Lower limb amputation 2: once the decision to amputate has been made.
This is the second of four articles on lower limb amputation. The first article (Vol 6(17): 970-7) discussed the indications for amputation and briefly outlined the treatment options that may be tried before the amputation stage is reached. This second article examines the factors that need to be addressed once the decision to amputate has been made. It stresses the importance of preparing the patient and his/her family both psychologically and physiologically for the operation. The techniques and rationale for selecting the optimum level of amputation are then discussed. Finally, the specific levels of lower limb amputation are outlined. The next article in this series will explore the nurse's role in preparing the patient for an amputation, and the final article will address the issues raised when a patient decides that death is preferable to living as an amputee.


[Effect of pregnancy and labor on serotonin metabolism].
Several complications of pregnancy have been reported to be associated with alterations of serotonin (5-hydroxytryptamine; 5-HT) metabolism. Reported data regarding changes of 5-HT metabolism in pregnancy are partially contradictory. The presented study tries to describe pregnancy-associated changes in 5-HT metabolism. Urine and blood samples were taken from 20 pregnant women 4 weeks before, within 24 hours and on the 4th day following delivery. 17 non-pregnant age-matched women served as controls. 5-HT and its main metabolite 5-hydroxyindoleacetic acid (5-HIAA) were analysed. We observed a continuously increasing production and excretion of unbound 5-HT and 5-HIAA during pregnancy. Four days after delivery 5-HT production returned to baseline levels, while excretion remained elevated. 5-HIAA excretion increased in pregnancy and return to baseline levels on the day following delivery. Increased 5-HT metabolism and excretion results in a decreased 5-HT serum concentration despite increased 5-HT production during pregnancy. Our results help to understand the contradictory observations of elevated 5-HT production on the one hand and decreased 5-HT activity during pregnancy on the other.


Regulatory genes of simian immunodeficiency viruses from west African green monkeys (Cercopithecus aethiops sabaeus).
The high seroprevalence of simian immunodeficiency viruses (SIVs) in African green monkeys (AGMs) without immunological defects in their natural hosts has prompted consideration of SIV-infected AGMs as a model of apathogenic SIV infection. Study of the molecular mechanisms of SIVagm asymptomatic infection could thus provide clues for understanding the pathogenesis of human immunodeficiency viruses. Regulatory genes could be candidates for genetic control of SIVagm apathogenicity. We have characterized Vpr, Tat, Rev, and Nef genes of two SIVagm strains isolated from naturally infected sabaeus monkeys captured in Senegal. The results provide further evidence that SIVagm from West African green monkeys is the most divergent class of AGM viruses, with structural features in long terminal repeat sequences and Vpr and Tat genes that distinguish them from viruses isolated from other AGM species (vervet, grivet, and tantalus monkeys).


Slow relaxation of the magnetization, reversible solvent exchange and luminescence in 2D anilato-based frameworks.
A series of multifunctional 2D frameworks prepared with Dy(iii) and the bromanilato ligand, formulated as: [Dy2(C6O4Br2)3(G)n]·nG with G = H2O, dimethylformamide (dmf) and dimethylsulfoxide (dmso), can exchange the coordinated and non-coordinated solvent molecules (G) in a reversible way. These multifunctional frameworks show field induced slow relaxation of the magnetization and luminescence that can be easily and reversibly modified by solvent exchange.


Cul-de-sac hypernasality test with pattern recognition of LPC indices.
Acoustic differences between samples of [i], [u], and [a] uttered in nose-open and nose-obstructed condition were studied in 6 women with isolated cleft palate and pathological nasalance scores and 9 healthy women with normal nasalance scores. The speech samples were depicted by 14-component vocal tract area feature vectors obtained by linear prediction and the differences between the samples were studied with a self-organized feature map. Each location on the map corresponds to a certain signal pattern, neighboring locations to similar patterns. The group of healthy subjects differed from the patients for vowels [i] and [u] but not for [a]. In the patients the nose obstruction induced a significant change in the location of these vowel samples on the map. In healthy subjects no such changes were detected. The results agreed with perceived differences between the subjects.


A giant herniated disc following intradiscal electrothermal therapy.
The introduction of intradiscal electrothermal therapy for the management of discogenic back pain has been met with intense interest over the past few years. During this time there have been several noncontrolled studies published on the procedure, most of which have shown excellent outcomes but few, if any, complications. The authors describe a 29-year-old, 152-kg active duty male soldier who underwent two-level intradiscal electrothermal therapy for L4-L5 and L5-S1 discogenic pain. Before the procedure, the patient had a small L5-S1 contained herniation, with no signs of radiculitis. Postprocedure, the patient developed radicular symptoms and was noted on MRI to have a large L5-S1 disc herniation effacing the left S1 nerve root. Follow-up discography revealed a negative discogram at L4-L5. The patient proceeded to undergo a single-level lumbar fusion, which resulted in nearly complete relief of his radicular and axial low back pain. Two years post-surgery, he is off all narcotic medications and continues to work full-time as a soldier. This case illustrates both the potential benefits and complications that may be associated with intradiscal electrothermal therapy.


Assessment of disease-drug-drug interaction between single-dose tocilizumab and oral contraceptives in women with active rheumatoid arthritis.
The objective of this study was to evaluate the effect of a single intravenous dose of tocilizumab (TCZ) on pharmacokinetics (PK) of oral contraceptive (OC; norethindrone (NE) and ethinyl estradiol (EE)) and on sex hormone levels (progesterone (PG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)) in subjects with active rheumatoid arthritis (RA) who were on stable doses of methotrexate. This was an open-label, nonrandomized, multicenter, two-parallel group, one-sequence crossover study. In Group 1, Cycle 1 was a baseline cycle to determine the PK of OC and levels of sex hormones. At the start of Cycle 2, patients continued to receive OC and single TCZ dosing on Day 1. In Cycle 2, we determined the PK of OC and levels of sex hormones when OC and TCZ were combined. In Cycle 3, we determined the PK of OC and the levels of sex hormones after TCZ treatment was stopped. PK for EE and NE were analyzed serially on Day 7 when maximum TCZ effect on inflammation as indicated by C-reactiv protein (CRP) was expected. Hormone levels (PG, LH and FSH) were measured mid-cycle (cycle Days 12 - 16 and Day 21) during each cycle. Group 2 (healthy subjects) was studied to compare the levels of OC PK exposures with those in each cycle of Group 1 (RA subjects). Levels of PG, LH and FSH were not affected by the combination of TCZ/OC treatment in RA patients studied. No breakthrough bleeding was attributed to the initiation of TCZ treatment in subjects receiving OCs. PK exposures of EE and NE were similar between RA and healthy subjects at baseline and were not affected by single-dose TCZ. Administration of OC with or without a single dose of TCZ was well tolerated. Data from this study indicated that the PK and sex hormone levels were not affected in RA subjects who had active disease and were on a stable regimen of methotrexate.


Atlas of voluntary facial muscle activation: Visualization of surface electromyographic activities of facial muscles during mimic exercises.
Complex facial muscle movements are essential for many motoric and emotional functions. Facial muscles are unique in the musculoskeletal system as they are interwoven, so that the contraction of one muscle influences the contractility characteristic of other mimic muscles. The facial muscles act more as a whole than as single facial muscle movements. The standard for clinical and psychosocial experiments to detect these complex interactions is surface electromyography (sEMG). What is missing, is an atlas showing which facial muscles are activated during specific tasks. Based on high-resolution sEMG data of 10 facial muscles of both sides of the face simultaneously recorded during 29 different facial muscle tasks, an atlas visualizing voluntary facial muscle activation was developed. For each task, the mean normalized EMG amplitudes of the examined facial muscles were visualized by colors. The colors were spread between the lowest and highest EMG activity. Gray shades represent no to very low EMG activities, light and dark brown shades represent low to medium EMG activities and red shades represent high to very high EMG activities relatively with respect to each task. The present atlas should become a helpful tool to design sEMG experiments not only for clinical trials and psychological experiments, but also for speech therapy and orofacial rehabilitation studies.


Dissecting genetic diversity and genomic background of Petunia cultivars with contrasting growth habits.
The cultivated petunia (Petunia ×hybrida) is derived from the progenitor species P. axillaris and P. integrifolia. The hybridization dates back only to the 1830s, though intensive breeding efforts have yielded cultivars exhibiting incredible diversity for many traits, including growth habit, flower color, and flower size. Until now, little is known about the genetic diversity and genomic background of modern cultivars. Here we selected a panel of 13 cultivars with contrasting growth habits and three wild species (the progenitors and P. exserta) to estimate the genomic contribution from the ancestral species and to study whether the variation of the genetic origin could be associated with different breeding programs or morphological variability. Transcriptome sequencing identified 1,164,566 SNPs representing 98.4% (32,451) of the transcripts that cover 99.2% (of 52,697,361 bp) of the P. axillaris transcriptome. Cultivars with an upright growth habit had more homozygous alleles and more P. axillaris-derived alleles than trailing cultivars, while mounded cultivars had intermediate heterozygosity. Unlike previous studies, we found the proportions of alleles derived from each progenitor species varied across cultivars but overall were not biased toward one progenitor species, suggesting diverse selection during cultivar development. For trailing cultivars, alleles potentially introgressed from other wild species ("out" alleles) were enriched. The "out" alleles were clustered in particular regions of chromosomes, suggesting that these regions may be hotspots of introgression. Transcripts in these regions were enriched with gene ontology terms associated with growth habit. This study provides novel insight into the contributions of progenitor species to the genomic background of modern petunia cultivars and identifies genome regions that may harbor genes conferring the trailing growth habit for further exploration.


