Effect of 3-hydroxy-3-methylglutaric acid on cholesterol metabolism in female Japanese quail.
The compounds 3-hydroxy-3-methylglutaric acid (HMG) and HMG diethylester were administered to laying Coturnix hens to evaluate their potential in reducing yolk cholesterol concentrations. The administration of HMG did not produce consistent differences from controls in tissue levels of either cholesterol or triglycerides. The administration of HMG diethylester appeared to increase the de novo synthesis of cholesterol and the mobilization of cholesterol from liver to serum, as assayed by the uptake and conversion of [1-14C]acetate into 14C-cholesterol. Neither HMG diethylester nor HMG significantly decreased the amount of cholesterol deposited in egg yolk.


Sertraline treatment of children and adolescents with obsessive-compulsive disorder or depression: pharmacokinetics, tolerability, and efficacy.
To evaluate the pharmacokinetics, safety, and efficacy of sertraline in children (6 to 12 years old) and adolescents (13 to 17 years old). Children (n = 29) and adolescents (n = 32) with major depression, obsessive-compulsive disorder (OCD), or both received a single dose of 50 mg of sertraline followed, 1 week later, by 35 days of sertraline treatment as follows: (1) either a starting dose of 25 mg/day titrated to 200 mg/day in 25-mg increments or (2) a starting dose of 50 mg/day titrated to 200 mg/day in 50-mg increments. Sertraline and desmethylsertraline pharmacokinetics were determined approximately weekly, and efficacy measures were assessed before drug administration and at the end of treatment. Mean area under the plasma concentration-time curve (AUC), peak plasma concentration (Cmax), and elimination half-life (t1/2) for sertraline and desmethylsertraline were similar to previously reported adult values. No titration-dependent pharmacokinetic or safety differences were seen. While Cmax and AUC0-24 were greater for children versus adolescents, these differences disappeared after parameters were normalized for body weight. Sertraline was well tolerated in both children and adolescents, with adverse experiences similar to those previously reported by adult patients. Efficacy measurements indicated improvement (p < .001) in depression and OCD symptomatology. Sertraline can be safely administered to pediatric patients using the currently recommended adult titration schedule.


Sequence-scrambling fragmentation pathways of protonated peptides.
The gas-phase structures and fragmentation pathways of the N-terminal b and a fragments of YAGFL-NH(2), AGLFY-NH(2), GFLYA-NH(2), FLYAG-NH(2), and LYAGF-NH(2) were investigated using collision-induced dissociation (CID) and detailed molecular mechanics and density functional theory (DFT) calculations. Our combined experimental and theoretical approach allows probing of the scrambling and rearrangement reactions that take place in CID of b and a ions. It is shown that low-energy CID of the b(5) fragments of the above peptides produces nearly the same dissociation patterns. Furthermore, CID of protonated cyclo-(YAGFL) generates the same fragments with nearly identical ion abundances when similar experimental conditions are applied. This suggests that rapid cyclization of the primarily linear b(5) ions takes place and that the CID spectrum is indeed determined by the fragmentation behavior of the cyclic isomer. This can open up at various amide bonds, and its fragmentation behavior can be understood only by assuming a multitude of fragmenting linear structures. Our computational results fully support this cyclization-reopening mechanism by showing that protonated cyclo-(YAGFL) is energetically favored over the linear b(5) isomers. Furthermore, the cyclization-reopening transition structures are energetically less demanding than those of conventional bond-breaking reactions, allowing fast interconversion among the cyclic and linear isomers. This chemistry can lead in principle to complete loss of sequence information upon CID, as documented for the b(5) ion of FLYAG-NH(2). CID of the a(5) ions of the above peptides produces fragment ion distributions that can be explained by assuming b-type scrambling of their parent population and a --> a*-type rearrangement pathways ( Vachet , R. W. , Bishop , B. M. , Erickson , B. W. , and Glish , G. L. J. Am. Chem. Soc. 1997, 119, 5481 ). While a ions easily undergo cyclization, the resulting macrocycle predominantly reopens to regenerate the original linear structure. Computational data indicate that the a --> a*-type rearrangement pathways of the linear a isomers involve post-cleavage proton-bound dimer intermediates in which the fragments reassociate and the originally C-terminal fragment is transferred to the N-terminus.


Relationship Between Acylcarnitine and the Risk of Retinopathy in Type 2 Diabetes Mellitus.
Diabetic retinopathy is a common complication of type 2 diabetes mellitus (T2DM). Due to the limited effectiveness of current prevention and treatment methods, new biomarkers are urgently needed for the prevention and diagnosis of DR. This study aimed to explore the relationships between plasma acylcarnitine with DR in T2DM. From May 2015 to August 2016, data of 1032 T2DM patients were extracted from tertiary hospitals. Potential non-linear associations were tested by binary logistic regression models, and ORs and 95% CIs of the research variables were obtained. Correlation heat map was used to analyze the correlation between variables. The change of predictive ability was judged by the area under the receiver operating characteristic curve. Of the 1032 patients with T2DM, 162 suffered from DR. After adjusting for several confounding variables, C2 (OR:0.55, 95%CI:0.39-0.76), C14DC (OR:0.64, 95%CI:0.49-0.84), C16 (OR:0.64, 95%CI:0.49-0.84), C18:1OH (OR:0.51, 95%CI:0.36-0.71) and C18:1 (OR:0.60, 95%CI:0.44-0.83) were negatively correlated with DR. The area under the curve increased from 0.794 (95% CI 0.745 to 0.842) to 0.840 (95% CI 0.797 to 0.833) when C2, C14DC, C18:1OH and C18:1 added to the traditional risk factor model. There was a negative correlation between C2, C14DC, C16, C18:1OH, and C18:1 and the risk of retinopathy in patients with T2DM. C2, C14DC, C18:1OH, and C18:1 may be new predictors and diagnostic markers of DR.


Surgical anatomy of the right hepatic artery in Rouviere's sulcus evaluated by preoperative multidetector-row CT images.
Lymph node dissection in Rouviere's sulcus (RS) is essential during left-sided hepatectomy and caudate lobectomy for hilar cholangiocarcinoma. However, the small segmental or subsegmental arteries (SA/SSA) are often encountered in RS and must be preserved to prevent critical complications, such as liver infarction or liver failure. The aim of this study is to elucidate the anatomy of SA/SSA around RS, which should be understood preoperatively. Between January 2008 and April 2013 from a total of 124 consecutive patients with hilar cholangiocarcinoma, preoperative multidetector-row computed tomography (MDCT) images were obtained at our institution and evaluated. The bifurcation patterns of the SA/SSA, the courses of the posterior SA/SSA and the bifurcation site of the SA/SSA were investigated using MDCT images. The typical form, in which right hepatic artery (RHA) bifurcated into the anterior (Aant) and posterior (Apost) hepatic artery and thereafter, Aant/Apost bifurcated into the SA and SSA, was observed in 75 patients (60.5 %). On the other hand, the atypical forms, in which the SA/SSA were independently branched off from RHA before the main bifurcation of the Aant and Apost, were observed in 43 patients (34.7 %). The prior branched arteries supplied the whole or ventral area of segment VI (A6 or A6a) in 11 patients (8.9 %), which was most commonly observed in the atypical form. 15 patients (34.9 %) of the 43 patients with atypical form had partially supraportal posterior branches, that showed early-bifurcated posterior SA/SAA following supraportal course, while the other posterior SA/SSA followed infraportal course. The SA/SSA were extrahepatically bifurcated in 82 patients (66.1 %), comprised of all 43 atypical form and 39 of typical form, while the SA/SSA were intrahepatically bifurcated in remaining 36 patients of typical forms (29.0 %). The extrahepatic bifurcation of the SA/SSA from RHA was relatively common. The early-bifurcated SA/SSA was often observed (34.7 % of total cohort) and, in 34.8 % of those atypical forms, posterior SA/SSA from RHA followed a supraportal course. The detailed preoperative knowledge of the anatomy, including SA/SSA, is crucial for left-sided hepatectomy for hilar cholangiocarcinoma.


[Preliminary study to investigate dynamic extract process of Huanglian Jiedu Tang and the mechanism of subsidence produce].
To study the phenomenon of subsidence emergence in the process of Huanglian Jiedu Tang decoction extraction, and the mechanism of subsidence emergence. UV was applied to determine the concentration of total alkaloids and total flavones; Simultaneous determination of berberine, jatrorrhizine, palmatine, baicalin and geniposide were carried out by HPLC; The solid holdup and precipitation rate were calculated by the formula. The relativity among these parameters was analyzed by the SPSS software program. The contains of berberine, jatrorrhizine, palmatine in total alkaloids showed a good correlation with total alkaloids. The correlation between baicalin and total flavones was lower than that between geniposide and total flavones. Compared to precipitation rate, solided hold up shows a larger relevance with index component With the change of time, the total alkaloids represented by berberine alkaloids and baicalin at a certain concentration can be regarded as the equilibrium point, or one generated by the critical point of precipitation, the reaction can generate "sediments"; because "precipitation objects" generated, reducing the concentration of the above-mentioned components, destroy the" balance". The relevant components of herbal medicine increased dissolution rate, at the same time might partly dissolved sediment, reaching a new equilibrium state.


Noisy galvanic vestibular stimulation modulates the amplitude of EEG synchrony patterns.
Noisy galvanic vestibular stimulation has been associated with numerous cognitive and behavioural effects, such as enhancement of visual memory in healthy individuals, improvement of visual deficits in stroke patients, as well as possibly improvement of motor function in Parkinson's disease; yet, the mechanism of action is unclear. Since Parkinson's and other neuropsychiatric diseases are characterized by maladaptive dynamics of brain rhythms, we investigated whether noisy galvanic vestibular stimulation was associated with measurable changes in EEG oscillatory rhythms within theta (4-7.5 Hz), low alpha (8-10 Hz), high alpha (10.5-12 Hz), beta (13-30 Hz) and gamma (31-50 Hz) bands. We recorded the EEG while simultaneously delivering noisy bilateral, bipolar stimulation at varying intensities of imperceptible currents - at 10, 26, 42, 58, 74 and 90% of sensory threshold - to ten neurologically healthy subjects. Using standard spectral analysis, we investigated the transient aftereffects of noisy stimulation on rhythms. Subsequently, using robust artifact rejection techniques and the Least Absolute Shrinkage Selection Operator regression and cross-validation, we assessed the combinations of channels and power spectral features within each EEG frequency band that were linearly related with stimulus intensity. We show that noisy galvanic vestibular stimulation predominantly leads to a mild suppression of gamma power in lateral regions immediately after stimulation, followed by delayed increase in beta and gamma power in frontal regions approximately 20-25 s after stimulation ceased. Ongoing changes in the power of each oscillatory band throughout frontal, central/parietal, occipital and bilateral electrodes predicted the intensity of galvanic vestibular stimulation in a stimulus-dependent manner, demonstrating linear effects of stimulation on brain rhythms. We propose that modulation of neural oscillations is a potential mechanism for the previously-described cognitive and motor effects of vestibular stimulation, and noisy galvanic vestibular stimulation may provide an additional non-invasive means for neuromodulation of functional brain networks.


