Health care of villagers in northeast Thailand--a health diary study.
A one-month health diary was used as a research instrument for measuring health care in the northeastern rural area of Thailand during the month of November, 1992. Three hundred forty-five respondents, which represents 22.2% of the total households in 12 villages from 2 districts in the Khon Kaen province of northeast Thailand, completed the health diaries. Self-medication was most practiced for health care (37.5% of ill persons) followed by health service utilization at local health center (19.4%), at community hospital (11.4%), at private clinic (11.4%), and by "wait and see" (9.0%). Analgesics were the most frequently used drugs for relief of fever, headache, common cold and abdominal pain. The use of a combination of drug (eg. a cocktail) was common as self-medication for relief of back and leg pain. Traditional or herbal drugs were a frequently chosen alternative for self-medication, both in adult and children. The authors suggest that the villagers should be educated concerning drug hazards in order to increase their background knowledge on drug use.


Septorhinoplasty for Destructed Septal L-Strut in Patients with Previously Applied Porous High-Density Polyethylene Implants (Medpor®).
Porous high-density polyethylene implants (Medpor®) have been extensively used for septal extension grafts in Asian rhinoplasty. However, studies on the long-term complications associated with Medpor® have not been reported. Therefore, the purpose of this study was to evaluate the long-term complications of septal extension grafts using Medpor® and present a reconstructive strategy for destructed septal L-struts. We conducted a 12-year retrospective medical chart review of 428 patients who visited our center for septorhinoplasty. Among 428 patients, 43 patients had Medpor® for septal extension grafts previously applied at other clinics. The quadrangular cartilage was devoid or destructed in the area where Medpor® was previously applied. Therefore, all patients underwent secondary septorhinoplasty using autogenous cartilage grafts. Patient outcome was assessed to evaluate satisfaction, hardness of nasal tip, functional nasal obstruction symptom evaluation (NOSE) scores, and pain scores. Anthropometric analyses were carried out with patients' photographs. Postoperative complications were also evaluated. After septal L-strut reconstruction, 87% of patients were satisfied with their aesthetic results. Hardness of nasal tip, NOSE scores, and pain scores also improved after reconstruction. Anthropometric analyses demonstrated that increased nasal length and decreased columellar-labial angle were achieved in patients with short nose deformities. No postoperative complications related to the reconstruction were recorded for any patient. The devastated destruction of nasal support lines was found after the use of Medpor® for septorhinoplasty. Therefore, the use of Medpor® should be reduced. Autogenous cartilage grafts are the last resort for reconstruction of destructed septal L-struts. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Sexual stage-specific expression of a third calcium-dependent protein kinase from Plasmodium falciparum.
A third calcium-dependent protein kinase (CDPK) gene has been isolated from the human malaria parasite Plasmodium falciparum by vectorette technology. The gene consists of five exons and four introns. The open reading frame resulting from removal of the four introns encodes a protein of 562 amino acid residues with a predicted molecular mass of 65.3 kDa. The encoded protein, termed PfCDPK3, consists of four distinct domains characteristic of a member of the CDPK family and displays the highest homology (46% identity and 69% similarity) to PfCDPK2, the second CDPK of P. falciparum. The N-terminal variable domain is rich in serine/threonine and lysine and contains multiple consensus phosphorylation sites for a range of protein kinases. The catalytic domain possesses all conserved motifs of the protein kinase family except for the highly conserved glutamic acid residue in subdomain VIII, which is replaced by a glutamine residue. The sequence of the junction domain comprising 31 amino acid residues is less conserved. The calmodulin-like regulatory domain contains four EF-hand calcium-binding motifs, each consisting of a loop of 12 amino acid residues which is flanked by two alpha-helices. Southern blotting of genomic DNA digests showed that the Pfcdpk3 gene is present as a single copy per haploid genome. A 2900 nucleotide transcript of this gene is expressed specifically in the sexual erythrocytic stage, indicating that PfCDPK3 is involved in sexual stage-specific events. It is proposed that PfCDPK3 may serve as a link between calcium and gametogenesis of P. falciparum.


[Results of optic reconstructive interventions in children with ocular injuries].
Optic reconstructive interventions were carried out in 36 children with ocular injuries aged 3-14 years. Perforating keratoplasty was combined with measures aimed at repair of the normal anatomic status of the eye and the transparency of its optic media. Microsurgical interventions were performed for penetrating corneal wounds in 27 cases, for penetrating corneoscleral injuries in 8, and for eye contusion in 1 case. The patients were followed up for 1 year after surgery. Taking in of donor cornea, time course of visual acuity, intra- and postoperative complications, and the risk factors of the graft failure were evaluated. Transparent healing of donor cornea was observed after 1 month in 94% cases and after 1 year in 60%. In the immediate postoperative period, vision improved in 32 patients, deteriorated in 1, and did not change in 3 patients. In 56% children visual acuity with correction of 0.05 diopters and higher was attained, while before the intervention the predominant (in 80% children) variant was pr. certae. Among the complications, the most incident were graft rejection crises and secondary glaucoma liable to conservative therapy. Vitreoretinal injury is one of the unfavorable factors fraught with the graft failure. Hence, perforating keratoplasty is an effective and obligatory surgical procedure ensuring sufficient visual rehabilitation in the majority of children with severe ocular injuries.


Management and treatment of contact lens-related Pseudomonas keratitis.
Pubmed and Medline were searched for articles referring to Pseudomonas keratitis between the years 2007 and 2012 to obtain an overview of the current state of this disease. Keyword searches used the terms "Pseudomonas" + "Keratitis" limit to "2007-2012", and ["Ulcerative" or "Microbial"] + "Keratitis" + "Contact lenses" limit to "2007-2012". These articles were then reviewed for information on the percentage of microbial keratitis cases associated with contact lens wear, the frequency of Pseudomonas sp. as a causative agent of microbial keratitis around the world, the most common therapies to treat Pseudomonas keratitis, and the sensitivity of isolates of Pseudomonas to commonly prescribed antibiotics. The percentage of microbial keratitis associated with contact lens wear ranged from 0% in a study from Nepal to 54.5% from Japan. These differences may be due in part to different frequencies of contact lens wear. The frequency of Pseudomonas sp. as a causative agent of keratitis ranged from 1% in Japan to over 50% in studies from India, Malaysia, and Thailand. The most commonly reported agents used to treat Pseudomonas keratitis were either aminoglycoside (usually gentamicin) fortified with a cephalosporin, or monotherapy with a fluoroquinolone (usually ciprofloxacin). In most geographical areas, most strains of Pseudomonas sp. (≥95%) were sensitive to ciprofloxacin, but reports from India, Nigeria, and Thailand reported sensitivity to this antibiotic and similar fluoroquinolones of between 76% and 90%.


EHD1 mediates vesicle trafficking required for normal muscle growth and transverse tubule development.
EHD proteins have been implicated in intracellular trafficking, especially endocytic recycling, where they mediate receptor and lipid recycling back to the plasma membrane. Additionally, EHDs help regulate cytoskeletal reorganization and induce tubule formation. It was previously shown that EHD proteins bind directly to the C2 domains in myoferlin, a protein that regulates myoblast fusion. Loss of myoferlin impairs normal myoblast fusion leading to smaller muscles in vivo but the intracellular pathways perturbed by loss of myoferlin function are not well known. We now characterized muscle development in EHD1-null mice. EHD1-null myoblasts display defective receptor recycling and mislocalization of key muscle proteins, including caveolin-3 and Fer1L5, a related ferlin protein homologous to myoferlin. Additionally, EHD1-null myoblast fusion is reduced. We found that loss of EHD1 leads to smaller muscles and myofibers in vivo. In wildtype skeletal muscle EHD1 localizes to the transverse tubule (T-tubule), and loss of EHD1 results in overgrowth of T-tubules with excess vesicle accumulation in skeletal muscle. We provide evidence that tubule formation in myoblasts relies on a functional EHD1 ATPase domain. Moreover, we extended our studies to show EHD1 regulates BIN1 induced tubule formation. These data, taken together and with the known interaction between EHD and ferlin proteins, suggests that the EHD proteins coordinate growth and development likely through mediating vesicle recycling and the ability to reorganize the cytoskeleton.


Cigarette sidestream smoke delays nucleotide excision repair: inhibited accumulation of repair proteins at DNA lesions.
Cigarette sidestream smoke (CSS) contains many carcinogens that induce DNA damage. DNA damage plays an important role in the initiation of cancer and several diseases, and repair is the major defense mechanism; however, the relationship between CSS and the repair of DNA damage remains unclear. We herein investigated whether CSS influences nucleotide excision repair (NER) in vivo and in vitro. HR-1 hairless mouse skin treated with CSS was exposed to UVB, as a result of which pyrimidine dimers (cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs)) were formed and repaired via the NER pathway. The immunohistochemical staining of CPDs revealed that their repair was delayed by the CSS treatment. This delay in NER and the underlying mechanisms were examined in the human skin cell lines, HaCaT and HSC-1. Dot-blot assays, enzyme-linked immunosorbent assay and local ultraviolet irradiation assays demonstrated that CSS delayed the repair of CPDs and 6-4PPs. The recruitment of the repair molecules, TFIIH, XPA and XPG to pyrimidine dimers was markedly inhibited by CSS. Semicarbazide, which reacts with aldehydes, recovered the CSS-induced inhibition of NER, and formaldehyde exerted similar inhibitory effects to those of CSS. These results suggest that aldehydes in CSS interfere with the recruitment of NER molecules to damaged sites, leading to a delay in the repair of pyrimidine dimers.


Feasibility study: phosphospecific flow cytometry enabling rapid functional analysis of bone marrow samples from patients with multiple myeloma.
Multiple myeloma (MM) is an incurable cancer accounting for about 2% of cancer deaths. Its diagnosis is based on a combination of criteria, which are not always easily measurable. Flow cytometry now allows multiplex analysis of intracellular signaling at the single cell level. We investigated the feasibility of using intracellular protein phosphorylation analysis by flow cytometry on primary plasma cells from bone marrow and its usefulness in MM diagnosis. Cells from frozen bone marrow of five MM patients and four normal donors were stimulated with LPS, IL-6, IL-21, IFNα and TNFα. Cells were stained by fluorescent cell barcoding to allow multiplex analysis. Staining with antibodies against phosphorylated NFkB-p65, Stat1, Stat3, and p38 were used to identify cellular responses following stimulation. Activation profiles of MM and normal plasma cells have been established. MM cells showed heterogeneous response profiles while normal cells responses were homogeneous between donors. We also noticed that many MM samples seemed to show elevated basal level of Stat3 phosphorylation. These results suggest that different response profiles in primary MM cells might correspond to different subtypes of the disease. Thus, we provide an example of how these results may be used as a criterion for MM subtypes classification. We demonstrate that flow cytometry can be used to study signaling pathways in primary MM cells. The heterogeneity observed in MM cells from different patients can prove valuable for MM characterization and represents an interesting avenue for future research in MM diagnosis.