Prophylaxis and therapy with factor VII concentrate (human) immuno, vapor heated in patients with congenital factor VII deficiency: a summary of case reports.
Hereditary factor VII deficiency is a rare autosomal recessive condition, usually associated with normal or reduced levels of a functionally defective molecule. The available means of treating this condition in North America presents serious health risks to the patient. Transfusion with fresh frozen plasma carries a risk of volume overload and a significant risk for viral transmission. Sustained prothrombin complex therapy is associated with a high risk for thrombogenic complications. This communication describes the use of Factor VII Concentrate (Human) Immuno, Vapor Heated--an intermediate purity factor VII concentrate from Immuno A.G.--for the treatment of 13 patients with factor VII deficiency. Treatment regimens described include those for long-term prophylaxis (three children), acute hemorrhages (two children, one adult), peripartum prophylaxis (one patient), and surgical coverage (two children, four adults). Prophylaxis and therapy were successful in all cases, the medication was well-tolerated, and there were no complications. In the three cases of long-term prophylaxis in children, doses of 10-50 IU/kg were given one to three times a week; one patient has undergone long-term prophylaxis for approximately 8 years, one patient for 1 year, and one patient for 1 1/2 years. Three cases in which Factor VII Concentrate was principally used for treatment of acute episodes of bleeding are described. One infant received Factor VII Concentrate on about 50 occasions for treatment of mucosal bleeding; a correction to 40-100% resulted in cessation of bleeding within 15 min in all cases. For treatment of an episode of intracranial bleeding, an 8-year-old boy received a dose of 37 IU/kg Factor VII Concentrate every 6 hr for peak factor VII levels of approximately 100% and troughs as low as 4% over the 11-day treatment period. A 37-year-old adult male with intracranial bleeding received alternating doses of 16 IU/kg and 8 IU/kg every 6 hr for 10 days with peak factor VII levels in the upper thirties (%). The peak favor VII level during surgical coverage with Factor VII Concentrate (neurosurgery, open reduction of ankle bones, dental surgery, pituitary adenoma surgery, closed liver biopsy) was approximately 100% in all cases, with trough levels ranging from 8 to 65% over treatment periods of 24 hr to 16 days using treatment intervals of 6-12 hr.


Prostaglandin E2 exerts catabolic effects in osteoarthritis cartilage: evidence for signaling via the EP4 receptor.
Elevated levels of PGE(2) have been reported in synovial fluid and cartilage from patients with osteoarthritis (OA). However, the functions of PGE(2) in cartilage metabolism have not previously been studied in detail. To do so, we cultured cartilage explants, obtained from patients undergoing knee replacement surgery for advanced OA, with PGE(2) (0.1-10 muM). PGE(2) inhibited proteoglycan synthesis in a dose-dependent manner (maximum 25% inhibition (p < 0.01)). PGE(2) also induced collagen degradation, in a manner inhibitable by the matrix metalloproteinase (MMP) inhibitor ilomastat. PGE(2) inhibited spontaneous MMP-1, but augmented MMP-13 secretion by OA cartilage explant cultures. PCR analysis of OA chondrocytes treated with PGE(2) with or without IL-1 revealed that IL-1-induced MMP-13 expression was augmented by PGE(2) and significantly inhibited by the cycolooygenase 2 selective inhibitor celecoxib. Conversely, MMP-1 expression was inhibited by PGE(2), while celecoxib enhanced both spontaneous and IL-1-induced expression. IL-1 induction of aggrecanase 5 (ADAMTS-5), but not ADAMTS-4, was also enhanced by PGE(2) (10 muM) and reversed by celecoxib (2 muM). Quantitative PCR screening of nondiseased and end-stage human knee OA articular cartilage specimens revealed that the PGE(2) receptor EP4 was up-regulated in OA cartilage. Moreover, blocking the EP4 receptor (EP4 antagonist, AH23848) mimicked celecoxib by inhibiting MMP-13, ADAMST-5 expression, and proteoglycan degradation. These results suggest that PGE(2) inhibits proteoglycan synthesis and stimulates matrix degradation in OA chondrocytes via the EP4 receptor. Targeting EP4, rather than cyclooxygenase 2, could represent a future strategy for OA disease modification.


Clinical pathways in treatment of asthma.
Although the number of medications for the treatment of status asthmaticus is relatively limited, strategies for the management of acute asthma vary widely both among and within institutions. The choice of drugs, doses, timing of administration, duration of treatment, and assessment measures are often left to the discretion of individual physicians; plans are often not formulated on the basis of data showing efficacy, but rather on local availability and the experience and preference of physicians. The elimination of treatment that adds cost but not improved quality of care can be an effective strategy to optimize the care of acute asthma.


An unusual presentation of large pneumoencephaly after frequent falls in an elderly patient.
Pneumoencephaly is usually a complication of head trauma or craniotomy. We present a patient with large pneumoencephaly with acute neurological deficit after frequent falls, but without recent major trauma or surgery. Skull X-ray films show intracranial air in the frontal region and in the 2nd, 3rd, and 4th ventricles, reminiscent of an pneumoencephalogram. Computed tomography (CT) of the head shows air in the right frontal region and lateral ventricles. After craniotomy to relieve the pressure of the air, the clinical condition of the patient improved significantly after six months.


[Research advances on the molecular mechanisms of vascular permeability in sepsis].
Sepsis is one of the critical illnesses caused by burns, trauma, shock, infection, and so on. In patients with sepsis, vascular permeability is prone to develop through various pathophysiological mechanisms and thus could result in accumulation of tissue fluid, insufficient intravascular fluid, and finally cause septic shock and multiple organ dysfunction syndrome. Recent studies have shown that various factors and mediators involved in the regulation of vascular permeability in sepsis are expected to become targets for clinical treatment of sepsis. In this paper, we have reviewed the research advances on some molecules which are significantly associated with vascular permeability in sepsis, such as vascular endothelial growth factor, angiopoietin, sphingosine-1-phosphate, heparin-binding protein, and Slit2.


Gender-specific responses of lean body composition and non-gender-specific cardiac function improvement after GH replacement in GH-deficient adults.
GH deficiency (GHD) in adulthood is accompanied by physical and psychological impairments. One hundred fifteen patients (67 male, 48 female) with pronounced GHD were enrolled in a randomized, double-blind, placebo-controlled study with objectives that included effects on body composition, cardiac structure, and function and safety of replacement therapy with recombinant human GH (Saizen). Sixty patients (31 male, 29 female) received GH at a dose of 0.005-0.010 mg/kg.d, and 55 patients (36 male, 19 female) received placebo for 6 months. Assessment of body composition by dual-energy x-ray absorptiometry demonstrated a treatment difference in lean body mass increase of 2.1 kg (between-group comparison, P < 0.0001), which was significantly greater among males than females (P < 0.0001) [males: GH, +3.13 kg (2.42, 3.84); placebo, +0.11 kg (-0.60, 0.82); and females: GH, +0.64 kg (-0.15, 1.44); placebo: -0.90 kg (-2.20, 0.39)] [mean change 0-6 months (95% confidence limits)] and was associated with IGF-I changes. The decrease in fat mass of 2.8 kg (between-group comparison, P < 0.0001) noted by DEXA was also evident from bioelectric impedance and anthropometric measurements. Echocardiography showed comparable improvement in left ventricular systolic function after GH treatment in both genders. End-systolic volume decreased by 4.3 +/- 10.5 ml (from 35.8 +/- 17.6 ml; between-group comparison, P = 0.035) and ejection fraction increased by 5.1 +/- 10.0% (from 55.0 +/- 11.2%; between-group comparison, P = 0.048), approaching normalcy. Diastolic function did not change as assessed by isovolumic relaxation time, early diastolic flow, diastolic flow secondary to atrial contraction, or ratio of peak mitral early diastolic and atrial contraction velocity. GH treatment was well tolerated, with adverse events primarily related to effects on fluid balance. No apparent relationship between IGF-I levels and the occurrence or severity of adverse events was identified. In conclusion, GH replacement therapy in adults with GHD demonstrated beneficial effects on lean body mass composition that was more pronounced in males than females. In contrast, cardiac function improvement appears to benefit both genders equally.


Predictor of Hand Radiological Progression in Patients With Rheumatoid Arthritis Receiving TNF Antagonist Therapy by Change in Grayscale Synovitis-A Preliminary Study.
This prospective study aimed to compare synovial ultrasound scores to conventional measures (DAS28, CRP levels) in predicting radiographic progression in patients with rheumatoid arthritis under TNF antagonist therapy. Patients with RA who received TNF antagonist therapy were enrolled, all of whom underwent clinical, laboratory, and ultrasonographic assessments with grayscale and power Doppler assessments of bilateral elbows (anterior and posterior recess), wrists (dorsal, palmar, and ulnar aspects), second and third MCP joints (dorsal and palmar recess), and PIP II and III (dorsal and palmar) at baseline and at 1, 3 months. Hand radiographic damage was evaluated using van der Heijde modified Total Sharp Score (TSS) at baseline and 12 months. Thirty-two patients (384 joints, 832 synovial sites) continued the same treatment regimen for 12 months and completed the study, 41.6% of whom showed radiographic progression during the study period. Baseline DAS28 (P = 0.123), CRP level (P = 0.177), grayscale synovitis (P = 0.092), and power Doppler synovitis (P = 0.120) could not predict radiological damage in the TNF antagonist therapy group. However, ΔTSS was significantly related to changes in grayscale synovitis between baseline and 1 month (P = 0.011), but not at 3 months (P = 0.591), and was not related to changes in the power Doppler score at 1 (P = 0.634) and 3 months (P = 0.298). Our data confirm that delayed improvement in grayscale synovitis between baseline and 1 month more accurately reflects 1-year radiological damage than conventional measures such as DAS28 score and CRP level. Therefore, we recommend serial ultrasound follow-up of patients with RA receiving TNF antagonist therapy.


Quantum relaxation in a system of harmonic oscillators with time-dependent coupling.
In the context of the de Broglie-Bohm pilot-wave theory, numerical simulations for simple systems have shown that states that are initially out of quantum equilibrium-thus violating the Born rule-usually relax over time to the expected |ψ|2 distribution on a coarse-grained level. We analyse the relaxation of non-equilibrium initial distributions for a system of coupled one-dimensional harmonic oscillators in which the coupling depends explicitly on time through numerical simulations, focusing on the influence of different parameters such as the number of modes, the coarse-graining length and the coupling constant. We show that in general the system studied here tends to equilibrium, but the relaxation can be retarded depending on the values of the parameters, particularly to the one related to the strength of the interaction. Possible implications on the detection of relic non-equilibrium systems are discussed.


Predictors of medication adherence in pediatric inflammatory bowel disease patients at the Stollery Children's Hospital.
Patients with inflammatory bowel disease (IBD) often do not take their medications as prescribed. To examine self-reported adherence rates in IBD patients at the Stollery Children's Hospital (Edmonton, Alberta) and to determine predictors of medication adherence. A survey was mailed to 212 pediatric IBD patients of the Stollery Children's Hospital. A chart review was completed for those who returned the survey. A total of 119 patients completed the survey. The nonresponders were significantly older than responders (14.5 years versus 13.2 years; P=0.032). The overall adherence rate was 80%. Nonadherence was associated with older age (14.6 years versus 13.0 years; P=0.04), longer disease duration (5.0 years versus 3.1 years; P=0.004) and reported use of herbal medications (40.0% versus 13.6%; P=0.029). The most common reasons reported for missing medications were forgetfulness, feeling better and too many medications. In addition, patients reported being more likely to take anti-inflammatory medications and less likely to take herbal medicines. Identified predictors of nonadherence such as age, disease duration and use of herbal treatments may enable the development of specific strategies to improve adherence in adolescents with IBD.