JAK2V617F mutation and hydroxyurea treatment as determinants of immature platelet parameters in essential thrombocythemia and polycythemia vera patients.
Immature platelets (IPFs), which are hemostatically more active than mature platelets, have been found elevated in essential thrombocythemia and polycythemia vera, 2 myeloproliferative neoplasms (MPN) characterized by an increased risk of thrombosis. It is not known whether the IPF levels are influenced by pathogenetic factors, including JAK2V617F mutational status, or by treatment regimen. To address this point, in 46 essential thrombocythemia and 38 polycythemia vera consecutive patients, we measured IPF and correlated the results to JAK2V617F mutation and myelosuppressive treatment with hydroxyurea. This analysis provides 2 new elements regarding IPF and MPN. The first finding is that the JAK2V617F mutation is linked to the quantity of IPF in patients with MPN, which might contribute to the prothrombotic phenotype in these patients. The second finding is that IPF is susceptible to myelosuppressive treatment, which may additionally explain the favorable effect of hydroxyurea therapy on MPN outcome as well as the associated thrombotic risk.


[Prevalence of hypercholesterolemia and influence factors in residents aged 18-65 years in Beijing].
Objective: To understand the prevalence of hypercholesterolemia and related risk factors in residents aged 18-65 years in Beijing and provide scientific evidence for the prevention and control of hypercholesterolemia. Methods: The data were collected from Beijing Non-communicable and Chronic Disease Survey and stratified cluster sampling method was used to select study subjects, and questionnaire investigation, physical measurement and laboratory examination were conducted to collect information. Results: The prevalence of hypercholesterolemia and borderline hypercholesterolemia was 6.26% and 21.34% respectively in 17 662 residents surveyed, the average total cholesterol level was (4.69±0.95) mmol/L. The prevalence of hypercholesterolemia was 6.33% in men and 6.20% in women, the difference was not significant (Z=1.64, P=0.10). The prevalence was higher inurban area than in suburb (6.73% vs. 5.59%; Z=-7.27, P<0.01). The prevalence of hypercholesterolemia increased with age (trend χ(2)=308.85, P<0.01). The trend was observed in men (trend χ(2)=81.65, P<0.01), in women (trend χ(2)=318.04, P<0.01), in urban area (trend χ(2)=201.77, P<0.01) and in suburb (trend χ(2)=114.65, P<0.01). Multiple logistic regression showed age, being female (OR=1.23, 95%CI: 1.04-1.45), overweight (OR=1.56, 95%CI: 1.34-1.81), obesity (OR=1.82, 95%CI: 1.54-2.16), smoking (OR=1.24, 95%CI: 1.03-1.50), alcohol use (OR=1.40, 95%CI: 1.12-1.75), beef and mutton intake >1 time per week (OR=1.19, 95%CI: 1.02-1.39) were risk factors. Conclusion: The prevalence of hypercholesterolemia in Beijing was lower than national level, and age, gender, location, BMI, smoking, alcohol use, beef and mutton intake were main influencing factors.


[Free-living amoebae as vehicles of pathogenic bacteria].
The free-living amoebae are ubiquitous organisms. They are found in humid soil and all water reservoirs, i.e. fresh, sea, freezing and hot water. They mainly feed on bacteria. Pathogenic properties of amoebae and the mechanisms underlying pathological changes induced during human infection have not yet been fully elucidated. They are the causative agents of primary amoebic meningo-encephalitis (PAM), granulomatous amebic encephalitis (GAE), a chronic progressive disease of the central nervous system, amebic keratitis (AK), a chronic eye infection; amebic pneumitis (AP), a chronic lung infection, and skin infection. Only a few isolates are strongly and permanently pathogenic to humans. Some isolates lose their pathogenic properties after one passage. It has been assumed that such "temporary", unstable pathogenic properties of the amoebae may be caused by internal factors carried by them. It is generally known that the free-living amoebae may be naturally infected with pathogenic bacteria, which have the ability to survive for a long time and to proliferate in the amoebae cells. The role of the amoeba in the process of maintaining, propagating and transmitting human pathogens has not been well recognized. It has been suggested that some infections can be acquired by inhaling aerosols containing amoebae cells filled with bacteria. The presence of bacteria inside the free-living amoebae possess a great challenge to organisations responsible for testing and inspecting the quality and cleanliness of surface waters, swimming pools and drinking water intakes.


Urethritis in men at the Genito-Urinary Medicine Clinic Kuala Lumpur Hospital.
The clinical features and aetiology of 100 consecutive symptomatic heterosexual male patients with urethritis were studied from March 1994 to August 1994 in the Genito-Urinary Medicine (GUM) Clinic, Kuala Lumpur Hospital. Gonococcal urethritis (GU) was found to be more common (53%) than non-gonococcal urethritis(47%). All patients with GU confirmed microbiologically had clinically evident urethral discharge. Almost half (41%) of the patients with GU developed post-gonococcal urethritis (PGU). The most common organism isolated in PGU was Ureaplasma urealyticum (37%) whilst only 4% had both Chlamydia trachomatis and Ureaplasma urealyticum. Of the 47% of patients with non-gonococcal urethritis (NGU), 50% had no microorganism isolated, 32% had Ureaplasma urealyticum, 7% Chlamydia trachomatis and 11% both Chlamydia trachomatis and Ureaplasma urealyticum.


Activity of three-beta-hydroxysteroid dehydrogenase in granulosa cells treated in vitro with luteinizing hormone, follicle-stimulating hormone, prolactin, or a combination.
Three-beta-hydroxysteroid dehydrogenase (3beta-HSD) is a key enzyme in the pathway that produces progesterone. Hy-Line hens (W36, W98, and Brown) were subjected to mild heat stress [36 degrees C for 24 h (acute heat stress, AHS) or 2 wk (chronic heat stress, CHS)] or maintained at 22 degrees C (thermoneutral, TN). Granulosa cells (GC) from the 3 largest follicles were isolated, dispersed, and incubated with luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), a combination, or no hormone (control), and then with pregnenolone nitro blue tetrazolium to determine 3beta-HSD activity. Treatment by LH (TN, P = 0.04; AHS, CHS, P < 0.0001) and by LH+FSH (TN, AHS, CHS, P < 0.0001) resulted in increased enzyme activity compared with the respective controls. In TN and CHS, LH+FSH increased the activity to a greater extent than LH alone (TN, P = 0.02; CHS, P = 0.0004); in AHS the increase was not significant (P = 0.29). Treatment with FSH, PRL, or LH+PRL decreased (TN, AHS) or had no effect (CHS) on 3beta-HSD activity. In TN and AHS cells, FSH and PRL reduced enzyme activity (P = 0.006 and 0.0580, respectively). When LH was added to PRL, suppression by PRL was mitigated somewhat. When LH and FSH were added to PRL, 3beta-HSD activity in AHS and CHS cells actually increased compared with the respective controls (P = 0.052 and 0.003) but remained below the activity of cells incubated with LH+FSH or LH alone. This suggests that gonadotropic actions of LH and LH+FSH are countered by the antigonadotropic action of PRL and, conversely, that PRL reduces the stimulatory action of LH and FSH. Strain differences in GC response to hormones were observed primarily in the CHS-treated birds; generally, W98 was highest; Browns showed the weakest response, and W36 was intermediate. In earlier studies, HS reduced circulating LH and GC progesterone and 3beta-HSD activity in vitro and increased circulating PRL. The results suggest a mechanism by which reduced activity of 3beta-HSD and progesterone by GC during HS might be explained, particularly with the differences in strains observed.


100 years on: the impact of the discovery of insulin on clinical outcomes.
Throughout history, up to the early part of the 20th century, diabetes has been a devastating disorder, particularly when diagnosed in childhood when it was usually fatal. Consequently, the successful pancreatic extraction of insulin in 1921 was a miraculous, life-changing advance. In this review, the truly transformative effect that insulin has had on the lives of people with type 1 diabetes and on those with type 2 diabetes who are also dependent on insulin is described, from the time of its first successful use to the present day. We have highlighted in turn how each of the many facets of improvements over the last century, from advancements in the properties of insulin and its formulations to the evolution of different methods of delivery, have led to continued improvement in clinical outcomes, through the use of illustrative stories from history and from our own clinical experiences. This review concludes with a brief look at the current challenges and where the next century of technological innovation in insulin therapy may take us.


Stereological evaluation of human spermatogenesis after suppression by testosterone treatment: heterogeneous pattern of spermatogenic impairment.
Testosterone (T) treatment suppresses gonadotropin levels in normal men and is a promising reversible contraceptive that induces azoospermia in approximately 70% of subjects and oligospermia in the remainder; however, the basis of this variable response is unclear. This study aimed to investigate this reported variable response by examining the spermatogenic process and quantitating germ cell number in men after T-induced gonadotropin withdrawal. Ten normal fertile men (31-46 yr), already planning to undergo vasectomy, either received T enanthate (200 mg, i.m., weekly) for 19-24 weeks (n = 5; TE group) or proceeded directly to surgery (n = 5; controls), at which time a unilateral testicular biopsy was taken, and germ cell numbers were estimated using the optical disector stereological method. In response to TE treatment, serum T levels rose 2-fold, and FSH/LH levels became undetectable. Sperm counts fell to azoospermia in 4 men and to 21 million/mL in the fifth man. The mean number of type A spermatogonia per 100 Sertoli cells was unchanged, but type B spermatogonia fell markedly to 10% of the control values, and later germ cell types decreased to 11-18% of the control values. The pattern of germ cell suppression varied widely and showed no relationship with sperm count or the time to azoospermia. Despite the presence of elongated spermatids (1.4-20% of the control), four men remained azoospermic. Two TE subjects with similar early germ cell complements and elongated spermatid numbers had sperm counts of zero and 21 million/mL; the latter man demonstrated marked variability in germ cell numbers between adjacent tubules. We conclude that 1) the principal spermatogenic lesion in TE-treated men is the marked (90%) inhibition of type A-->B spermatogonial maturation. Other sites are also affected, particularly the release and/or survival of elongated spermatids during transit; and 2) a steady state in germ cell number may not be established even after 4-5 months of TE treatment. The findings suggest that TE treatment does not adequately or consistently withdraw hormonal support for spermatogenesis, leading to variable between- and within-individual patterns of germ cell suppression.