[Biological fluid-related accidents amongst professionals working in clinical laboratories in Maracaibo, Venezuela].
Determining the occupational exposure to biological fluids of medical technicians working in public clinical laboratories caused by accidental percutaneous contact, associated factors and compliance with post-exposure biological measures. This was a descriptive cross-sectional study. The sample consisted of 156 medical technicians assigned to clinical laboratories in the metropolitan area of Zulia state in Venezuela. Data was collected by applying an instrument for exploring exposure and related factors, as well as compliance with established post-biological exposure measures. There was evidence of exposure caused by percutaneous accidents, mainly represented by a moderate level of needle-pricks and cuts (2-3.99 mean). There was a moderate level of factors regarding percutaneous injury in the hands and fingers associated with hollow needles, blood and blood products and superficial severity in sample taking and processing areas when recapping needles or handling sharp or cutting objects. A medium level (2-3.99 mean) of compliance was obtained for post-exposure handling. A significant correlation was found (p<001) between percutaneous exposure and level of compliance with post-exposure management. The magnitude and characteristics of exposure to biological fluids detected in this work represents a problematic situation which can affect staff health and must be approached by institutions to ensure effective prevention management and risk control.


An association between maternal diet and colonic diverticulosis in an animal model.
Maternal diet may have an effect on the health of the offspring in middle and later life. This study used the laboratory rat as an animal model to examine whether the fibre content of the maternal diet during pregnancy affected subsequent development of colonic diverticula in the offspring fed lifelong fibre deficient or higher fibre diets. The parents of experimental animals were fed either a diet that was known to predispose to colonic diverticulosis or a control diet for one month prior to mating. The offspring were fed one of these diets for 18 months. The incidence of colonic diverticulosis, submucosal collagen content, collagen solubility in weak acid, and the composition of intestinal contents were then measured. Offspring of rats fed a higher fibre diet from higher fibre diet fed parents had 0% incidence of colonic diverticulosis. When offspring (regardless of parental diet) were fed a low fibre diet for life the acid solubility was lowered compared with rats fed lifelong higher fibre diet mean (SD) (0.044 (0.0007) v 0.073 (0.0015) sigmoid colon (ratio of soluble:insoluble collagen)); 21.1% had diverticulosis and there was reduced fibre fermentation. However, when the diet of the parents of the fibre deficient diet fed rats was considered, the animals whose mothers had a fibre deficient diet had lower acid solubility (0.032 (0.0007)) and an increased incidence of colonic diverticulosis (42.1%) than the animals fed a fibre deficient diet from higher fibre diet fed parents (p < 0.01 in all instances). Maternal diet and the subsequent nutrition of the progeny seem to be of importance in the development of colonic diverticulosis in the rat.


[Baroreflex sensitivity: diagnostic importance, methods of determination and a model of baroreflex blood-pressure regulation].
Baroreflex regulation of blood pressure primarily moderates its fluctuations and also affects mean blood pressure. Heart rate baroreflex sensitivity is described as changes of the inter-beat interval induced by a change of blood pressure of 1 mmHg (BRS). BRS is decreased in many cardiovascular diseases (hypertension, diabetes mellitus, obesity, cardiac failure, etc.). Decreased BRS in disposed individuals, especially after myocardial infarction, increases the risk of sudden cardiac death. Therefore, early diagnosis of BRS decrease gains in importance. This article describes different methods of determination of baroreflex sensitivity. The methods are based on evaluation of the spontaneous fluctuation of heart rate and blood pressure (spectral, sequential or nonlinear methods), or of primary changes of blood pressure induced by a vasoactive substance or a physiological manoeuvre and corresponding changes of cardiac intervals (Valsalva manoeuvre, phenylephrine administration). Each method has its advantages and disadvantages resulting from a different difficulty of calculation or from inclusion of different deviations in the results, which are not directly linked with baroreflex. Baroreflex regulating total peripheral resistance is less described. A mathematical model of baroreflex blood pressure regulation by fluctuation of heart rate and peripheral resistance is presented in this paper.


Long Noncoding RNA SNHG6 Functions as an Oncogene in Non-Small Cell Lung Cancer via Modulating ETS1 Signaling.
Non-small cell lung cancer (NSCLC) is a great threat to human health and the biology of the NSCLC still remains largely unknown. Aberrantly expressed long non-coding RNA (lncRNA) Small nucleolar RNA host gene 6 (SNHG6) was involved in the tumorigenesis and progression of various cancers. The aim of this study is to investigate the roles of SNHG6 in NSCLC. qRT-PCR and Western blot assays were applied to detect gene expressions. Cell proliferation and migration assays were used to analyze the gene functions. Luciferase reporter assay, RNA Immunoprecipitation assay and Chromatin immunoprecipitation assay were performed to investigate the molecular mechanism. We found that SNHG6 expression was significantly increased in NSCLC tissues and cell lines and its high expression was correlated with malignant features of NSCLC. In in vitro assays, knockdown of SNHG6 significantly depressed the proliferation vitality and migration activity of NSCLC cells. Research on mechanisms revealed that SNHG6 exerted its tumorigenesis role by promoting ETS1 expression via competitively binding with miR-944 and miR-181d-5p. We also demonstrated that ETS1 enhanced the expression of WIPF1 via binding to its promoter and SNHG6 could thereby regulate the expression of ETS1 target genes including WIPF1, MMP2 and MMP9. Our study illustrates that SNHG6 is an oncogene in NSCLC and involved in NSCLC tumorigenesis by regulating ETS1 signaling via miR-944 and miR-181d-5p.


[Antiplatelet therapy: should it be withdrawn before any invasive procedure?].
Antiplatelet therapy is the leading therapy for the primary and secondary prevention for the atherosclerotic arterial disease. The practical question of withdraw alavoiding or continuation of oral antiplatelet agents accurs currently before any invasive procedure. It is important to compare the relative thrombotic vs hemorrhagic risk. For most interventions, it is recommended to continue antiplatelet therapy. It is particularly important in patients who benefited from drug-eluting stents where the thrombotic risk is major.


Building the mental health care network for children and adolescents: interventions in the territory.
Children with mental disorders may develop serious adverse effects in their functional performance. A structured care network may favor psychosocial components, such as self-confidence and problem solving capacity. This work seeks to identify the care network for children with mental disorders and develop interventions in the territory, highlighting changes achieved from these actions. This is a descriptive study based on the action research methood using an eco-Map for data presentation. The results indicate that the majority of children have stressful relationships within the family, and relationships of greater intensity and quality with the Community Health Workers, Primary Care and Education, with childcare, compared with specialist health services. The interventions were based on the guidelines of Family Health, Support Center and stressed the strengthening of family ties, and liaison with health services and schools/ daycare centers.


[Effects of propranolol on mitosis-inhibiting activity of G2-chalone and adrenaline in cell culture of Ehrlich's ascites tumor].
Chalone-containing preparation from ascite Ehrlich's tumour blocks these cell transition from G2-phase to mitosis and its motion in mitosis in vitro (G2-block, M-block). Adrenaline blocks these cell transition from G2-phase to mitosis. Propranolol raises G2-block of chalone or adrenaline. Consequently this way of chalones action on cell division includes beta-adrenergic receptors influence of preparation on cell motion in mitosis doesn't change with addition of propranolol. Consequently this way of chalone system action on mitosis doesn't include beta-adrenergic receptors.


Novel chip for applying mechanical forces on human skin models under dynamic culture conditions.
In recent years the need for in vitro skin models as a replacement for animal studies has resulted in significant progress in the development of skin-on-a-chip models. These devices allow the fine control of the microenvironment of the model and the incorporation of chemical and physical stimuli. Here we describe the development of an easy and low-budget open-top dynamic microfluidic device for skin-on-a-chip experiments using PDMS (Polydimethylsiloxane) and a porous polyethylene terephthalate (PETE) membrane. The chip allows the incorporation of compressive stimuli during the cultivation period by the use of syringe pumps. Proof-of-concept results show the successful differentiation of the cells and establishment of the skin structure in the chip. The microfluidic skin-on-a-chip models presented in this study can serve as a platform for future drug and feasibility studies.


Structural features of extraocular muscles of children with strabismus.
Ninety extraocular muscle (EOM) biopsy specimens from 80 children with strabismus and normal ocular alignment were studied by light microscopy, enzyme histochemistry, and electron microscopy. Light microscopy showed considerable variation in muscle fiber shape and size with sarcomere disruption, sharp increases in endomysial and perimysial collagen, numerous vacuoles and subsarcolemmal inclusions. Electron microscopy showed disruption of myofilaments, nemaline rods, abnormal mitochondria, leptomeric profiles, occasional "myelin figures," glycogen, and lipid-like droplets. Some intramuscular nerves contained long-spacing collagen ("Luse bodies"). Unlike somatic skeletal muscle, EOM showed a consistent lack of mosaic pattern and reciprocal stain activity between fiber types noted by enzyme histochemistry. Quantitative observations indicate that minimal but consistent morphologic differences exist between strabismic and nonstrabismic EOM. The role these changes play in the pathogenesis of strabismus and their significance remains unclear.


Peptoniphilus methioninivorax sp. nov., a Gram-positive anaerobic coccus isolated from retail ground beef.
Strain NRRL B-23883(T) was isolated from retail ground beef as part of a study on the genetic diversity of Clostridium perfringens. The strain was found to be a strictly anaerobic, Gram-positive coccus that was able to utilize peptone as a sole carbon source. Analysis of the 16S rRNA gene sequence revealed that the strain was closely related to species within the genera Peptoniphilus and Anaerosphaera, but it was substantially different from the closest recognized species by nearly 10 % sequence divergence. The strain was also found to be closely related (>99 % sequence similarity) to an uncultured bacterial strain that was sequenced from a 16S rRNA gene clone library constructed to characterize the bacterial community of faeces from a captive spotted hyena. Strain NRRL B-23883(T) shared the peptidoglycan type A4β, l-Orn-d-Glu with members of the genus Peptoniphilus. Further phenotypic analysis revealed that strain NRRL B-23883(T) was able to utilize glycyl l-methionine as a sole carbon source, in contrast to other species of the genus Peptoniphilus. Therefore, it is proposed that the isolate represents a novel species, Peptoniphilus methioninivorax sp. nov.; the type strain is NRRL B-23883(T) ( = DSM 22461(T)).