Periurethral granuloma following injection with dextranomer/hyaluronic acid copolymer for stress urinary incontinence.
Periurethral injection of bulk-enhancing agents provides a simpler and cost-effective therapeutic approach for stress incontinence in women. We report a case of periurethral granuloma secondary to dextranomer/hyaluronic acid (Dx/HA) copolymer injection. A 73-year-old woman with history of radiotherapy for cervical carcinoma at the age of 55 presented with stress urinary incontinence. She underwent periurethral injection of Dx/HA copolymer, and incontinence was resolved. At 4 months postoperatively, a 3-4 cm noninflammatory painless mass in the external genitalia was noted. Cystic images compatible with urethral diverticula were seen in the magnetic resonance imaging scan, but voiding cystourethrography was unrevealing. Transvaginal tumor puncture yielded abundant creamy material, the culture of which was negative. Microscopic examination revealed refractile foreign material surrounded by foreign body giant cells. Surgical debridement of the granuloma using a cold scalpel was performed. Stress urinary incontinence recurred but resolved spontaneously within 1 month. One year later, the patient continues to be asymptomatic.


Radionuclide therapy in neuroendocrine tumours: a systematic review.
The purpose of this systematic review was to investigate the effects of therapeutic radiopharmaceuticals in patients with different types of advanced neuroendocrine tumour (NETs). A literature search was carried out in MEDLINE and EMBASE from January 1998 to November 2010. The Cochrane Library (to Issue 10, 2010) and the Standards and Guidelines Evidence Inventory of Cancer Guidelines, including over 1100 English-language cancer guidelines from January 2003 to June 2010, were also checked. No existing systematic reviews or clinical practice guidelines based on a systematic review or randomised controlled trials focusing on this topic were found. Twenty-four fully published articles were abstracted and summarised: 16 articles focused on five peptide receptor radionuclide therapy ((111)In-DTPAOC, (90)Y-DOTALAN, (90)Y-DOTATOC, (90)Y-DOTATATE, and (177)Lu-DOTATATE) and eight focused on (131)I-MIBG treatment. Limited evidence from a historical comparison of studies in one centre supported that (177)Lu-DOTATATE might be associated with greater clinical outcomes compared with (90)Y-DOTATOC or (111)In-DTPAOC. The severe toxicities for (177)Lu-DOTATATE included hepatic insufficiency in 0.6%, myelodysplastic syndrome in 0.8% and renal insufficiency in 0.4% of patients in this study. Insufficient evidence suggested efficacy of (131)I-MIBG in adult NET patients, but the overall tumour response rate from (131)I-MIBG was 27-75% for malignant neuroblastoma, paraganglioma or pheochromocytoma. Haematological toxicities were the main severe side-effects after (131)I-MIBG and 4% of patients developed secondary malignancies in one study. To date, peptide receptor radionuclide therapy seems to be an acceptable option and is relatively safe in adult advanced NET patients with receptor uptake positive on scintigraphy, but patients' renal function must be monitored. (131)I-MIBG may be effective for malignant neuroblastoma, paraganglioma or pheochromocytoma, but its side-effects need to be considered. No strong evidence exists to support that one therapeutic radiopharmaceutical is more effective than others. Well-designed and good-quality randomised controlled trials are required on this research topic.


Activities of potential tumour marker enzymes during induced differentiation in HL-60 and U-937 cells.
HL-60 and U-937 cells were used as models to assess the involvement of the enzymes of thymidine metabolism in differentiation. Both cell types showed decreased thymidine kinase and thymidylate synthase but increased thymidine phosphorylase activities in response to the induction of differentiation by dimethylsulfoxide and 12-O-tetradecanoylphorbol 13-acetate. This was accompanied by a greater than three-fold increase in the stimulation of superoxide production in both cell lines. Thymidylate synthase and thymidine kinase activities were noted as potential markers of leukaemic cell proliferation while thymidine phosphorylase and superoxide production correlated well with differentiated phenotypes. Prolonged treatment of U-937 by 12-O-tetradecanoylphorbol 13-acetate resulted in a marked de-differentiation, indicating overstimulation of one or more of the isoforms of protein kinase C.


Femoral tunnel widening after quadrupled hamstring anterior cruciate ligament reconstruction.
To evaluate the extent of femoral tunnel widening after quadrupled hamstring anterior cruciate ligament reconstruction using femoral cross pin fixation in contrast to bioabsorbable screw fixation augmented with Endopearl. 16 patients underwent cross pin femoral fixation and the next 15 underwent bioabsorbable screw fixation augmented with Endopearl. The patients were evaluated radiographically for femoral tunnel widening. Standard posteroanterior radiographs of the knee in full extension were taken at postoperative year 2 and 5. The tunnel width was measured at the opening, the widest and the most proximal parts of the femoral tunnel. In the femoral cross pin and bioabsorbable screw fixations, the mean femoral tunnel sizes were 7.6 and 8.0 mm, respectively. The overall mean tunnel widening at all measured sites were 2.7 and 1.8 mm at the 2-year follow-up and were 2.5 and 1.8 mm at the 5-year follow-up, respectively. The femoral tunnel widening was greater in the cross pin than the bioabsorbable screw group, but only the difference in the most proximal part was significant (p=0.01 at year 2 and p<0.001 at year 5). Femoral tunnel widening was greater in femoral cross pin fixation, probably related to the windshield-wiper and bungee-cord effects. It usually occurred in the first 2 years after the operation and remained static thereafter.


The effects of the Triple P-Positive Parenting Program on preschool children with co-occurring disruptive behavior and attentional/hyperactive difficulties.
Two variants of a behavioral family intervention (BFI) program known as Triple P were compared using 87 preschoolers with co-occurring disruptive behavior and attentional/hyperactive difficulties. Families were randomly allocated to enhanced BFI (EBFI), standard BFI (SBFI), or a waitlist (WL) control group. At postintervention both BFI programs were associated with significantly lower levels of parent-reported child behavior problems, lower levels of dysfunctional parenting, and greater parental competence than the WL condition. The EBFI condition was also associated with significantly less observed child negative behavior in comparison to the WL. The gains achieved at postintervention were maintained at 1-year follow-up. Contrary to predictions, the enhanced program was not shown to be superior to the standard program using any of the outcome measures at either postintervention or follow-up. Each of the programs produced significant reductions in children's co-occurring disruptive behavior and attentional/hyperactive difficulties with 80% of the children showing clinically reliable improvement in observed negative behavior from preintervention to follow-up.


Bonding and structure of oxofluoroniobate-based glasses.
Glasses based on the oxofluoroniobate anion have been characterized by vibrational and solid-state NMR spectroscopy. The mechanism of glass formation in the systems K2NbOF5-MF3 (M = Al, In) has been suggested. A glass network is built from the chains of corner-sharing octahedra through -Nb-F(O)-M- and -Nb-F-Nb- bridges. Isolated NbOF5(2-) octahedra are also present, which is consistent with the glass composition. The high ionic mobility of NbOF5(2-) due to its fast reorientations results in equalization of the Nb-O and Nb-F distances, which is reflected in the appearance of the IR band at 700-800 cm(-1) not observed in the Raman spectrum. Its assignment to bridging -Nb-O-Nb- species accepted in the literature was not proven.


Applications of biological monitoring in occupational health practice: practical application of urinary 2-ethoxyacetic acid to assess exposure to 2-ethoxyethyl acetate in large format silk-screening operations.
A practical application of urinary 2-ethoxyacetic acid (EAA) to assess occupational exposure to 2-ethoxyethyl acetate (EGEE-Ac) during a large format silk-screening operation is described. Industrial hygiene air monitoring of employees of a silk-screen shop producing large aircraft interior panel coverings revealed a broad range of exposures to EGEE-Ac. Time weighted exposures averaged 12 ppm (range 2.9-34 ppm) in press operators during production press runs, exceeding the 5 ppm Washington State permissible exposure limit. Employees were instructed to use organic vapor respirators until engineering controls could be developed. Urinary monitoring of EAA was conducted on 30 employees by the company medical department to aid in exposure risk assessment and to assess compliance. Results obtained ranged from 1.1-27 mg EAA/g creatinine which compares favorably with the proposed Biological Exposure Index (BEI) of 100 mg EAA/g creatinine. Results of representative air and biological monitoring, and observations of work practices for different exposure groups indicated that inhalation exposure was the predominant route of exposure. Follow-up testing to assess the efficacy of a newly installed ventilation upgrade is planned.


[Pulmonary aspergillosis: clinical findings and surgical treatment].
Between 1980 and 1995, 10 patients underwent thoracotomy for pulmonary aspergillosis. In six patients, hemoptysis and bloody sputum were the chief complaints. The other complaints were nonspecific. Six patients had a history of pulmonary tuberculosis, and two of those patients underwent upper lobectomy. Aspergillosis had developed in the residual space. A fungus ball was observed on the preoperative chest X-ray and CT scan films in seven patients. Lobectomy was done in three patients, segmentectomy in two, and partial pulmonary resection in four. The patients with lesions that had grown in the residual space underwent curettage with muscle plombage. Three patients underwent thoracoplasty. An additional operation was done in two patients because of poor residual lung expansion. No patient had recurrence. We conclude that surgical treatment should be based on symptoms and on pathological findings.