Biochemical characteristics of maltose phosphorylase MalE from Bacillus sp. AHU2001 and chemoenzymatic synthesis of oligosaccharides by the enzyme.
Maltose phosphorylase (MP), a glycoside hydrolase family 65 enzyme, reversibly phosphorolyzes maltose. In this study, we characterized Bacillus sp. AHU2001 MP (MalE) that was produced in Escherichia coli. The enzyme exhibited phosphorolytic activity to maltose, but not to other α-linked glucobioses and maltotriose. The optimum pH and temperature of MalE for maltose-phosphorolysis were 8.1 and 45°C, respectively. MalE was stable at a pH range of 4.5-10.4 and at ≤40°C. The phosphorolysis of maltose by MalE obeyed the sequential Bi-Bi mechanism. In reverse phosphorolysis, MalE utilized d-glucose, 1,5-anhydro-d-glucitol, methyl α-d-glucoside, 2-deoxy-d-glucose, d-mannose, d-glucosamine, N-acetyl-d-glucosamine, kojibiose, 3-deoxy-d-glucose, d-allose, 6-deoxy-d-glucose, d-xylose, d-lyxose, l-fucose, and l-sorbose as acceptors. The kcat(app)/Km(app) value for d-glucosamine and 6-deoxy-d-glucose was comparable to that for d-glucose, and that for other acceptors was 0.23-12% of that for d-glucose. MalE synthesized α-(1→3)-glucosides through reverse phosphorolysis with 2-deoxy-d-glucose and l-sorbose, and synthesized α-(1→4)-glucosides in the reaction with other tested acceptors.


Limitations of human umbilical vein grafts.
Sixty modified human umbilical vein (HUV) grafts were used for arterial reconstruction in 48 patients between December 1979 and December 1981. Forty-four patients had limb-threatening ischemia (rest pain or tissue loss) and four had disabling claudication. Thirty-four patients had HUV grafting after a primary arterial reconstruction had failed. Fourteen had HUV used for their initial arterial bypass. The distal anastomosis was to the popliteal artery in 27 grafts (5 above and 22 below the knee) and the distal calf arteries in 33 (anterior tibial 10, posterior tibial 9, peroneal 14). The cumulative patency rate, calculated by the modified life-table method, was 34% at 1 year and 18% at 2 years. Fifteen patients required major amputation after graft failure; 13 of these healed below the knee. Preoperative and postoperative ankle/brachial systolic pressure indices and intraoperative blood flow did not correlate with graft failure. These results reflect the limitations of HUV as a graft material in patients with severe ischemia of the lower extremities. The prognostic factors that determined the outcome of arterial reconstruction with HUV in these patients remain to be defined.


A novel pore-region mutation, c.887G > A (p.G296D) in KCNQ4, causing hearing loss in a Chinese family with autosomal dominant non-syndromic deafness 2.
Hereditary non-syndromic hearing loss is the most common inherited sensory defect in humans. The KCNQ4 channel belongs to a family of potassium ion channels that play crucial roles in physiology and disease. Mutations in KCNQ4 underlie deafness non-syndromic autosomal dominant 2, a subtype of autosomal dominant, progressive, high-frequency hearing loss. A six-generation Chinese family from Hebei Province with autosomal dominantly inherited, sensorineural, postlingual, progressive hearing loss was enrolled in this study. Mutation screening of 129 genes associated with hearing loss was performed in five family members by next-generation sequencing (NGS). We also carried out variant analysis on DNA from 531 Chinese individuals with normal hearing as controls. This family exhibits postlingual, progressive, symmetrical, bilateral, non-syndromic sensorineural hearing loss. NGS, bioinformatic analysis, and Sanger sequencing confirmed the co-segregation of a novel mutation [c.887G > A (p.G296D)] in KCNQ4 with the disease phenotype in this family. This mutation leads to a glycine-to-aspartic acid substitution at position 296 in the pore region of the KCNQ4 channel. This mutation affects a highly conserved glutamic acid. NGS is a highly efficient tool for identifying gene mutations causing heritable disease. Progressive hearing loss is common in individuals with KCNQ4 mutations. NGS together with Sanger sequencing confirmed that the five affected members of this Chinese family inherited a missense mutation, c.887G > A (p.G296D), in exon 6 of KCNQ4. Our results increase the number of identified KCNQ4 mutations.


Proportions distribution of pneumoconiosis stages in China: a study based on a meta-analysis and field investigation.
Occupational pneumoconiosis is the most serious work-related disease in China. In this paper, pneumoconiosis stages distribution was obtained to study the stages severity of occupational pneumoconiosis patients in China. A meta-analysis was conducted among screening the published literature on the pneumoconiosis epidemiology in China by Stata 15.0. Moreover, a field survey was conducted on 510 migrant workers suffering from pneumoconiosis in four provinces of China, and the results were analyzed by simple linear analysis and ordinal logistic regression analysis. The stage I, II and III pneumoconiosis accounted for 0.71, 0.21, 0.08, respectively, by the results of meta-analysis. The publication bias of these articles is not obvious based on the Egger's test and funnel plots. There was no significant linear correlation between the distribution of pneumoconiosis stages and the economic status and medical conditions in this study. Migrant workers pneumoconiosis stage I, II and III accounted for 0.14, 0.2, 0.66 respectively, which was significantly correlated with length of work and provinces. In China, migrant workers lack effective occupational health protection so that they have higher occupational health risks than urban workers. Therefore, occupational health protection for migrant workers in the occupational health management system needs to be strengthened.


Psychosocial functioning of the patient with spinal cord and whiplash injury: A case report.
Whiplash is a soft tissue injury of the cervical spine that is generally caused by trauma from a motor vehicle accident or gunshot. It is associated with a wide range of clinical symptoms, including neck pain and stiffness, pain and restricted movement in the upper arms. We report the manifestations of this trauma within the beliefs and psychological functioning based on a comprehensive psychological assessment that include a review of hospital records, clinical examinations, a structured clinical interview, an inventory of psychosocial function, and a post-traumatic maladaptive belief scale. The results show that the patient's traumatic cervical syndrome manifested as moderate impairment in friendships and romantic relationships which reveal severe daily impairment in work, parenting, and self-care activities. The study further suggests that the injury is associated with maladaptive beliefs and significant impairment in psychosocial functioning.


Weight-gain patterns from prepregnancy until delivery among women in Central Java, Indonesia.
Representative data on pregnancy weight-gain patterns from developing countries are scarce. The reasons include difficulties in obtaining population-based samples and in collecting data before and throughout pregnancy. The objective was to measure weight-gain patterns from prepregnancy until after delivery in a population-based sample of rural Indonesian women. Two cross-sectional surveys of nutritional status among nonpregnant women of reproductive age were carried out through a surveillance system in Purworejo District, Central Java, Indonesia, in 1996 and 1997. Between 1996 and 1998, 846 newly pregnant women were enrolled in a cohort study in which weight was monitored monthly throughout pregnancy. Prepregnancy weights and other anthropometric measures were available for 251 of the women who had live births. Before pregnancy, 16.7% of the women had chronic energy deficiency and 10.0% were obese. The mean total pregnancy weight gain for all the women was 8.3 +/- 3.6 kg, and 79% did not meet the international recommendation regarding weight gain for their prepregnant body mass index. The rate of weight gain was highest during the second trimester (0.34 kg/wk). In the first and third trimesters, it was 0.08 and 0.26 kg/wk, respectively. Total weight gain was associated with prepregnant body mass index, education, and socioeconomic status. Many women in rural Central Java, Indonesia, enter pregnancy with suboptimal nutritional status. For most of these women, total weight gain during pregnancy is insufficient. It is likely that this contributes to adverse health outcomes for both the mothers and their newborns.


Reducing risks while improving care.
The inherent risks in critical care and the vulnerability of its patients demand a rigorous attention to detail. This article gives the critical care nurse a sound basis in risk management principles and existing policies, including those of the Joint Commission on Accreditation of Healthcare Organizations. Understanding risk management can help nurses improve patient care while reducing the chances for litigation.


Consideration of Dose Error in Dynamic MLC IMRT Using MLC Speed Control with Dose Rate Change.
In dynamic multi-leaf collimator (MLC) intensity-modulated radiotherapy (IMRT), the accuracy of delivered dose is influenced by the positional accuracy of the moving MLC. In order to assess the accuracy of the delivered dose during dynamic MLC IMRT, the delivered dose error in dynamic MLC IMRT using the MLC speed control with dose rate change was investigated. Sweeping gap sequence irradiation was performed with constant MLC leaf speed at 0.6 to 5 cm/s or changed MLC speed (4 steps). The positional accuracy of the moving MLC was evaluated from the trajectory log file. Absorbed dose measurements with sweeping field (Field size: 10 cm×10 cm, MLC leaf speed: 0.6 to 2.7 cm/s, MLC leaf gap width: 0.2 to 2.0 cm) were performed. The delivered dose error at each gap width was evaluated according to MLC leaf speed change. MLC positional errors and changes in delivered dose according to MLC leaf speed were within 0.07 mm and 0.6%, respectively, for all measurements. Beam hold-off did not occur under any conditions. We confirmed that TrueBeam can regulate MLC leaf speed below the maximum limit (2.5 cm/s) by changing the dose rate in real-time during irradiation in dynamic MLC IMRT. MLC gap error during irradiation was estimated within 0.2 mm at the maximum dose rate from the results of absolute dose measurements using dynamic MLC irradiation. In conclusion, TrueBeam can use the maximum dose rate for the treatment planning of dynamic MLC IMRT, which has an advantage of shorter treatment time.