Elasticity properties of lung parenchyma derived from experimental distortion data.
Distortion data for dog lungs obtained experimentally by Hoppin et al. (1975) are used to arrive at a general mathematical model (strain energy function) which describes finite deformation of lung parenchyma. The strain energy function is correlated with average alveolus model proposed by Frankus and Lee (1974). The latter predicts parenchyma distortion properties from uniformly ventilated pressure-volume data only.


Induction of FPN1 transcription by MTF-1 reveals a role for ferroportin in transition metal efflux.
Ferroportin (Fpn) is the only known iron exporter in vertebrate cells and plays a critical role in iron homeostasis regulating cytosolic iron levels and exporting iron to plasma. Ferroportin1 (FPN1) expression can be transcriptionally regulated by iron as well as other transition metals. Fpn can also be posttranslationally regulated by hepcidin-mediated internalization and degradation. We demonstrate that zinc and cadmium induce FPN1 transcription through the action of Metal Transcription Factor-1 (MTF-1). These transition metals induce MTF-1 translocation into the nucleus. Zinc leads to MTF-1 binding to the FPN1 promoter, while iron does not. Silencing of MTF-1 reduces FPN1 transcription in response to zinc but not in response to iron. The mouse FPN1 promoter contains 2 MTF-1 binding sites and mutation of those sites affects the zinc and cadmium-dependent expression of a FPN1 promoter reporter construct. We demonstrate that Fpn can transport zinc and can protect zinc sensitive cells from high zinc toxicity.


Witness of unsatisfiability for a random 3-satisfiability formula.
The random 3-satisfiability (3-SAT) problem is in the unsatisfiable (UNSAT) phase when the clause density α exceeds a critical value α(s)≈4.267. Rigorously proving the unsatisfiability of a given large 3-SAT instance is, however, extremely difficult. In this paper we apply the mean-field theory of statistical physics to the unsatisfiability problem, and show that a reduction to 3-XORSAT, which permits the construction of a specific type of UNSAT witnesses (Feige-Kim-Ofek witnesses), is possible when the clause density α>19. We then construct Feige-Kim-Ofek witnesses for single 3-SAT instances through a simple random sampling algorithm and a focused local search algorithm. The random sampling algorithm works only when α scales at least linearly with the variable number N, but the focused local search algorithm works for clause density α>cN(b) with b≈0.59 and prefactor c≈8. The exponent b can be further decreased by enlarging the single parameter S of the focused local search algorithm.


[Sclerosing cholangitis and biliary sequelae of hydatid cyst of the surgically treated liver].
Worldwide literature and ten or so personal cases are reviewed as a basis for distinction or intrication of two aspect of post-hydatid sclerosing cholangitis; that of a localized lesion of diffuse lesions of the biliary tract. In both cases the action of the hydatid cyst is not due to toxins but to pressure on biliary duct walls, very variable according to site and size. This local action may be the only cause, provoking a specific type of lesion, a true sequela of an incomplete or delayed operation. In certain regions, or in the presence of biliary stasis and angiocholitis, passage of hydatid fluid into biliary tracts, normally tolerated by healthy biliary pathways, leads to a diffuse sclerosing cholangitis. The serious consequence of this eventuality is proved by the failure of many treatments, with subsequent inevitable liver transplants. Clinical circumstances and data explaining this complication allow necessary precautions to be taken. Furthermore, early treatment of hydatidosis or as radical as possible therapy for advanced lesions is curative of localized forms of the disease.


Detection of the activity of ion channels and pores by circular dichroism spectroscopy: G-quartets as functional CD probes within chirogenic vesicles.
We introduce a method to detect the activity of ion channels and pores with circular dichroism (CD) spectroscopy. G-quartets obtained by potassium templated self-assembly of 5'-guanosine monophosphate (GMP) are used as CD probes, the bee-toxin melittin as representative pore and gramicidin A as representative ion channel. To detect the activity of pores with CD spectroscopy, vesicles were loaded with GMP at concentrations above the dissociation constant (K(D)) of G-quartets. GMP efflux through added pores was detectable as CD silencing due to G-quartet disassembly by local dilution. The Hill plot of melittin with Hill coefficient n = 4 was faithfully reproduced with CD detection. The same was true for counterion-activated cell-penetrating peptides, confirming their ability to mediate the export of anions such as GMP. The same method is not applicable to the CD detection of the activity of ion channels because GMP efflux does not occur. To do that, the potassium selectivity of G-quartets was used. Namely, vesicles were loaded with GMP at concentrations above the dissociation constant (K(D)) of G-quartets stabilized by potassium. External M/K cation exchange resulted in CD silencing by M/K antiport through the added ion channel followed by G-quartet disassembly within the vesicle. Reversal of the direction of M/K antiport was achieved with Cs-loaded vesicles and detected as the appearance of the CD signature of G-quartets in response to K influx. Corroborative examples with gramicidin A include CD detection of the Eisenman I selectivity sequence and the Hill coefficient.


A novel approach to evaluating the reproducibility of a replication technique for the manufacture of electroconductive replicas for use in quantitative clinical dental wear studies.
The assessment of the progression of tooth surface loss has until recently been limited to either the application of subjective ranking scales or visual comparison of sequential study casts. The development of quantitative measuring techniques offers the potential of greater accuracy and sensitivity. As direct intra-oral measurement is problematical such approaches often utilize impressions of the teeth, recorded at different epochs, to construct replicas for mapping and comparison. This in vitro investigation sought to determine the reproducibility of such an approach taking into account the total process chain. Two inlay cavities (one large, one small) were prepared in the palatal aspect of a plastic maxillary central incisor and restored with two flush fitting inlays. A series of impressions of this tooth were recorded, using a special tray and an addition cured light bodied silicone impression material (President, Coltene, Switzerland), with (a) both inlays in (b) both inlays out (c) large inlay out and small inlay in (d) large inlay in and small inlay out - a total of 16 impressions. Electroconductive replicas were fabricated from these and mapped using a computer controlled probe. Each series simulated wear of the tooth. A surface matching and difference detection algorithm was then used to compare each series of replicas and calculate the proportion of the surface undergoing simulated wear by a direct comparison of (a) matched to (b) or, indirectly as the summation of the results of matches of (a) with (c) and (a) with (d). The mean proportion of the surface with wear calculated directly was 26.6% (s.d.=0.6) and indirectly 26.1% (s.d. = 0.5). A one-way anova revealed no significant difference (P > 0.05). It is concluded that determining wear by this method is highly reproducible.


The pharmacogenomics of carbamazepine-induced cutaneous adverse drug reaction in the South of Vietnam.
Background: The relationship between HLA-B*15:02 and Severe Cutaneous Adverse Reactions was rigorously examined in Japanese, Han Chinese, Thais, and Caucasians. However, the number of studies about this topic in Vietnamese population is still limited and mostly focuses on the North of Vietnam. Objective: This study aims to clarify the genetic culprit of SCARs in Vietnamese population, particularly in the South of Vietnam, and to validate our result by a meta-analysis about this topic in Vietnamese. Method: A retrospective case-control study with 37 patients treated with carbamazepine monotherapy. Statistical calculation and meta-analysis were performed by R software. Result: HLA-B*15:02 increases the risk of SJS 12.5 times higher in CBZ-treated patients (p-value = 0.017). However, this allele has no impact on MCARs (Mild Cutaneous Adverse Reactions) of CBZ. The number needed to test and the number needed to genotype is two and nine patients respectively. Conclusion: This study recommends more investigations about the cost-effectiveness of this test to accelerate the protection of Southern Vietnamese from SCARs.


Treatment of wound infections.
Postoperative wound infections and infections linked to various traumatic and thermal injuries all contribute to patient morbidity and mortality, as well as to increased hospital costs. Standard practices of wound management include debridement of devitalized tissue, drainage, irrigation, and loose packing of the open wound. Antibiotics are usually effective as adjuncts to these procedures and to host resistance. Their choice, whenever possible, should be based on cultures of fresh pus (anaerobes must be obtained by airless syringe) to select an agent active against implicated pathogens. In rapidly developing infections, the choice must often be based on known probabilities until culture results are available. Specific management techniques are indicated for postoperative wounds, where brief prophylactic treatment may be needed. Traumatic wounds may require combination antibiotic therapy, and possible lack of immunity to tetanus should be considered. Most burn wound infections tend to be nosocomial; topical antiseptic agents often control burn infections while preventing the emergence of resistant bacteria.


Increasing resistance to fluoroquinolones in escherichia coli from urinary tract infections in the netherlands.
In continuous surveillance of routine samples from five Dutch laboratories, we studied resistance to the antibiotics most commonly prescribed for urinary tract infections (UTI) in The Netherlands, namely norfloxacin, amoxycillin, trimethoprim and nitrofurantoin, from 1989 to 1998 in >90000 Escherichia coli isolates. Resistance to norfloxacin increased from 1.3% in 1989 to 5.8% in 1998. Multiresistance, defined as resistance to norfloxacin and at least two of the other three antibiotics, increased from 0.5% in 1989 to 4. 0% in 1998. Multivariate analysis of the norfloxacin resistance demonstrated that this yearly increase (the odds ratio was 1.0 in 1989, 1.6 in 1992, 2.9 in 1995 and 6.1 in 1998) was independent of other determinants of resistance to norfloxacin, such as age, gender and origin of the isolate. Analysis of strata, classified by year, age and gender, demonstrated an association between prescription of fluoroquinolones (defined daily doses per case of UTI) and resistance to norfloxacin in E. coli (P < 0.001). There was no significant association with the prescription of nitrofuran derivatives (nitrofurantoin) and trimethoprim with or without sulphamethoxazole. The yearly increase of resistance to fluoroquinolones in E. coli from UTI may stem from increased prescription of fluoroquinolones for UTI. Resistance of E. coli to these agents is likely to increase further as fluoroquinolone use increases in future.