Strong association of rheumatoid arthritis with the presence of a polymorphic Ia epitope defined by a monoclonal antibody: comparison with the allodeterminant DR4.
Among individuals with rheumatoid arthritis the presence of the polymorphic Ia antigen epitope detected by the monoclonal antibody 109d6 is more strongly correlated with disease susceptibility than are other specificities, such as HLA DR4, DRw53 (MT3) or the antigenic determinant, defined by the monoclonal antibody 17-3-3S. The cells of 93% of Caucasian and Hispanic patients react with the 109d6 reagent. As was the case in normal individuals, all DR4-positive patients express the 109d6 determinant; however, 26% of those with rheumatoid arthritis have the epitope recognized by antibody 109d6, but lack the specificity DR4. Of these, one-third expresses only HLA DR1 and DQw1 (MT1, MB1) determinants. Studies of family members reveal that here the determinants 109d6, DR1, and DQw1 are encoded by the same unusual haplotype. In certain other individuals with rheumatoid arthritis who express DR4, DRw53, and the 109d6 determinants, family studies show that the 109d6 epitope is encoded not only by the haplotype specifying DR4 but also by the opposite haplotype that does not bear the genes for DR4. This suggests that homozygosity for certain Ia epitopes is relevant to determining the disease-susceptibility state. These studies emphasize the utility of monoclonal antibodies as reagents for the recognition of Ia epitopes that are more closely involved in the determination of disease susceptibility than are allomorphic molecules detected by conventional typing alloantisera.


A selective delta opioid receptor agonist SNC80, but not KNT-127, induced tremor-like behaviors via hippocampal glutamatergic system in mice.
Although delta opioid receptors (DOP) are now known to play a major role in modulating chronic pain and controlling emotional processes, unfortunately, some DOP agonists, such as SNC80, reportedly produced convulsive-like behaviors manifesting as tremor-like behaviors in a preclinical study. Therefore, these induced convulsions limit the progress of the clinical development of DOP agonists. However, mechanisms underlying DOP-induced convulsant activity remain unclarified. Thus, the study aimed to elucidate mechanisms that could cause tremor-like behaviors of SNC80. These drugs were microinjected into the ventral hippocampus CA3 (vCA3), amygdala (AMY), and insular cortex (IC) of mice. In addition, we examined the extracellular glutamate levels after DOP agonist local treatment. Microinjection of SNC80 into the vCA3 increased the number of tremor-like behaviors and extracellular glutamate levels but did not cause tremor-like behaviors in mice when microinjected into IC and AMY. Pretreatment with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainite receptor antagonist CNQX into vCA3 totally inhibited the SNC80-induced increases in tremor-like behaviors. In contrast, another DOP agonist, KNT-127, did not cause tremor-like behaviors in any of the tested brain areas. Further, the extracellular glutamate levels in the hippocampus were significantly lower in the KNT-127-treated mice than in the SNC80-treated mice. Our results showed that the administration of SNC80, but not KNT-127, into vCA3 induced tremor-like behaviors by activating glutamatergic neurons in mice. We propose that KNT-127 should be further studied clinically as a DOP agonist that is expected to have a low risk for convulsions than those resulting in antinociceptive and antidepressant effects.


Shear wave elastography for breast masses is highly reproducible.
To evaluate intra- and interobserver reproducibility of shear wave elastography (SWE) for breast masses. For intraobserver reproducibility, each observer obtained three consecutive SWE images of 758 masses that were visible on ultrasound. 144 (19%) were malignant. Weighted kappa was used to assess the agreement of qualitative elastographic features; the reliability of quantitative measurements was assessed by intraclass correlation coefficients (ICC). For the interobserver reproducibility, a blinded observer reviewed images and agreement on features was determined. Mean age was 50 years; mean mass size was 13 mm. Qualitatively, SWE images were at least reasonably similar for 666/758 (87.9%). Intraclass correlation for SWE diameter, area and perimeter was almost perfect (ICC ≥ 0.94). Intraobserver reliability for maximum and mean elasticity was almost perfect (ICC = 0.84 and 0.87) and was substantial for the ratio of mass-to-fat elasticity (ICC = 0.77). Interobserver agreement was moderate for SWE homogeneity (κ = 0.57), substantial for qualitative colour assessment of maximum elasticity (κ = 0.66), fair for SWE shape (κ = 0.40), fair for B-mode mass margins (κ = 0.38), and moderate for B-mode mass shape (κ = 0.58), orientation (κ = 0.53) and BI-RADS assessment (κ = 0.59). SWE is highly reproducible for assessing elastographic features of breast masses within and across observers. SWE interpretation is at least as consistent as that of BI-RADS ultrasound B-mode features. • Shear wave ultrasound elastography can measure the stiffness of breast tissue • It provides a qualitatively and quantitatively interpretable colour-coded map of tissue stiffness • Intraobserver reproducibility of SWE is almost perfect while intraobserver reproducibility of SWE proved to be moderate to substantial • The most reproducible SWE features between observers were SWE image homogeneity and maximum elasticity.


Keratinocyte growth factor inhibits cross-linked envelope formation and nucleosomal fragmentation in cultured human keratinocytes.
Keratinocyte growth factor (KGF) exhibits paracrine action on numerous epithelia, including skin. We have found that cultures of normal human keratinocytes must attain confluence before KGF promotes an increase in cell number relative to untreated controls. In postconfluent cultures, treatment with KGF promoted tight packing of keratinocytes with a small basal cell morphology. Based on these observations, we hypothesized that KGF increased cell number in postconfluent cultures by affecting the ability of normal keratinocytes to undergo terminal differentiation and/or programmed cell death. In support of this hypothesis, keratinocytes treated with KGF produced fewer cross-linked envelopes and exhibited reduced membrane-associated transglutaminase activity relative to cells treated with epidermal growth factor or untreated controls. We also found that nucleosomal fragmentation was reduced in postconfluent cultures of KGF-treated keratinocytes. Furthermore, KGF-treated keratinocytes were more resistant to suspension-induced nucleosomal fragmentation than control or epidermal growth factor-treated cultures. Therefore, it appears that KGF modulates aspects of keratinocyte terminal differentiation which share features with programmed cell death. We propose that stromally-derived KGF may act as a paracrine survival factor in skin and perhaps other renewal tissues.


High diversity of Caligus species (Copepoda: Siphonostomatoida: Caligidae) in Taiwanese waters.
Caligidae, commonly known as sea lice, is the most speciose family of symbiotic copepods comprising over 490 species classified in 31 genera. Caligus Müller, 1785 is the largest genus of this family comprising 255 species. Fifty-three species of Caligus have been reported from Taiwan so far, representing 20.78 % of Caligus currently known in the world. Nevertheless, we believe many more species of Caligus are yet to be discovered from the waters of Taiwan, because only 17.71 % (553/3,121 species) of the potential fish hosts occurring in Taiwanese waters have been examined for parasitic copepods so far. Among the countries in the Far East, Taiwan exhibits the shortest coastline yet displays the highest diversity of Caligus species. This seemingly contradictory phenomenon may be explained by the fact that the Island of Taiwan is straddling over the border of two ecological realms in the western North Pacific, viz. the Temperate Northern Pacific Realm and the Central Indo-Pacific Realm. Pseudocaligus longipes Moon & Kim, 2012 is formally transferred to the genus Caligus as C. longipes (Moon & Kim, 2012) comb. nov.


Fluorescence Imaging of Mitochondrial DNA Base Excision Repair Reveals Dynamics of Oxidative Stress Responses.
Mitochondrial function in cells declines with aging and with neurodegeneration, due in large part to accumulated mutations in mitochondrial DNA (mtDNA) that arise from deficient DNA repair. However, measuring this repair activity is challenging. We employ a molecular approach for visualizing mitochondrial base excision repair (BER) activity in situ by use of a fluorescent probe (UBER) that reacts rapidly with AP sites resulting from BER activity. Administering the probe to cultured cells revealed signals that were localized to mitochondria, enabling selective observation of mtDNA BER intermediates. The probe showed elevated DNA repair activity under oxidative stress, and responded to suppression of glycosylase activity. Furthermore, the probe illuminated the time lag between the initiation of oxidative stress and the initial step of BER. Absence of MTH1 in cells resulted in elevated demand for BER activity upon extended oxidative stress, while the absence of OGG1 activity limited glycosylation capacity.


Molecular imaging in cardiovascular magnetic resonance imaging: current perspective and future potential.
The development of novel imaging agents and techniques is allowing some biological events to be imaged in vivo with magnetic resonance imaging (MRI) at the cellular and subcellular level. In this paper, the use of novel gadolinium chelates and superparamagnetic iron oxide nanoparticles for molecular MRI of the cardiovascular system is extensively reviewed. The physical properties of these imaging agents and the pulse sequences best suited to their visualization are extensively discussed. The application of molecular MRI in diseases of the vasculature and myocardium is then reviewed. The clinical experience to date, as well as the promise and potential impact of molecular MRI, is extensively discussed.


Early abdominal incision recurrence in a patient with stage I adenocarcinoma of the endometrium.
Although most patients with a surgical stage I endometrial cancer have an excellent prognosis, some patients will experience a recurrence. Endometrial cancer typically recurs at the vaginal cuff or in the pelvis; however, it can recur distantly in the abdomen or lung. Although recurrences have been reported at laparoscopic trochar sites, it is unusual to have a recurrence in the abdominal incision after laparotomy. A 51-year-old woman was diagnosed with stage Ib grade 2 adenocarcinoma of the endometrium and stage IV endometriosis. Six months after surgery, she presented with a mass in the lateral aspect of her Maylard incision. Computed tomography scans of the chest, abdomen, and pelvis showed no evidence of recurrent disease. The mass was resected and confirmed to be an adenocarcinoma similar to the endometrial primary. This case is interesting because of the rapid recurrence of the endometrial primary at an unusual site-the abdominal incision. It illustrates the need to carefully evaluate all suspicious masses, even as early as 6 months after diagnosis and surgical staging.


Effectiveness of ECT combined with risperidone against aggression in schizophrenia.
Aggressive behavior in schizophrenic patients can often be problematic not only for the patients themselves, but for their families and others. This study examined the effect of electroconvulsive therapy (ECT) in combination with risperidone in an open trial in 10 male schizophrenic patients with significant aggressive behaviors. Patients were given bilateral ECT five times a week in combination with risperidone. The mean total number of times of ECT was 6.6 (range 5-9). The aggressive behavior in five of the six patients, who showed positive symptoms, was rapidly ameliorated within 12 days. The ECT/risperidone regimen also eliminated aggressive behavior in four patients showing no positive symptoms within 10 days. These treatment effects lasted for at least 6 months in 9 (of the 10) patients. The results suggest that ECT, combined with risperidone, produce a rapid and effective elimination of aggressive behaviors in schizophrenic patients. In addition, there was a resolution of aggression in four patients with no positive symptoms. This suggests that aggression in some schizophrenic patients develops as a primary symptom of schizophrenia and is not related to other positive symptoms of the disease or the patient's personality traits.


