Mitofusin-2 mediates doxorubicin sensitivity and acute resistance in Jurkat leukemia cells.
Mitochondria oscillate along a morphological continuum from fragmented individual units to hyperfused tubular networks. Their position at the junction of catabolic and anabolic metabolism couples this morphological plasticity, called mitochondrial dynamics, to larger cellular metabolic programs, which in turn implicate mitochondria in a number of disease states. In many cancers, fragmented mitochondria engage the cell with the biosynthetic capacity of aerobic glycolysis in service of proliferation and progression. Chemo-resistant cancers, however, favor remodeling dynamics that yield fused mitochondrial assemblies utilizing oxidative phosphorylation (OXPHOS) through the electron transport chain (ETC). In this study, expression of Mitofusin-2 (MFN-2), a GTPase protein mediator of mitochondrial fusion, was found to closely correlate to Jurkat leukemia cell survival post doxorubicin (DxR) assault. Moreover, this was accompanied by dramatically increased expression of OXPHOS respiratory complexes and ATP Synthase, as well as a commensurate escalation of state III respiration and respiratory control ratio (RCR). Importantly, CRISPR knockout of MFN-2 resulted in a considerable decrease of doxorubicin (DxR) median lethal dose compared to a treated wildtype control, suggesting an important role of mitochondrial fusion in chemotherapy sensitivity and acute resistance.


Endoscopic Papillary Large Balloon Dilatation Without Sphincterotomy for the Treatment of Large Common Bile Duct Stone: Long-Term Outcomes at a Single Center.
Endoscopic papillary large balloon dilatation (EPLBD) without endoscopic sphincterotomy (EST) is an accepted, simplified endoscopic technique for large common bile duct (CBD) stone removal. However, little is known about the long-term outcomes of this technique. The purpose of this study was to evaluate the long-term outcomes of EPLBD without EST for the treatment of large CBD stones. This retrospective study of EPLBD without EST for a large CBD stone was conducted between June 2005 and October 2010. A total of 128 patients with a large CBD stone were included. The primary outcome measurement was complete CBD stone removal after EPLBD. Clinical data obtained from medical records were analyzed. The overall complete stone removal rate was 94.5 %. Mechanical lithotripsy was needed in 18 (14.1 %) patients. Post-procedural pancreatitis and asymptomatic hyperamylasemia occurred in 1 (0.8 %) and 11 (8.6 %) patients, respectively. One (0.8 %) patient experienced minor bleeding. The rate of stone recurrence was 13.1 %, and median time to stone recurrence was 600 days (range 144-2284 days). Over a half (64.3 %) of stone recurrences occurred during the 2 years following stone removal. Recurrence tended to be more frequent in patients with a large CBD diameter and in patients requiring multiple endoscopic sessions for complete CBD stone retrieval. EPLBD without EST may be safe and effective in patients with a large bile duct stone.


Numerical simulation and experimental research on mechanical behaviour of hydraulic disc brakes based on multi-body dynamics.
As a vital road construction machine, the bridge erecting machine works in a very complex environment. The brake as an important link to maintain the safety and stability of the bridge erecting machine, it will have serious consequences if it is failed. Establishing the brake simulation model and specifying the fault characteristics according to the actual operation status will make it more efficient to find the cause of faults and maintain the safety of machine for a long time. A simulation model of brake of the bridge erecting machine was established by Adams. The brake arms and center axis with obvious data characteristics were flexibly processed, and finite elements were analysed using Abaqus. To verify the accuracy of simulation models, rectangular rosettes were applied to special geometric points, and the strain data were gathered by using the DH3816N collector and compared with the simulation model. The Adams kinematic simulation model was used to simulate the actual operating conditions by the experiment of the disc springs. Two typical fault phenomena were selected: reduced insufficient of disc spring and oil pressure, and two fault characteristics were extracted: variation of the brake shoe clearance and variation of the braking system pressure. When the brake generates the fault characteristics, the normal operation of the brake will not be affected if the fault characteristics are in the first stage. When the fault characteristics are beyond the critical threshold, the faults phenomena of the brake are generated. The results of the simulation experiments proved that the method of using the simulation model to extract the fault characteristics of the braking system and distinguish the causes of the fault was feasible.


Permeabilization of transformed mouse fibroblasts by 3'-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate and the desensitization of the process.
A photoreactive analogue of ATP, 3'-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate (BzATP) altered the plasma membrane permeability of transformed 3T6 mouse fibroblasts to normally impermeant molecules as previously reported for ATP, but at lower concentrations. BzATP-induced permeabilization was modulated by pH, temperature, and the ionic composition of the medium similar to the permeabilizing effects of ATP. Conditions known to enhance ATP-induced permeabilization, such as treatment with the mitochondrial uncoupler carbonyl cyanide-m-chlorophenylhydrazone (CCCP) or the Ca2+-calmodulin antagonist trifluoperazine also enhanced BzATP-induced permeabilization. Conditions inhibitory to ATP-induced permeabilization, including chloride replacement or treatment with furosemide or dithiothreitol (DTT), inhibited permeabilization induced by BzATP. The ionic strength of the medium modulated the responsiveness of the cells to ATP and BzATP; a decrease in the ionic strength below isotonicity increased the sensitivity of the cells to the nucleotides, whereas an increase in ionic strength above isotonicity inhibited permeabilization. Prolonged exposure to ATP under non-permeabilizing conditions caused the cells to become insensitive to ATP and BzATP. The densensitization phenomenon provides support for the theory that the permeabilization process is mediated by a receptor for ATP.


SJP-L-5, a novel small-molecule compound, inhibits HIV-1 infection by blocking viral DNA nuclear entry.
Small-molecule compounds that inhibit human immunodeficiency virus type 1 (HIV-1) infection can be used not only as drug candidates, but also as reagents to dissect the life cycle of the virus. Thus, it is desirable to have an arsenal of such compounds that inhibit HIV-1 infection by various mechanisms. Until now, only a few small-molecule compounds that inhibit nuclear entry of viral DNA have been documented. We identified a novel, small-molecule compound, SJP-L-5, that inhibits HIV-1 infection. SJP-L-5 is a nitrogen-containing, biphenyl compound whose synthesis was based on the dibenzocyclooctadiene lignan gomisin M2, an anti-HIV bioactive compound isolated from Schisandra micrantha A. C. Smith. SJP-L-5 displayed relatively low cytotoxicity (50% cytoxicity concentrations were greater than 200 μg/ml) and high antiviral activity against a variety of HIV strains (50% effective concentrations (EC50)) of HIV-1 laboratory-adapted strains ranged from 0.16-0.97 μg/ml; EC50s of primary isolates ranged from 1.96-5.33 μg/ml). Analyses of the viral DNA synthesis indicated that SJP-L-5 specifically blocks the entry of the HIV-1 pre-integration complex (PIC) into the nucleus. Further results implicated that SJP-L-5 inhibits the disassembly of HIV-1 particulate capsid in the cytoplasm of the infected cells. SJP-L-5 is a novel small-molecule compound that inhibits HIV-1 nuclear entry by blocking the disassembly of the viral core.


Acute inhibition of nitric oxide exacerbates airway hyperresponsiveness, eosinophilia and C-C chemokine generation in a murine model of fungal asthma.
This study examined the role of nitric oxide in changes in airway physiology and inflammation in a murine model of fungal allergy induced by Aspergillus fumigatus (A. fumigatus) by treatment of A. fumigatus-sensitized mice with NG-nitro-L-arginine methyl ester (L-NAME) or D-NAME (8 mg/kg; i.p.). Female CBA/J mice received A. fumigatus antigen dissolved in incomplete Freund's adjuvant (10 mg/100 ml i.p. and s.c.) followed 2 weeks later by A. fumigatus antigens (20 mg; i.n.) and a subsequent i.t. challenge 4 days later. Airway physiology and inflammation were examined (24 to 72 h) following i.t. challenge. L-NAME-treated mice had lower lung nitrite levels 24 h after A. fumigatus challenge, but higher airway hyperresponsiveness and inflammation compared to D-NAME controls. Airway inflammation in the L-NAME treatment group (72 h) was characterized by a greater bronchoalveolar lavage (BAL), peribronchial eosinophilia and augmented levels of CC chemokines compared to controls. These findings suggest that nitric oxide is an important modulator of airway hyperresponsiveness, inflammation and C-C chemokine generation during allergic airway responses to A. fumigatus.


Effect of vaporizing cannabis rich in cannabidiol on cannabinoid levels in blood and on driving ability - a randomized clinical trial.
The aim of this prospective, placebo-controlled, double-blind, randomized, cross-over study was to determine cannabinoid levels in blood and driving-related ability after single (S1) and repetitive (S2) vaporization of cannabis rich in cannabidiol (CBD) containing < 1% Δ9-etrahydrocannabinol (THC). Healthy adult volunteers (Nsingle = 27, Nrepetitive = 20) with experience in smoking vapor-inhaled two low-THC/CBD-rich cannabis products both with < 1% THC (product 1: 38 mg CBD, 1.8 mg THC; product 2: 39 mg CBD, 0.6 mg THC) and placebo. Main outcomes were THC- and CBD-levels in whole blood and overall assessment of driving-related ability by computerized tests. Among 74 participants included, 27 (mean age ± SD, 28.9 ± 12.5 years) completed S1, and 20 (25.2 ± 4.0) completed S2. Peak concentrations and duration of detectability depended on the THC-content of the product. After single consumption THC dropped below 1.5 µg/L after 1.5 h, but was detected in some participants up to 5 h. Pairwise comparison of driving-related ability revealed no significant differences between low-THC/CBD-rich products (P1, P2) and placebo. Detection of THC after consumption of low-THC/CBD-rich cannabis might have legal consequences for drivers. Regarding overall driving-related ability, no significant differences were observed between the interventional products. This trial was registered with the German Clinical Trials Register (DRKS00018836) on 25.10.2019 and with the Coordination Office for Human Research (kofam) which is operated by the Federal Office of Public Health (FOPH) (SNCTP000003294).


Factors influencing endoscopic dacryocystorhinostomy outcome.
Endoscopic dacryocystorhinostomy (DCR) is a widely accepted treatment option for epiphora and dacryocystitis. To elucidate the cause of treatment failure after surgery, we analyzed patients' characteristics and perioperative background in association with poor outcome. We analyzed 165 patients with 213 sides who had endoscopic DCR. The influence of age, duration of symptoms, occlusion site and stent insertion were analyzed. Symptoms were completely cured in 85.0% (181/213) sides. Higher age (≥65 years) and proximal obstruction were associated with a poor prognosis while stent insertion and duration of symptoms were not. Higher age and proximal obstruction site were associated with a poor prognosis. Patients with a long history can be treated as per normal. The stent is not necessarily inserted in cases where the obstruction occurs distal to the lacrimal sac.