[In situ distribution and configuration of rDNA in the nucleolus of Pisum sativum].
Distribution and configuration of nucleolar DNA in the nucleolus of pea (Pisum sativum) were analyzed using cytochemical NAMA-Ur DNA specific stain method. The results showed that nucleolar DNA distributed in FC and juncture of FC/DFC in the forms of surrounding FC. rDNA in different positions existed in either condensed or uncondensed forms. Nucleolus-associated chromatin outside nucleolus extended in the periphery of FC via channels in the nucleolus.


Identification of quantitative trait loci for rice grain quality and yield-related traits in two closely related Oryza sativa L. subsp. japonica cultivars grown near the northernmost limit for rice paddy cultivation.
Quantitative trait loci (QTLs) associated with eating quality, grain appearance quality and yield-related traits were mapped in recombinant inbred lines (RILs) derived from closely related rice (Oryza sativa L. subsp. japonica) cultivars, Yukihikari (good eating quality) and Joiku462 (superior eating quality and high grain appearance quality). Apparent amylose content (AAC), protein content (PC), brown grain length (BGL), brown grain width (BGWI), brown grain thickness (BGT), brown grain weight per plant (BGW) and nine yield-related traits were evaluated in 133 RILs grown in four different environments in Hokkaido, near the northernmost limit for rice paddy cultivation. Using 178 molecular markers, a total of 72 QTLs were detected, including three for AAC, eight for PC, two for BGL, four for BGWI, seven for BGT, and six for BGW, on chromosomes 1, 2, 3, 4, 6, 7, 8, 9, 11 and 12. Fifteen intervals were found to harbor multiple QTLs affecting these different traits, with most of these QTL clusters located on chromosomes 4, 6, 8, 9 and 12. These QTL findings should facilitate gene isolation and breeding application for improvement of eating quality, grain appearance quality and yield of rice cultivars.


Surgical Technique of Glans Wings Creation with Preservation of Glanular Vascular Arcade and Creating Flaps for Tension-Free Glansplasty in Hypospadias Repair.
The objective of this study is to report the technical nuances of glans wings creation in anatomical plane facilitating liberal glans wings mobilization with preservation of glanular vessels for tension-free glansplasty in surgery of hypospadias in primary and redo cases. Eighty-six primary hyposapdias and 7 cases of distal hypospadias, operated elsewhere and presented with glans and urethroplasty dehiscence, undergoing tubularized-incised-plate (TIP) repair were included after ethical approval. Technical points of glans wings creation in the subfascial plane included (i) creation of Buck's fascia window, just proximal and lateral to the point of bifurcation of corpus spongiosum, (ii) creation of subfascial-pret unical plane on the tunica albuginea of corpora cavernosa up to ventral limit of laid open glanular meatus, (iii) release of pillars of corpus spongiosum off the glans base keeping the basal lamina propria covering the vascular arcade intact, (iv) release of glans base off the tip of corpora cavernosa and composite flap of corpus spongiosum pillars with Buck's fascia off the corpora cavernosa, (v) approximation of glans wings over the tubularized-incised-plate covered with dartos, and (vi) approximation of fasciospongioplasty flaps at hypospadiac meatus. Outcome measurement included (i) intra and postoperative problems and (ii) elimination of glans dehiscence. There occurred 1 injury to the tunica albuginea of ventral corpora cavernosa and 1 button-hole injury to subcoronal mucosal collars. Flaps for fasciospongioplasty were short in 11. One glans dehiscence occurred in flat glans. This technique is effective in creating glans wings in the anatomical plane with the preservation of glanular vessels and flaps for fasciospongioplasty eliminating the possibility of glans dehiscence in both fresh and redo cases.


Intraoperative complications of high volume sutureless cataract surgery in Nepal: a prospective study.
With high backlog of cataract blindness in the developing countries sutureless high volume cataract surgery is preferred surgical technique. To report the intraoperative complications of high volume sutureless cataract surgery at secondary level eye care centre of Nepal. This prospective study consisting 1087 eyes that underwent manual small incision cataract surgery from 2nd to 28th December 2007 at Shree Janaki Eye Hospital, Janakpur, Nepal and operated by a single eye surgeon. Preoperative and postoperative ocular findings together with intraoperative complications were carefully noted in every individual case. At post operative day one each patient was examined including uncorrected visual acuity and post operative complications which were subsequently recorded in Performa. Data were analysed using SPSS 11.5. Sixty-three eyes (5.8%) of 1087 eyes developed intraoperative complications. Out of 63 eyes that had intra operative complications, posterior capsular rupture were seen in 42 (3.9%), sclera corneal tunnel suturing in 12 eyes (1.1%), iridodialysis 5 eyes (0.5%) and Descemet stripping in 4 eyes (0.4%). 62.1% of patients attained uncorrected visual acuity 6/18 or better and in 91.7% of eyes, there were no post operative complications. High volume suture less cataract surgery is safe surgery and should be continue in developing countries to achieve the goal of vision 2020, where there is huge backlog of cataract blindness.


[Emission tomography of the brain (author's transl)].
Emission tomography (ET) is a method for visualization of radionuclide distribution in transaxial section of a body region, especially the brain. Both single-photon emitting and positron emitting radionuclides may be utilized. Conventional radiopharmaceuticals are used for single-photon ET; it shows three-dimensional distribution of radionuclides in normal and pathological brain structures and, when fast scanning techniques are used, permits the quantitative measurement of flow in small brain regions without interference from overprojection of differently perfused tissues. Coincidence detection of short-lived positron emitting radionuclides has the advantage of good attenuation correction so that quantitative determination of the concentration of the radionuclide in small tissue volumes is possible. With these short-lived, usually cyclotron-produced radionuclides, dynamic and metabolic processes may be followed (e.g. regional oxygen consumption with 15O2, regional blood volume with 11CO, C15O or 68Ga, regional perfusion with 13NH3, C15O2 or 77Kr) and the consumption and distribution of labelled organic compounds may be quantified (e.g. local metabolic rate of glucose with 18F-deoxyglucose or glucose distribution with 11C-methylglucose). The clinical application of these techniques may render new insight into pathophysiological mechanisms and the therapeutic management of diseases of the central nervous system.


Deep Neural Networks: A New Framework for Modeling Biological Vision and Brain Information Processing.
Recent advances in neural network modeling have enabled major strides in computer vision and other artificial intelligence applications. Human-level visual recognition abilities are coming within reach of artificial systems. Artificial neural networks are inspired by the brain, and their computations could be implemented in biological neurons. Convolutional feedforward networks, which now dominate computer vision, take further inspiration from the architecture of the primate visual hierarchy. However, the current models are designed with engineering goals, not to model brain computations. Nevertheless, initial studies comparing internal representations between these models and primate brains find surprisingly similar representational spaces. With human-level performance no longer out of reach, we are entering an exciting new era, in which we will be able to build biologically faithful feedforward and recurrent computational models of how biological brains perform high-level feats of intelligence, including vision.


Sequential Therapy for Remission Induction in Severe Antineutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis.
The introduction of combination therapy with glucocorticoids (GC) and cyclophosphamide (CYC) or rituximab (RTX) has resulted in remission rates exceeding 90% in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). However, early treatment-related mortality remains a major concern and has driven the search for safer induction regimens exploring minimization or avoidance of GC and CYC. Most trials have excluded patients with severe renal disease. We report the outcomes of AAV patients with severe renal disease treated with sequential therapy (ST) starting with (GC) and oral (CYC) followed by transition to (RTX). Patients with new or relapsing severe AAV who presented with severe renal disease and/or rapidly progressive glomerulonephritis (RPGN) were identified. RPGN was defined as at least a 20% decrease in estimated glomerular filtration rate (eGFR) over a 2-week period along with hematuria and proteinuria. Induction treatment included pulse (GC) for 3 days followed by oral prednisone tapered to 5 mg by month 6, oral (CYC) adjusted for GFR until improvement in Birmingham Vasculitis Activity Score (BVAS), and serum creatinine at which point (CYC) was stopped and induction dose of (RTX) was given. Use of plasmapheresis (PLEX) was allowed. The primary outcome was complete remission defined as BVAS of zero by 6 months. Descriptive data are presented as median with range and mean with SD. Nine patients met the inclusion criteria. Median age at diagnosis was 63 years. The majority were females, myeloperoxidase ANCA positive, and had a new diagnosis. The mean nadir (SD) eGFR was 12 (5) with 3 requiring dialysis. The median BVAS at the time of diagnosis was 15. All patients received ST and 3 received PLEX. The median exposure to oral CYC was 35 days. The mean (SD) eGFR and median BVAS were 26 (12) and 3, respectively, at the time of switching to RTX. The median prednisone dose at 6M was 5 mg. The median follow-up was 44 months. All patients achieved remission. One patient with relapsing disease reached ESRD. The mean (SD) eGFR in the remaining 8 patients at last FU was 37 (27), and the mean (SD) eGFR rise at 1 year was 26 (25). Adverse events included 2 patients with pneumonia and 3 with bone marrow suppression. There were no deaths. ST with GC and CYC followed by RTX is effective for in AAV patients with severe renal disease. Therapy-related adverse events are comparable to other studies, and further modification in ST with decrease in GC dosage should be explored.


Evolution of DNA polymerase alpha, beta and terminal deoxynucleotidyl transferase in hamster lymphoid populations during the development of different types of tumors.
We followed the evolution of DNA polymerase alpha, beta and terminal deoxynucleotidyl transferase (TdT) in the thymus, spleen and bone marrow of tumor bearing hamsters. Tumors were induced by spontaneously transformed fibroblasts (EHB), by SV40 (ZD) or by 20-methylcholanthrene (MCH2) transformed fibroblasts. We have shown that, in the thymus, the TdT activity of the various tumor bearing hamsters is generally inferior to the TdT activity of the control. In the spleen of animals bearing viral or spontaneously induced (ZD or EHB) tumors, the TdT activities were higher than in the controls. Moreover, DNA polymerase alpha and DNA polymerase beta activities in the spleen of the EHB tumor bearing hamsters were higher than in the controls. This fact, however, was not observed in the two other kinds of tumor, possibly because EHB tumors were growing much faster and led to earlier changes in DNA polymerases activities, as well as in spleen size and cellular populations. Finally, in the bone marrow, TdT, polymerase alpha and beta of ZD and EHB tumor bearers reached much higher activities than in the controls; for the MCH2 tumor bearing hamsters, no difference with the controls could be observed.