Cost containment, solidarity and cautious experimentation: Swedish dilemmas.
This paper uses secondary data analysis and a literature review to explore a "Swedish Dilemma": Can Sweden continue to provide a high level of comprehensive health services for all regardless of ability to pay--a policy emphasizing "solidarity"--or must it decide to impose increasing constraints on health services spending and service delivery--a policy emphasizing "cost containment?" It examines recent policies and longer term trends including: changes in health personnel and facilities; integration of health and social services for older persons; introduction of competition among providers; cost sharing for patients; dismantling of dental insurance; decentralization of government responsibility; priority settings for treatment; and encouragement of the private sector. It is apparent that the Swedes have had considerable success in attaining cost containment--not primarily through "market mechanisms" but through government budget controls and service reduction. Further, it appears that equal access to care, or solidarity, may be adversely affected by some of the system changes.


Dual-targeting immunotherapy of lymphoma: potent cytotoxicity of anti-CD20/CD74 bispecific antibodies in mantle cell and other lymphomas.
We describe the use of novel bispecific hexavalent Abs (HexAbs) to enhance anticancer immunotherapy. Two bispecific HexAbs [IgG-(Fab)(4) constructed from veltuzumab (anti-CD20 IgG) and milatuzumab (anti-CD74 IgG)] show enhanced cytotoxicity in mantle cell lymphoma (MCL) and other lymphoma/leukemia cell lines, as well as patient tumor samples, without a crosslinking Ab, compared with their parental mAb counterparts, alone or in combination. The bispecific HexAbs have different properties from and are more potent than their parental mAbs in vitro. The juxtaposition of CD20 and CD74 on MCL cells by the HexAbs resulted in homotypic adhesion and triggered intracellular changes that include loss of mitochondrial transmembrane potential, production of reactive oxygen species, rapid and sustained phosphorylation of ERKs and JNK, down-regulation of pAkt and Bcl-xL, actin reorganization, and lysosomal membrane permeabilization, culminating in cell death. They also displayed different potencies in depleting lymphoma cells and normal B cells from whole blood ex vivo and significantly extended the survival of nude mice bearing MCL xenografts in a dose-dependent manner, thus indicating stability and antitumor activity in vivo. Such bispecific HexAbs may constitute a new class of therapeutic agents for improved cancer immunotherapy, as shown here for MCL and other CD20(+)/CD74(+) malignancies.


The influence of eccentric contractions and stretch on alpha motoneuron excitability in normal subjects and subjects with spasticity.
Application of eccentric contractions and muscle stretch are clinically effective in reducing spasticity and increasing ROM (7). This may be explained by a change in the excitability of motoneurons supplying the spastic muscle. Excitability of motoneurons can be indirectly assessed using the H-reflex. Experiments were performed on 20 normal subjects and 17 subjects with spasticity resulting from neurological disorder. Subjects were seated in a secure position and the ankle joint was moved from 30 degrees plantarflexion to 20 degrees dorsiflexion at a velocity of 30 degrees/sec. Sixty eccentric contractions of the triceps surae muscle were performed using a Kin-Com dynamometer (Chattanooga Corp, Tennessee). Two protocols were used: (1) eccentric contractions only, and (2) eccentric contractions with a 5s stretch of the relaxed triceps surae after each contraction. Two sets of 10 H-reflexes were collected from the soleus muscle before (trial 1 & 2) and after (trial 3 & 4) eccentric and eccentric + stretch protocols. The mean peak to peak H-reflex amplitude was calculated for each trial and compared using ANOVA. Eccentric contractions resulted in a significant and maintained increase in the H-reflex in neurological compared to normal subjects (P < 0.05). Eccentric contractions in subjects with spasticity resulted in an increase in motoneuron excitability which may assist in corticospinal activation of motoneurons during voluntary movement. The eccentric + stretch protocol, resulted in a decrease in the mean amplitude of H-reflexes in neurological subjects, however, this was not significant. The application of a stretch following eccentric contractions decreased motoneuron excitability and may thus be beneficial to decrease spasticity whilst strengthening muscle.


Connecting discrete stereoclusters by using DFT and NMR spectroscopy: the case of nivariol.
The structural determination of small organic molecules is mainly undertaken by using NMR techniques, although it is increasingly supplemented by using computational methods. NMR parameters, such as chemical shifts and coupling constants, are extremely sensitive indicators of local molecular conformation and are a source of structural evidence. However, their interpretation is fairly challenging in many circumstances, such as the case of the new polyether squalene derivative nivariol, the structure of which was elucidated by means of NMR spectroscopy and DFT calculations. The potential flexibility of this molecule and the high number of quaternary carbon atoms that it contains make its configurational assignment very difficult. Moreover, the relative configuration of four separated stereoclusters was established and subsequently connected by using NOE and J-based analysis, as well as by a comparison of its experimental (13)C NMR chemical shifts with the corresponding population-weighted values, as calculated by using DFT methods. Limitations of these used approaches became apparent but were overcome by combining the two methods.


Gender differences in depression and PTSD symptoms following combat exposure.
This research examined gender as a moderator of the association between combat exposure (CE) and depression as well as CE and PTSD symptoms among a nonclinical sample of Soldiers following deployment in support of operations in Afghanistan and Iraq. Cases included 6,943 (516 women, 6,427 men) active duty Soldiers that were retrospectively analyzed from a pre- and post-deployment screening database at a large Army installation. Gender moderated the association between CE and depressive and PTSD symptoms such that higher levels of CE were more strongly associated with depression and PTSD symptoms in women compared to men. Female Soldiers also reported higher severity of depressive symptoms compared to male Soldiers, whereas men reported higher levels of CE and a greater number of previous deployments compared to women. CE was a stronger predictor of post-deployment depression and PTSD symptoms for women compared to men. These results provide evidence for gender-based differences in depression and PTSD risk. Screening for degree of CE in addition to symptoms associated with depression and PTSD can help with the care for service members who are returning from deployments to combat zones.


Central effects of cinnarizine: restricted use in aircrew.
Our aim was to establish the effects of cinnarizine, a drug used for the treatment of motion sickness, on daytime sleepiness and performance. The effects of cinnarizine (15, 30, and 45 mg) were assessed on digit symbol substitution, tracking, vigilance, and on subjective and objective (daytime sleep latencies) sleepiness in six healthy volunteers between the ages of 20 and 34 yr (mean 27 yr) from 1.0 h prior to ingestion to 8.0 h after ingestion. The study was placebo-controlled and double-blind in a six-way, cross-over design. Promethazine (10 mg) was used as an active control. No effects of 15 mg cinnarizine were observed on performance. Sleep latencies were reduced at 3.5 and 5.0 h after ingestion, and the subjects as a group reported increased sleepiness at 5.0 and 6.5 h after ingestion. With 30 mg cinnarizine there was evidence of impaired performance at 5.0, 6.5, and 8.0 h after ingestion. Sleep latencies were not reduced, but the subjects as a group reported increased sleepiness 5.0 h after ingestion. With 45 mg cinnarizine there was evidence of impaired performance 5.0 h after ingestion. Sleep latencies were reduced at 5.0 and 6.5 h after ingestion, and the subjects as a group reported increased sleepiness 6.5 h after ingestion. Promethazine (10 mg) shortened sleep latencies from 2.5 to 5.0 h after ingestion, and the subjects as a group reported increased sleepiness overthis period. Cinnarizine is not free of central activity over the usual therapeutic dose range of 15 to 30 mg. It is contraindicated for motion sickness in aircrew involved in the control of aircraft. Caution should be exercised in the use of the drug by other aircrew who may be involved in tasks which demand continued attention.


Nucleotide sequence of the bla(RTG-2) (CARB-5) gene and phylogeny of a new group of carbenicillinases.
We determined the nucleotide sequence of the bla gene for the Acinetobacter calcoaceticus beta-lactamase previously described as CARB-5. Alignment of the deduced amino acid sequence with those of known beta-lactamases revealed that CARB-5 possesses an RTG triad in box VII, as described for the Proteus mirabilis GN79 enzyme, instead of the RSG consensus characteristic of the other carbenicillinases. Phylogenetic studies showed that these RTG enzymes constitute a new, separate group, possibly ancestors of the carbenicillinase family.


Rupture risk prediction of cerebral aneurysms using a novel convolutional neural network-based deep learning model.
Cerebral aneurysms should be treated before rupture because ruptured aneurysms result in serious disability. Therefore, accurate prediction of rupture risk is important and has been estimated using various hemodynamic factors. To suggest a new way to predict rupture risk in cerebral aneurysms using a novel deep learning model based on hemodynamic parameters for better decision-making about treatment. A novel convolutional neural network (CNN) model was used for rupture risk prediction retrospectively of 123 aneurysm cases. To include the effect of hemodynamic parameters into the CNN, the hemodynamic parameters were first calculated using computational fluid dynamics and fluid-structure interaction. Then, they were converted into images for training the CNN using a novel approach. In addition, new data augmentation methods were devised to obtain sufficient training data. A total of 53,136 images generated by data augmentation were used to train and test the CNN. The CNNs trained with wall shear stress (WSS), strain, and combination images had area under the receiver operating characteristics curve values of 0.716, 0.741, and 0.883, respectively. Based on the cut-off values, the CNN trained with WSS (sensitivity: 0.5, specificity: 0.79) or strain (sensitivity: 0.74, specificity: 0.71) images alone was not highly predictive. However, the CNN trained with combination images of WSS and strain showed a sensitivity and specificity of 0.81 and 0.82, respectively. CNN-based deep learning algorithm using hemodynamic factors, including WSS and strain, could be an effective tool for predicting rupture risk in cerebral aneurysms with good predictive accuracy.


Perfluorocarbon Emulsion Contrast Agents: A Mini Review.
Perfluorocarbon emulsions offer a variety of applications in medical imaging. The substances can be useful for most radiological imaging modalities; including, magnetic resonance imaging, ultrasonography, computed tomography, and positron emission tomography. Recently, the substance has gained much interest for theranostics, with both imaging and therapeutic potential. As MRI sequences improve and more widespread access to 19F-MRI coils become available, perfluorocarbon emulsions have great potential for new commercial imaging agents, due to high fluorine content and previous regulatory approval as antihypoxants and blood substitutes. This mini review aims to discuss the chemistry and physics of these contrast agents, in addition to highlighting some of the past, recent, and potential applications.


