/kg BW) in Cd intoxicated rats, the altered biochemical indices and pathological changes were recovered significantly (P > 0.05) which showed ameliorative effect of PBE against Cd induced hepatic oxidative stress. From the above findings, we suggested that the pre-administration of P. betle leaf extract exhibited remarkable protective effects against cadmium-induced oxidative hepatic injury in rats.


Cross-correlation between neurons: a source of information about the nervous system.
Impulse trains of spiking neurons are a stochastic process; however, the impulse trains of related neurons are generally not statistically independent. Cross-correlation may be due to either a common input that affects the firing of both cells, or to direct synaptic influence of the one neuron upon the other. By analyzing the distributions of intervals preceding and those following the coincident firings relative to that of all the intervals between impulses in each train, it is possible to infer restrictions upon the ways in which the correlating influence interacts with other sources of variability for each cell. This is applied to pairs of cells in two systems, one in which the coincident firing is due to an input common to the two cells, and one in which one cell is presynaptic to the other.


Current status and prospects of androgen depletion therapy for prostate cancer.
The old concept of androgen depletion therapy (ADT) for prostate cancer, which had been established on the basis of clinical experiences essentially on the far advanced disease, should be changed. The recent major increase in the diagnosis of localized and locally advanced prostate cancer due to prostate-specific antigen (PSA) screening prompts us to make clear the role of ADT for such an early stage of prostate cancer. Recent literature has proved that combination therapy of castration (medical or surgical) and non-steroidal anti-androgens (maximal androgen blockade, MAB, or combined androgen blockade, CAB) is markedly effective on non-metastatic prostate cancer. It is important to promote basic and clinical research based on the understanding that cure of prostate cancer is almost always possible with ADT if progression to the hormone-independent prostate cancer which accompanies metastatic disease can be avoided.


Ecological role of earthworm intestinal bacteria in terrestrial environments: A review.
Increasing evidence demonstrated the critical role the earthworm gut played in sustaining earthworm's metabolism and transformation of nutrients and pollutants in the environment. Being rich in nutrients, the earthworm gut is favorable for the colonization of (facultative) anaerobic bacteria, which bridge the host earthworm gut with adjacent terrestrial environment. Therefore, the status quo of earthworm gut research was primarily reviewed in this work. It was found that most studies focused on the bacterial composition and diversity of the earthworm gut, and their potential application in nutrient element and pollutant transformation, such as nitrification, methanogens, heavy metal detoxification, etc. Yet limited information was available about the specific mechanism of intestinal bacteria in nutrient and pollutant transformation. Therefore, in this work we highlighted the current problems and concluded the future prospect of worm's intestinal bacteria research. On one hand, high throughput sequencing and bioinformatics tools are critical to break the bottleneck in the intestinal bacteria research via clarifying the molecular mechanism involved in the transformation processes described above. In addition, a global dataset concerning worm gut bacteria will be needed to provide comprehensive information about intestinal bacteria pool, and act as a communication platform to further encourage the progress of worm gut research.


Machine Learning Algorithms Predict Clinically Significant Improvements in Satisfaction After Hip Arthroscopy.
To develop machine learning algorithms to predict failure to achieve clinically significant satisfaction after hip arthroscopy. We queried a clinical repository for consecutive primary hip arthroscopy patients treated between January 2012 and January 2017. Five supervised machine learning algorithms were developed in a training set of patients and internally validated in an independent testing set of patients by discrimination, Brier score, calibration, and decision-curve analysis. The minimal clinically important difference (MCID) for the visual analog scale (VAS) score for satisfaction was derived by an anchor-based method and used as the primary outcome. A total of 935 patients were included, of whom 148 (15.8%) did not achieve the MCID for the VAS satisfaction score at a minimum of 2 years postoperatively. The best-performing algorithm was the neural network model (C statistic, 0.94; calibration intercept, -0.43; calibration slope, 0.94; and Brier score, 0.050). The 5 most important features to predict failure to achieve the MCID for the VAS satisfaction score were history of anxiety or depression, lateral center-edge angle, preoperative symptom duration exceeding 2 years, presence of 1 or more drug allergies, and Workers' Compensation. Supervised machine learning algorithms conferred excellent discrimination and performance for predicting clinically significant satisfaction after hip arthroscopy, although this analysis was performed in a single population of patients. External validation is required to confirm the performance of these algorithms. Level III, therapeutic case-control study.