Interactions of Lipid Genetic Risk Scores With Estimates of Metabolic Health in a Danish Population.
There are several well-established lifestyle factors influencing dyslipidemia and currently; 157 genetic susceptibility loci have been reported to be associated with serum lipid levels at genome-wide statistical significance. However, the interplay between lifestyle risk factors and these susceptibility loci has not been fully elucidated. We tested whether genetic risk scores (GRS) of lipid-associated single nucleotide polymorphisms associate with fasting serum lipid traits and whether the effects are modulated by lifestyle factors or estimates of metabolic health. The single nucleotide polymorphisms were genotyped in 2 Danish cohorts: inter99 (n=5961) for discovery analyses and Health2006 (n=2565) for replication. On the basis of published effect sizes of single nucleotide polymorphisms associated with circulating fasting levels of total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, or triglyceride, 4 weighted GRS were constructed. In a cross-sectional design, we investigated whether the effect of these weighted GRSs on lipid levels were modulated by diet, alcohol consumption, physical activity, and smoking or the individual metabolic health status as estimated from body mass index, waist circumference, and insulin resistance assessed using homeostasis model assessment of insulin resistance. All 4 lipid weighted GRSs associated strongly with their respective trait (from P=3.3×10(-69) to P=1.1×10(-123)). We found interactions between the triglyceride weighted GRS and body mass index and waist circumference on fasting triglyceride levels in Inter99 and replicated these findings in Health2006 (P(interaction)=9.8×10(-5) and 2.0×10(-5), respectively, in combined analysis). Our findings suggest that individuals who are obese may be more susceptible to the cumulative genetic burden of triglyceride single nucleotide polymorphisms. Therefore, it is suggested that especially these genetically at-risk individuals may benefit more from targeted interventions aiming at obesity prevention.


Acetaminophen cytotoxicity in HepG2 cells is associated with a decoupling of glycolysis from the TCA cycle, loss of NADPH production, and suppression of anabolism.
Acetaminophen (APAP) is one of the most commonly used analgesics worldwide, and overdoses are associated with lactic acidosis, hepatocyte toxicity, and acute liver failure due to oxidative stress and mitochondrial dysfunction. Hepatoma cell lines typically lack the CYP450 activity to generate the reactive metabolite of APAP observed in vivo, but are still subject to APAP cytotoxicity. In this study, we employed metabolic profiling and isotope labelling approaches to investigate the metabolic impact of acute exposure to cytotoxic doses of APAP on the widely used HepG2 cell model. We found that APAP exposure leads to limited cellular death and substantial growth inhibition. Metabolically, we observed an up-regulation of glycolysis and lactate production with a concomitant reduction in carbon from glucose entering the pentose-phosphate pathway and the TCA cycle. This was accompanied by a depletion of cellular NADPH and a reduction in the de novo synthesis of fatty acids and the amino acids serine and glycine. These events were not associated with lower reduced glutathione levels and no glutathione conjugates were seen in cell extracts. Co-treatment with a specific inhibitor of the lactate/H+ transporter MCT1, AZD3965, led to increased apoptosis in APAP-treated cells, suggesting that lactate accumulation could be a cause of cell death in this model. In conclusion, we show that APAP toxicity in HepG2 cells is largely independent of oxidative stress, and is linked instead to a decoupling of glycolysis from the TCA cycle, lactic acidosis, reduced NADPH production, and subsequent suppression of the anabolic pathways required for rapid growth.


Investigator profile. An interview with Russell D. Fernald, Ph.D. Interview by Vicki Glaser.
Russell D. Fernald, Ph.D., is a Professor of Biological Sciences and the Benjamin Scott Crocker Professor in Human Biology at Stanford University (California). He received his Bachelor's degree from Swarthmore College (Swarthmore, PA) and his Ph.D. from the University of Pennsylvania (Philadelphia). Dr. Fernald completed a postdoctoral fellowship with Dr. O. Creutzfeldt at the Max-Planck-Institute for Psychiatry, in Munich, Germany, and a postdoctoral fellowship with Dr. Konrad Lorenz at the Max-Planck-Institute for Behavioral Physiology. In 2004 he shared the Rank Prize for discoveries about lens function. Dr. Fernald's lab uses an African cichlid fish species to study how social experience influences the brain and how retinal progenitor cell division and differentiation are controlled.


The Royal College of Nursing's information needs survey of nurses and health professionals.
To find out about the nursing community's needs in the following areas: information or knowledge to improve practice in the clinical area; information to support lifelong learning and formal study. A questionnaire was circulated in summer 2004 containing questions on types of information source used for particular types of problem or question; specific sources used; ease of access to various information sources including computers and the Internet, and local health library; and workplace culture and environment. A total of 1715 usable questionnaires were completed and returned. Significant numbers of the nursing community have currently no or limited access to computers. Nursing staff in the independent sector had less access to computers and the Internet than those working for the National Health Service (NHS). Workplace culture was as important as access to IT equipment. As a result of the survey, the Royal College of Nursing (RCN) is working with the NHS and the independent health sector to improve access and provide complementary services for the whole nursing community.


[The efficacy of vaccination and serotherapy in tick-borne encephalitis in the Maritime Territory].
The use of different vaccines manufactured in the USSR under the condition of the Far East has revealed that killed vaccines do not produce a protective effect, sufficient for the prophylaxis of tick-borne encephalitis (TBE). This is probably due to the circulation of a highly virulent population of TBE virus at the Territory. This virus population may produce a severe course of infection and aggravate the clinico-epidemiological characteristics of the effectiveness of vaccines. Besides, low levels of specific and nonspecific humoral resistance factors in the residents of the Far East, especially in spring and summer, contribute to this fact. The negative effect of specific serotherapy for persons over 40 years of age has been established.


Monitoring the lifetime risk of revision knee arthroplasty over a decade : a population-level analysis of Australian national registry data.
This study aimed to describe the use of revision knee arthroplasty in Australia and examine changes in lifetime risk over a decade. De-identified individual-level data on all revision knee arthroplasties performed in Australia from 2007 to 2017 were obtained from the Australian Orthopaedic Association National Joint Replacement Registry. Population data and life tables were obtained from the Australian Bureau of Statistics. The lifetime risk of revision surgery was calculated for each year using a standardized formula. Separate calculations were undertaken for males and females. In total, 43,188 revision knee arthroplasty procedures were performed in Australia during the study period, with a median age at surgery of 69 years (interquartile range (IQR) 62 to 76). In 2017, revision knee arthroplasty rates were highest for males aged 70 to 79 years (102.9 procedures per 100,000 population). Lifetime risk of revision knee arthroplasty for females increased slightly from 1.61% (95% confidence interval (CI) 1.53% to 1.69%) in 2007 to 2.22% (95% CI 2.13% to 2.31%) in 2017. A similar pattern was evident for males, with a lifetime risk of 1.43% (95% CI 1.36% to 1.51%) in 2007 and 2.02% (95% CI 1.93% to 2.11%) in 2017. A decline in procedures performed for loosening/lysis (from 41% in 2007 to 24% in 2017) and pain (from 14% to 9%) was evident, while infection became an increasingly common indication (from 19% in 2007 to 29% in 2017). Well-validated national registry data can help us understand the epidemiology of revision knee arthroplasty, including changing clinical indications. Despite a small increase over a decade, the lifetime risk of revision knee arthroplasty in Australia is low at one in 45 females and one in 50 males. These methods offer a population-level approach to quantifying revision burden that can be used for ongoing national surveillance and between-country comparisons. Cite this article: Bone Joint J 2022;104-B(5):613-619.


MiR-153-5p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Paclitaxel by Inducing G2M Phase Arrest.
Paclitaxel (PTX) resistance is a main obstacle for the treatment of triple-negative breast cancers (TNBC). Evidences have shown that miR-153-5p could induce the apoptosis of breast cancer cells. Thus, this study aimed to investigate the effect of miR-153-5p on PTX-resistance TNBC cells. Cell Counting Kit-8, flow cytometry and wound healing assays were used to detect the viability, apoptosis and migration of MDA-MB-231/PTX cells, respectively. The luciferase reporter assay was used to explore the potential binding targets of miR-153-5p. The expressions of CDK1, cyclin B1 and p-Akt in MDA-MB-231/PTX cells were detected with Western blot. In vivo animal study was performed finally. In this study, the inhibitory effects of PTX on the proliferation and migration of MDA-MB-231/PTX cells were significantly enhanced following transfection with miR-153-5p. In addition, overexpression of miR-153-5p markedly enhanced the pro-apoptotic effect of PTX on MDA-MB-231/PTX cells. Luciferase reporter assay validated that cyclin-dependent kinase 1 (CDK1) was a potential binding target of miR-153-5p. Moreover, overexpression of miR-153-5p prominently increased PTX-induced cell cycle arrest at G2/M phase in MDA-MB-231/PTX cells via downregulation of CDK1, cyclin B1 and p-Akt. In vivo experiments confirmed that overexpression of miR-153-5p notably enhanced PTX sensitivity in MDA-MB-231/PTX xenograft model. We found that overexpression of miR-153-5p could reverse PTX resistance in PTX-resistant TNBC cells via inducing G2/M phase arrest, indicating that miR‑153-5p may be a promising agent for patients with PTX-resistant TNBC.


[New blood substitutes of polyfunctional action].
The paper deals with two categories of new oxygen-carrying blood substitute solutions (OCBSS), based on a modified hemoglobin (MG) and perfluor-organic carbon emulsion (PCE), and with crystalloid and colloid blood substitutes of the antihypoxic action containing the Crebs' substrate (sodium fumarat). Described are the results of clinical use of Russian OCBSS based on MG (Gelenpol) and on PCE (Perftoran) in 151 patients with hemorrhagic shock and intraoperative blood loss. Both drugs are allowed for medical application in Russia. Gelenpol was administered at 1 to 6 units, perftoran--at 10-15 ml/kg. An improved oxygen status as well as normalization of hemodynamics, microcirculation, rheology, and of blood acid-base balance (ABB) were registered. Gelenpol had a hematosis-stimulating action. The combined use of both drugs or one of them alone in surgery is under discussion. The OCBSS efficiency can be enhanced when they are used jointly with the first Russian infusion antihypoxants containing sodium furmarat, i.e. Mufasol and Polyoxyfumarin. Both of them were shown to normalize the oxidation in tissues, to recover the mitochondrial metabolism in the liver and myocardium and to improve the blood ABB when used in hypovolemic and hypoxic conditions of different etiologies, in substituting for intraoperative blood losses (gastrointestinal hemorrhages), in polytrauma and destructive cholecystitis as well as in preoperative preparations of patients with diffuse peritonitis. The OCBSS preparations and antihypoxants are undoubtedly drugs of choice in emergency infusion-transfusion therapy and in cases of multiple victims from accidents.