Role of virtual bronchoscopy in the evaluation of bronchial lesions: a pictorial essay.
Bronchoscopy is an important diagnostic method for the tracheobronchial, thoracic, and mediastinal lesions. It is limited by the physical progression of the bronchoscope. This represents a problem when assessing difficult airways, such as a lumen narrowed from any cause. Bronchoscopy can be performed with flexible fiberoptic bronchoscopy (FOB), which remains the best modality for the evaluation of endoluminal and mucosal lesions of the respiratory tract. However, FOB has important limitations. It cannot view structures outside the bronchial wall, such as the mediastinal lymph nodes and vascular structures. Additionally, FOB frequently provides little information about the extent of the extraluminal diseases or airway patency distal to high-grade bronchial stenosis. In view of these limitations, some authors have suggested that virtual bronchoscopy (VB) may replace FOB. VB is a novel computed tomography-based imaging technique. It allows a noninvasive intraluminal evaluation of the tracheobronchial tree. In addition to its direct roles in patient care, VB has great potential in education, bronchoscopy training, and procedure planning. VB can be performed when FOB is contraindicated or considered risky, as in cases with airway narrowing. Also, it can be done as a preliminary evaluation before FOB. VB is not effective for the detection of subtle mucosal abnormalities, such as erythema or early sessile lesions. The aim of this pectoral essay is to present overview of VB and the author's experience of using of VB, based on computed tomography data, in diagnosis of different tracheobronchial lesions.


Accuracy and reproducibility of dental measurements on tomographic digital models: a systematic review and meta-analysis.
The aim of this systematic review with meta-analysis was to assess the accuracy and reproducibility of dental measurements obtained from digital study models generated from CBCT compared with those acquired from plaster models. The electronic databases Cochrane Library, Medline (via PubMed), Scopus, VHL, Web of Science, and System for Information on Grey Literature in Europe were screened to identify articles from 1998 until February 2016. The inclusion criteria were: prospective and retrospective clinical trials in humans; validation and/or comparison articles of dental study models obtained from CBCT and plaster models; and articles that used dental linear measurements as an assessment tool. The methodological quality of the studies was carried out by Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A meta-analysis was performed to validate all comparative measurements. The databases search identified a total of 3160 items and 554 duplicates were excluded. After reading titles and abstracts, 12 articles were selected. Five articles were included after reading in full. The methodological quality obtained through QUADAS-2 was poor to moderate. In the meta-analysis, there were statistical differences between the mesiodistal widths of mandibular incisors, maxillary canines and premolars, and overall Bolton analysis. Therefore, the measurements considered accurate were maxillary and mandibular crowding, intermolar width and mesiodistal width of maxillary incisors, mandibular canines and premolars, in both arches for molars. Digital models obtained from CBCT were not accurate for all measures assessed. The differences were clinically acceptable for all dental linear measurements, except for maxillary arch perimeter. Digital models are reproducible for all measurements when intraexaminer assessment is considered and need improvement in interexaminer evaluation.


[Odontoid fracture: Long-term subarachnoid hemorrhage after anterior screw fixation. Case report and literature review].
Odontoid fractures have been classified by Anderson and D'Alonzo into three main categories. The most unstable injuries, type II fractures involve the base of the odontoid peg at the junction with the C2 body. Due to the proximity of vital neural structures, fracture of the odontoid process may result in instability and fatal neurological damage. Treatment aims to re-establish stability of the atlanto-axial complex by restoring the odontoid process. This may be achieved by conservative or surgical treatment. Anterior screw fixation of the odontoid peg is an interresting alternative surgical option but this technique has a significant complication rate. However, vascular injury is very rare with three case reported in the literature: one case of an intracranial vertebral artery (VA) injury, one case of a cervical internal carotid artery (ICA) injury and one case of anterior pseudoaneurysm of the spinal artery branch. We report a new case of long term vascular injury after screw fixation revealed by a subarachnoid hemorrhage. We discuss the incidence, the mechanisms of injury and the conditions necessary for the occurrence of this complication.


[Intentional self-poisonings among children and youth hospitalized in pediatric clinic].
The aim of the study was to identify the most important factors that can favour suicide attempts among children and to establish the age of highest risk, and note the extent of the phenomenon on the base of admissions to hospital within five years. The research covered 42 patients of Paediatric clinic at the age of 12-17 years. Clinical intervention and observation, psychological evaluation and psychiatric examination were carried out. Fifty percent of the patients came of an incomplete (single-parent) families. Thirty one percents of patients' families were affected by alcoholism, nearly half of poisoned children were 14-15 years of age. There was a significant prevalence of girls in the group (88%). Seventeen percents of them had a history of multiple suicidal attempts. Children hospitalized by reason of intentional self-poisoning constituted, according to a year of observation, 0.45-1.34% (mean 0,81%) of all patients of the Paediatric Clinic. Female sex and age of 15-16 years is a time of highest risk. Alcoholism is a frequent problem in families of children attempting suicide. Children with disturbed personality, behaviour and emotionality are particularly at risk of repeating an suicidal attempt and require longer psychological and psychiatrical care.


Association of Dietary Patterns with Components of Metabolic Syndrome and Inflammation among Middle-Aged and Older Adults with Metabolic Syndrome in Taiwan.
This study examined the correlation of dietary patterns with components of metabolic syndrome (MetS) and inflammation among middle-aged and older adults with MetS in Taiwan. This cross-sectional study used data from the Mei Jau International Health Management Institution in Taiwan between 2004 and 2013. A total of 26,016 subjects aged 35 years and above were selected for analysis. MetS was defined according to the International Diabetes Federation. Three dietary patterns were identified by principal component analysis. High intake of a meat-instant food dietary pattern (rich in animal protein, saturated fat, sweets, sodium, and food additives) was positively associated with components of MetS and C-reactive protein (CRP), while high intake of a vege-seafood dietary pattern (rich in dietary fiber, vitamins, minerals, and unsaturated fat) or a cereal-dairy dietary pattern (rich in dietary fiber, antioxidants, phytochemicals, complex carbohydrate, prebiotics, and probiotics) was inversely associated with components of MetS and CRP. Our findings suggested that intake of a vege-seafood dietary pattern or a cereal-dairy dietary pattern decreased the risk of developing MetS and inflammation among middle-aged and older adults with MetS.


[Association of the polymorphism of platelet membrane glycoprotein I a gene with myocardial infarction].
Platelet membrane glycoprotein (GP) Ia/IIa complex is the major collagen receptor on platelets. Platelet activation by GP Ia/ IIa dependent adhesion leads to cellular events that catalyze prothrombin conversion and fibrin clot formation. Correlation between the polymorphism of platelet membrane GP Ia gene and myocardial infarction (MI) was explored. A total of 137 patient s with myocardial infarction and 175 controls with no history of coronary heart disease, thrombogenic and hemorrhagenic diseases were studied by case-control. Platelet GP I a gene 807 C/T polymorphisms were checked by polymerase chain reaction-sequence specific primers. There were significant differences in the distribution of T and C alleles between MI and control groups (T:42.70% vs 32.00%, C:57.30% vs 68.00%, P<0.001). No matter among all subjects or among subjects aged <or= 60 years, the prevalence of genotypes (TT+TC) in MI group was significantly higher than that in control group [in all subjects; 69.34% vs 51.43%, P<0.005, odds ratio(OR)=2.14, 95% CI: 1.34-3.41; in subjects aged <or= 60 years; 75.90% vs 51. 52%, P<0.005, OR=2.96,95% CI 1.58-5.55]. Platelet GP Ia T allele was significantly associated with MI by multiple logistic regression (OR=4.96, 95% CI:2.55-10.90). The above data suggest that there is a strong association between the presence of GP Ia T allele and MI. T allele ca n be a marker of genetic susceptibility to MI. These need to be substantiated by a large scale and prospective study.


Psychotherapeutic Applications of Mobile Phone-based Technologies: A Systematic Review of Current Research and Trends.
There is a growing interest in using mobile phone technology to offer real-time psychological interventions and support. However, questions remain on the clinical effectiveness and feasibility of such approaches in psychiatric populations. Our aim was to systematically review the published literature on mobile phone apps and other mobile phone-based technology for psychotherapy in mental health disorders. To achieve this, electronic searches of PubMed, ScienceDirect, and Google Scholar were carried out in January 2016. Generated abstracts were systematically screened for eligibility to be included in the review. Studies employing psychotherapy in any form, being delivered through mobile-based technology and reporting core mental health outcomes in mental illness were included in the study. We also included trials in progress with published protocols reporting at least some outcome measures of such interventions. From a total of 1563 search results, 24 eligible articles were identified and reviewed. These included trials in anxiety disorders (8), substance use disorders (5), depression (4), bipolar disorders (3), schizophrenia and psychotic disorders (3), and attempted suicide (1). Of these, eight studies involved the use of smartphone apps and others involved personalized text messages, automated programs, or delivered empirically supported treatments. Trial lengths varied from 6 weeks to 1 year. Good overall retention rates indicated that the treatments were feasible and largely acceptable. Benefits were reported on core outcomes in mental health illness indicating efficacy of such approaches though sample sizes were small. To conclude, mobile phone-based psychotherapies are a feasible and acceptable treatment option for patients with mental disorders. However, there remains a paucity of data on their effectiveness in real-world settings, especially from low- and middle-income countries.


Microtubules and axon regeneration in C. elegans.
Axon regeneration is a fundamental and conserved process that allows the nervous system to repair circuits after trauma. Due to its conserved genome, transparent body, and relatively simple neuroanatomy, C. elegans has become a powerful model organism for studying the cellular and molecular mechanisms underlying axon regeneration. Various studies from different model organisms have found microtubule dynamics to be pivotal to axon regrowth. In this review, we will discuss the latest findings on how microtubule dynamics are regulated during axon regeneration in C. elegans. Understanding the mechanisms of axon regeneration will aid in the development of more effective therapeutic strategies for treatments of diseases involving disconnection of axons, such as spinal cord injury and stroke.