Immunoprecipitation of native chromatin: NChIP.
Chromatin immunoprecipitation (ChIP) is widely used in many fields to analyze the distribution of specific proteins, or their modified isoforms, across defined DNA domains. ChIP procedures fall into two main categories, namely, those that use native chromatin prepared by nuclease digestion (designated NChIP), and those that use chromatin in which DNA and proteins are crosslinked, either chemically or with UV light (designated XChIP). Each procedure has its own advantages and drawbacks. Here, we outline the methods currently in use in our laboratory to isolate and immunoprecipitate native chromatin from cultured cells, and to isolate and analyze immunoprecipitated protein and DNA.


A microscale procedure for isolating and sequencing the viroid RNA present in one gram of infected leaf tissue.
A microscale procedure for the isolation and purification of viroid RNA from one gram of viroid-infected leaf tissue and for its subsequent sequencing at the cDNA level is described using potato spindle tuber viroid (PSTV) as model system. Total nucleic acids are phenol-extracted and salt-fractionated with 2 M LiCl. The viroid-containing fraction is then subjected to bidirectional polyacrylamide gel electrophoresis. This removes all co-fractionated cellular RNAs from the circular viroid RNA which is finally recovered from the gel in pure form by isotachophoresis. Thus, from one gram of PSTV-infected tomato leaf tissue, about 100-250 ng of circular PSTV RNA can be obtained and used as template for several DNA primer-directed reverse transcription reactions. From the primer-extended overlapping cDNAs the entire sequence of the viroid progeny synthesized in an individual plant or plant leaf can thus be established by Maxam-Gilbert sequencing. This renders the procedure especially suited for the routine analysis of the in vivo fate of viroid mutants constructed in vitro.


Treatment of MRSA infections in an African-American male with G6PD deficiency.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency affecting erythrocytes is the most common enzymopathy in humans. It requires caution with the intake of oxidizing substances (e.g., medications and foods) because of the threat of hemolysis. Less recognized is the threat of a deficiency in G6PD that alters neutrophil function, which can compromise the killing of microbes by the oxidative burst mechanism. This results from a secondary alteration in the NADPH oxidase pathway. Methicillin-resistant Staphylococcus aureus (MRSA) infection, which is usually observed after exposure in the hospital setting, is becoming increasingly common in a community setting. Here we show the risk of MRSA and G6PD deficiency and discuss the pitfalls of G6PD deficiency.


Atrial Fibrillation/flutter Hospitalizations among US Medicaid Recipients with and without Systemic Lupus Erythematosus.
Systemic lupus erythematosus (SLE) is a multisystem chronic inflammatory autoimmune disease with high prevalence of several risk factors for atrial fibrillation/flutter (AF). However, the incidence and risk of AF in SLE have not been well quantified. We used the United States Medicaid Analytic eXtract from 2007 to 2010 to identify beneficiaries aged 18-65 years, with prevalent SLE, each matched by age and sex to 4 non-SLE general Medicaid recipients. We estimated the incidence rates (IR) per 1000 person-years (PY) for AF hospitalizations and used multivariable Cox regression to estimate the HR for AF hospitalization. We identified 46,876 US Medicaid recipients with SLE, and 187,504 age- and sex-matched non-SLE controls (93% female; mean age 41.5 ± 12.2 yrs). Known AF risk factors such as hypertension (HTN), cardiovascular disease (CVD), and kidney disease were more prevalent in patients with SLE. During a mean followup of 1.9 ± 1.1 years for SLE, and 1.8 ± 1.1 years for controls, the IR per 1000 PY for AF was 1.4 (95% CI 1.1-1.6) among patients with SLE and 0.7 (95% CI 0.6-0.8) among non-SLE controls. In age- and sex-matched and race-adjusted Cox models, the HR for AF was 1.79 (95% CI 1.43-2.24); after adjustment for baseline HTN and CVD, the adjusted HR was reduced to 1.17 (95% CI 0.92-1.48). SLE was associated with a doubled rate of hospitalization for AF compared to age- and sex-matched general Medicaid patients. In a race-adjusted model, the risk was 80% higher. However, the AF risk factors HTN and CVD were more prevalent among patients with SLE and accounted for the excess risk.


Possible Rickettsia massiliae Infection in Greece: an Imported Case.
Tick-borne rickettsioses are endemic in Greece; however, until recently, only Rickettsia typhi and R. conorii were tested routinely in human samples arriving at the National Reference Center. During the last few years, the identification of different rickettsia species in ticks led to the introduction of other spotted fever group rickettsiae in routine analysis. Under the new scheme, R. massiliae is now tested routinely in human samples; herein, we describe a human case of this infection.


Traumatic intracranial internal carotid aneurysm due to gunshot wound. Case report.
This patient developed an intracranial carotid artery aneurysm after a bullet wound. A review of the related literature, and the pathogenesis of traumatic false and true aneurysms are presented.


Gene expression in peripheral blood of patients with hypertension and patients with type 2 diabetes.
To evaluate the expression of atherosclerosis-associated genes in patients with hypertension and type 2 diabetes mellitus. Twenty-seven patients (14 men, 13 women), mean age 43.26 ± 11.69 years, were included in the study, which was divided into three groups: group 1 - patients with newly diagnosed hypertension and normal glucose tolerance (n = 9), group 2 - normotensive individuals with newly diagnosed type 2 diabetes (n = 9), and control group - normotensive individuals with normal glucose tolerance (n = 9). Gene expression analysis was performed with Human Atherosclerosis RT2 Profiler PCR Array. In patients with hypertension, we found eight genes with increased expression - FABP3, FAS, FN1, IL1R2, LPL, SERPINE1, TGFB1, and VCAM1. Decreased expression was observed for two genes - SELPLG and SERPINEB2. In patients with type 2 diabetes we found seven up-regulated genes - APOE, BAX, MMP1, NFKB1, PDGFB, SPP1, and TGFB2, whereas no specifically down-regulated genes were observed. Three genes - KLF2, PDGFRB, and PPARD were found to be expressed only in groups 1 and 2. Hypertension is associated with increased expression of FABP3, FAS, FN1, IL1R2, LPL, SERPINE1, TGFB1, and VCAM1 and decreased expression of SELPLG and SERPINEB2. The up-regulation of FAS, FN1, SERPINE1, TGFB1, and VCAM1 might be associated with an increased cardiovascular risk. Type 2 diabetes is associated with increased expression of APOE, BAX, MMP1, NFKB1, PDGFB, SPP1, and TGFB2. KLF2 and PPARD might be part of protective mechanisms that limit target organ damage in both disease conditions. Expression of PDGFRB might play an important role in the pathogenesis of both hypertension and type 2 diabetes.


A network analysis framework of genetic and nongenetic risks for type 2 diabetes.
Both genetic and nongenetic factors have been found to be associated with type 2 diabetes, however, the correlation between them is still unclear. In the present study, we aimed to fully decipher the nongenetic and genetic factor association network for type 2 diabetes. We identified risk factors for type 2 diabetes by systematically searching for related meta-analyses and genome-wide association studies (GWAS) database. Among a total of 27,822 studies screened, 202 articles were eligible, from which 174 nongenetic factors and 210 genetic factors associated with type 2 diabetes were identified. Then, we obtained 584 associations between the nongenetic and genetic factors of type 2 diabetes, based on which a risk factor association network was conducted. The nongenetic factors could be classified into seven categories according to the Global Burden of Diseases (GBD). Of these seven categories of nongenetic factors, five were found to be correlated with genes associated with type 2 diabetes, including environmental risks, behavioral risks, metabolic risks, related disease of type 2 diabetes, and treatments. Specifically, air pollutants of environmental risks, alcohol using of behavioral risks, obesity of metabolic risks, rheumatoid arthritis of related disease risk, and simvastatin of treatment was correlated with the largest number of genes. In summary, the correlation between genetic factors and nongenetic factors identified in this study indicates that there is a common phenotype-genotype association in type 2 diabetes, with the combinations of genotypes ("genetic signature") clustering in phenotypes related to type 2 diabetes. Thus, we should take a systematic approach to explore the relationship of various factors for type 2 diabetes, as well as other noncommunicable diseases.


Cobe Spectra is superior to Fenwal CS 3000 Plus for collection of hematopoietic stem cells.
One hundred and seventy-seven stem cell apheresis procedures performed on 91 patients using the Fenwal CS 3000 Plus cell separator and 61 procedures performed on 37 patients using the Cobe Spectra cell separator were studied to compare the CD34(+) cell collection efficiencies (CE; the proportion of the total CD34(+) cell content in the blood volumes processed that is harvested) of the two machines. The absolute peripheral blood CD34(+) cell count was comparable for the two groups (P = 0.27). A strong correlation was seen between the blood CD34(+) cell count and the total number of CD34(+) cells collected for the Spectra (r(2) = 0.59; P < 10(-6)) and for the CS 3000 Plus (r(2) = 0.60; P < 10(-6)). No significant correlation emerged between the peripheral blood CD34(+) cell count and the CE of either machine. The total number of CD34(+) cells collected per procedure was comparable (P = 0.51): median 113 x 10(6) for CS 3000 Plus and median 218 x 10(6)for Spectra. CE was significantly higher with the Spectra (median 45.7%, range 9.8-98.6%) than the CS 3000 Plus (median 30.3%, range 1.7-89.3%; P < 0.00001). We conclude that the CD34(+) cell CE of the Spectra is superior to that of the CS 3000 Plus. Therefore, under the usual clinical conditions, Cobe Spectra should be used preferentially for peripheral blood progentor cell collection to maximize the number of hematopoietic stem cells collected.