How well did experts and laypeople forecast the size of the COVID-19 pandemic?
Throughout the COVID-19 pandemic, social and traditional media have disseminated predictions from experts and nonexperts about its expected magnitude. How accurate were the predictions of 'experts'-individuals holding occupations or roles in subject-relevant fields, such as epidemiologists and statisticians-compared with those of the public? We conducted a survey in April 2020 of 140 UK experts and 2,086 UK laypersons; all were asked to make four quantitative predictions about the impact of COVID-19 by 31 Dec 2020. In addition to soliciting point estimates, we asked participants for lower and higher bounds of a range that they felt had a 75% chance of containing the true answer. Experts exhibited greater accuracy and calibration than laypersons, even when restricting the comparison to a subset of laypersons who scored in the top quartile on a numeracy test. Even so, experts substantially underestimated the ultimate extent of the pandemic, and the mean number of predictions for which the expert intervals contained the actual outcome was only 1.8 (out of 4), suggesting that experts should consider broadening the range of scenarios they consider plausible. Predictions of the public were even more inaccurate and poorly calibrated, suggesting that an important role remains for expert predictions as long as experts acknowledge their uncertainty.


Long-term outcome of medial open reduction in developmental dysplasia of hip.
Long-term outcome of medial open reduction (MOR) was examined. We aimed to evaluate the effects of MOR on hip development in developmental dysplasia of hip (DDH). One hundred and ten hips of 74 patients that admitted to our clinic were evaluated. 15 (20.27 %) were male, 59 (79.73 %) were female. The mean age at the time of MOR was 17.71 ± 7.71 months (range 6-48 months). The mean duration of follow-up was 13.97 ± 4.89 years (range 5-24 years). Radiological results were Severin 1 and 2 in 86.37 % of the hips, Severin 3 in 10.0 % of the hips and Severin 4 in 3.63 % of the hips. Functional results were excellent (94.55 %) or good (5.45 %) according to modified McKay's criteria. When we excluded the hips that underwent additional operations, radiological results were Severin 1 and 2 in 82.05 % of the hips, and Severin 3 and 4 in 17.95 % of the hips. Acetabular angles and ACM, CE, Sharp angles were evaluated at last follow-up. Acetabular development was better in patients that were treated before the age of 18 months. Additional operations were performed to 32 hips (29.09 %). No additional operation was performed to the patients that were treated with MOR before the age of 12 months. The patients that were treated with MOR between 19 and 24 months of age had a higher proportion (47.61 %) for additional operations. Avascular necrosis rate was 17.27 %. Avascular necrosis rate was decreased to 6.3 % when type 1 differences were excluded. Avascular necrosis rate was 12.82 % when the hips that underwent additional operations were excluded. Medial open reduction is effective and safe treatment method in DDH. Early concentric stable reduction with MOR improved results.


Contemporary management of common bile duct stone: What you need to know.
Choledocholithiasis is a common presentation of symptomatic cholelithiasis encountered by the acute care surgeon. There is a wide spectrum of variation in management of this disease due to evolutions in laparoscopic and endoscopic techniques. Intricacies in management are related to the timing of diagnosis as well as locally available imaging modalities, surgical expertise, and ancillary advanced endoscopy and interventional radiological support. While individual patient demographics and institutional characteristics will determine management of choledocholithiasis, it is incumbent for the treating surgeon to be well versed in all manners of therapy currently available. The objective of this review is to provide an evidence-based summary of the contemporary management of choledocholithiasis.


Maintenance hormonal treatment improves progression free survival after a first line chemotherapy in patients with metastatic breast cancer.
The present study was conducted in patients with metastatic breast cancer. Its aim was to identify the factors which influence progression -free survival (PFS) and overall survival (OS) after the first line of chemotherapy in patients with positive tumour hormone receptor status. The patients with early disease progression during first-line chemotherapy were not included. In total, 560 patients who achieved a stable disease or a response to first-line chemotherapy were studied. The factors identified to improve the duration of PFS or OS in multivariate analysis were: number of metastatic sites (p = .01; p = .01), metastatic sites (p = .02; p = .04), Disease free interval (p = .001; p < .0001), previous hormonal therapy (p = .03; p = ns), response to first line chemotherapy (p < .0001; p = 0.0001) and an administration of maintenance hormonal therapy (p < .0001; p = .001). The major impact obtained by maintenance hormonal treatment after first-line chemotherapy in this study seems to indicate that this strategy should be recommended in patients with an ER or PgR positive tumour.


Contraceptive use among U.S. women with HIV.
To describe trends in and correlates of use of contraception and sterilization among women with the human immunodeficiency virus (HIV). This was a longitudinal cohort study of HIV-infected and uninfected women at risk for pregnancy, including structured questions on contraceptive use every 6 months. Proportions of women using contraception were calculated. Multivariate generalized estimating equation models were applied, and correlates of use were determined using logistic regression. Sterilization was assessed using a Kaplan-Meyer plot. Across 26,832 visits among 2784 women from 1994 to 2005, barrier methods were used at 30.5%-36.3% of visits, sterilization at 21.8%-26.5%, hormones at <10%, and no contraception at >30%. Dual use of barrier and hormones or barrier and spermicide was uncommon. In multivariable analysis, HIV serostatus was not correlated with barrier use (OR 1.10, 95% CI 0.96-1.26, p = 0.18 compared with no method), but hormonal contraception was less likely in women with HIV (OR 0.73, 95% CI 0.60-0.89, p = 0.002). Among HIV-seropositive women, barrier use was more likely among women who had been pregnant (OR 1.37, 95% CI 1.03- 1.83, p = 0.03) and among those with higher CD4 lymphocyte counts (OR 1.10, 95% CI 1.04- 1.16, p = 0.0006), whereas hormone use was linked to higher CD4 counts (OR 1.12, 95% CI 1.03-1.23, p = 0.01). HAART use was not associated with barrier or hormone use. HIV serostatus was linked to sterilization in Cox analysis (HR 1.32, 95% CI 0.89-1.94, p = 0.17). CONCLUSIONS. Underuse of highly effective contraception and barriers leaves women with HIV at risk for unintended pregnancy and disease transmission.


Renal cell carcinoma bone metastasis: epidermal growth factor receptor targeting.
Renal cell carcinoma frequently metastasizes to the skeleton in the later stages of the disease. Patients with bone metastasis from renal cell carcinoma experience severe pain, neurologic compromise, and frequent pathologic fractures. These tumors are relatively resistant to chemotherapy and radiation, and the 5-year survival of patients is less than 10%. The epidermal growth factor receptor is overexpressed in human renal cell carcinoma and hypothesized to be a potential target in the treatment of bone metastasis. Using in vitro studies, it was shown that blockade of the epidermal growth factor receptor was effective in decreasing proliferation and receptor autophosphorylation of a human bone-derived renal cell carcinoma cell line. In an experimental nude mouse model, treatment with Taxol and protein tyrosine kinase inhibitor 166, a small molecule receptor tyrosine kinase inhibitor, blocked the growth of renal cell carcinoma in the tibia and resulted in decreased bone destruction. The use of protein tyrosine kinase inhibitor 166 and Taxol was cytostatic and nontoxic in long-term animal experiments. Epidermal growth factor receptor blockade is an exciting potential therapy for renal cell carcinoma bone metastasis in humans, but because it is cytostatic rather than cytotoxic, its optimal role may be as a supplement to cytotoxic chemotherapy. It ultimate role and its relationship to other therapeutic interventions remains to be elucidated and validated.


The Ups and Downs of STAT Inhibition in Acute Myeloid Leukemia.
Aberrant Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is implicated in the pathogenesis of acute myeloid leukemia (AML), a highly heterogeneous hematopoietic malignancy. The management of AML is complex and despite impressive efforts into better understanding its underlying molecular mechanisms, survival rates in the elderly have not shown a substantial improvement over the past decades. This is particularly due to the heterogeneity of AML and the need for personalized approaches. Due to the crucial role of the deregulated JAK-STAT signaling in AML, selective targeting of the JAK-STAT pathway, particularly constitutively activated STAT3 and STAT5 and their associated upstream JAKs, is of great interest. This strategy has shown promising results in vitro and in vivo with several compounds having reached clinical trials. Here, we summarize recent FDA approvals and current potential clinically relevant inhibitors for AML patients targeting JAK and STAT proteins. This review underlines the need for detailed cytogenetic analysis and additional assessment of JAK-STAT pathway activation. It highlights the ongoing development of new JAK-STAT inhibitors with better disease specificity, which opens up new avenues for improved disease management.


Single-port extraperitoneal transvesical adenomectomy: initial operative experience.
Laparoscopic extraperitoneal adenomectomy is occasionally performed for symptomatic large-volume benign prostatic hyperplasia. Two different multichannel ports were used during operations. We describe the technique of single-port extraperitoneal transvesical adenomectomy and present the initial operative experience. Three patients in whom an open adenomectomy was indicated underwent single-port extraperitoneal transvesical adenomectomy. Following preparation of the extraperitoneal space via an umbilical incision, a multichannel port was inserted. A transverse cystotomy adjacent to the prostatovesical junction, incision of mucosa overlying the adenoma, subcapsular plane development, prostatic adenomectomy and cystotomy repair were performed as the standard steps of the laparoscopic procedure. All cases were completed without conversion to standard laparoscopy. Mean operative time was 105 min. Mean blood loss was 190 ml. Hospital stay was 4 days and catheter duration was 6 days for all patients. No intraoperative or postoperative complication occurred. Single-port extraperitoneal transvesical adenomectomy for large benign prostate hyperplasia is feasible with excellent cosmetic results and minimal morbidity.