Optimal priming of poxvirus vector (NYVAC)-based HIV vaccine regimens for T cell responses requires three DNA injections. Results of the randomized multicentre EV03/ANRS VAC20 Phase I/II Trial.
DNA vectors have been widely used as a priming of poxvirus vaccine in prime/boost regimens. Whether the number of DNA impacts qualitatively or quantitatively the immune response is not fully explored. With the aim to reinforce T-cell responses by optimizing the prime-boost regimen, the multicentric EV03/ANRS VAC20 phase I/II trial, randomized 147 HIV-negative volunteers to either 3xDNA plus 1xNYVAC (weeks 0, 4, 8 plus 24; n = 74) or to 2xDNA plus 2xNYVAC (weeks 0, 4 plus 20, 24; n = 73) groups. T-cell responses (IFN-γ ELISPOT) to at least one peptide pool were higher in the 3xDNA than the 2xDNA groups (91% and 80% of vaccinees) (P = 0.049). In the 3xDNA arm, 26 (37%) recipients developed a broader T-cell response (Env plus at least to one of the Gag, Pol, Nef pools) than in the 2xDNA (15; 22%) arms (primary endpoint; P = 0.047) with a higher magnitude against Env (at week 26) (P<0.001). In both groups, vaccine regimens induced HIV-specific polyfunctional CD4 and CD8 T cells and the production of Th1, Th2 and Th17/IL-21 cytokines. Antibody responses were also elicited in up to 81% of vaccines. A higher percentage of IgG responders was noted in the 2xDNA arm compared to the 3xDNA arm, while the 3xDNA group tended to elicit a higher magnitude of IgG3 response against specific Env antigens. We show here that the modulation of the prime strategy, without modifying the route or the dose of administration, or the combination of vectors, may influence the quality of the responses.


A Compressive Sensing Approach for 3D Breast Cancer Microwave Imaging With Magnetic Nanoparticles as Contrast Agent.
In microwave breast cancer imaging magnetic nanoparticles have been recently proposed as contrast agent. Due to the non-magnetic nature of human tissues, magnetic nanoparticles make possible the overcoming of some limitations of conventional microwave imaging techniques, thus providing reliable and specific diagnosis of breast cancer. In this paper, a Compressive Sensing inspired inversion technique is introduced for the reconstruction of the magnetic contrast induced within the tumor. The applicability of Compressive Sensing theory is guaranteed by the fact that the underlying inverse scattering problem is linear and the searched magnetic perturbation is sparse. From the numerical analysis, performed in realistic conditions in 3D geometry, it has been pointed out that the adoption of this new tool allows improving resolution and accuracy of the reconstructions, as well as reducing the number of required measurements.


Novel "Elements" of Immune Suppression within the Tumor Microenvironment.
Adaptive evolution has prompted immune cells to use a wide variety of inhibitory signals, many of which are usurped by tumor cells to evade immune surveillance. Although tumor immunologists often focus on genes and proteins as mediators of immune function, here we highlight two elements from the periodic table-oxygen and potassium-that suppress the immune system in previously unappreciated ways. While both are key to the maintenance of T-cell function and tissue homeostasis, they are exploited by tumors to suppress immuno-surveillance and promote metastatic spread. We discuss the temporal and spatial roles of these elements within the tumor microenvironment and explore possible therapeutic interventions for effective and promising anticancer therapies. Cancer Immunol Res; 5(6); 426-33. ©2017 AACR.


Reaction and degradation mechanism in all-solid-state lithium-air batteries.
The reaction and degradation mechanism in all-solid-state Li-air batteries was investigated to improve the cycling performance. It is suggested that Li2O2 is first produced by the H2O-mediated electrochemical reactions during discharging and Li2CO3 is produced by the following chemical reactions. Disruption of the CNTs and residual discharge products, which cause the capacity degradation during cycling, were observed.


The impact of early-onset cannabis use on functional brain correlates of working memory.
Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation during verbal working memory challenge in (1) early-onset (onset before the age of sixteen; n=26) and (2) late-onset cannabis users (age at onset at least sixteen; n=17). Early-onset users showed increased activation in the left superior parietal lobe. Correlational analyses confirmed the association between an earlier start of use and increased activity. Contrariwise neither cumulative dose, frequency nor time since last use was significantly associated with cortical activity. Our findings suggest that an early start of cannabis use is associated with increased cortical activation in adult cannabis users, possibly reflecting suboptimal cortical efficiency during cognitive challenge. The maturing brain might be more vulnerable to the harmful effects of cannabis use. However, due to a lack of a non-using control group we cannot exclude alternative interpretations.


Role of monocytes/macrophages in renin-angiotensin system-induced hypertension and end organ damage.
The renin-angiotensin system (RAS) is a central modulator of cardiovascular physiology. Pathophysiology of hypertension is commonly accompanied by hyper-activation of RAS. Angiotensin II receptor blockers (ARBs) and Angiotensin-converting enzyme (ACE) inhibitors are the gold standard treatment for hypertension. Recently, several studies highlighted the crucial role of immune system in hypertension. Angiotensin-II-induced hypertension is associated with low grade inflammation characterized by innate and adaptive immune system dysfunction. Throughout the progression of hypertension, monocyte/macrophage cells appear to have a crucial role in vascular inflammation and interaction with the arterial wall. Since myelomonocytic cells potentially play a key role in angiotensin-II-induced hypertension and organ damage, pharmacological targeting of RAS components in monocyte/macrophages may possibly present an innovative strategy for treatment of hypertension and related pathology.


Automated gas burette system for evolved hydrogen measurements.
This paper reports a simple and efficient gas burette system that allows automated determination of evolved gas volume in real time using only temperature and pressure measurements. The system is reliable and has been used successfully to study the hydrogen release kinetics of ammonia borane thermolysis. The system is especially suitable for bench scale studies involving small batches and potentially rapid reaction kinetics.


Breastfeeding During a Pandemic: The Influence of COVID-19 on Lactation Services in the Northeastern United States.
Pandemic-related restrictions have limited traditional models of lactation support. The primary aim of this study was to determine changes to breastfeeding support services during the coronavirus-2019 pandemic according to trained lactation providers. The secondary aim was to assess strengths and limitations of telehealth services. A prospective survey was conducted entirely online using the Qualtrics platform during June 2020. Gatekeepers at Connecticut agencies and breastfeeding networks were forwarded an anonymous survey link to distribute to eligible lactation staff. A variety of participants (N = 39) completed the survey and the majority (69.2%; n = 27) were providing only telehealth services. More than half (58.1%; n = 18) of the participants who conducting telehealth in any form, found that virtual lactation support was moderately effective compared to in-person support. Weakness of virtual support included technical and logistical difficulties, challenges assisting with latching or reading body language over the phone or online, and accurately assessing infant growth. Strengths related to virtual support included the flexibility and convenience of home-based support, expanded communication strategies, and safety from virus exposure. Further, visits with a lactation professional decreased significantly during the pandemic. Limited in-hospital and pediatrician support were also noted, particularly among groups without access to telehealth resources. As a result of the pandemic and associated shifts in lactation services, breastfeeding disparities may be further exacerbated among those without equitable access to lactation support. Challenges and innovations in virtual support may influence adaptive options in the field moving forward.


All-phononic amplification in coupled cantilever arrays based on gap soliton dynamics.
We present a mechanism of amplification of phonons by phonons on the basis of nonlinear band-gap transmission phenomenon. As a concept the idea may be applied to the various number of systems; however we introduce the specific idea of creating an amplification scenario in the chain of coupled cantilever arrays. One chain is driven at the constant frequency located in the upper band of the ladder system, thus no wave enters the system. However the frequency is specifically chosen to be very close to the maximum value of the frequency corresponding to the dispersion relation of the system. An amplification scenario happens when a counter phase pulse of the same frequency with a small amplitude is introduced to the second chain. If both signals exceed a threshold amplitude for the band-gap transmission a large amplitude soliton enters the system-therefore we have an amplifier. Although the concept may be applied in a variety of contexts, all-optical or all-magnonic systems, we choose the system of coupled cantilever arrays and represent a clear example of the application of the presented conceptual idea. Logical operations is the other probable field, where such a mechanism could be used, which might significantly broaden the horizon of the considered applications of band-gap soliton dynamics.


Psychotherapy of adults with attention-deficit disorder.
The multimodal treatment of adults with attention-deficit disorder (ADD) is described as consisting of a sequence of overlapping therapeutic measures. The initial objective is symptom amelioration through adequate pharmacotherapy. Once this has been accomplished, a period of psychoeducational therapy is recommended to teach the individual to live successfully with a chronic disorder. These two aspects of treatment may suffice for some ADD adults, but many others may require an additional course of psychotherapy to deal with dysfunctional personality characteristics resulting from having grown up with ADD. Among these are modes of defenses against painful affects, resistances to treatment, and inaccurate estimations and expectations of the self and others.


A charge-coupled-device camera image analysis system for quantifying DNA distributions in agarose gels after pulsed-field gel electrophoresis.
A charge-coupled-device camera system was coupled to a personal computer and, with uniformity in illumination and detection (within 4-8%) along each lane, was used for quantifying the distribution of DNA molecules that migrate from the PFGE well (plug) into the lane at distances varying from 1 to 50 mm (with 0.5 mm/pixel). By using a specially designed transmission filter for transmitting 470-725 nm fluorescence from ethidium bromide-stained DNA while eliminating most of the fluorescence (< 400 nm) from the agarose gel, and by using neutral density filters to prevent saturation of the camera, the fluorescence intensity is linearly related to the amount of DNA varying from approximately 0.03 micrograms in a 3-mm-diameter cylindrical plug 5 mm long (equal to background) to approximately 4 micrograms (where ethidium bromide staining saturates). The percentage DNA released from the plug and distribution in the lane (with 1-2 mm resolution) obtained by quantifying DNA fluorescence were not significantly different from the same data obtained by analysis of radioactivity of the same DNA labeled with [3H]dThd. However, scattering of fluorescence from one lane into an adjacent lane 3 mm away and as far as 10 mm from the plug into the lane presented a problem. This problem was overcome by using a form with slots to cover every other lane when the images were obtained and either (1) cutting the lane from the plug and moving it 15 mm away or (2) imaging the intact gel and applying a correction for approximately 7% of the fluorescence from the plug tailing out approximately 10 mm beyond the first 1 mm in the lane. In addition, the following were required: (1) carefully controlled staining and destaining procedures, and (2) a low background that is obtained as an average uniform background in each lane 5 mm beyond where DNA migration stops.