Reliability analysis of Cobb angle measurements of congenital scoliosis using X-ray and 3D-CT images.
Therapeutic decisions for congenital scoliosis rely on Cobb angle measurements on consecutive radiographs. There have been no studies documenting the variability of measuring the Cobb angle using 3D-CT images in children with congenital scoliosis. The purpose of this study was to compare the reliability and measurement errors using X-ray images and those utilizing 3D-CT images. The X-ray and 3D-CT images of 20 patients diagnosed with congenital scoliosis were used to assess the reliability of the digital 3D-CT images for the measurement of the Cobb angle. Thirteen observers performed the measurements, and each image was analyzed by each observer twice with a minimum interval of 1 week between measurements. The analysis of intraobserver variation was expressed as the mean absolute difference (MAD) and standard deviation (SD) between measurements and the intraclass correlation coefficient (IaCC) of the measurements. In addition, the interobserver variation was expressed as the MAD and interclass correlation coefficient (IeCC). The average MAD and SD was 4.5° and 3.2° by the X-ray method and 3.7° and 2.6° by the 3D-CT method. The intraobserver and interobserver intraclass ICCs were excellent in both methods (X-ray: IaCC 0.835-0.994 IeCC 0.847, 3D-CT: IaCC 0.819-0.996 IeCC 0.893). There was no significant MAD difference between X-ray and 3D-CT images in measuring each type of congenital scoliosis by each observer. Results of Cobb angle measurements in patients with congenital scoliosis using X-ray images in the frontal plane could be reproduced with almost the same measurement variance (3°-4° measurement error) using 3D-CT images. This suggests that X-ray images are clinically useful for assessing any type of congenital scoliosis about measuring the Cobb angle alone. However, since 3D-CT can provide more detailed images of the anterior and posterior components of malformed vertebrae, the volume of information that can be obtained by evaluating them has contributed greatly to the development of strategies for the surgical treatment of congenital scoliosis.


Brain protective effect and hemodynamics of dexmedetomidine hydrochloride in patients with intracranial aneurysm.
The purpose of the study was to investigate the effect of dexmedetomidine hydrochloride (Dex) on the recovery of cognitive function, hemodynamics, and postoperative analgesia in patients undergoing intracranial aneurysm craniotomy. general anesthesia was performed on patients undergoing intracranial aneurysm craniotomy in neurosurgery. Patients were randomly divided into three groups: Dex 1 group (Dex dose: 1 μg/kg), Dex 2 group (Dex dose: 0.5 μg/kg), and blank control group (normal saline). The changes of heart rate, arterial pressure, intraoperative brain function index, and postoperative pain score were recorded and compared. in Dex 1 group and Dex 2 group, the heart rate of T1 and T2 phase was significantly lower than that of T3-T7 phases (P < 0.05); compared with the control group, the heart rate of Dex 1 group and Dex 2 group was significantly lower (P < 0.05). The average arterial pressure of the control group and Dex groups was significantly different (P < 0.05). Compared with the control group, there were significant differences between Dex 1 group and Dex 2 group: S100 β protein in T7-T10, NSE (neuron specific enolase) in T9 and T10, pain score in T8, T9 and T10 after operation. the application of Dex in the resection of intracranial aneurysms can protect the brain of patients, minimize the influence of operation on hemodynamics, and relieve postoperative pain, which is worthy of clinical application.


Atomic proximity between S4 segment and pore domain in Shaker potassium channels.
A recently proposed model for voltage-dependent activation in K+ channels, largely influenced by the KvAP X-ray structure, suggests that S4 is located at the periphery of the channel and moves through the lipid bilayer upon depolarization. To investigate the physical distance between S4 and the pore domain in functional channels in a native membrane environment, we engineered pairs of cysteines, one each in S4 and the pore of Shaker channels, and identified two instances of spontaneous intersubunit disulfide bond formation, between R362C/A419C and R362C/F416C. After reduction, these cysteine pairs bound Cd2+ with high affinity, verifying that the residues are in atomic proximity. Molecular modeling based on the MthK structure revealed a single position for S4 that was consistent with our results and many other experimental constraints. The model predicts that S4 is located in the groove between pore domains from different subunits, rather than at the periphery of the protein.


Psychoffarmacologica IV.
Deze aflevering gaat over een probleem van naamgeving. Door de recente trends op het gebied van de indicatiestelling van psychofarmaca worden we meer en meer in de war gebracht. Uit het verloop van dit verhaal zult u wel zien waarom en de vraag is of u de redactie van advies wilt en kunt dienen. In de meeste farmacologische textboeken worden de psychofarmaca ingedeeld naar de klinische werking, zoais u weet, en drie hoofdgroepen worden onder-scheiden: de psychoanaleptica, de psycholeptica en de psychodysleptica. Hier zullen we ons beperken tot de eerste twee groepen. Tot de belangrijkste typen farmaca van de eerste groep worden de antidepressiva en soms de lithiumzouten gerekend en tot de tweede groep behoren de ataractica (zoals de ben-zodiazepinen) en de antipsychotica. Hoe verhoudt zieh zo'n indeling ten opzichte van andere farmaco-therapeutische indelingen in de geneeskunde: worden eiders farmaca gerubrieeerd volgens de klinische indicaties of volgens de primaire aangrijpingspunten c.q. chemische karakteristie-ken? Soms volgt de indeling het werkingsprineipe, dan weer het ziektebeeld of symptoom, waarbij het middel het meest wordt toegepast.


Complementary health insurance in France. Who pays? Why? Who will suffer from public disengagement?
The study is based on a rare database with information about health status, socioeconomic characteristics and the complementary health insurance choices of the French population. We intend to characterise a two-stage decision process: first, the decision to purchase complementary health insurance, and then the factors related to choice of policy quality. Our econometric study indicates that (i) income level has a strong and significant effect on the decision to purchase complementary insurance, whilst there is no evidence that health risk considerations affect this decision at all; (ii) the individual decision about quality is associated barely if at all with any rational explanatory variables. The population's concrete behaviour, revealed by the study, is consistent with an allocation of low-risk people to private insurance and high-risk people to public insurance. Complementary insurance is not especially relevant to patients with serious diseases, who depend much more on the public system. If the public insurance system were to disengage significantly from coverage of serious illness, a vacuum would be created that would leave people at high risk without full coverage. These results have broad implications for numerous national systems of social protection seeking a new mix between private and public insurance.


Caffeine restores feeding response to 2-deoxy-D-glucose in 6-hydroxydopamine-treated rats.
A large portion of the central catecholaminergic nerve terminals of the rat are destroyed by administering 6-hydroxydopamine (6-HDA) via the cerebrospinal fluid. Animals lesioned in this way often appear normal, yet show many subtle behavioural abnormalities. We have been examining one example of this phenomenon, the failure of 6-HDA-lesioned rats to increase food intake when given a systemic injection of 2-deoxy-D-glucose (2-DG) (refs 5, 6). This glucose analogue seems to elicit feeding in intact rats due to its inhibition of glycolysis in cerebral chemoreceptor cells. We have proposed that lesioned animals do not eat because of an insufficient central catecholaminergic response to the severe decrease in glucose utilisation induced by 2-DG (ref. 10). If so, then pretreatments which serve to augment this neurochemical response might be expected to reinstate behavioural function. Consistent with this hypothesis, very large increases in telencephalic tyrosine hydroxylase activity in 6-HDA-lesioned animals, which occur following chronic insulin treatment, are associated with the restoration of 2-DG-induced feeding. Many of the physiological effects of catecholamines in the sympathetic nervous system seem to be mediated by an increase in the cyclic AMP concentration of the target cells. Methylxanthenes, such as caffeine and theophylline, inhibit phosphodiesterase, prevent cyclic AMP degradation, and thereby potentiate the catecholamine-stimulated rise in cyclic nucleotide. They also enhance many of the behavioural and physiological effects of catecholamines, presumably by the same mechanism. We therefore sought to determine whether the acute administration of those sympathomimetic agents, in intact and 6-HDA-lesioned rats, also would potentiate 2-DG-induced feeding, a behaviour that seems to be mediated, in part, by central catecholaminergic neurons. We report that caffeine restores the 2-DG-induced feeding response.


Sequential development of multiple aortic aneurysms in a neonate post umbilical arterial catheter insertion.
A neonate in whom multiple aortic aneurysms developed as a result of umbilical arterial catheterization is presented. Initially a single aneurysm was diagnosed by ultrasound. Serial sonographic examinations showed enlargement of the first as well as formation and subsequent enlargement of additional aneurysms.


3,3',5,5'-tetramethylbenzidine/H2O2 staining is not specific for heme proteins separated by gel electrophoresis.
Staining of sodium dodecyl sulfate or lithium dodecyl sulfate gels with 3,3',5,5'-tetramethylbenzidine (TMBZ)/H2O2 after electrophoresis has frequently been used as a specific method of detecting heme proteins. That TMBZ is an electron donor for O2 reduction by the nonheme-soluble cytochrome oxidase/nitrite reductase from Nitrosomonas europaea is now shown; this protein is detected by the TMBZ/H2O2 method. A method for the determination of TMBZ oxidase activity is given; hence, the detection of artifactual staining due to proteins of this type is possible.


Effect of influenza vaccination on serum clozapine and its main metabolite concentrations in patients with schizophrenia.
To study the effect of influenza vaccine on serum clozapine, N-desmethylclozapine and clozapine-N-oxide steady-state concentrations in patients with schizophrenia. This was an open-label study in 14 schizophrenic inpatients (with 2 drop-outs) using clozapine. Serum trough concentrations of clozapine. N-desmethylclozapine and clozapine-N-oxide, as well as the concentration of c-reactive protein (CRP), were measured immediately before conventional trivalent influenza vaccination and 2, 4, 7 and 14 days after the vaccination. Influenza vaccination had no significant effect on serum concentrations of clozapine, N-desmethylclozapine or clozapine-N-oxide. No changes in the clinical effects of clozapine were observed after vaccination. Influenza vaccination did not increase CRP. However, two drop-out patients who developed upper respiratory and abdominal symptoms had increased and elevated serum concentrations of clozapine, compared with the baseline. Influenza vaccination using conventional trivalent influenza vaccine does not affect serum concentrations of clozapine or its main metabolites. However, an infection-related increase in CRP may be associated with increased serum concentration of clozapine.


Role of radionuclide imaging in the orthopedic patient.
Since its introduction more than 40 years ago, nuclear medicine has played an important role in the diagnosis and detection of soft tissue and skeletal disorders. Skeletal scintigraphy or bone scanning is a diagnostic study used to evaluate the distribution of osteoblastic activity or active bone formation within the body. Because no single imaging technique is ideal in all clinical situations, selecting an appropriate imaging test depends on understanding the pathophysiology of the suspected condition and limitations of each technique. This article provides a brief overview of bone scintigraphy, infection imaging, and positron emission tomography in the context of current, adult orthopedic practice.