Functional modulation of brain sodium channels by cAMP-dependent phosphorylation.
Voltage-gated Na+ channels, which are responsible for the generation of action potentials in brain, are phosphorylated by cAMP-dependent protein kinase in vitro and in intact neurons. Phosphorylation by cAMP-dependent protein kinase reduces peak Na+ currents 40%--50% in membrane patches excised from rat brain neurons or from CHO cells expressing type IIA Na+ channels. Inhibition of basal cAMP-dependent protein kinase activity by transfection with a plasmid encoding a dominant negative mutant regulatory subunit increases Na+ channel number and activity, indicating that even the basal level of kinase activity is sufficient to reduce Na+ channel activity significantly. Na+ currents in membrane patches from kinase-deficient cells were reduced up to 80% by phosphorylation by cAMP-dependent protein kinase. These effects could be blocked by a specific peptide inhibitor of cAMP-dependent protein kinase and reversed by phosphoprotein phosphatases. Convergent modulation of brain Na+ channels by neurotransmitters acting through the cAMP and protein kinase C signaling pathways may result in associative regulation of electrical activity by different synaptic inputs.


Feasibility study of alternate-day S-1 as adjuvant chemotherapy for gastric cancer: a randomized controlled trial.
The Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer established oral S-1 administration for 1 year as the standard postoperative adjuvant chemotherapy for gastric cancer in Japan. We conducted a multicenter cooperative prospective study comparing daily and alternate-day S-1 administration as postoperative adjuvant therapy for gastric cancer. Patients with Stage II or III gastric cancer who underwent curative surgery were randomly assigned to receive standard daily S-1 administration [group A: 80-120 mg/day S-1 depending on body surface area (BSA); days 1-28 every 6 weeks for 1 year] or alternate-day administration (group B: 80-120 mg/day S-1 depending on BSA; alternate days for 15 months). Treatment completion rate was the primary endpoint, and relative dose intensity and safety, overall survival, and relapse-free survival (RFS) were secondary endpoints. Seventy-three patients were enrolled. The treatment completion rate was 72.2 % in group A and 91.8 % in group B; the relative dose intensity was 67.5 % in group A and 81.2 % in group B; and compliance was better in group B. Digestive system adverse effects were less frequent in group B than in group A. Median follow-up time was 2.8 years; 3-year survival rate was 69.6 % in group A and 87.3 % in group B; and 3-year RFS rate was 76.4 % in group A and 73.1 % in group B. Our data show improved compliance and fewer adverse effects with alternate-day S-1 administration, which appears to be a more sustainable option for adjuvant chemotherapy for Stage II or III gastric cancer.


Distribution patterns of nitrogen micro-cycle functional genes and their quantitative coupling relationships with nitrogen transformation rates in a biotrickling filter.
The present study explored the distribution patterns of nitrogen micro-cycle genes and the underlying mechanisms responsible for nitrogen transformation at the molecular level (genes) in a biotrickling filter (biofilter). The biofilter achieved high removal efficiencies for ammonium (NH4(+)-N) (80-94%), whereas nitrate accumulated at different levels under a progressive NH4(+)-N load. Combined analyses revealed the anammox, nas, napA, narG, nirS, and nxrA genes were the dominant enriched genes in different treatment layers. The presence of simultaneous nitrification, ammonium oxidation (anammox), and dissimilatory nitrate reduction to ammonium (DNRA) were the primary factors accounted for the robust NH4(+)-N treatment performance. The presence of DNRA, nitrification, and denitrification was determined to be a pivotal pathway that contributed to the nitrate accumulation in the biofilter. The enrichment of functional genes at different depth gradients and the multi-path coupled cooperation at the functional gene level are conducive to achieving complete nitrogen removal.


The impact of COVID-19 in hemodialysis patients: Experience in a hospital dialysis unit.
COVID-19 is a very high transmission disease with a variable prognosis in the general population. Patients in hemodialysis therapy are particularly vulnerable to developing an infectious disease, but the incidence and prognosis of hemodialysis patients with COVID-19 is still unclear. The main objective is to describe the experience of our dialysis unit in preventing and controlling the spread of SARS-CoV-2 infection. Preventive structural and organizational changes were applied to all patients and health care personnel in order to limit the risk of local transmission of SARS-CoV-2 infection. The Nephrology department at Sant Joan Despí Moises Broggi Hospital-Consorci Sanitari Integral is a reference for two satellite hemodialysis centers caring for 156 patients. We combine our own hemodialysis maintenance program for 87 patients with hospitalized patients from peripheral hemodialysis centers. In this area, the reported incident rate of COVID-19 in these peripherical hemodialysis centers was 9.5% to 19.9% and the death rate 25% to 30.5%. In our hemodialysis program, the incidence rate was 5.7%. Three out of five required hospitalization (60%) and nobody died. Although the risk of local transmission of the disease was very high due to the increase in hemodialysis patients from peripheral centers admitted to hospital, the incidence rate of COVID-19 was very low in our own hemodialysis patients. We believe that the structural and organizational changes adopted early on and the diagnosis algorithm played an important role in minimizing the spread of the disease.