Dynamic mechanisms of exercise to improve body satisfaction: Perceived or actual fat loss?
We examined the dynamic mechanisms of aerobic training (AT) and strength training (ST) to improve body satisfaction. Sixty-six participants were randomised to either the AT or ST condition and completed an 8-week intervention. Participants completed 3 weekly, 30-minute sessions of moderate intensity AT (65-75% VO2 max) or ST (65-75% 1-RM). The energy consumption of each session was approximately equivalent under both conditions. Body satisfaction, body composition, perceived fitness and exercise self-efficacy were measured at baseline and biweekly during the intervention. Exercise improved individuals' body satisfaction (p < .05). When the energy expenditures of AT and ST were equal, there was no difference in body satisfaction improvement. There were dynamic mechanisms underlying the effects of exercise on body satisfaction. Specifically, perceived fitness influenced body satisfaction improvements during the early stages of the exercise program, while changes in body composition influenced body satisfaction toward the end of the exercise program. There were sex differences in the mechanisms underlying body satisfaction. For women, perceived fat was more important in the early intervention period; for men, actual body fat was more valuable in the late intervention period. An effective strategy to improve body satisfaction is to initially target perceived fitness before focusing on changing body composition.


The Anophthalmic Socket - Reconstruction Options.
Keeping the eye is impossible, functionality is lost and aesthetic requirements are high. What do we do? Which approach is right? This is the dilemma we face whenenucleation or evisceration are unavoidable. The patient loses a sensory organ with a very important function and, at the same time, is faced with a major aesthetic defect, leading to significant anxiety. The purpose of this article is to describe the different reconstruction techniques for anophthalmic sockets. In preparing the anopthalmic socket for prosthesis fitting we have several options: dermis-fat graft with a very good biocompatibility, the Guthoff artificial implant, which provides better motility or the methyl methacrylate implant inside the muscle cone. Each option has advantages and disadvantages but the choice of technique should be adapted to the needs and expectations of the patient, taking into account both time and cost.


Moonlighting is mainstream: paradigm adjustment required.
Moonlighting--the performance of more than one function by a single protein--is becoming recognized as a common phenomenon with important implications for systems biology and human health. The different functions of a moonlighting protein may use different regions of the protein structure, or alternative structures that occur due to post-translational modifications and/or differences in binding partners. Often the different functions of moonlighting proteins are used at different times or in different places. The existence of moonlighting functions complicates efforts to understand metabolic and regulatory networks, as well as physiological and pathological processes in organisms. Because moonlighting functions can play important roles in disease processes, an improved understanding of moonlighting proteins will provide new opportunities for pharmacological manipulations that specifically target a function involved in pathology while sparing physiologically important functions.


2-pyrones possessing antimicrobial and cytotoxic activities.
The 2-pyrone sub-unit is found in a number of natural products possessing broad spectrum biological activity. Such compounds are validated as being capable of binding to specific protein domains and able to exert a remarkable range of biological effects. In an effort to identify synthetic 2-pyrones with interesting biological effects, herein we report the synthesis and biological evaluation of 4-substituted-6-methyl-2-pyrones. Synthetic routes to 4-alkyl/alkenyl/aryl/alkynyl-6-methyl-2-pyrones have been developed utilising Sonogashira, Suzuki and Negishi cross-coupling starting from readily available 4-bromo-6-methyl-2-pyrone. Specific conditions for each organometallic protocol were required for successful cross-coupling. In particular, a triethylamine/acetonitrile--base/solvent mixture was crucial to Sonogashira alkynylation of 4-bromo-6-methyl-2-pyrone, whereas thallium carbonate was a mandatory base for the Suzuki cross-coupling of trialkylboranes. The 2-pyrones demonstrate potent inhibitory activity against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Schizosaccharomyces pombe and Botrytis cinerea. The growth inhibitory activities of selected 2-pyrones were determined in A2780 human ovarian carcinoma and K562 human chronic myelogenous leukaemia cell lines using an in vitro cell culture system (MTT assay). These studies demonstrate that 4-phenylethynyl-, 4-tetrahydropyranylpropargyl ether- and 4-ethynyl-6-methyl-2-pyrones have excellent potential as a new class of anticancer agents.


CXCR4 modulates contractility in adult cardiac myocytes.
The inflammatory response is critical to the development and progression of heart failure. Chemokines and their receptors are a distinct class of inflammatory modulators that may play a role in mediating myocardial dysfunction in heart failure. Levels of the chemokine CXCL12, also known as stromal cell-derived factor (SDF), and its receptor, CXCR4, are elevated in patients with heart failure, and we undertook this study to determine whether this chemokine system can directly affect cardiac function in the absence of leukocytes. Murine papillary muscles and adult rat cardiac myocytes treated with CXCL12, the only identified ligand of CXCR4, demonstrate blunted inotropic responses to physiologic concentrations of calcium. The negative inotropic effects on cardiac myocytes are accompanied by a proportional diminution of calcium transients. The effects are abrogated by AMD3100, a specific CXCR4 inhibitor. Overexpression of the receptor through adenoviral infection with a CXCR4 construct accentuates the negative inotropic effects of CXCL12 on cardiac myocytes during calcium stimulation. CXCR4 activation also attenuates beta-adrenergic-mediated increases in calcium mobilization and fractional shortening in cardiac myocytes. In electrophysiologic studies, CXCL12 decreases forskolin- and isoproterenol-induced voltage-gated L-type calcium channel activation. These studies demonstrate that activation of CXCR4 results in a direct negative inotropic modulation of cardiac myocyte function. The specific mechanism of action involves alterations of calcium channel activity on the membrane. The presence of functional CXCR4 on cardiac myocytes introduces a new target for treating cardiac dysfunction.


Laying the groundwork for enterprise-wide medical language processing services: architecture and process.
A systematic and standard process for capturing information within free-text clinical documents could facilitate opportunities for improving quality and safety of patient care, enhancing decision support, and advancing data warehousing across an enterprise setting. At Partners HealthCare System, the Medical Language Processing (MLP) services project was initiated to establish a component-based architectural model and processes to facilitate putting MLP functionality into production for enterprise consumption, promote sharing of components, and encourage reuse. Key objectives included exploring the use of an open-source framework called the Unstructured Information Management Architecture (UIMA) and leveraging existing MLP-related efforts, terminology, and document standards. This paper describes early experiences in defining the infrastructure and standards for extracting, encoding, and structuring clinical observations from a variety of clinical documents to serve enterprise-wide needs.


Low diversity in the major histocompatibility complex class II DRB1 gene of the Spanish ibex, Capra pyrenaica.
During the last two centuries, the Spanish ibex (Capra pyrenaica) has shown a significant demographic decline as a result of the progressive destruction of its natural habitat, disease epidemics, and uncontrolled hunting. Partial sequencing of the class II MHC DRB1 gene revealed that the Spanish ibex has remarkably low levels of genetic variation at this locus, with only six different DRB1 alleles and an observed heterozygosity of 0.429-0.579. The rates of nonsynonymous vs synonymous substitutions were significantly different in the peptide-binding region (dN/dS=5.347, P=0.002), a feature that indicates that the DRB1 gene is under positive selection. A phylogenetic analysis of the Spanish ibex and a set of domestic goat DRB1 alleles revealed that the reported sequences represent four major allelic lineages. The limited allelic repertoire of the DRB1 gene in the Spanish ibex is likely the direct result of the recent history of population bottlenecks and marked demographic decline of this species. A genetic survey of 13 microsatellite loci was consistent with this idea. The Spanish ibex subspecies C. p. hispanica and C. p. victoriae consistently showed considerably lower levels of microsatellite heterozygosity (Ho=0.184-0.231) and allelic diversity (mean number of alleles per locus=2-2.4) than those reported in other wild ruminants. This study demonstrates the significance of both natural selection and the demographic history of populations in determining patterns of genetic variation at MHC loci. In addition, our results emphasize the importance of locally adapted populations for the preservation of genetic diversity.


A Novel Recombinant Chlorophyllase1 from Chlamydomonas reinhardtii for the Production of Chlorophyllide Derivatives.
Natural chlorophyll metabolites have exhibited physiological activity in vitro. In this study, a recombinant chlorophyllase1 gene from Chlamydomonas reinhardtii (CrCLH1) was isolated and characterized. Recombinant CrCLH1 can perform chlorophyll dephytylation and produce chlorophyllide and phytol. In a transient assay, the subcellular localization of CrCLH1-green fluorescent protein was determined to be outside the chloroplast. Biochemical analyses of the activity of recombinant CrCLH1 indicated that its optimal pH value and temperature are 6.0 and 40 °C, respectively. Enzyme kinetic data revealed that the recombinant CrCLH1 had a higher catalytic efficiency for chlorophyll a than for chlorophyll b and bacteriochlorophyll a. According to high-performance liquid chromatography analysis of chlorophyll hydrolysis, recombinant CrCLH1 catalyzed the conversion of chlorophyll a to pheophorbide a at pH 5. Therefore, recombinant CrCLH1 can be used as a biocatalyst to produce chlorophyllide derivatives.


Lifestyle-tailored interventions for South Asians with type 2 diabetes living in high-income countries: a systematic review.
To summarize evidence on the effectiveness of educational interventions for type 2 diabetes control in South Asians living in high-income countries. We systematically searched PubMed, EMBASE, Cinahl and the Cochrane Library, using Medical Subject Heading and free-text terms. The considered outcomes were: mortality, morbidity, glycaemic control, blood pressure, practice (diet, physical activity and self-care), attitudes/awareness and knowledge. Papers published up to July 2015 were considered. Two reviewers independently screened the title and abstract and then read the full text of selected papers. Nine studies were included, four non-randomized studies of interventions and five randomized controlled trials. All studies except one were conducted in the UK. Target population ranged from 39 to 1486 individuals; the follow-up ranged from 1 to 24 months. The interventions were mostly based on a tailored educational package, individually or group administered, conducted by lay link workers, health professionals or both. No study measured mortality or morbidity. An effect on glycaemic control was observed only in before/after studies, while a randomized study showed a non-significant improvement (percentage of glycated haemoglobin -0.15, P = 0.11). Two randomized studies found a reduction in blood pressure. Changes in practice and attitudes showed heterogeneous results, mostly favouring intervention. There was weak evidence that interventions using link workers and tailored education can modify attitudes, self-care skills and blood pressure in South Asian migrants to industrialized countries. Only one larger trial, with adequate follow-up, showed a small non-significant improvement of glycaemic control.