Rate of complications due to neuromuscular scoliosis spine surgery in a 30-years consecutive series.
The aim of this study was to evaluate the rate of intraoperative and postoperative complications in a large series of patients affected by neuromuscular scoliosis. It was a monocentric retrospective study. In this study have been considered complications those events that significantly affected the course of treatment, such as getting the hospital stay longer, or requiring a subsequent surgical procedure, or corrupting the final result of the treatment. Of the 358 patients affected by neuromuscular scoliosis treated from January 1985 to December 2010, 185 that met the inclusion criteria were included in the study. There were recorded 66 complications in 55/185 patients. Of that 66 complications, 54 complications occurred in 46/120 patients with Luque's instrumentation, while only 12 complications occurred in 9/65 patients with hybrid instrumentation and this difference was statistically significant (p < 0.05); 11/126 patients with pelvic fixation and 5/59 without pelvic fixation, as well as 45/156 patients treated by posterior approach alone and 10/29 patient that underwent combined anterior-posterior approach suffered complications but both this did not result in a statistical significant difference (p > 0.05). The surgical treatment in neuromuscular scoliosis is burdened by a large number of complications. An accurate knowledge of possible complications is mandatory to prepare strategies due to prevent adverse events. A difference in definitions could completely change results in good or bad as well as in our same series the adverse events amounted at almost 30% of cases, but complications that due to complete failure would amount at 9.19% of patients.


Estimating Catastrophic Health Expenditures from Household Surveys: Evidence from Living Standard Measurement Surveys (LSMS)-Integrated Surveys on Agriculture (ISA) from Sub-Saharan Africa.
Out of pocket (OOP) payments for healthcare remain a significant health financing challenge in sub-Saharan Africa (SSA). Understanding the drivers and impacts of this financial health burden is both an economic and a public health priority. This study examines how the burden of OOP health expenditures varies with different thresholds for financial catastrophe. The analysis is based on Livings Standards Measurement Surveys (LSMS)-Integrated Surveys on Agriculture (ISA) for five SSA countries-Ethiopia, Malawi, Nigeria, Tanzania, and Uganda. We estimate the degree by which OOP payments as share of total household non-food expenditures exceed either the 15 or 25% threshold. For the countries considered, the severity of OOP payments is substantial-the average positive overshoot (beyond the 25% threshold) is above 10%, except for Nigeria. This reflects a higher percentage of OOP in total household health expenditures-compared to taxes and contributions-especially among the poor in these specific countries. Regarding sensitivity of distribution of catastrophic health expenditures, we find that households with low non-food expenditures are more likely to incur catastrophic payments with the exception for Uganda where catastrophic payments increase with the increase of non-food household expenditures. The burden of catastrophic health expenditures remains large. In order to reduce this burden, public health expenditures need to be expanded as an alternative. This calls for renewed attention to expand public revenues as the most sustainable methods of financing health expenditures in Africa.


Decreased protein staining after chemical crosslinking.
Reaction of several proteins with the homobifunctional amino group-directed reagents dithiobissuccinimidyl propionate or methylmercaptobutyrimidate is shown to decrease the subsequent Coomassie blue or silver staining of these proteins after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The decreased dye response is not due to the proximity of the crosslinked proteins since the monomers generated after bisection of the crosslinkers with beta-mercaptoethanol show reduced staining. Quantitation of dye absorbance relative to protein content (assayed by radioactivity) indicates that the decreased staining effect is variable, depending on the particular stain, crosslinker, and protein.


Toxicity of Fusarium mycotoxins on maize plants.
Synergistic effects of Fusarium - toxins mixture (moniliformin, fumonisin B1, fusaproliferin, zearalenone, zearalenol and deoxynivalenol, each at concentration 3.5 μg mL-1) on maize plants of resistant and susceptible cultivars were studied. After 72-hour treatment the biomass production with both cultivars was approximately 6% lower than in the respective controls. In the resistant cultivar chlorophyll content was increased comparing to control, with higher increase in chlorophyll b. In susceptible cultivar chlorophyll content was slightly decreased, particularly with chlorophyll b.No significant differences between treated and non-treated plants were found in the cell ultrastructure. In susceptible plants the young root cells were more vacuolated and plasmolysis occurred in the cells of outer cortex. In leaves of this cultivar also disorganization of thylakoids in some chloroplasts was observed.


Low Levels of Alcohol Consumption and Risk of Intestinal Metaplasia: A Cohort Study.
The impact of alcohol drinking on gastric precancerous lesions remains unclear. We investigated the relationship of alcohol intake with risk of atrophic gastritis (AG) and intestinal metaplasia (IM). This study included 202,675 Korean adults free from AG and IM on their initial endoscopy who were followed with repeated endoscopic examinations. A parametric proportional hazards model was used to estimate the adjusted HR (aHR) with 95% confidence interval (CI) for incident AG and IM based on endoscopic diagnosis. During a mean follow-up of 4.7 years, 64,853 incident AG cases and 4,536 IM cases were identified. Alcohol consumption including drinking frequency, quantity, and binge drinking were consistently associated with increased risk of both AG and IM in a dose-response manner. After adjustment for confounders, the multivariable aHRs (95% CIs) for incident IM comparing average alcohol intake of <10, 10-<20, 20-<40, and ≥40 g/day with lifetime abstainers were 1.27 (1.02-1.56), 1.34 (1.07-1.66), 1.50 (1.20-1.86), and 1.54 (1.23-1.93), respectively. Former drinkers were also at a higher risk for AG and IM compared with lifetime abstainers. These associations were consistently observed in never smokers and in time-dependent analyses. In a large cohort of Korean individuals, alcohol intake even at low levels was independently associated with increased risk of developing endoscopic AG and IM, supporting a role of alcohol consumption in the pathogenesis of AG and IM, the precursor lesions of stomach cancer. Alcohol consumption from low-level drinking may contribute to gastric carcinogenesis.


Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model.
Monitoring cancer and aging in vivo remains experimentally challenging. Here, we describe a luciferase knockin mouse (p16(LUC)), which faithfully reports expression of p16(INK4a), a tumor suppressor and aging biomarker. Lifelong assessment of luminescence in p16(+/LUC) mice revealed an exponential increase with aging, which was highly variable in a cohort of contemporaneously housed, syngeneic mice. Expression of p16(INK4a) with aging did not predict cancer development, suggesting that the accumulation of senescent cells is not a principal determinant of cancer-related death. In 14 of 14 tested tumor models, expression of p16(LUC) was focally activated by early neoplastic events, enabling visualization of tumors with sensitivity exceeding other imaging modalities. Activation of p16(INK4a) was noted in the emerging neoplasm and surrounding stromal cells. This work suggests that p16(INK4a) activation is a characteristic of all emerging cancers, making the p16(LUC) allele a sensitive, unbiased reporter of neoplastic transformation.


Patterns in nutrient concentrations and biological quality indices across the upper Thames river basin, UK.
This paper examines the nutrient chemistry and biological quality indices [Mean Trophic Rank (MTR) and Trophic Diatom Index (TDI)] for rivers within the upper Thames basin. The predominant sources of nitrogen within the rivers monitored were diffuse and agricultural in nature. However, phosphorus showed both diffuse and point source signals. MTR surveys undertaken both upstream and downstream of major STWs indicate that these rivers are 'at risk' of eutrophication or 'badly damaged'. MTR surveys also indicate increased trophic status downstream of STWs, whereas TDI does not indicate such a consistent pattern. Phosphorus treatment at selected major sewage treatment works in the upper Thames basin resulted in significant reductions in in-stream P concentrations and reductions in fluxes by a half to two thirds. However, the effects of P-reduction on in-stream ecology (measured as MTR and TDI) were more difficult to ascribe, owing to: (1) the high variability in river flow rates experienced since P-reduction was introduced; (2) lag effects related to P stores in river bed sediments; and (3) diffuse and smaller point source inputs upstream. The results of this study indicate that control of upstream sources of phosphorus may prove critical in improving the biological quality status of UK lowland rivers, including ecological responses to P-source controls on the major sewage treatment works downstream. Upstream sources include both diffuse (agricultural) sources and small point source inputs which, at present, are not classified as 'qualifying discharges' under the Urban Wastewater Treatment Directive (UWWTD) and are thus not subject to phosphorus control measures. These results are of relevance for integrated, sustainable management and protection of European freshwater resources, particularly in terms of new ecological targets for water quality management under the new Water Framework Directive.


The impact of Middle Eastern Origin, HIV, HCV, and HIV/HCV co-infection in the development of hypovitaminosis D in adults.
A relationship between hypovitaminosis D and infection with HIV and HCV has been established in the scientific literature. Studies comparing these illnesses to other risk factors for development of hypovitaminosis D, such as being of Middle Eastern origin, have been lacking. The goals of this study were: (a) to document vitamin D levels in groups of individuals at high risk of developing its deficiency, (b) analyze the data collected to numerically determine which group had the lowest average vitamin D levels, and (c) discuss the impact of the findings and offer possible explanations. This retrospective observational study involved reviewing medical charts and documenting recent vitamin D levels. Our subgroups were: (a) individuals infected with HIV, (b) individuals infected with HCV, (c) individuals co-infected with HIV/HCV, and (d) people of Middle Eastern origin. The gathered data was subsequently subjected to statistical analysis. People of Middle Eastern origin were found more likely to be vitamin D deficient as compared to those infected with HIV, HCV, or co-infected with both HIV and HCV. This suggests that genetic and environmental factors unique to otherwise healthy Middle Eastern people are more detrimental, in terms of developing hypovitaminosis D, than being chronically infected with the aforementioned illnesses.


Progression level of extracapsular spread and tumor budding for cervical lymph node metastasis of OSCC.
The progression level of extracapsular spread (ECS) for cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) was previously divided into three types, and their relationships with the prognosis of patients were re-examined. The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis. ECS was detected in 216 cases of OSCC and analyzed. The 5-year overall survival and RFS rates of patients with type C, which was microscopically defined as tumor invasion to perinodal fat or muscle tissue, were significantly poor at 40.6 and 37.8%, respectively. The results of a univariate analysis suggested that the prognosis of ECS in OSCC patients is associated with its progression level, particularly type C. The 5-year RFS rate of type C with tumor budding was significantly poor at 31.5%. Type C with tumor budding correlated with local and regional recurrence as well as distant metastasis. In a multivariate analysis, tumor budding was identified as an independent prognostic factor. These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients. This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients.