[Efficacy of the combined use of taurine for hyperbilirubinemia caused by UFT therapy after surgery for colonic cancer].
For postoperative adjuvant chemotherapy, UFT was administered to 69 cases of stage II and III colonic cancer following surgery with a radical curability of A. Among these patients, 8 developed hyperbilirubinemia. UFT administration was discontinued for those who developed overt jaundice or dermatological symptoms, experienced a relapse of an earlier asthmatic respiratory difficulty, or for those who were found with multiple hepatic metastases. For the 4 who had developed subclinical jaundice with a total bilirubin level of 1.6 to 2.2 mg/dl, UFT was combined with taurine. The combination successfully eliminated hyperbilirubinemia. All 4 are currently alive with no recurrence at this writing. Taurine ameliorates one's capacity to excrete bile, blood flow, and augments the actions of hepatocytes. It is effective in treating the hyperbilirubinemia that develops during UFT therapy.


Rheumatoid arthritis and comorbidity.
Data collected from 288 patients with rheumatoid arthritis (RA) indicated that 54% of respondents also reported other chronic conditions, and that 20% rated at least one of these other conditions as severe. Both the frequency and severity of these comorbidities affected scores on measures of depressive symptoms, social connectedness and on the Arthritis Impact Measurement Scales. These findings suggest that the absence of controls for comorbidity may bias measures of functional status among patients with RA.


Partial status epilepticus induced by hypocupremia in a patient with Wilson's disease.
Although seizures are rarely encountered in Wilson's disease (WD), seizures related to hypocupremia have not been reported before. We report a patient presenting with partial status epilepticus who was on strict low-copper diet and chelating therapy for WD. Despite other rare causes of seizures in WD including penicillamine-induced pyridoxine deficiency, cerebral copper deposition and metabolic encephalopathy, the most probable cause of resistant status epilepticus in this patient was found as hypocupremia from overzealous treatment. This case exemplifies that hypocupremic states should be kept in mind as a risk factor for resistant seizures.


Mixed gonadal dysgenesis in a 45,X neonate with chromosome Y material in the dysgenetic gonad.
We report on a neonate with a disorder of sex development, Prader 3-4 external genitalia and a palpable structure in the right inguinal canal suggestive of gonadal tissue. Chromosome studies on blood lymphocytes showed monosomy of chromosome X. Laparoscopy identified a streak-like gonad on the left side, unicorn uterus and a dysgenetic testis on the right, attached to a Fallopian tube. Because of the unilateral palpable gonad and the presence of ambiguous genitalia we investigated further for the presence of Y material. Quantitative fluorescent PCR analysis of material from the dysgenetic gonad and skin fibroblasts revealed the presence of chromosome Y-derived sequences, suggesting sex chromosome mosaicism. In 45,X/46,XY mosaicism, chromosome studies carried out on peripheral lymphocytes do not always reflect the proportion of cell lines in the gonads. The detection of Y chromosome material in a dysgenetic gonad is extremely significant, due to the high risk of malignant transformation.


Water-clear cell adenoma of the parathyroid. A case report with immunohistochemistry and electron microscopy.
We report a water-clear cell adenoma of the parathyroid gland, a lesion which to our knowledge has not been described previously. Like its rare but well-described hyperplastic counterpart, water-clear cell hyperplasia, this adenoma is composed of cells with abundant foamy-to-granular cytoplasm and mild nuclear pleomorphism. The cells form glandular structures and cell nests separated by fine fibrovascular septae. The tumor cells stain positively with anti-parathyroid hormone and show characteristic glassy and flocculate material by electron microscopy. Unlike water-clear cell hyperplasia, water-clear cell adenoma is a solitary lesion that compresses the residual nonneoplastic parathyroid gland.


Characterization of the transferrin-iron uptake system in Neisseria meningitidis.
The transferrin-iron uptake system of six Neisseria meningitidis strains was characterized using 125I-transferrin in receptor assays and 55Fe-loaded transferrin in uptake assays. Receptors for transferrin varied among the strains both in number (from 700 to 4700 receptors per cell) and in their affinity constants for the protein (Ka ranged from 0.7 x 10(7) to 4.0 x 10(7) l mol-1). Neither receptor numbers nor affinity constants were significantly different in carrier and invasive strains, although the Ka seem to be somewhat higher in the latter. Iron uptake from transferrin was also variable among the strains, but showed the same lack of correlation with their origin.


Mast cells numbers and peritumoral microvessel density of the prostatic adenocarcinomas and correlation with prognostic parameters.
To determine the utility of mast cell numbers and microvascular density (MVD) in evaluating acinar type of prostatic adenocarcinoma (PCa), and to ascertain a relationship between the number of mast cells with prognostic parameters (larger tumor volume, high Gleason score, lymphovascular, perineural, seminal vesicles invasion, metastatic lymph node). The study comprised 97 radical prostatectomy specimens. The paraffin sections were stained with anti-CD31, anti- CD34 and Toluidine Blue. The numbers of positive staining of cells and microvessels in 10 high-power fields were counted systematically. A statistically significant relationship was found between MVDn and number of MC (r=0.218 and p=0. 032). There was no correlation between age and MC and MVD (p=0.406 and p=0.671, respectively). A correlation between mast cell number and microvascular density cannot depend on tumor angiogenesis or this relationship can be an independent parameter. More comprehensive studies could reveal relationship with prognostic parameters.


Assessment of residual urine in men following catheterisation.
There is a certain volume of urine left within the bladder which cannot be drained by a catheter. A dilutional method was used to calculate this residual volume in 15 men; 10 had acute retention secondary to benign prostatic hyperplasia and 5 had permanent indwelling catheters for neurogenic urinary incontinence. The mean catheterised residual volume was 98.53 ml for patients with acute retention and 14.48 ml for patients with long-term catheters. The explanation for higher post-catheterisation volumes in the acute retention group is probably multifactorial; bladder sacculation and diverticula, detrusor tone and reflux may all play a role.


Cyclic GMP-gated channel and peripherin/rds-rom-1 complex of rod cells.
The cGMP-gated channel and the peripherin/rds-rom-1 complex are two oligomeric membrane proteins that play key roles in the structure and function of photoreceptor outer segments. The channel is localized on the plasma membrane where it controls the flow of Na+ and Ca2+ into the outer segment in response to light-induced changes in cGMP. The rod channel consists of two homologous subunits, designated alpha and beta, which assemble into a heterotetrameric complex. Both subunits contain a core structural unit consisting of six transmembrane segments, a pore region and a cGMP binding domain. The alpha subunit is the dominant functional subunit since it forms a functional channel by itself. The beta subunit does not assemble into a functional channel by itself, but modulates the activity of the channel. The peripherin/rds-rom-1 complex is localized along the rim region of disk membranes where it plays a crucial role in disk morphogenesis. This complex consists of two peripherin/rds and two rom-1 subunits that interact non-covalently to form a heterotetramer. Peripherin/rds is the dominant subunit since, in the absence of rom-1, it self-assembles into a homotetramer that effectively supports outer segment disk formation and structure. Rom-1 on its own does not initiate outer segment formation. Instead, it plays a minor role in fine tuning disk structure. Recently, peripherin/rds-containing tetramers have been shown to form disulfide-mediated higher-order oligomers. This novel oligomerization is suggested to play a central role in outer segment disk formation.


[Establishment and evaluation of a murine model of brain injury induced by high altitude hypoxic inflammation].
The aim of this study was to develop a murine model of brain injury induced by high altitude hypoxic inflammation. In the study, we used a decompression chamber to mimic an acute hypobaric hypoxia, and 8-week-old male C57BL/6 mice were intraperitoneally injected with 5 mg/kg lipopolysaccharide (LPS) to induce inflammatory response. We determined the levels of pro-inflammatory factors (IL-6, TNF-α) and anti-inflammatory factor (IL-10) in mice serum using ELISA assays to confirm the high altitude hypoxic inflammation, and verified the brain injury after the inflammation using hematoxylin-eosin (HE) staining. The results showed that, among four experiment groups (ctrl, acute hypobaric hypoxia, LPS, and acute hypobaric hypoxia plus LPS groups), the acute hypobaric hypoxia plus LPS treatment group displayed the highest levels of IL-6, TNF-α, and IL-10. Meanwhile, the acute hypobaric hypoxia plus LPS treatment group showed the most severe cortex and hippocampus injuries, including cellular swelling, the widened pericellular spaces, angiogenesis, and shrunken neurons with darkly stained pyknotic nuclei, etc. Strikingly, nuclei ventrales posteriors thalami were found to be more sensitive to acute hypobaric hypoxia plus LPS treatment, and their destroy degrees were higher than those neurons in cortex and hippocampus. These results suggested that we established a reliable murine model of brain injury induced by high altitude hypoxic inflammation, and might be useful to the relevant studies.


Bogota Bag in Abdominal Compartment Syndrome at Kathmandu Model Hospital.
The gold standard of quick and definitive treatment of Abdominal compartment syndrome (ACS) is surgical decompression by opening the abdomen and leaving it open until intra-abdominal pressure decreases. Temporary abdominal closure techniques are used to postpone definite closure until predisposing factors causing pathologic elevation of intra-abdominal pressure are resolved.This study aim to analyze feasibility of Bogota Bag placement as a way of temporary abdominal closure. Cases admitted in the period of eight years that were diagnosed to have or at risk to develop ACS and managed with 'Bogota Bag', irrespective of primary diagnosis were reviewed retrospectively. Cause of ACS, reasons to place Bogota bag, its complications and final outcome in terms of mortality related or not related with Bogota Bag placement were assessed. Total of ten patients had placement of Bogota Bag in the period of eight years. Laparotomy for bowel perforation with peritonitis was the most common primary condition contributing to ACS. Bogota bag was placed in two cases after emergency decompression as a therapeutic measure whereas others were done as prophylactic measure. There were two mortalities (20%) which were not directly related to abdominal compartment syndrome. Abdomen closure with Bogota Bag for patients with ACS or likely to develop ACS is a feasible technique with minimal procedure related morbidities.