Monoclonal antibodies to bluetongue virus define two neutralizing epitopes and a hemagglutinating epitope.
Monoclonal antibodies were used to characterize neutralizing epitopes on VP2 of bluetongue virus serotype 10 (BTV-10). Six neutralizing monoclonal antibodies that immune precipitated VP2 demonstrated two distinct patterns of reactivity in the competitive enzyme-linked immune absorbent assay (ELISA). These results suggest that there are at least two distinct domains of neutralization on VP2 of BTV. Monoclonal antibodies defining the two domains were serotype-restricted in plaque neutralization, immune precipitation or ELISA. One of the two neutralizing domains also demonstrated significant hemagglutinating activity. Both cattle and sheep infected with BTV-10 produce antibodies to the two neutralizing epitopes.


Corneal graft transparency: is 100% an achievable goal?
In a series of 56 patients who underwent penetrating keratoplasty in 86 eyes, 96% of the grafted corneas achieved clarity during a follow-up period of 6 months to 6 years. The reason for this high success rate was the very strict patient selection, which almost entirely excluded cases with dry eye syndrome, active inflammation of the eye and elevated intraocular pressure. Donor material was also very carefully selected.


Hippocampectomy disrupts acquisition and retention of learned conditional responding.
The effects of bilateral hippocampal and neocortical lesions were examined on acquisition and retention of classically conditioned responses based on (a) simple associations, (b) a nonconditional discrimination, and (c) a conditional discrimination in the same subjects. Results showed that combined hippocampal and neocortical damage permanently prevented (within the limits tested) both acquisition and retention of learned behavior based on the conditional discrimination but had no effect on behaviors based on the nonconditional discrimination or simple associations. Neocortical lesions alone had no effect on either conditional or nonconditional discriminative responding, but they did temporarily disrupt acquisition and retention of behavior dependent on CS-CS (two conditioned stimuli) associations. Neither lesion affected learned behaviors mediated by CS-US (conditioned stimulus and unconditioned stimulus) associations. Thus, results showed that hippocampal damage selectively disrupted learned conditional behaviors and also revealed that central nervous system control of conditional discrimination performance, within-compound associations, and CS-US associations is mediated by different neural mechanisms.


Nonenzymatic glycation of peripheral and central nervous system proteins in experimental diabetes mellitus.
Nonenzymatic glycation of neural proteins could underlie diabetic peripheral neuropathy. Cytoskeletal and myelin protein fractions of central nervous system and peripheral nervous system (PNS) tissue from rats with streptozotocin-induced diabetes of 1.5 and 8 months duration were analyzed for glycation products. In sciatic nerve cytoskeletal preparations from both diabetic and control animals we found high levels of the early glycation product (measured as furosine) after 6 weeks, which had fallen markedly by 8 months. Conversely the advanced glycation end product (AGE), pentosidine, was low at 6 weeks and high by 8 months in diabetic animals. The levels of glycation products were much lower in spinal cord and spinal nerve from diabetic animals. There was increased borotritride labeling of neurofilament subunits, and of cross-linked material, in cytoskeletal fractions of diabetic sciatic nerves. These results show that the PNS cytoskeleton is vulnerable to nonenzymatic glycation, resulting in AGE formation, in diabetic rats and to a lesser extent in normals.


Activated protein C resistance due to a factor V mutation associated with familial ischemic stroke.
Recent findings have indicated the association between activated protein C (APC)-resistance and cerebrovascular disease. These reports prompted us to investigate whether resistance to APC could be found in patients suffering from transient ischaemic attacks or stroke. Therefore, we studied APC-resistance in 14 young adults belonging to three different families with a history of transient ischemic attacks (TIAs) and stroke. Nine out of fourteen subjects showed APC-resistance but no deficiencies in the anticoagulant proteins AT III, PC and PS. The family history demonstrated a distribution of APC-resistance compatible with dominant autosomal inheritance. A rapid screening method to detect factor V R506Q (Leiden) mutation without sequencing or restriction enzyme digestion has been set-up after biochemical analyses. DNA analysis showed a guanine to adenine transition at nucleotide 1,691 in patients and their relatives with poor response to activated protein C detected by APTT tests. Of 14 investigated subjects and their family members, 5 were normals, 6 were heterozygotes and 3 were homozygotes for factor V mutation. The mutation, in heterozygous form, was also found in 1.3% of our normal population (n = 75). Our findings indicate a possible involvement of APC-resistance in the pathogenesis of arterial thrombosis in young adults.


Antiatherosclerotic effect of farnesoid X receptor.
The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that functions as an endogenous sensor for bile acids and regulates cholesterol and fatty acid metabolism. The effect of FXR activation on aortic plaque formation was assessed by feeding apolipoprotein E-deficient (ApoE-/-) mice with the synthetic FXR ligand INT-747, a cheno-deoxycholic acid derivative, at doses of 3 and 10 mg x kg(-1) x day(-1), or with rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, at the dose of 10 mg x kg(-1) x day(-1) for 12 wk. Administration of INT-747 reduced formation of aortic plaque area by 95% (P < 0.01), and a similar antiplaque activity was exerted by administration of rosiglitazone. INT-747 administration to ApoE-/- mice reduced aortic expression of IL-1beta, IL-6, and CD11b mRNA, while it upregulated the expression of FXR and its target gene, the small heterodimer partner (SHP). FXR activation reduced the liver expression of sterol regulatory element binding protein 1c, resulting in reduced triglyceride and cholesterol content in the liver and amelioration of hyperlipidemia. FXR expression, mRNA and protein, was detected in human macrophages and macrophage cell lines. FXR activation by natural and synthetic ligands in these cell types attenuated IL-1beta, IL-6, and TNF-alpha gene induction in response to Toll-like receptor 4 activation by LPS. Using spleen monocytes from wild-type and FXR-/- mice, we demonstrated that FXR gene ablation exacerbates IL-6 and TNF-alpha generation by LPS-stimulated macrophages. FXR was also able to reduce cholesterol uptake on macrophages by regulation of CD36 and ABCA1 expression. We found that FXR and SHP are expressed in the aorta and macrophages and that FXR ligands might have utility in prevention and treatment of atherosclerotic lesions.


Factors which facilitate or impede patient engagement with pulmonary and cardiac rehabilitation: a rapid evaluation mapping review.
There is a considerable body of systematic review evidence considering the effectiveness of rehabilitation programmes on clinical outcomes. However, much less is known about effectively engaging and sustaining patients in rehabilitation. There is a need to understand the full range of potential intervention strategies. We conducted a mapping review of UK review-level evidence published 2017-21. We searched MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health (CINAHL) and conducted a narrative synthesis. Included reviews reported factors affecting commencement, continuation or completion of cardiac or pulmonary rehabilitation, or an intervention to facilitate these factors. Study selection was undertaken independently by two reviewers. In total, we identified 20 review papers that met our inclusion criteria. There was a bias towards reviews considering cardiac rehabilitation, with these numbering 16. An additional 11 unpublished interventions were also identified through internet searching of key websites. The reviews included 60 identifiable UK primary studies that considered factors which affected attendance at rehabilitation; 42 considered cardiac rehabilitation and 18 considering pulmonary rehabilitation. They reported on factors from the patients' point of view, as well as the views of professionals involved in referral or treatment. It was more common for factors to be reported as impeding attendance at rehabilitation rather than facilitating it. We grouped the factors into patient perspective (support, culture, demographics, practical, health, emotions, knowledge/beliefs and service factors) and professional perspective (knowledge: staff and patient, staffing, adequacy of service provision and referral from other services, including support and wait times). We found considerably fewer reviews (n = 3) looking at interventions to facilitate participation in rehabilitation. Although most of the factors affecting participation were reported from a patient perspective, most of the identified interventions were implemented to address barriers to access in terms of the provider perspective. The majority of access challenges identified by patients would not therefore be addressed by the identified interventions. The more recent unevaluated interventions implemented during the COVID-19 pandemic may have the potential to act on some of the patient barriers in access to services, including travel and inconvenient timing of services. The factors affecting commencement, continuation or completion of cardiac or pulmonary rehabilitation consist of a web of complex and interlinked factors taking into consideration the perspectives of the patients and the service providers. The small number of published interventions we identified that aim to improve access are unlikely to address the majority of these factors, especially those identified by patients as limiting their access. Better understanding of these factors will allow future interventions to be more evidence based with clear objectives as to how to address the known barriers to improve access. Time limitations constrained the consideration of study quality and precluded the inclusion of additional searching methods such as citation searching and contacting key authors. This may have implications for the completeness of the evidence base identified. High-quality effectiveness studies of promising interventions to improve attendance at rehabilitation, both overall and for key patient groups, should be the focus moving forward. This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HSDR programme or the Department of Health. The study protocol is registered with PROSPERO [CRD42022309214].


Use of bovine colostrum in periapical defects following surgical endodontics: Two case reports.
Periapical lesions are the most common pathological conditions involving teeth which often require surgical intervention. To achieve optimal healing both clinically and radiographically, bone grafts and barrier membranes have been used to fill the periapical defect after degranulation of the lesion. Colostrum is one of the new materials, which has osteoinductive or regenerative potential. The present case reports describe the use of bovine colostrum in the treatment of periapical inflammatory lesion with a follow-up period of 12 months. These case reports suggest that colostrum can be used to fill the periapical defect after degranulation, which has a favorable outcome.


Contrast, visibility, and color balance between the microscope versus intracameral illumination in cataract surgery using a 3D visualization system.
To compare image resolution and depth between the microscope versus intracameral illumination images during 3D heads-up cataract surgery. We collected 25 consecutive patients who had cataract surgery using the 3D viewing system. Based on bright, contrast, visibility, and color balance, the digital images (RGB color and three monochromes) extracted at the same point of the procedures were compared between the two illuminations. Contrast values of green and blue channels except for red channel and visibility values of all three channels were higher in the intracameral illumination images than in the microscope images (P < 0.001, t-test). Color balance values of both green/red and blue/red were higher in the intracameral illumination images than in the microscope images (P < 0.001, t-test). The digital images in the digitally assisted cataract surgery were enhanced by using the intracameral illumination. Considering the contrast and color balance in the 3D cataract surgery, the intracameral illumination may be better than the microscope illumination.