Serum lecithin-cholesterol acyltransferase activity in children with familial hyperbetalipoproteinaemia.
Serum (non-fasting) was obtained from 71 healthy school children (12-14 years) and from 16 children with the heterozygous form of familial hyperbetalipoproteinaemia being treated by diet or ion-exchange resin. The activity of lecithin-cholesterol acyltransferase (EC 188.8.131.52) expressed as nmol cholesterol esterified/hour/ml serum did not change with increasing concentrations of unesterified cholesterol in the healthy children. In children with familial hyperbetalipoproteinaemia, lecithin-cholesterol acyltransferase activity was higher than in the healthy children and this activity increased with increasing concentrations of unesterified cholesterol.


A mini review of xylanolytic enzymes with regards to their synergistic interactions during hetero-xylan degradation.
This review examines the recent models describing the mode of action of various xylanolytic enzymes and how these enzymes can be applied (sequentially or simultaneously) with their distinctive roles in mind to achieve efficient xylan degradation. With respect to homeosynergy, synergism appears to be as a result of β-xylanase and/or oligosaccharide reducing-end β-xylanase liberating xylo-oligomers (XOS) that are preferred substrates of the processive β-xylosidase. With regards to hetero-synergism, two cross relationships appear to exist and seem to be the reason for synergism between the enzymes during xylan degradation. These cross relations are the debranching enzymes such as α-glucuronidase or side-chain cleaving enzymes such as carbohydrate esterases (CE) removing decorations that would have hindered back-bone-cleaving enzymes, while backbone-cleaving-enzymes liberate XOS that are preferred substrates of the debranching and side-chain-cleaving enzymes. This interaction is demonstrated by high yields in co-production of xylan substituents such as arabinose, glucuronic acid and ferulic acid, and XOS. Finally, lytic polysaccharide monooxygenases (LPMO) have also been implicated in boosting whole lignocellulosic biomass or insoluble xylan degradation by glycoside hydrolases (GH) by possibly disrupting entangled xylan residues. Since it has been observed that the same enzyme (same Enzyme Commission, EC, classification) from different GH or CE and/or AA families can display different synergistic interactions with other enzymes due to different substrate specificities and properties, in this review, we propose an approach of enzyme selection (and mode of application thereof) during xylan degradation, as this can improve the economic viability of the degradation of xylan for producing precursors of value added products.


Recurrent Unprovoked Venous Thrombosis (Cerebral Sinus Thrombosis and Mesenteric Vein Thrombosis) in Young Patient with Crohn's Disease: A Case Report and Review.
Inflammatory bowel disease (IBD) patients have a higher risk of thrombosis. Most data about thrombosis in inflammatory bowel disease are related mainly to inpatients with disease activity, but in this article, we report one case of inflammatory bowel disease with two different sites of venous thrombosis which happened in a patient with nonactive IBD at an outpatient setting.


The association between affective psychopathic traits, time incarcerated, and cortisol response to psychosocial stress.
Previous research has demonstrated that psychopathic personality traits are significantly predictive of blunted cortisol reactivity to a performance-based stressor task (Trier Social Stress Test; TSST) in college students. However, the relationship between cortisol reactivity and psychopathy has not been explored in high risk samples such as incarcerated populations. Further, the role of imprisonment in relation to cortisol stress reactivity has not been previously explored, but could have practical and conceptual consequences in regard to rehabilitation and biological sensitivity to context, respectively. The current study tested the hypotheses that both psychopathic personality traits and amount of time incarcerated are related to cortisol blunting in response to stress among incarcerated young adults. A sample of 49 young adult male offenders was recruited to complete the TSST. Salivary hormone samples were taken just prior to and 20 min post-stressor, and participants were interviewed with the Psychopathy Checklist-Youth Version. Variables quantifying the amount of time at the present facility prior to the date of testing and number of commitments in juvenile facilities were also collected. Correlational analyses indicated that only number of incarcerations was related to blunted cortisol. Hierarchical Linear Modeling revealed that time incarcerated and number of commitments were related to a blunted cortisol response among responders and declining cortisol reactivity among nonresponders, respectively. Controlling for time incarcerated, psychopathic traits were significantly related to cortisol decline in response to the stressor among nonresponders, but were not related to blunted cortisol among responders. Results of this project highlight the potential biological effects of prolonged and repeated incarcerations, and extend our understanding about the relationship between psychopathic traits and cortisol reactivity in an incarcerated sample.


The CDR1 and Other Regions of Immunoglobulin Light Chains are Hot Spots for Amyloid Aggregation.
Immunoglobulin light chain-derived (AL) amyloidosis is a debilitating disease without known cure. Almost nothing is known about the structural factors driving the amyloidogenesis of the light chains. This study aimed to identify the fibrillogenic hotspots of the model protein 6aJL2 and in pursuing this goal, two complementary approaches were applied. One of them was based on several web-based computational tools optimized to predict fibrillogenic/aggregation-prone sequences based on different structural and biophysical properties of the polypeptide chain. Then, the predictions were confirmed with an ad-hoc synthetic peptide library. In the second approach, 6aJL2 protein was proteolyzed with trypsin, and the products incubated in aggregation-promoting conditions. Then, the aggregation-prone fragments were identified by combining standard proteomic methods, and the results validated with a set of synthetic peptides with the sequence of the tryptic fragments. Both strategies coincided to identify a fibrillogenic hotspot located at the CDR1 and β-strand C of the protein, which was confirmed by scanning proline mutagenesis analysis. However, only the proteolysis-based strategy revealed additional fibrillogenic hotspots in two other regions of the protein. It was shown that a fibrillogenic hotspot associated to the CDR1 is also encoded by several κ and λ germline variable domain gene segments. Some parts of this study have been included in the chapter "The Structural Determinants of the Immunoglobulin Light Chain Amyloid Aggregation", published in Physical Biology of Proteins and Peptides, Springer 2015 (ISBN 978-3-319-21687-4).


[Effects of glycyrrhizic acid on the growth and acid-producing of Streptococcus mutans in vitro].
To investigate the antibacterial activity of glycyrrhizic acid against Streptococcus mutans (S. mutans, ATCC 25175) in vitro. The minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of glycyrrhizic acid against S. mutans were detected using doubling dilution. The effects of glycyrrhizic acid on the growth and acidogenic profile of S. mutans and the inhibition ratio of glycyrrhizic acid on growth and acid-producing of S. mutans were investigated by detecting the Abs of bacteria suspension and the pH value of medium at definite time intervals (0 h, 3 h, 7 h, 12 h, 23 h, 40 h) during cultivation. The MIC determined for glycyrrhizic acid was 1.57 mg/mL and there was no bactericidal effect when concentration of glycyrrhizic acid up to 12.5 mg/mL. The glycyrrhizic acid inhibited the multiplication and acid-producing of S. mutans significantly and the effects became stronger with concentration increasing. When concentration up to 1.57 mg/mL, the inhibition ratio of glycyrrhizic acid on the growth and acid-producing of S. mutans were exceeded 80 and 70 percent, respectively. The glycyrrhizic acid can inhibit the growth and acid-producing of S. mutans in vitro.


Characterization of four mitochondrial genomes from superfamilies Noctuoidea and Hyblaeoidea with their phylogenetic implications.
In the present study, the newly sequenced mitogenomes of three Noctuoid and one Hyblaeoid (Insecta: Lepidoptera) species were annotated based on next-generation sequence data. The complete mitogenome lengths of Oraesia emarginata, Actinotia polyodon, Odontodes seranensis, and Hyblaea puera were 16,668 bp, 15,347 bp, 15,419 bp, and 15,350 bp, respectively. These mitogenomes were found to encode 37 typical mitochondrial genes (13 protein-coding, 22 transfer RNA, 2 ribosomal RNA) and a control region, similar to most Lepidoptera species. Maximum likelihood (ML) methods and Bayesian inference (BI) were used to reconstruct the phylogenetic relationships of the moths. This study showed the relationships of Noctuoid families as follows: (Notodontidae + (Erebidae + (Nolidae + (Euteliidae + Noctuidae)))). Furthermore, the species H. puera was separately clustered from the Noctuoidea member groups. Till now, the species from the superfamily Hyblaeoidea have not been discussed for their phylogenetic relationships. In this study, the complete mitochondrial genome of one species from the superfamily Hyblaeoidea was analysed.


Germ cell tumors of the ovary: the experience of the National Cancer Institute of Milan. I. Dysgerminoma.
The experience of the Istituto Nazionale Tumori of Milan on dysgerminoma is presented. Between 1970 and December of 1982, 25 patients were treated with a unique protocol which considered surgery and radiotherapy with different schedules according to the extension of the disease. With this treatment protocol all 13 patients at Stage I were alive and free of disease with a median follow-up of 77 months. Of 12 patients at Stage III (10 retroperitoneal and 2 retroperitoneal and peritoneal) 4 relapsed. The 5-year relapse-free survival of Stage III patients was 61.4% and the overall survival 89.5%. Amenorrhea due to radiation dose absorbed by the contralateral shielded ovary was found in 7.7%. The excellent results in Stage I patients were balanced by the unsatisfactory results in Stage III patients. A more aggressive treatment and the knowledge of other prognostic factors seem necessary.


The dependence of finger tip touch-pressure upon the condition of Braille reading.
The finger motions and quickness of braille reading were investigated by way of recording the finger tip pressure on the braille and its time process. Subjects were separated into two groups. One group consisted of 5 experienced blinds and the other group consisted of 5 blinds who were beginners in braille reading. The comparison of obtained results from two groups gave some evidence for the following conclusion. The finger tip pressure was considerably increased for careful or difficult reading.


A preliminary validation of the Brief COPE instrument for assessing coping strategies among people living with HIV in China.
The Brief COPE instrument has been utilized to conduct research on various populations, including people living with HIV (PLWH). However, the questionnaire constructs when applied to PLWH have not been subjected to thorough factor validation. A total of 258 PLWH were recruited from two provinces of China. They answered questions involving the scales of three instruments: the Brief COPE, the Perceived Social Support Scale, and the Perceived Discrimination Scale for PLWH. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were conducted. The CFA found a poor goodness of fit to the data. The subsequent EFA identified six preliminary factors, forming subscales with Cronbach's alphas, which ranged from 0.61 to 0.80. Significant correlation coefficients between the subscales and measures of perceived social support and perceived discrimination were reported, giving preliminary support to the validity of the new empirical factor structure. This study showed that the original factor structure of the Brief COPE instrument, when applied to PLWH in China, did not fit the data. Thus, the Brief COPE should be applied to various populations and cultures with caution. The new factor structure established by the EFA is only preliminary and requires further validation.