Maintenance of size and function of influenza virus hemagglutinin specific transgenic T-cell clone during life.
Immunization induces less protective immunity against infectious diseases in old compared to young subjects. We have studied the effect of age on the in vitro and in vivo function of murine transgenic T cells expressing a receptor for influenza hemagglutinin 110-120 peptide. During aging the transgenic T cells undergo the age-associated shift from naive to memory phenotype but maintain, despite thymic involution, their number as well as their cytokine production and proliferative responses induced by the hemagglutinin 110-120 peptide in vitro. The maintenance of the size and functions of transgenic T cells during the aging may be related to low expression of CTLA-4 molecules known to exhibit a negative regulatory effect subsequent to interaction with costimulatory molecules as well as of stimulation of T cells by unknown cross reactive endogenous factors but not by nominal antigen since innate immunity prevents natural infection with influenza virus of murine species. This suggests that the impaired immunity induced by immunization in old subjects reflects defects in the development and maintenance of T cell memory and not in the expression of effector activity.


Sequential processing from cell lysis to protein assay on a chip enabling the optimization of an F(1)-ATPase single molecule assay condition.
We developed an integrated protein assay device, "Single Molecule MicroTAS (SMM)," which enables cell lysis, protein extraction, purification, and activity assay. The assay was achieved at the single-molecule scale for a genetically engineered protein, F(1)-ATPase, which is the smallest known rotary motor. A cell lysis condition, with a wide range of applied voltages (50-250 V) and other optimized values (pulse width: 50 micros; duty: 0.01%; electrode gap: 25 microm; total flow rate: 5 microL min(-1)) provided a high enough protein concentration for the assay. Successively, the protein was extracted and purified by specific binding in a microfluidic channel. During the assay process, the diffusion effect of lysate between a two-phase laminar flow contributes to optimizing the single-molecule assay condition, because the concentration of the original lysate from the E. coli solution is too high to assay. To achieve the most efficient assay condition, the protein diffusion effect on the assay was experimentally and numerically evaluated. The results reveal that, in our experimental conditions, concentrations of F(1) and other contaminated effluents are optimized for the F(1) rotational assay at a channel position. The adenosine triphosphate (ATP)-driven rotation speed measured in the SMM was compatible with that obtained by conventional purification and assay. Such a sequential process from cell lysis to assay proves that the SMM is an example of a sample-in-answer-out system for F(1) protein evaluation.


Treatment of recurrence after transanal endoscopic microsurgery (TEM) for T1 rectal cancer.
The aim of this study was to evaluate the management and outcome of local recurrences after transanal endoscopic microsurgery for T1 rectal cancer. Consecutive patients who underwent transanal endoscopic microsurgery for pT1 rectal cancer at a Dutch referral center (IJsselland Hospital) were registered in a prospective database. Follow-up was according to Dutch guidelines on rectal cancer, with additional rigid rectoscopy and endorectal ultrasound examinations every 3 months for the first 2 years, and every 6 months thereafter. Annual MRI of the lesser pelvis was added during the last 2 years of the study. Patients with local recurrence during follow-up were selected for individual analysis of outcome. Of a total of 88 patients who underwent transanal endoscopic microsurgery for pT1 rectal cancer, 18 patients (20.5%) had a local recurrence. Median time to local recurrence was 10 (range, 4-50) months. Median age at diagnosis of recurrence was 74 (range, 56-84) years. Of the 18 patients, 2 did not undergo further surgery because of concomitant metastatic disease, and 16 underwent salvage surgery, without need for multivisceral resections. No postoperative mortality was observed. In 15 patients (94%), a microscopically negative excision margin was obtained; in 1 patient, the excision margin was microscopically positive. Median follow-up after salvage surgery was 20 (range, 2-112) months. One patient had a local renewal of recurrence, and 7 patients (39%) had distant metastases. At 3 years, overall survival was 31%; cancer-related survival was 58%. Recurrent disease after transanal endoscopic microsurgery for T1 rectal cancer is a major problem. Although salvage surgery for achieving local control is feasible in most patients, survival is limited, mainly because of distant metastases. Tailoring selection of T1 rectal cancers and exploring possible adjuvant treatment strategies following salvage procedures should be the next steps toward improving survival.


Synthesis and Anticancer Activity of New Thiopyrano[2,3-d]thiazoles Based on Cinnamic Acid Amides.
Novel rel-(5R,6S,7S)-2-oxo-5-phenyl-7-aryl(hetaryl)-3,7-dihydro-2H-thiopyrano [2,3-d]thiazole-6-carboxylic acid amides were synthesized in a hetero-Diels-Alder reaction with a series of cinnamic acid amides. The synthesized compounds were tested for their anticancer activity in vitro in the standard National Cancer Institute 60 cancer cell line assay. Promising compounds 3e, 3g, and 3h with moderate antitumor activity were identified among the synthesized series.


Recovery of Salmonella from Fluid Milk.
Methodology was developed for isolation of Salmonella from skim milk, 2% fat milk, whole milk and buttermilk. Lactose broth, lactose broth plus brilliant green dye, buffered peptone water and each milk type plus brilliant green dye were evaluated as preenrichment broths. Incubation temperatures of 35 and 43°C were compared for use at the preenrichment stage. The recovery of Salmonella was determined after selective enrichment in selenite cystine, tetrathionate and Rappaport-Vassiliadis broths. Results indicated that fluid milk should be examined for Salmonella by being preenriched in lactose broth, subcultured to selenite cystine and tetrathionate broths and streaked to selective agars, with 35°C as the incubation temperature throughout the analysis.


Prevalent Drug Usage Practices in Adults and Children With Idiopathic Inflammatory Myopathies: Registry-Based Analysis From the MyoCite Cohort.
Idiopathic inflammatory myopathies (IIMs) form a heterogeneous group of disorders with a deficit of quality evidence regarding its management. Therefore, we aimed to explore the prevalent treatment practices in the MyoCite cohort from India. Drug usage patterns, their predictors, drug retention rates, efficacy, and adverse drug reactions were analyzed for adults and children newly diagnosed with IIM (2017-2020) and followed prospectively and compared with real-world data by performing a medical records review. GraphPad Prism version 8.4.2 was used for statistical analysis. Of 181 adults (male-to-female ratio, 1:4.6) and 30 children (M:F, 1.3:1), dermatomyositis (41% adults, 93% children) was the most common subtype. Methotrexate (MTX) was the drug of choice (67% adult, 90% children) followed by azathioprine (AZA) and mycophenolate mofetil (MMF). The MMF, AZA, cyclophosphamide, and rituximab (RTX) were preferred for those with antisynthetase syndrome (ASSD) and those with lung involvement, whereas MTX was avoided in them. Functional class and family income did not determine drug preferences. Glucocorticoids were initiated at a lower dose in overlap myositis (45% vs 80%, p = 0.001), and the time to achieve the lowest dose of glucocorticoids was longer than 24 months for ASSD (77% vs 14%, p = 0.002).Over a median of 35 months, the overall retention rate was the highest for RTX (75%) followed by MTX (58%). Relapse-free survival was the highest for RTX followed by MTX. The most common reasons for discontinuation were adverse drug reactions for MTX and MMF, inefficacy for AZA, and cost for RTX. In this first analysis of drug usage and retention in patients with IIM in Northern India, MTX emerged as the most preferred drug in both adults and children, with the exception of those with ASSD or lung disease. Organ involvement and subtype of IIM are key determinants of drug preference. Overall, RTX and MTX were well-tolerated with high retention rates, followed by AZA and MMF.


Coronary pseudoaneurysm after angioplasty.
Coronary pseudoaneurysm is a complication of angioplasty occurring in 4-5% of cases. The likely etiology of the pseudoaneurysm is an iatrogenic dissection. Although increasingly identified, they are infrequently reported and no large series has been documented. The case of a 64-year-old patient with a post-PTCA coronary pseudoaneurysm that was treated surgically is presented. A review of the world's literature identifies stenosis as a major cofactor in operative intervention and raises the possibility that aneurysm formation promotes stenosis.


Postprocedure Anticoagulation in Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.
This study sought to assess the association between postprocedural anticoagulation (PPAC) use and several clinical outcomes. PPAC after primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI) may prevent recurrent ischemic events but may increase the risk of bleeding. No consensus has been reached on PPAC use. Using data from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome registry, conducted between 2014 and 2019, we stratified all STEMI patients who underwent pPCI according to the use of PPAC or not. Inverse probability of treatment weighting and a Cox proportional hazards model with hospital as random effect were used to analyze differences in in-hospital clinical outcomes: the primary efficacy endpoint was mortality and the primary safety endpoint was major bleeding. Of 34,826 evaluable patients, 26,272 (75.4%) were treated with PPAC and were on average younger, more stable at admission with lower bleeding risk score, more likely to have comorbidities and multivessel disease, and more often treated within 12 hours of symptom onset than those without PPAC. After inverse probability of treatment weighting adjustment for baseline differences, PPAC was associated with significantly reduced risk of in-hospital mortality (0.9% vs 1.8%; HR: 0.62; 95% CI: 0.43-0.89; P < 0.001) and a nonsignificant difference in risk of in-hospital major bleeding (2.5% vs 2.2%; HR: 1.05; 95% CI: 0.83-1.32; P = 0.14). PPAC in STEMI patients after pPCI was associated with reduced mortality without increasing major bleeding complications. Dedicated randomized trials with contemporary STEMI management are needed to confirm these findings.


Electroanalytical point-of-care detection of gold standard and emerging cardiac biomarkers for stratification and monitoring in intensive care medicine - a review.
Determination of specific cardiac biomarkers (CBs) during the diagnosis and management of adverse cardiovascular events such as acute myocardial infarction (AMI) has become commonplace in emergency department (ED), cardiology and many other ward settings. Cardiac troponins (cTnT and cTnI) and natriuretic peptides (BNP and NT-pro-BNP) are the preferred biomarkers in clinical practice for the diagnostic workup of AMI, acute coronary syndrome (ACS) and other types of myocardial ischaemia and heart failure (HF), while the roles and possible clinical applications of several other potential biomarkers continue to be evaluated and are the subject of several comprehensive reviews. The requirement for rapid, repeated testing of a small number of CBs in ED and cardiology patients has led to the development of point-of-care (PoC) technology to circumvent the need for remote and lengthy testing procedures in the hospital pathology laboratories. Electroanalytical sensing platforms have the potential to meet these requirements. This review aims firstly to reflect on the potential benefits of rapid CB testing in critically ill patients, a very distinct cohort of patients with deranged baseline levels of CBs. We summarise their source and clinical relevance and are the first to report the required analytical ranges for such technology to be of value in this patient cohort. Secondly, we review the current electrochemical approaches, including its sub-variants such as photoelectrochemical and electrochemiluminescence, for the determination of important CBs highlighting the various strategies used, namely the use of micro- and nanomaterials, to maximise the sensitivities and selectivities of such approaches. Finally, we consider the challenges that must be overcome to allow for the commercialisation of this technology and transition into intensive care medicine.