Signaling pathways in the epithelial origins of pulmonary fibrosis.
Pulmonary fibrosis complicates a number of disease processes and leads to substantial morbidity and mortality. Idiopathic pulmonary fibrosis (IPF) is perhaps the most pernicious and enigmatic form of the greater problem of lung fibrogenesis with a median survival of three years from diagnosis in affected patients. In this review, we will focus on the pathology of IPF as a model of pulmonary fibrotic processes, review possible cellular mechanisms, review current treatment approaches and review two transgenic mouse models of lung fibrosis to provide insight into processes that cause lung fibrosis. We will also summarize the potential utility of signaling pathway inhibitors as a future treatment in pulmonary fibrosis. Finally, we will present data demonstrating a minimal contribution of epithelial-mesenchymal transition in the development of fibrotic lesions in the transforming growth factor-alpha transgenic model of lung fibrosis.


Detection of Human Bocavirus DNA by Multiplex PCR Analysis: Postmortem Case Report.
Human bocavirus (HBoV) is a virus belonging to the Parvoviridae family, which has been newly discovered to be associated with respiratory tract infections in children. There are many reports worldwide on the endemicity of this virus. Since it is relatively new, it is not routinely detected in clinical laboratory investigations. We demonstrated that HBoV infection caused the death of a 5-month-old girl with a history of high fever and wheezing. Human bocavirus (HBoV 1/2/3/4) was found in a nasopharyngeal swab, paraffin-embedded lung tissue and stool samples by multiplex PCR methods using postmortem microbiological analysis. This case suggests that lower respiratory tract infections due to HBoV may cause severe and life-threatening diseases. Postmortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. To our knowledge, this report is the first document of a HBoV postmortem case in Turkey.


Psychobiological effects of an eHealth psychoeducational intervention to informal caregivers of persons with dementia: a pilot study during the COVID-19 pandemic in Italy.
The workload associated with caring for a person with dementia (PwD) could negatively affect informal caregivers' physical and mental health. According to the recent literature, there is a need for studies testing the implementation of affordable and accessible interventions for improving caregivers' well-being. This study aimed to explore the feasibility and effectiveness of an 8 week eHealth psychoeducation intervention held during the COVID-19 pandemic in Italy in reducing the psychological burden and neuroendocrine markers of stress in caregivers of PwD. Forty-one informal caregivers of PwD completed the eHealth psychoeducation intervention. Self-reported (i.e., caregiver burden, anxiety symptoms, depressive symptoms, and caregiver self-efficacy) and cortisol measurements were collected before and after the intervention. Following the intervention, the caregivers' self-efficacy regarding the ability to respond to disruptive behaviours improved (t = - 2.817, p = 0.007), anxiety and burden levels decreased (state anxiety: t = 3.170, p = 0.003; trait anxiety: t = 2.327, p = 0.025; caregiver burden: t = 2.290, p = 0.027), while depressive symptoms and cortisol levels did not change significantly. Correlation analyses showed that the increase in self-efficacy was positively associated with the improvement of caregiver burden from pre- to post-intervention (r = 0.386, p = 0.014). The intervention had a low rate of dropout (n = 1, due to the patient's death) and high levels of appreciation. The positive evidence and participation rate support the feasibility and effectiveness of the proposed eHealth psychoeducational intervention to meet the need for knowledge of disease management and possibly reduce detrimental effects on caregivers' psychological well-being. Further placebo-controlled trials are needed to test the generalizability and specificity of our results.


Oxidative stress-mediated aldehyde adduction of GRP78 in a mouse model of alcoholic liver disease: functional independence of ATPase activity and chaperone function.
Pathogenesis in alcoholic liver disease (ALD) is complicated and multifactorial but clearly involves oxidative stress and inflammation. Currently, conflicting reports exist regarding the role of endoplasmic reticulum (ER) stress in the etiology of ALD. The glucose-regulated protein 78 (GRP78) is the ER homolog of HSP70 and plays a critical role in the cellular response to ER stress by serving as a chaperone assisting protein folding and by regulating the signaling of the unfolded protein response (UPR). Comprising three functional domains, an ATPase, a peptide-binding, and a lid domain, GRP78 folds nascent polypeptides via the substrate-binding domain. Earlier work has indicated that the ATPase function of GRP78 is intrinsically linked and essential to its chaperone activity. Previous work in our laboratory has indicated that GRP78 and the UPR are not induced in a mouse model of ALD but that GRP78 is adducted by the lipid electrophiles 4-hydroxynonenal (4-HNE) and 4-oxononenal (4-ONE) in vivo. As impairment of GRP78 has the potential to contribute to pathogenesis in ALD, we investigated the functional consequences of aldehyde adduction on GRP78 function. Identification of 4-HNE and 4-ONE target residues in purified human GRP78 revealed a marked propensity for Lys and His adduction within the ATPase domain and a relative paucity of adduct formation within the peptide-binding domain. Consistent with these findings, we observed a concomitant dose-dependent decrease in ATP-binding and ATPase activity without any discernible impairment of chaperone function. Collectively, our data indicate that ATPase activity is not essential for GRP78-mediated chaperone activity and is consistent with the hypothesis that ER stress does not play a primary initiating role in the early stages of ALD.


Therapeutic approaches to target alpha-synuclein pathology.
Starting two decades ago with the discoveries of genetic links between alpha-synuclein and Parkinson's disease risk and the identification of aggregated alpha-synuclein as the main protein constituent of Lewy pathology, alpha-synuclein has emerged as the major therapeutic target in Parkinson's disease and related synucleinopathies. Following the suggestion that alpha-synuclein pathology gradually spreads through the nervous system following a stereotypic pattern and the discovery that aggregated forms of alpha-synuclein can propagate pathology from one cell to another, and thereby probably aggravate existing deficits as well as generate additional symptoms, the idea that alpha-synuclein is a viable therapeutic target gained further support. In this review we describe current challenges and possibilities with alpha-synuclein as a therapeutic target. We briefly highlight gaps in the knowledge of the role of alpha-synuclein in disease, and propose that a deeper understanding of the pathobiology of alpha-synuclein can lead to improved therapeutic strategies. We describe several treatment approaches that are currently being tested in advanced animal experiments or already are in clinical trials. We have divided them into approaches that reduce alpha-synuclein production; inhibit alpha-synuclein aggregation inside cells; promote its degradation either inside or outside cells; and reduce its uptake by neighbouring cells following release from already affected neurons. Finally, we briefly discuss challenges related to the clinical testing of alpha-synuclein therapies, for example difficulties in monitoring target engagement and the need for relatively large trials of long duration. We conclude that alpha-synuclein remains one of the most compelling therapeutic targets for Parkinson's disease, and related synucleinopathies, and that the multitude of approaches being tested provides hope for the future.


[Reactive growth of the mesothelium of the parietal leaf of the peritoneum].
In the process of reparative regeneration of the mesothelium caused by suturing of a portion of the jugular vein into the peritoneum defect the inflammatory mesothelial growings are formed. They have different configuration, consist only of the mesotheliumor the connective tissue covered with the mesothelium and are observed from the 4th day till 3 months after operation, being always faced to the abdominal cavity. The capacity of mesothelial cells to high mitotic activity and wedging out from the layer underlies the formation of posttraumatic structures of the mesothelium.


How COVID-19 has affected staffing models in intensive care: A qualitative study examining alternative staffing models (SEISMIC).
To understand how COVID-19 affected nurse staffing in intensive care units (ICUs) in England, and to identify factors that influenced, and were influenced by, pandemic staffing models. Exploratory qualitative study. Semi-structured, online interviews conducted July-September 2020 with regional critical care leaders including policy leads (n = 4) and directors/lead nurses (n = 10) across critical care networks in England. The six themes emerging from the framework analysis illustrate how the pre-pandemic ICU culture influenced ICU staffing models during the pandemic. Changes in staffing impacted on the workforce and the care delivered, whilst it was necessary to learn from, and adjust to, a rapidly changing situation. Variation across and between networks necessitated variation in responses. The overwhelming outcome was that the pandemic has challenged the central tenets of ICU nurse staffing. Pandemic nurse staffing models resulted in changes to ICU skill-mix and staffing numbers. Factors such as the impact of nurse staffing on care practices and on the workforce need to be taken into account when developing and testing future nurse staffing models for ICU. The extent to which ICUs will return to former staffing models is not yet known but there seems to be an appetite for change. In common with many countries, nurse staffing in English ICUs was adapted to address surge requirements during the COVID-19 pandemic. Findings highlight the challenge COVID-19 presented to pre-pandemic ICU nurse staffing guidelines, the impact on patient and staff well-being and the potential legacy for future staffing models. Study findings have implications for ICU nurse managers, researchers and policy makers: nurse staffing models need to be adaptable to the local context of care and future research should investigate the impact of different models on patients, staff and health service outcomes.


Alterations in hepatocyte lysosomes in experimental hepatic copper overload in rats.
Although Wilson's disease is characterized by an accumulation of copper within hepatocyte lysosomes, the effects of excess copper on hepatic lysosomes are unknown. We studied the effects of excess copper on the structure, physicochemical properties, and pH of hepatocyte lysosomes using a rodent model. Rats were copper loaded with 0.125% copper acetate in water for 6 weeks. Copper was measured by atomic absorption spectrophotometry. Morphology was studied by electron microscopy. Lysosomal membrane fluidity was studied by fluorescence polarization, and lipid composition was determined by gas chromatography. Hepatocyte lysosomal pH was determined by flow cytometry. Copper overload resulted in a 10-fold increase in hepatic copper. Hepatocyte lysosomes were enlarged and abnormally shaped with a 27-fold increase in copper, increased in vitro fragility, and decreased lysosomal membrane fluidity. Thiobarbituric acid reactive substances, a measure of lipid peroxidation, doubled in isolated lysosomal membranes. Polyunsaturated fatty acids increased, saturated fatty acids decreased, and membrane content of selected fatty acids was modified after copper overload. Lysosomal pH increased from 4.67 +/- 0.02 to 4.87 +/- 0.02. Copper overload causes alterations in lysosomal morphology, increases lysosomal fragility, decreases membrane fluidity, alters membrane fatty acid composition, and increases lysosomal pH. Copper catalyzed lipid peroxidation represents the likely mechanism for these alterations.