Social support and incentives programme for patients with tuberculosis: experience from the Russian Federation.
Tuberculosis (TB) services including social support and incentive programmes in four Russian regions (Orel, Vladimir, Belgorod Oblasts and Republic of Mari-El). To determine reasons for TB treatment default among non-adherent patients and to describe patient views of social support programmes and the organisation of treatment. Standard anonymous questionnaires were administered to new pulmonary TB patients registered for treatment. A total of 87 non-adherent patients and 1302 adherent patients were interviewed. The leading reasons for treatment default given by non-adherent patients were the need to earn money (30%), alcohol use (30%) and not perceiving themselves as being sick (25%). Monetary incentives were preferred by the majority of patients (67%), followed by food/hot meals (41%) and transportation reimbursement (32%). Overall, among the proposed social support programmes, those that offered small daily incentives (23%) or a big final bonus (21%) were the most popular. The majority of patients (67%) preferred out-patient treatment. Collaboration between TB services and social organisations and substance abuse services as well as availability of psychological testing/counselling for patients are social support modalities for improving adherence suggested by study findings. Social support should be combined with a patient-centred approach to TB treatment.


An in vitro comparison of subjective image quality of panoramic views acquired via 2D or 3D imaging.
The objective of this study is to compare subjective image quality and diagnostic validity of cone-beam CT (CBCT) panoramic reformatting with digital panoramic radiographs. Four dry human skulls and two formalin-fixed human heads were scanned using nine different CBCTs, one multi-slice CT (MSCT) and one standard digital panoramic device. Panoramic views were generated from CBCTs in four slice thicknesses. Seven observers scored image quality and visibility of 14 anatomical structures. Four observers repeated the observation after 4 weeks. Digital panoramic radiographs showed significantly better visualization of anatomical structures except for the condyle. Statistical analysis of image quality showed that the 3D imaging modalities (CBCTs and MSCT) were 7.3 times more likely to receive poor scores than the 2D modality. Yet, image quality from NewTom VGi® and 3D Accuitomo 170® was almost equivalent to that of digital panoramic radiographs with respective odds ratio estimates of 1.2 and 1.6 at 95% Wald confidence limits. A substantial overall agreement amongst observers was found. Intra-observer agreement was moderate to substantial. While 2D-panoramic images are significantly better for subjective diagnosis, 2/3 of the 3D-reformatted panoramic images are moderate or good for diagnostic purposes. Panoramic reformattings from particular CBCTs are comparable to digital panoramic images concerning the overall image quality and visualization of anatomical structures. This clinically implies that a 3D-derived panoramic view can be generated for diagnosis with a recommended 20-mm slice thickness, if CBCT data is a priori available for other purposes.


Concentrations of immunoglobulin classes in subcompartments of the sheep lung.
The concentrations of IgA, IgG and IgM were measured in plasma, lung lymph and lung lavage fluid from adult sheep. Immunoglobulin concentrations in lymph and lavage fluid should fall sequentially during diffusive flux from the vascular compartment as a result of molecular sieving at the capillary endothelium and the alveolar epithelium. This was seen only for the IgG class. High concentrations of IgA and IgM in the interstitial (lymph) and luminal (lavage) compartments of the lung (relative to plasma levels) suggest either local synthesis of these classes or the existence of class specific active transport.


The Art of Endoscopic Dilation: Lessons Learned Over 4 Decades of Practice.
The author offers his approach to esophageal dilation based on 40 years of a practice specializing in swallowing disorders and esophageal disease. He discusses general concepts in the management of esophageal strictures and then provides an approach to dilation of different types of esophageal stenotic lesions.


Neuronal network coherent with hand kinematics during fast repetitive hand movements.
We quantified the coupling between magnetoencephalographic (MEG) cortical signals and the kinematics of fast repetitive voluntary hand movements monitored by a 3-axis accelerometer. Ten healthy right-handed adults performed self-paced flexion-extension movements of right-hand fingers at ~3Hz with either touching the thumb during flexions (TOUCH) or not (noTOUCH). At the sensor level, we found in all subjects and conditions significant coherence at the movement frequency (F0) and its first harmonic (F1). Coherence values were significantly higher in TOUCH compared to noTOUCH. At the group level, dynamic imaging of coherent sources localized the main source of coherent activity at the left primary motor (M1) hand area, except at F0 TOUCH were the main source was localized at the left primary sensory (S1) hand area. Other coherent brain areas were also identified at right S1-M1 cortices (F0), left dorsolateral prefrontal cortex (F1), left posterior parietal cortex (F0 TOUCH and F1 noTOUCH) and left medial S1-M1 areas (TOUCH). This study highlights the prominent role of rhythmic neuronal activity phase-locked to movements for the encoding and the integration of key sensori-motor features of limb kinematics. This study also suggests that somatosensory afferences play a key role to sustain a high synchronization level between the neuronal activity in coherent brain areas and hand acceleration. Some coherent brain regions differed between F0 and F1 in both conditions, suggesting that distinct cortical areas are involved in different features of hand kinematics.


ABO blood group incompatibility and infertility in Nigerian couples.
ABO blood group substances were determined in either the seminal plasma (male patients) or saliva of 100 infertile couples and 100 control subjects. Comprehensive infertility evaluation was performed in all patients. Results were analysed in groups of couples with respect to their ABO blood group and compared with fertile control subjects. Over 70% of fertile marriages were compatible. Comparison of infertile and fertile couples for either ABO compatibility or incompatibility did not reveal any statistically significant difference (P greater than 0.05). This suggests some measure of low zone tolerance to ABO antigens on spermatozoa, for only a small minority of sperm introduced during coitus gains access to the oviduct and ultimately to the peritoneal cavity.


[Effect of benzamide derivatives on convulsions induced by the toxic action of oxygen in rats].
The reversible MAO-A inhibitor moclobemide (5 mg/kg) was shown to prevent seizures in rats during exposure to toxic oxygen (6 ata). Benzamide derivatives increased the latent period of oxygen seizures and decreased the lethality following hyperbaric oxygenation. The range of anti-MAO activity of moclobemide and clorgyline in the rat brain and heart after toxic oxygenation was studied. It was distinct from those in control animals. Clorgyline was found to be more active in inhibiting MAO during toxic oxygenation in the heart and moclobemide-in the brain. The possibility is shown to prevent oxygen seizures not only with irreversible MAO-A inhibitors (clorgyline), but also with reversible ones (moclobemide).


Hemoglobin Thailand [alpha 56 (E 5) Lys leads to Thr]: a new abnormal human hemoglobin.
A healthy Thai male was found to have an abnormal hemoglobin moving faster than Hb A in starch-gel electrophoresis, in addition to the normal hemoglobin constituents. The abnormal hemoglobin constituted 28% of the whole hemoglobin. The subject was asymptomatic and had normal hematologic findings. Structural characterization revealed that the amino acid substitution was alpha 56 Lys leads to Thr. This variant has never been described previously and it is named Hb Thailand.


Application of Alamar blue/5-carboxyfluorescein diacetate acetoxymethyl ester as a noninvasive cell viability assay in primary hepatocytes from rainbow trout.
We have adopted the application of two fluorescent indicator dyes to studying the viability of monolayers of primary rainbow trout hepatocytes. The two fluorescent dyes--Alamar blue, which indicates metabolic activity of a cell, and 5-carboxyfluorescein diacetate acetoxymethyl ester (CFDA-AM), which is an indirect measure of cell membrane integrity-are noninvasive and can be monitored conveniently directly in multiwell plates. According to these dyes, L-15 culture medium supported hepatocyte viability over 96 h more stably than did M199. The two dyes proved to be capable of detecting a concentration-dependent toxic insult to hepatocytes caused by the model compound, pentachlorophenol. In contrast, a lack of impact on cell viability was indicated for up to 10(-5) M 17beta-estradiol, and that observation was supported by the induction of vitellogenin (VTG) mRNA/protein as indicator of hepatocyte-differentiated function. Application of the Alamar blue/CFDA-AM for 30 min did not alter gene expression either specifically as reflected by VTG or generally as reflected by a random selection of gene sequences that were amplified by differential display reverse transcription PCR (dd-rt-PCR). Thus, the assay represents a resource-efficient way of integrating measures of cell viability and gene expression that should aid in the interpretation of in vitro results. The assay can be applied repeatedly to the same set of cells and can be performed just prior to analysis of gene expression.


Insulin radioimmunoassay measurement by the polyethyleneglycol separation technique using the ROTOP kit reagents. Some clinical applications.
The technique described in the instructions booklet of the radioimmunoassay Insulin kit commercially known as the ROTOP-Insulin kit (CCR) tested both in our and in other laboratories did not show the desired reproducibility. Using the main ROTOP reagents (anti-insulin serum and 125I-Insulin) in radioimmunoassay (RIA) systems with other separation techniques (double antibody, dextran-charcoal and polyethyleneglycol) we observed that these reagents are suitable for a sensitive and precise RIA system. The intra-assay variations observed were caused by the separation technique with 86% ethanol as proposed by the procedure. This work describes an insulin-RIA system modified in order to be able to use the ROTOP reagents with the polyethyleneglycol (PEG) separation technique. This variant is used for more than three years in our laboratory but was adopted also in other RIA laboratories in Romania.


Efficient BLG-Cre mediated gene deletion in the mammary gland.
Using the phage P1-derived Cre/loxP recombination system, we have developed a strategy for efficient mammary tissue specific inactivation of floxed genes. Transgenic mice were generated which express Cre DNA-recombinase under the control of the mammary gland specific promoter of the ovine beta-lactoglobulin (BLG) gene. To test the specificity of Cre mediated recombination, we crossed these mice to animals harbouring a floxed DNA ligase I allele. We show that the BLG-Cre construct specifies mammary specific gene deletion, and furthermore that it is temporally regulated, predominantly occurring during lactation. We fully characterised the extent of gene deletion in one line (line 74). In this strain the virgin gland is characterised by low levels (7%) of Cre mediated deletion, whereas 70-80% of cells within the lactating mammary gland have undergone recombination. Immunohistochemistry and indirect in situ PCR were used respectively to demonstrate that both Cre protein and Cre activity were evenly distributed throughout the population of secretory epithelial cells. The level of background recombination in non-mammary tissues was found to be < or = 1.1%, irrespective of mammary gland developmental status. Crossing the transgenic BLG-Cre strain described here to mice harbouring other floxed alleles will facilitate the functional analysis of those genes during differentiation and development of the mammary gland.