Protection or sensitization by thiols or ascorbate in irradiated solutions of DNA or deoxyguanosine.
The initial aim of this study was to investigate how charge and other chemical properties of some radical scavengers influence the radiation-induced formation of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) in two model systems. The target molecule, deoxyguanosine (dG), was either organized in the DNA-helix form or present as a free nucleoside in an aerated aqueous phosphate buffer. Samples were irradiated with 137Cs gamma rays, alone or in the presence of different thiols, alcohols or ascorbate with net charges from -1 to +1. The formation of 8-oxo-dG was assayed with reverse-phase HPLC coupled to an electrochemical detector. In the absence of radical scavengers, the radiation-induced formation of 8-oxo-dG in DNA was extensive, and the ratio for formation of 8-oxo-dG was 20-fold higher for DNA compared to dG. The yields of 8-oxo-dG in DNA and dG were 7.7 x 10(-3) micromol J(-1) and 3.8 x 10(-4) micromol J(-1), respectively. Yield-dose plots showed that the efficiency of the positively charged thiol cysteamine to counteract the radiation-induced formation of 8-oxo-dG in DNA was significantly (P < 0.001) greater compared to the uncharged or negatively charged thiols. Uncharged thiols were significantly (0.001 < P < 0.05) more effective in protecting DNA compared to negatively charged thiols. In contrast to the protection against oxidative damage provided by thiols and ascorbate when they were present during irradiation of DNA, the formation of 8-oxo-dG was significantly increased when these compounds were present during irradiation of dG in solution. Compared to the irradiated control, the increase was 11- to 116-fold for thiols and ascorbate, respectively. The enhanced oxidative damage of dG observed in the presence of ascorbate or thiols suggests that secondarily formed radicals from thiols or ascorbate may react with dG, or that transformation of different primary sites of damage on dG to 8-oxo-dG is enhanced.


Antibiotic-eluting medical devices for various applications.
Infection is defined as a homeostatic imbalance between the host tissue and the presence of microorganisms. It is associated with a large variety of wound occurrences ranging from traumatic skin tears and burns to chronic ulcers and complications following surgery and device implantations. If the wound setting manages to overcome the microorganism invasion by a sufficient immune response then the wound should heal. If not, the formation of an infection can seriously limit the wound healing process. Evidence of increasing bacterial resistance is on the rise, and complications associated with infections are therefore expected to increase. The main goal in treating various types of wound infections is to decrease the bacterial load in the wound to a level that enables wound healing processes to take place. Conventional systemic delivery of antibiotics entails poor penetration into ischemic and necrotic tissue and can cause systemic toxicity with associated renal and liver complications, which result in a need for hospitalization for monitoring. Alternative local delivery of antibiotics by either topical administration or by a delivery device may enable the maintenance of a high local antibiotic concentration for an extended duration of release without exceeding systemic toxicity. The present review describes approaches for local prevention of bacterial infections based on antibiotic-eluting medical devices. These devices include bone cements, fillers and coatings for orthopedic applications, wound dressings based on synthetic and natural polymers, intravascular devices, vascular grafts and periodontal devices. Part of the review is dedicated to our novel composite drug-eluting fibers and structured drug-eluting films, which are designed to be used as basic elements of various devices. In this review emphasis is placed on processing techniques, microstructure, drug release profiles, biocompatibility and other relevant aspects necessary for advancing the therapeutic field of antibiotic-eluting devices.


[Significance of peritonectomy for peritonitis carcinomatosis].
We analyzed patients who underwent multimodal treatment with peritonectomy as an aggressive treatment for peritonitis carcinomatosis. Peritonectomy was treated in eighteen cases (eleven gastric cancer, seven colon cancer). Out of these eighteen cases, nine were initial operation, six were recurrence after first operation and three were for relief after palliative operation for peritoneal dissemination. Five cases of recurrence included ileus. Of all eighteen patients, ten had received preoperative chemotherapies. Peritonectomy made complete resection possible principle, and the procedure included resection of the primary lesion, subtotal colectomy and peritonectomy. An intestinal stoma was needed in nine cases, consequently. All patients cases underwent continuous hyperthermic peritoneal perfusion (CHPP). Early postoperative peritoneal chemotherapy was given in five cases. By peritonectomy for a first time operation, macroscopically complete resection was possible in six cases. In relief and recurrence cases few tumor cells remained in five cases. Ileus due to peritoneal carcinomatosia was eliminated in all cases, and caloric intake became possible. Fourteen cases had postoperative complication (morbidity 78%), and treatment-related death occurred in three cases (mortality 17%). It became possible to resect even the peritoneal dissemination that was inoperable by conventional surgery, and improvement of QOL was achieved by peritonectomy in cases of carcinomatous peritonitis. However, postoperative care is important since aggression becomes more intense.


Functional expression and characterization in Xenopus laevis oocytes of the ABCG2 transporter derived from A549 human lung adenocarcinoma cells.
We cloned the ATP-binding cassette sub-family G member 2 (ABCG2) transporter, the most recently identified among several major human multidrug-resistance pumps, from A549 human lung adenocarcinoma cells in order to characterize its function and substrate specificity. In a previous report, we confirmed that a stem cell-like side population of A549 cells highly expressed the ABCG2 gene and had a unique ability to resist the anticancer drug methotrexate (MTX). In this study, ABCG2 cDNA was cloned by RT-PCR and converted into cRNA by an in vitro transcription system for expression in Xenopus laevis (X. laevis) oocytes. The transcribed cRNA of the ABCG2 gene was injected into the oocytes under the absence of cofactors or heterologous partner proteins or some lipids from the media. A high expression of ABCG2 was observed on the oocyte surface by immunofluorescence and confocal laser microscopy. We tested the functional effect of ABCG2 expression on drug efflux by directly injecting MTX into X. laevis oocytes. The drug concentration within the oocytes was quantified with LC-MS/MS; the analysis showed that the accumulation of MTX was significantly decreased in the X. laevis oocytes expressing ABCG2 compared with the control oocytes not expressing ABCG2. These findings show that the ABCG2 protein has an important role in the efflux of MTX through the cell membrane of X. laevis oocytes. Therefore, it might be that ABCG2, abundantly expressed in the stem cell population of A549 cells, can modulate resistance to MTX in lung cancer therapy.


Improving the intake of nutritious food in children aged 6-23 months in Wuyi County, China -- a multi-method approach.
To develop affordable, appropriate, and nutritious recipes based on local food resources and dietary practices that have the potential to improve infant feeding practices. We carried out a mixed methods study following the World Health Organization's evaluation guidelines on the promotion of child feeding. We recruited caregivers with children aged 6-23 months in Wuyi County, Hebei Province, China. The study included a 24-hour dietary recall survey, local food market survey, and development of a key local food list, food combinations, and recipes. Mothers tested selected recipes at their homes for two weeks. We interviewed mothers to obtain their perceptions on the recipes. The 24-hour dietary recall survey included 110 mothers. Dietary diversity was poor; approximately 10% of children consumed meat and only 2% consumed vitamin A-rich vegetables. The main reason for not giving meat was the mothers' belief that their children could not chew and digest meat. With the help of mothers, we developed six improved nutritious recipes with locally available and affordable foods. Overall, mothers liked the recipes and were willing to continue using them. This is the first study using a systematic evidence-based method to develop infant complementary recipes that can address complementary feeding problems in China. We developed recipes based on local foods and preparation practices and identified the barriers that mothers faced toward feeding their children with nutritious food. To improve nutrition practices, it is important to both give mothers correct feeding knowledge and assist them in cooking nutritious foods for their children based on locally available products. Further research is needed to assess long-term effects of those recipes on the nutritional status of children.


Teaching the Concept of Computational Thinking: A STEM-Based Program With Tangible Robots on Project-Based Learning Courses.
The twenty-first century is arguably the century of computing. In such a world saturated by computing, Computational Thinking is now recognized as a foundational competency for being an informed citizen and being successful in STEM work. Nevertheless, how to effectively import different types of teaching methods in university courses (lecture based learning, project based learning) is subjected to further evaluation. Currently, the arguments in favor of tangible robots including high interaction, great practicality, and specific operation results make themselves to be often used as a teaching medium and tool for teaching activities between teachers and students. Hence, in addition to cultivating students with computational thinking ability, this paper discussed how to integrate tangible robots into project-based learning courses of thinking skills training to improve the learning performance of the computational thinking ability. This study conducted in one semester on the 105 students from three classes. Experimental results show that the project-based learning method integrated with the teaching material of robotic visual programs approach had significantly better effectiveness in improving students' learning achievements than the traditional teaching method integrated with paper practice teaching materials approach. Analysis of the questionnaire results showed that the proposed learning approach did not increase the students' cognitive burden. In sum, the proposed approach helps students' learning achievement and cognitive load.


Folate and Vitamin B-12 Status Is Associated With Bone Mineral Density and Hip Strength of Postmenopausal Chinese-Singaporean Women.
The role of micronutrients such as folate and vitamin B-12 in bone quality has been widely studied with conflicting results. Ethnicity seems to play a large role on nutrient intake, as diet varies across cultures. In this study, we examined the relationships of BMD, proximal femur strength, and bone resorption with plasma folate and vitamin B-12 in a cohort of 93 healthy postmenopausal women of Chinese-Singaporean descent. The parameters examined were areal (aBMD) and volumetric BMD (vBMD) of the proximal femur and the third lumbar vertebra (L3), total body aBMD, proximal femur bending, compressive and impact strength indices (composite strength indices) and circulating levels of C-telopeptide of type I collagen. Eighteen participants (19.4%) had aBMD in the osteoporotic range (osteoporosis group), 59 (63.4%) in the osteopenic range (osteopenia group), and the remaining 16 (17.2%) in the normal range (normal BMD group). Circulating folate levels were significantly higher in the normal BMD group compared with the osteoporosis group. Using linear regression analysis, we found that overall, aBMD and vBMD are positively associated with folate concentrations, whereas composite strength indices were positively associated with vitamin B-12 concentrations. These findings support the existing literature and suggest a link between levels of circulating folate/vitamin B-12 and BMD/bone strength in the cohort examined. Further investigation is needed to examine if individuals with inadequate circulating levels of these nutrients could decrease their risk for fragility fractures through better nutrition or vitamin supplementation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.