Neuroendocrineimmunology (NEI) at the turn of the century: towards a molecular understanding of basic mechanisms and implications for reproductive physiopathology.
The interactions between the nervous, endocrine and immune systems require a complex communication network. The central nervous system (CNS) affects the immune system through endocrine, paracrine and neuronal mechanisms. Evidence that this bidirectional communication plays a vital role in the regulation of physiological homeostatic mechanisms while a disfunction of the neuroendocrineimmune balance favors the susceptibility to a number of diseases is derived largely by animal models but also by an increasing number of clinical studies in different fields, including endocrinology, reproductive physiology, pediatrics, oncology, neurology and psychiatry. An increasing number of endocrine hormones, neurotransmitters and neuropeptides are expressed in immune tissues and cells and are actively involved in the physiological regulation of immunity. Conversely, the endocrine and nervous systems harbor receptors for a wide variety of immunologically-derived substances, suggesting potential regulatory feedback loops between the three major integrative bodily systems. Major implications for the reproductive endocrinology field are that psychoneuroendocrine processes may alter fertility via immunomodulation, and that events that occur as part of immune responses influence the neuroendocrine axes, which in turn counter-regulate immune function. In the present article, some features of reproductive-immune interactions will be described, and the neuroendocrineimmune dialogue via the chief reproductive hormone, luteinizing hormone-releasing hormone (LHRH), will be summarized as prototype of intersystem crosstalk. A particular emphasis will be given to the cytokine-LHRH interrelationships both at central (i.e. especially with the astroglial compartment) and peripheral levels. The surprisingly similar communication network systems used by the gonads and the thymus will be summarized, and the sexually-driven dimorphisms dictating female versus male reproductive and immunological capacities reviewed. Evidence that neural, endocrine and immune systems work together as a single unit are emphasized in animal models and human pathologies where interruption of NEI feedback loops results in long lasting pathological consequences for the nervous, endocrine and immune functions.


Energy intake variability in free-living young children.
It has been suggested that young children regulate their daily energy intake very closely with highly stable day-to-day total energy intake. This hypothesis was developed on the basis of an experimental study of 15 children aged 26 to 62 months, which reported a within-subject coefficient of variation (CV) in daily energy intake of 10.4%. We tested the hypothesis that free-living energy intakes were highly stable on a day-to-day basis in a sample of free-living young children from Glasgow, Scotland. In 101 children (47 boys) aged 2.6-6.8 years, energy intake was measured using multiple-pass 24-h recalls. Within-subject CV was 19.2%, which was significantly higher than the 10.4% reported by previously Birch and colleagues (p<0.0001). In addition, we identified four other studies on free-living children with within-subject CVs ranging from 16.1-28.7%. This evidence indicates that young children show a wide intra-individual variation in day-to-day regulation of energy intake in a free-living environment.


The evaluation of malignant astrocytoma score (MAS).
At the moment there are few scoring systems for malignant astrocytoma but they are not widely accepted. The aim of this study was to evaluate malignant astrocytoma score (MAS) on a new group of patients with malignant astrocytoma, to compare MAS with other prognostic tools and to describe the use of MAS in everyday practice in neurooncology. The study was performed on 124 patients with supratentorial malignant astrocytoma grade III or IV. They were operated on and subsequently irradiated with 50-60 Gy. The mean age of the patients was 57.3 years. The mean Karnofski performance status (KPS) of the functional inpairment was 54. The removal of the tumor > 90% was done in 59.7% of patients. The mean survival was 9.1 months, and 27.4% of patients had a 12-month survival. The area under receiver operating characteristic (ROC) curve (AUC) of the MAS for predicting 6-, 12- and 18-month survival was 0.754, 0.783 and 0.882, respectively. We compared the MAS with the two mostly cited scoring systems. The AUC for the same prediction for medical research council (MRC) was 0.601, 0.693, 0.772 respectively. For the Radiation Therapy Oncology Group (RTOG) the AUC was 0.732, 0.765, 0.827, respectively. MAS represents a useful scoring system for determining illness severity and prognosis in patients with malignant supratentorial astrocytoma. It can be helpful in comparing single patients or groups of patients, as well as results of different treatments and in controlling the quality of hospital treatment and so on.


Augmentation of keratinized tissue at tooth and implant sites by using autogenous grafts and collagen-based soft-tissue substitutes.
To investigate the effect of three treatment modalities on the gain of keratinized tissue (KT) at tooth and implant sites in dogs. In five dogs, the distal roots of the mandibular second, third and fourth premolars were extracted, while the mesial roots were maintained. After 2 months of healing, implants were placed with KT excision. After another 2 months of healing, free gingival grafts, collagen-based matrices and apically positioned flap only were applied. The height of KT was measured during implant placement, immediately before soft-tissue grafting and after 10, 30 and 60 days. Two months after KT excision, spontaneous KT regrowth was greater at tooth sites than at implant sites (median, 2.0 mm vs. 1.1 mm). The outcomes of soft-tissue grafting at implant sites favoured the free gingival graft treatment, with a greater final median height (5.0-5.5 mm) and increase in KT (4.0-4.2 mm). Locations of the recipient sites significantly influenced KT regeneration at both tooth and implant sites. At implant sites, the free gingival graft treatment led to higher KT regeneration. At tooth sites, however, the differences between the three treatment modalities seemed clinically irrelevant.


Bifunctional T-cell-derived cytokines for the diagnosis of tuberculosis and treatment monitoring.
Diagnosis and treatment monitoring of patients with tuberculosis remain challenging. We have evaluated whether Mycobacterium-specific interferon (IFN)-γ and interleukin (IL)-2 bifunctional cytokine immune response assays improve the diagnosis of and correlate to treatment response in pulmonary tuberculosis. Early secretory antigenic target (ESAT)6/culture filtrate protein 10 (CFP10), microsomal triglyceride transfer protein 65 (MTP65) and the purified protein derivative (PPD) tuberculin-specific immune profiles were investigated in peripheral blood mononuclear cells from 19 patients with culture-confirmed tuberculosis and 23 healthy community controls (HCCs; 82.6% with latent M. tuberculosis infection) using a novel fluorescence-based dual-colour enzyme-linked immunospot (EliSpot) technology (FluoroSpot). The frequency of ESAT6/CFP10-induced IFN-γ+IL-2- producing cells was elevated (p < 0.001), whereas the percentages of specific IFN-γ-IL-2+ (p = 0.002) and IFN-γ+IL-2+ double producing cells (p = 0.037) were diminished in tuberculosis patients in comparison to HCCs. A 3-host marker model using a combination of those IFN-γ and IL-2 single-cell responses showed 93.8% sensitivity and 77.8% specificity for tuberculosis. During tuberculosis treatment, the PPD-induced immune responses shifted from an IFN-γ+IL-2- dominated profile towards a balance of IFN-γ-IL-2+ and IFN-γ+IL-2+ double producing cells (all p ≤ 0.05). The addition of antigen-specific IL-2 production to IFN-γ responses by EliSpot in IFN-γ release assays increases diagnostic sensitivity for active tuberculosis.


[Perspectives on researches in disaster psychiatry].
After experiencing the catastrophic Great East Japan Earthquake and Tsunami disaster in 2011, Tohoku University founded the International Research Institute of Disaster Science (IRIDeS) in April, 2012. IRIDeS, comprising 7 divisions and 36 laboratories with broad areas of specialization, from the humanities to natural sciences, aims to become a global center for the study of disasters and disaster mitigation, learning from and building upon past lessons in disaster management from Japan and around the world. In IRIDeS, the Department of Disaster Psychiatry is in charge of dealing with issues related to disaster psychiatry, including the psychosocial impact of disasters. Now, at more than 2 and a half years after the catastrophic disaster, the psychological impact actually seems to be getting stronger and wider, whereas the memory of the disaster seems to be waning in other areas of the country. In such a situation, where a number of problems need to be resolved, what can/should we do as psychiatrists? On the other hand, other natural disasters, such as storms and floods, have kept hitting Japan, and catastrophes seem to strike somewhere in the world every year. In addition, we need to prepare for the possibility of a Nankai Trough Quake and an earthquake directly hitting the Tokyo area, which may occur sometime in the future. Considering the situation, we need to establish an education system for disaster psychiatry, and proceed with research to collect useful information to prepare for coming disasters. The aim of our department is to integrate multi-faceted basic and clinical research approaches to investigate the following topics: 1) to identify social, psychological, and biological factors involved in the pathophysiology of and recovery from disaster-related mental health problems; 2) to develop systems for disaster prevention, disaster response, and recovery, considering disaster-related psychiatric and psychological issues; 3) to develop useful tools for the prevention, screening, diagnosis, and treatment of disaster-related disorders; 4) to archive information regarding disaster psychiatry; and 5) to corporate with other countries regarding disaster-related psychiatric issues. As knowledge regarding the above issues will be accumulated, and awareness of disaster-related psychiatric issues will be shared among mental health professionals and society, disaster psychiatry will be advanced.


Assessment of bone ingrowth into porous biomaterials using MICRO-CT.
The three-dimensional (3D) structure and architecture of biomaterial scaffolds play a critical role in bone formation as they affect the functionality of the tissue-engineered constructs. Assessment techniques for scaffold design and their efficacy in bone ingrowth studies require an ability to accurately quantify the 3D structure of the scaffold and an ability to visualize the bone regenerative processes within the scaffold structure. In this paper, a 3D micro-CT imaging and analysis study of bone ingrowth into tissue-engineered scaffold materials is described. Seven specimens are studied in this paper; a set of three specimens with a cellular structure, varying pore size and implant material, and a set of four scaffolds with two different scaffold designs investigated at early (4 weeks) and late (12 weeks) explantation times. The difficulty in accurately phase separating the multiple phases within a scaffold undergoing bone regeneration is first highlighted. A sophisticated three-phase segmentation approach is implemented to develop high-quality phase separation with minimal artifacts. A number of structural characteristics and bone ingrowth characteristics of the scaffolds are quantitatively measured on the phase separated images. Porosity, pore size distributions, pore constriction sizes, and pore topology are measured on the original pore phase of the scaffold volumes. The distribution of bone ingrowth into the scaffold pore volume is also measured. For early explanted specimens we observe that bone ingrowth occurs primarily at the periphery of the scaffold with a constant decrease in bone mineralization into the scaffold volume. Pore size distributions defined by both the local pore geometry and by the largest accessible pore show distinctly different behavior. The accessible pore size is strongly correlated to bone ingrowth. In the specimens studied a strong enhancement of bone ingrowth is observed for pore diameters>100 microm. Little difference in bone ingrowth is measured with different scaffold design. This result illustrates the benefits of microtomography for analyzing the 3D structure of scaffolds and the resultant bone ingrowth.