Plasma renin activity related to sodium balance, renal function and urinary vasopressin in the newborn infant.
Plasma renin activity was determined in 25 healthy, full-term, newborn infants aged 1 day to 9 weeks. High values were found, the mean level at 1-2 days of life (24.8 +/- 8.4 ng/ml/hr, SE) being significantly higher than the mean levels at 7-9 days (5.8 +/- 1.5) and at 4-9 weeks (8.1 +/- 1.3) (P less than 0.05). No correlation was found between plasma renin activity and systolic blood pressure, hematocrit, creatinine clearance, serum sodium, or serum potassium. Plasma renin activity (log values) was inversely correlated with sodium intake (r = -0.58) or with urinary sodium (r = -0.44), and positively with urinary osmolality (r = 0.67). The correlations reached higher coefficients if only infants aged less than or equal to 9 days were considered. In addition, vasopressin was measured by radioimmunoassay in the urine. The daily excretion was lower in newborn infants (9.4 +/- 1.6 ng/m2/day, SE, at 1-2 days of postnatal life) than in healthy children (37.1 +/- 5.6), and was significantly correlated with creatinine clearance (r = 0.69), but not with urinary osmolality.


Pneumococcal vaccination coverage among persons ≥65 years--United States, 2013.
Invasive pneumococcal disease is a major cause of illness in the United States, and rates are higher among persons ≥65 years. Pneumococcal vaccination has been recommended to adults ≥65 years since 1997. Data from the 2005-2013 Behavioral Risk Factor Surveillance System were analyzed. Weighted estimates of pneumococcal vaccination coverage were calculated by state and race/ethnicity and tests for linear trend were performed. In 2013, the median state vaccination coverage among adults ≥65 years was 69.5%, and coverage ranged from 61.9% in New Jersey to 75.6% in Oregon. Coverage overall among non-Hispanic whites (71.1%) was higher than coverage for non-Hispanic blacks (57.7%), Hispanics (51.9%), and non-Hispanic persons of other race (65.4%). Coverage increased from 2005 to 2013 overall and by racial/ethnic subgroups. Although pneumococcal vaccination coverage has improved in the past several years, coverage remains below the Healthy People 2020 target of 90% and racial/ethnic disparities exist.


Cardiologist-Performed Baseline Evaluation with an Assessment of Coronary Status for Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: Impact on Newly Diagnosed Coronary Artery Disease.
Given the potential cardiovascular risks of androgen deprivation therapy (ADT), it is essential to identify patients who may be at an increased risk for coronary artery disease (CAD). Despite the recent ESC recommendations, there is no consensus on when to refer a patient to a cardiologist for further evaluation. To report on new diagnoses of CAD in patients with prostate cancer (PCa) requiring ADT who underwent a systematic cardio-onco evaluation with an assessment of their coronary status. This is a retrospective, monocentric study that included patients with PCa who had completed a cardio-onco evaluation with an assessment of their coronary status in the cardio-oncology department at the Western Cancer Institute, Nantes, between January 2019 and August 2022. The baseline cardio-onco evaluation included a physical exam, transthoracic echography, and electrocardiogram, followed with a systematic evaluation of their coronary status. The primary objective was to determine the incidence of newly diagnosed CAD. The secondary objective was to evaluate the number of changes in cardiovascular treatment. Among the 34 patients who underwent cardio-onco evaluation, 7 (20.6%) were diagnosed with CAD, with a median time to diagnosis of 5 months. Most patients were asymptomatic, with one who experienced a myocardial infarction. Of the 27 patients without CAD, 44.4% underwent a therapeutic intervention by the cardiologist, with no cardiac deaths during follow-up. Overall, 55.9% of patients had a therapeutic intervention after the cardio-onco evaluation. The high incidence of newly diagnosed CAD in asymptomatic patients supports the need for screening for CAD in this population. Further research is needed to determine whether routine screening for CAD in patients receiving ADT would result in significant clinical benefits.


Controlled Allergen Challenge Facilities and Their Unique Contributions to Allergic Rhinitis Research.
The aim of this study is to review advances in basic and clinical allergic rhinitis (AR) research over the past decade that have been conducted using controlled allergen challenge facility (CACF) models of allergen challenge. Databases, including PubMed, Medline, and Web of Science were searched for articles employing an ambient pollen exposure in a controlled facility to study AR, published between 2004 and the present date, using the terms as follows: CACF, Environmental Exposure Unit (EEU), Vienna Challenge Chamber (VCC), Fraunhofer Institute Environmental Challenge Chamber, Atlanta Allergen Exposure Unit, Biogenics Research Chamber, Allergen BioCube, Chiba and Osaka Environmental Challenge Chamber, exposure unit, challenge chamber, or environmental exposure chamber. Articles were then selected for relevance to the goals of the present review, including important contributions toward clinical and/or basic science allergy research. CACFs offer sensitive, specific, and reproducible methodology for allergen challenge. They have been employed since the 1980s and offer distinct advantages over traditional in-season multicentre trials when evaluating new treatments for AR. They have provided clinically applicable efficacy and pharmacologic information about important allergy medications, including antihistamines, decongestants, antileukotrienes, immunotherapies, and nasal steroids. CACF models have also contributed to basic science and novel/experimental therapy research. To date, no direct studies have been conducted comparing outcomes from one CACF to another. Over the past decade, CACF models have played an essential role in investigating the pathophysiology of AR and evaluating new therapies. The future opportunities for this model continue to expand.


Malignant atrophic papulosis (Degos' disease)--diffuse involvement of brain and bowel in an African patient.
We report pathognomonic skin lesions of malignant atrophic papulosis, accompanied by lethal central nervous system and gastrointestinal disease in a 22-year-old black man. Histopathological studies of the brain and colon showed areas of infarction and an underlying vasculitis with leukocytoclasis.


A parallel glycolysis provides a selective advantage through rapid growth acceleration.
Glycolysis is a universal metabolic process that breaks down glucose to produce adenosine triphosphate (ATP) and biomass precursors. The Entner-Doudoroff (ED) pathway is a glycolytic pathway that parallels textbook glycolysis but yields half as much ATP. Accordingly, in organisms that possess both glycolytic pathways (for example, Escherichia coli), its raison d'être remains a mystery. In this study, we found that the ED pathway provides a selective advantage during growth acceleration. Upon carbon and nitrogen upshifts, E. coli accelerates growth faster with than without the ED pathway. Concurrent isotope tracing reveals that the ED pathway flux increases faster than that of textbook glycolysis. We attribute the fast response time of the ED pathway to its strong thermodynamic driving force and streamlining of glucose import. Intermittent nutrient supply manifests the evolutionary advantage of the parallel glycolysis; thus, the dynamic nature of an ostensibly redundant pathway's role in promoting rapid adaptation constitutes a metabolic design principle.


Application of Universal Design for Learning (UDL) Principles to Surgical Education During the COVID-19 Pandemic.
During the COVID-19 pandemic in 2020, we have faced unprecedented challenges in the delivery of surgical education. At the time of writing, changes to the structure and nature of the surgical workforce are occurring rapidly, even daily. Surgical educators are utilizing remote learning solutions, including flipped classroom approaches, online educational materials, telemedicine, and simulations, to continue education for surgical residents despite cancelations of face-to-face instruction. Our objective is to delineate an interdisciplinary strategy, utilizing the principles of Universal Design for Learning (UDL), by which we can optimize learning during this pandemic. This perspective describes the UDL framework which can be used to situate solutions to issues with delivery of surgical education during this pandemic within the broader view of strategic inclusive instructional design to meet diverse learning needs.. The principles of UDL can inform curricular and pedagogical changes in surgical education that may be employed during a time of social distancing, isolation, and quarantine. UDL involves planning flexibility into curricular design from the outset, recognizing that learners are varied in their learning preferences and capabilities, motivational characteristics, and environmental constraints. Viewing the design of remote learning opportunities through the UDL lens aims to remove barriers to learning during this pandemic by targeting three areas: expansion of the means that information is communicated, ways that learners are supported and motivated, and approaches to assessing learning through available distance learning technologies.


In vitro translation of rabbit lung Clara cell secretory protein mRNA.
The major secretory product of Clara cells is a low molecular weight protein (CCSP) whose extracellular function, at this time, is not known. The primary translation product of its mRNA is a protein with molecular weight approximately 1 kD greater than that of the native secreted protein (6.0 kD). The primary translation product is not detected in incubated lung tissue, only the secretory protein is found. The primary translation product is trypsin sensitive whereas the secretory protein is not. Cell free translation of the mRNA in the presence of microsomes results in cleavage of the signal peptide and the appearance of the lower molecular weight trypsin-resistant secretory protein. These data indicate that the low molecular weight Clara cell secretory protein is synthesized as a larger, trypsin sensitive, protein. Passage of the protein into the cisternae of the endoplasmic reticulum results in loss of the signal peptide and alterations to the tertiary structure of the protein rendering it trypsin insensitive.


Clinical evaluation of 104 hip resection arthroplasties after removal of a total hip prosthesis.
Functional results of resection arthroplasty are currently considered poor. In 104 hip prosthesis removals after either septic or aseptic loosening, pain, walking, joint motility, life style, and patient's opinion were evaluated. A satisfactory result was recorded in 72% of cases. Prognosis is poorer in patients who are young, have septic loosening, and have poor residual mobility. Resection arthroplasty should be considered a salvage procedure in cases of septic loosening and/or bone stock deficiency after a failed total hip arthroplasty.


Early diagnostic value of C-reactive protein as an inflammatory marker for moderate-to-severe bronchopulmonary dysplasia in premature infants with birth weight less than 1500 g.
Bronchopulmonary dysplasia (BPD) is a serious respiratory complication in premature infants and moderate-to-severe BPD may affect the long-term quality of life and lack of specific treatment once it happened. Therefore, it is necessary to identify early diagnostic biomarkers for moderate-to-severe BPD. This retrospective cohort study included all premature infants with birth weight <1500 g from March 1, 2015 to June 30, 2017. Patients were categorized into mild BPD, moderate-to-severe BPD and non BPD groups. Data collected included patient characteristics, C-reactive protein (CRP) tested at six time points, including 1d (2 h after birth and before the first feeding), 3d, 7d, 2w, 3w, and 4w after birth, and maternal factors. Ordinal regression analysis was used to identify independent predictors of moderate-to-severe BPD and receiver operating characteristic (ROC) curve was used to evaluate the value of CRP as an early diagnostic marker for moderate-to-severe BPD. A total of 831 patients were recruited. BPD occurred in 156/831 premature infants with birth weight less than 1500 g. Lower birth weight (OR = 0.998, 95% CI 0.997-0.999, P = 0.004), higher CRP level 3 days after birth (OR = 1.287, 95% CI 1.195-1.384, P = 0.000), and hemodynamically significant patent ductus arteriosus (HsPDA) (OR = 12.256, 95% CI 3.766-39.845, P = 0.000) were independent risk factors for moderate-to-severe BPD. The area under curve of the CRP level 3 days after birth for diagnosing moderate-to-severe BPD was 0.867 (95% CI, 0.823-0.912, P = 0.000). The sensitivity was 83.0% and the specificity was 78.3% when the cut-off value was set at 4.105 mg/L. The CRP level 3 days after birth may be used as an early diagnostic marker for moderate-to-severe BPD in preterm infants who have the risk factors for BPD with birth weight less than 1500 g.