Isolation of glycophorin with deoxycholate.
In a previous communication we reported that human erythrocyte glycophorin prepared by the lithium diiodosalicylate phenol procedure contains approximately 10 mol of lithium diiodosalicylate per mol of glycophorin, and further we showed that this bound lithium diiodosalicylate is difficult to remove by detergents or organic solvents (Romans, A.Y. and Segrest, J.P. (1978) Biochim. Biophys. Acta 511, 297-301). In the present communication we report an alternative purification procedure for glycophorin in which sodium deoxycholate is substituted for lithium diiodosalicylate; the sodium deoxycholate is subsequently removed by gel filtration. Utilizing this procedure, 25-30 mg glycophorin are obtained per gram of lyophilized erythrocyte ghosts. The glycophorin prepared by the sodium deoxycholate procedure, after a single gel filtration step, contains less than 1 mol of sodium deoxycholate per mol glycophorin and is colorless compared with glycophorin prepared by the lithium diiodosalicylate procedure, which has a distint reddish-brown cast.


Relationships of psychiatric disorders with sleep duration in an adult general population sample.
The objective was to explore psychiatric disorders as potential predictors of sleep duration. A cross-sectional survey study with a probability sample of residents of a northern German area was carried out. There were 4075 study participants, aged 18--64 years, with a participation rate of 70.2%. Face-to-face in-home computer-aided interviews (Composite International Diagnostic Interview) provided diagnoses of nicotine and alcohol dependence, alcohol abuse, depressive, anxiety and somatoform disorders according to the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV), and included questions about sleep duration. Results show that subjects with a short sleep duration of 5h or less had significantly increased odds ratios (OR) for current nicotine dependence (OR 1.9,; confidence interval, CI, 1.2--2.9), alcohol dependence (OR 2.6, CI 1.2--5.6), depressive disorder (OR 3.0, CI 1.7--5.4) or anxiety disorder (OR 2.1, CI 1.3--3.4) compared to individuals who never had the respective psychiatric disorder after adjustment for sex, age, and school education in a multinomial regression analysis. The conclusion is drawn that current nicotine or alcohol dependence, depressive, and anxiety disorders may add to short sleep duration in this random adult general population sample.


Commentary: Looking beyond Treatment Refusal.
This case illustrates the dilemma that occurs when a patient refuses treatment. When a patient refuses recommended interventions, it can cause much distress among the medical team and family. On the surface, the ethical issue appears to be in regard to treatment refusal. However, when we look deeper, it becomes evident that the question is truly about whether the patient has the ability to make this treatment decision, given her worsening dementia, recent hemorrhage, and depression. In this case, an essential component of an ethics consultation would be to assess this patient's decisionmaking capacity to determine if her refusals are informed. This case has another level of complexity. If the patient does not have decisionmaking capacity, then who would be willing to serve in the role of surrogate decisionmaker? The case raises several ethical questions and thus makes directing a patient's care and decisionmaking challenging.


Nasal symptoms in patients with obstructive sleep apnea and their impact on therapeutic compliance with continuous positive airway pressure.
Continuous positive airway pressure (CPAP) is the first line treatment for moderate to severe obstructive sleep apnea syndrome. Despite the high effectiveness of this treatment, its use is often limited by suboptimal compliance and/or intolerance. Nasal side effects are considered a major cause of low therapeutic compliance. At present, there are no data to predict which patients will develop CPAP intolerance caused by nasal symptoms and only few studies looked at the effect of treatment of nasal symptoms on CPAP compliance. The first section of this review focuses on the impact of nasal symptoms (pre-existing or as a side effect of CPAP) on CPAP compliance/intolerance. The second section deals with the effect of nasal symptom treatment on CPAP compliance.