[Stress fractures of the navicular bone--biomechanical and densitometry studies].
One of the most important pathogenetic mechanisms regarding stress fractures of the navicular bone lies in the hyperpronation movement of the foot. For recording the impacts of the pronation movement on the talonavicular joint, stress and pressure experiments are carried out and the radii of curvature as well as the bone density are measured. The stress experiments show a rotation movement of the talar head in a medioplantar direction of about 20 degrees. The radii of curvature of the articulating joint surfaces do not differ to a great extent. A possible incongruency in the joint therefore has to be attributed to the rotation movement of the talus during pronation of the foot. The pressure experiments show a very irregular distribution of pressure in the joint presenting a lateral and medial pressure maximum. Fractures preferably occur in the area in between these maxima. Areas of high subchondral bone density in the densitometric results are found in the central part of the talar head as well as in the medial part of the navicular bone. Within the functional adaptation the distribution of bone density expresses the rotation movement of the talus during pronation of the foot.


A copper(II)-mediated regioselective cyclization-acetoxylation of 6,8-dien-1-ones for the synthesis of functionalized cyclopentanes.
This paper describes a copper(II) acetate-mediated cyclization-acetoxylation of 6,8-dien-1-ones in the presence of sodium acetate as base. A variety of functionalized cyclopentanes containing synthetic useful allylic alcohol moieties with three contiguous stereogenic centers were synthesized in moderate to good yields with moderate to high regioselectivities.


Relation between germination and mycelium growth of individual fungal spores.
The relation between germination time and lag time of mycelium growth of individual spores was studied by combining microscopic and macroscopic techniques. The radial growth of a large number (100-200) of Penicillium expansum and Aspergillus niger mycelia originating from single spores was monitored macroscopically at isothermal conditions ranging from 0 to 30°C and 10 to 41.5°C, respectively. The radial growth curve for each mycelium was fitted to a linear model for the estimation of mycelium lag time. The results showed that the lag time varied significantly among single spores. The cumulative frequency distributions of the lag times were fitted to the modified Gompertz model and compared with the respective distributions for the germination time, which were obtained microscopically. The distributions of the measured mycelium lag time were found to be similar to the germination time distributions under the same conditions but shifted in time with the lag times showing a significant delay compared to germination times. A numerical comparison was also performed based on the distribution parameters λ(m) and λ(g), which indicate the time required from the spores to start the germination process and the completion of the lag phase, respectively. The relative differences %(λ(m)-λ(g))/λ(m) were not found to be significantly affected by temperatures tested with mean values of 72.5±5.1 and 60.7±2.1 for P. expansum for A. niger, respectively. In order to investigate the source of the above difference, a time-lapse microscopy method was developed providing videos with the behavior of single fungal spore from germination until mycelium formation. The distances of the apexes of the first germ tubes that emerged from the swollen spore were measured in each frame of the videos and these data were expressed as a function of time. The results showed that in the early hyphal development, the measured radii appear to increase exponentially, until a certain time, where growth becomes linear. The two phases of hyphal development can explain the difference between germination and lag time. Since the lag time is estimated from the extrapolation of the regression line of the linear part of the graph only, its value is significantly higher than the germination time, t(G). The relation of germination and lag time was further investigated by comparing their temperature dependence using the Cardinal Model with Inflection. The estimated values of the cardinal parameters (T(min), T(opt), and T(max)) for 1/λ(g) were found to be very close to the respective values for 1/λ(m), indicating similar temperature dependence between them.


The effects of laser welding on heterogeneous immunoassay performance in a microfluidic cartridge.
Sealing of a microfluidic cartridge is a challenge, because the cartridge commonly contains heat-sensitive biomolecules that must also be protected from contamination. In addition, the objective is usually to obtain a sealing method suitable for mass production. Laser welding is a rapid technique that can be accomplished with low unit costs. Even though the technique has been widely adopted in industry, the literature on its use in microfluidic applications is not large. This paper is the first to report the effects of laser welding on the performance of the heterogeneous immunoassay in a polystyrene microfluidic cartridge in which biomolecules are immobilized into the reaction surface of the cartridge before sealing. The paper compares the immunoassay performance of microfluidic cartridges that are sealed either with an adhesive tape or by use of laser transmission welding. The model analyte used is thyroid stimulating hormone (TSH). The results show that the concentration curves in the laser-welded cartridges are very close to the curves in the taped cartridges. This indicates, first, that laser welding does not cause any significant reduction in immunoassay performance, and second, that the polystyrene cover does not have significant effect on the signal levels. Interestingly, the coefficients of variance between parallel samples were lower in the laser-welded cartridges than in the taped cartridges.


Effects of perceptual salience on the matrix task performance of four- and six-year-old children.
The effects of salience on 4- and 6-year-old children's ability to classify multiplicatively was investigated. A rank-ordered salience hierachy consisting of 3 dimensions was first assessed for each S. Several weeks later half the Ss of each age group were presented with a series of 9 3 times 3 matrix problems consisting of values from 2 dimensions ranked high in salience. The remaining half received identically structured matrices consisting of values from 1 highly salient dimension and of others from a dimension ranked low in salience. The goal in each problem was to select that compound stimulus from a set of alternatives that appropriately filled an empty cell in the matrix. Prior to the matrix problems, half the Ss in each matrix condition received sensitization training designed to increase the salience of the relevant dimensions in the matrix problems. The results showed that the pre-assessed salience of the relevant dimensions affected matrix solution in that more accurate performance was associated with those problems with both relevant dimensions relatively high in salience than those with one high and one low. Although the older Ss solved more problems, the evidence for coordination in the younger Ss was clear. No effects of sensitization training were found.


Validation of the Continuous Glucose Monitoring System (CGMS) by the use of two CGMS simultaneously in pregnant women with type 1 diabetes mellitus.
In pregnant women with type 1 diabetes tight glycemic control reduces perinatal complications. Intensive observation of glucose profiles is essential in the achievement of tight glycemic control. The recent availability of the Continuous Glucose Monitoring System (CGMS, Minimed, Sylmar, CA) creates the opportunity to obtain more complete glucose profiles. This study was aimed at evaluating the accuracy of the CGMS in pregnant women with type 1 diabetes. Five pregnant women with type 1 diabetes were asked to use two CGMS devices simultaneously. The simultaneously measured glucose levels were analyzed using the Pearson correlation, the mean absolute difference, and Bland-Altman analysis. Second, the percentage of concordance of paired data in the hypoglycemic, normoglycemic, or hyperglycemic range was calculated. The correlation coefficient between simultaneously measured data was 0.94 (P < 0.001). The mean absolute difference was 1.1 +/- 0.8 mmol/L. Bland-Altman analysis shows that 95% of the data pairs have a difference < or = 1.74 mmol/L. Almost 80% of the data pairs could be classified in the same glucose range. In 81% of the non-concordant pairs, one glucose value was classified in the hypoglycemic range and one in the normoglycemic range. This study shows that the reproducibility of the CGMS in pregnant women with type 1 diabetes is adequate. This indicates that the CGMS is a useful tool in the management of type 1 diabetes in pregnant women. However, the CGMS should only be used as a supplementary method of daily glucose level measurement as a small degree of error, mainly in the hypoglycemic range, is present.


Applications of propolis encapsulation in food products.
Propolis has beneficial health properties attributed to of phenolic compounds. However, its application is limited. Thus, encapsulation protects the bioactive compounds of propolis from degradation, allowing their release under controlled and specific conditions and increasing their solubility. In addition to protecting flavonoids, encapsulation also minimises the undesirable characteristics of propolis, such as strong odour. We brought attention to the high antioxidant and antimicrobial activities of encapsulated propolis, and its maintained biological activity enables more uses in different areas. Encapsulated propolis can be applied in food products as an ingredient. This review describes recent advances in improving the bioactivity of propolis extracts by using encapsulation techniques, and biopolymer research strategies, focusing on applications in food products. Encapsulated propolis has a promising market perspective due to the industrial and scientific-technological advancement, the increase in the amount of research, the improvement of propolis extraction techniques, and the need of consumers for innovative products.


Cardiac transplantation following storage of the donor heart by a portable hypothermic perfusion system.
Four patients have undergone heterotopic heart transplantation with donor hearts stored by a portable hypothermic perfusion system. Total ischemic periods ranged from 6 hours 55 minutes to 16 hours 50 minutes. One heart, transplanted into a patient who had acutely rejected a previous graft, suffered accelerated, irreversible, acute rejection within five days, associated with strong antibody formation; donor heart function was never good. In the 3 remaining patients, donor heart function was good after initially being poor for a few hours in 2 patients. One patient died of long-term rejection after 6 months and 1 of tuberculous meningitis after 10 months; 1 remains alive at 15 months. Neither preservation of the donor heart for periods in excess of approximately 4 hours nor the use of continuous hypothermic perfusion as a method of preservation appears to have been reported previously in the context of the clinical situation.


Specification of polarity of teloblastogenesis in the oligochaete annelid Tubifex: cellular basis for bilateral symmetry in the ectoderm.
Ectodermal teloblastogenesis in the oligochaete annelid Tubifex is a spatiotemporally regulated process that gives rise to four bilateral pairs of ectoteloblasts (N, O, P, and Q) that assume distinct fates. Ectoteloblasts on either side of the embryo arise from an invariable sequence of asymmetric cell divisions of a proteloblast, NOPQ, which occur with a defined orientation with respect to the embryonic axes: the N teloblast is generated first and located ventralmost, and the Q teloblast, which is generated next, is located dorsalmost; finally, the O and P teloblasts are generated by almost equal division of their precursor cell, OP. Polarity of teloblastogenesis on one side of the embryo is a mirror image of the other; this mirror symmetry of ectoteloblasts about the embryo's midline gives rise to the bilaterally symmetric organization of the ectoderm. In this study, we examined whether cellular interactions are involved in specification of polarity of asymmetric cell divisions in NOPQ cells. A set of cell transplantation experiments demonstrated that NOPQ cells are initially uncommitted in terms of division pattern and cell fates: If a left NOPQ cell is transplanted to the right side of a host embryo, it exhibits a polarity comparable to that of right NOPQ cells. The results of another set of cell transplantation experiments suggest that contact between NOPQ cells serves as an external cue for their polarization, irrespective of their position in the embryo, and that in the absence of host NOPQ cells, transplanted NOPQ cells can be polarized according to positional information residing in the host embryo. The competence of NOPQ cells to respond to external cues tapers down before their division into N and OPQ. A set of cell ablation experiments demonstrated that neighboring cells such as posteriorly located M teloblasts and anterolaterally located micromeres play a role in controlling spatial aspects of NOPQ's behavior that gives rise to their division along the dorsoventral axis. These results suggest that NOPQ cells, which do not initially have a rigidly fixed polarity, become polarized through external cues. Possible sources of signals for this polarizing induction are discussed in the light of the present results.