Sensitive determination of tenofovir in human plasma samples using reversed-phase liquid chromatography.
A new high-performance liquid chromatography assay was developed for the determination of tenofovir, a nucleotide analogue, in plasma. A solid-liquid extraction procedure was coupled with a reversed-phase HPLC system. The system requires a mobile phase containing Na(2)HPO(4) buffer, tetrabutylammonium hydrogen sulfate and acetonitrile for different elution through a C(18) column with UV detection. The method proved to be accurate, precise and linear between 10 and 4000 ng/ml. The method was applied to determine trough levels of tenofovir in 11 HIV-infected patients with virologic failure under multiple antiretroviral therapy. This method was also successfully applied to a pharmacokinetic study in an HIV infected patient with renal failure.


Monoglyceride oleogels for lipophilic bioactive delivery - Influence of self-assembled structures on stability and in vitro bioaccessibility of astaxanthin.
The present study investigated the influence of self-assembled structures on stability and in vitro bioaccessibility of astaxanthin by modifying the structures with different processing conditions. The self-assembled structures of GMS oleogels were changed to produce smaller crystals and more compact network at higher glycerol monostearate (GMS) concentration and lower cooling temperature, resulting in higher hardness, oil binding capacity, and viscoelastic properties of oleogels. In the stability test, the highest retention ratio of astaxanthin was observed in oleogels formed at 4 °C and 10% GMS, indicating that the denser network structures were more effective to prevent the degradation of astaxanthin. During in vitro digestion, the self-assembled structures of oleogels and the nature of GMS molecules affected the lipolysis and micellization, which in turn regulated the bioaccessibility of astaxanthin. Collectively, GMS oleogels were effective delivery materials for improving the stability and bioaccessibility of lipophilic bioactives.


Enzyme activities of lung lavage in silicosis.
The cytotoxic effect of quartz on lung cells has been well documented by in vitro and animal studies, but the pertinence of these findings to humans has not yet been documented. We measured lactate dehydrogenase (LDH) activities in the lung lavage of 24 long-term workers in the Québec granite industry and 25 control subjects. We found significant increases in LDH activities in the workers' lung lavage, even in the absence of established silicosis (9 subjects). We looked at a similar observation in the sheep model of early silicosis, measured quartz content of lung lavage, and found significant correlation with LDH levels (R = 0.64, p less than 0.001). All of the quartz particles in human and sheep lung lavage were in the alveolar macrophages. To test further the relationship of macrophage damage (cytotoxicity of quartz) we measured the release of LDH by sheep alveolar macrophage in 24 h cell culture under control conditions, exposure to inert dust, titanium, minusil-5 quartz, or aluminum-treated quartz. The LDH release was at control levels during titanium exposure and showed a significantly dose-related increase during quartz exposure. The latter cytotoxic effect was largely attenuated by aluminum treatment of quartz. These in vitro data agreed with previous reports. This study presents evidence of a cytotoxic effect of quartz inhalation in humans. The effect is related to the intensity of quartz retention in the lung macrophages; it is not a nonspecific dust exposure effect and can be attenuated by surface modification of the quartz.


[Computerized tomography in agenesis of the corpus callosum: findings in 27 cases].
We describe a retrospective study of 27 cases of complete agenesis of the corpus callosum examined by CT and not associated to schizencephaly, holoprosencephaly and Dandy-Walker complex. Partial agenesis is also not included in the present study. The imaging findings are correlated to sex, age and symptoms.


Comparison of Estimated Glomerular Filtration Rate with Both Serum Creatinine and Cystatin C (eGFRcr-cys) versus Single Analyte (eGFRcr or eGFRcys) Using CKD-EPI and MDRD Equations in Tertiary Care Hospital Settings.
To assess and compare the glomerular filtration rate (eGFR) estimated through MDRD and CKD-EPIcr equations in early and late stages of chronic kidney disease on biochemical marker creatinine (eGFRcr), cystatin C (eGFRcys); and combined (eGFRcr-cys), using CKD-EPI equation. Observational, comparative cross-sectional study. Chemical Pathology and Endocrinology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi in collaboration with Armed Forces Institute of Urology (AFIU), Rawalpindi from October 2019 to March 2020. GFR was assessed on the basis of creatinine clearance taking serum and 24-hour urinary specimens. MDRD and CKD-EPI equations were applied to calculate eGFR by serum creatinine (eGFRcr), cystatin C (eGFRcys), and combined (eGFRcr-cys). Pearson correlation technique was used to compare eGFR calculated by different equations with creatinine clearance in different stages of CKD. Performance of equations was evaluated and compared in different stage of CKD. A total of 181 subjects were enrolled. Median age was 57 years (IQR, 25). Median (IQR) GFR (ml/min/1.73m2) calculated by CrCl, MDRD, CKD-EPIcr, CKD-EPIcys and CKD-EPIcr-cys equations were 45.1 (41.5), 50.6 (23.8), 52.0 (28.0), 43.0 (65.0) and 45 (47), respectively. eGFR calculated by CKD-EPIcr had positive and slightly higher correlation (r=0.880) than MDRD study equation (r=0.867). While comparing the markers, it was observed that CKD-EPIcys had better correlation in early stages of CKD (r=0.889); whereas, CKD-EPIcr performed better in late stages (r=0.896). CKD-EPIcr-cys had the highest correlation (r=0.984) at all stages of CKD. eGFR calculated by CKD-EPI equation considered as better diagnostic efficient response than MDRD equation in diagnosis and staging of chronic kidney disease. While applying CKD-EPI equation for measurement of eGFR, eGFRcr-cys performs better than any of eGFRcr or eGFRcys at all stages of CKD. Key Words: Estimated glomerular filtration rate (eGFR), Cystatin C (Cys), Creatinine (Cr), Creatinine clearance (CrCl), CKD-EPI equation, MDRD equation.


Antibiotic prescription after tooth extraction in adults: a retrospective cohort study in Austria.
Broad spectrum antibiotics are often used for the prophylaxis of infectious endocarditis and treatment of odontogenic infections, but there are limited data related to antibiotic use and adherence to prescription guidelines. METHODS: Data from patients with tooth extraction between 2014 and 2018 were selected from a database of a regional health insurance fund. We created three data sets, one based on all tooth extractions, one on multiple teeth extractions, and one including only single tooth extraction. After data collection, descriptive analysis was carried out. The differences in prescription pattern of antibiotic medicine were tested by χ2 test, Student´s t-test or ANOVA. From 43,863 patients with tooth extraction, 53% were female, and 3,983 patients (9.1%) filled a prescription for antibiotic medicine. From 43,863 patients, 157 patients (0.4%) had endocarditis risk, but only 8 patients of these (5.1%) filled an antibiotic prescription. In total, 9,234 patients had multiple and 34,437 patients had only one tooth extraction. Patients with more than one tooth extraction received more often antibiotic treatment (10.7%) compared to those with single tooth extractions (χ2 = 36; p < 0,001). Patients with more than one tooth extraction were older, however, younger patients received antibiotics more frequently (t = 28,774, p = 0.001). There was no relationship with endocarditis risk status. Clindamycin and amoxicillin/clavulanic acid were the most frequently prescribed antibiotic medicines. In this retrospective cohort study, dentists did not discriminate prophylactic antibiotic prescription with regard to endocarditis risk status. A factor influencing prescribing behaviour of antibiotic medicines was the number of extracted teeth.


The effect of metabarcoding 18S rRNA region choice on diversity of microeukaryotes including phytoplankton.
Metabarcoding using high throughput sequencing of amplicons of the 18S rRNA gene is one of the widely used methods for assessing the diversity of microeukaryotes in various ecosystems. We investigated the effectiveness of the V4 and V8-V9 regions of the 18S rRNA gene by comparing the results of metabarcoding microeukaryotic communities using the DADA2 (ASV), USEARCH-UNOISE3 (ZOTU), and USEARCH-UPARSE (OTU with 97% similarity) algorithms. Both regions showed similar levels of genetic variability and taxa identification accuracy. Richness for DADA2 datasets of both regions was lower than for UNOISE3 and UPARSE datasets, which is due to more accurate error correction in amplicons. Microeukaryotic communities (autotrophs and heterotrophs) structure identified using both regions showed a significant relationship with phytoplankton (autotrophs) communities structure based on microscopy in a seasonal freshwater sample series. The strongest relationship was found between the phytoplankton species and V8-V9 ASVs produced by DADA2.


Low-load/high-repetition elastic band resistance training in patients with COPD: a randomized, controlled, multicenter trial.
High-repetitive resistance training (RT) is recommended to increase peripheral muscular endurance in healthy adults; however, the effects of RT with this design on exercise capacity and health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD) is unknown. The study aimed to investigate if low-load/high-repetition elastic band RT could improve functional capacity, muscular function, endurance cycle capacity or HRQOL in patients with COPD. A prospective, randomized, controlled, multicentre trial was constructed with concealed allocation, blinded outcome assessment and intention-to-treat analysis. A total of 44 patients with moderate-to-very-severe COPD (forced expiratory volume during the first second, 44.6% predicted) were included. Patients were randomized to either the experimental group receiving 8 weeks of RT (three sessions/week) in combination with patient education (four occasions) or the control group receiving the patient education alone. At post-tests, the between-group differences were in favor of the experimental group on the 6-min walk test [mean difference (95% confidence interval)]: 34 m (14-54) and the 6-min pegboard and ring test [20 rings (3-37)]. No difference between groups was found on the chronic respiratory disease questionnaire [0.1 (-0.2 to 0.4)]. On secondary outcomes, results were in favor of the experimental group regarding upper extremity endurance capacity, muscular function and depression, but no difference was seen between groups on endurance cycle capacity and HRQOL. RT can increase functional capacity and muscular function but not cycle endurance capacity and HRQOL in patients with moderate-to-severe COPD.