Genetic polymorphisms of XRCC1, HOGG1 and MGMT and micronucleus occurrence in Chinese vinyl chloride-exposed workers.
In this study, a group of 313 workers occupationally exposed to vinyl chloride monomer (VCM) and 141 normal unexposed referents were examined for chromosomal damage using the cytokinesis-blocked micronucleus (CBMN) assay in peripheral lymphocytes. We explored the relationship between genetic polymorphisms of XRCC1 (Arg194Trp, Arg280His and Arg399Gln), MGMT(Leu84Phe) and hOGG1 (Ser326Cys) and susceptibility of chromosomal damage induced by VCM. Polymerase chain reaction-restriction fragment length polymorphism techniques were used to detect polymorphisms in XRCC1, hOGG1 and MGMT. It was found that the micronuclei (MN) frequency of exposed workers (4.86 +/- 2.80) per thousand was higher than that of the control group (1.22 +/- 1.24) per thousand (P < 0.01). Increased susceptibility to chromosomal damage as evidenced by higher MN frequency was found in workers with hOGG1 326 Ser/Cys genotype [frequency ratio (FR) = 1.21, 95% confidence interval (CI): 1.02-1.46; P < 0.05], XRCC1 194 Arg/Trp (FR = 1.12, 95% CI: 1.00-1.25; P < 0.05) and XRCC1 280 Arg/His and His/His genotypes (FR = 1.12, 95% CI 1.00-1.26, P < 0.05). Moreover, among susceptibility diplotypes, CGA/CAG carriers had more risk of MN frequency compared with individuals with wild-type CGG/CGG (FR = 1.67, 95% CI: 1.19-2.23; P < 0.05). MN frequency also increased significantly with age in the exposed group (FR = 1.13, 95% CI: 1.00-1.28; P < 0.05). Thus, CB-MN was a sensitive index of early damage among VCM-exposed workers. Genotype XRCC1 Arg194Trp, Arg280His, hOGG1 Ser326Cys, diplotype CGA/CAG and higher age may have an impact on the chromosome damage induced by VCM.


[Evaluation of chemoradiotherapy for the treatment of rectal cancer].
Chemoradiotherapy for the treatment of primary rectal cancers has been regarded as an effective adjuvant for surgical procedures. It has been expected to reduce local recurrence, increase the chance of sphincter-preserving operation and improve survival. However, recent advances in surgical technique for rectal cancers have reduced the local recurrence rate to no more than 10%, where the question may arise of whether adjuvant chemoradiotherapy is indeed necessary. Another matter to be elucidated is why adjuvant chemoradiotherapy does not necessarily improve overall survival for rectal cancers even when the local recurrence rate is reduced. In the treatment of locally recurrent lesions, either heavy ion radiotherapy or proton beam therapy is expected to be an effective alternative to the surgical procedure.


Comparison of methenamine silver nitrate and Giemsa stain for detection of Pneumocystis carinii in bronchoalveolar lavage specimens from HIV infected patients.
Seventy-seven bronchoalveolar lavages from human immunosuppressive virus infected patients with pulmonary symptoms were examined routinely for the presence of Pneumocystis carinii, using Giemsa stain to detect trophozoites and methenamine silver nitrate to detect cysts. Thirty-seven samples were found positive with both methods, but a further 10 were diagnosed with Giemsa indicating that the trophozoite stain is more sensitive. As Giemsa stain is simple, quick, cheap and familiar to most microbiological laboratories it should be used for screening of samples to be examined for Pneumocystis carinii. In cases where trophozoites are not detected by Giemsa a supplementary cyst stain may be performed in order to rule out the presumably few cases where cysts are present as the only evidence of Pneumocystis carinii infection.


[Effects of a Cognitive Training Program on Cognitive Function and Activities of Daily Living in Patients with Acute Ischemic Stroke].
The purpose of this study was to examine the effects of a cognitive training program on neurocognitive task performance and activities of daily living (ADL) in patients who had a stroke. The research design for this study was a nonequivalent control group non-synchronized design. Patients were assigned to the experimental (n=21) or control group (n=21). The experimental group received a 4-week cognitive training program and usual care (i.e., rehabilitation service), while the control was received usual care only. Cognitive function was measured with a standardized neurocognitive test battery and ADL was assessed at baseline and one and two months after completion of the intervention. Repeated measures ANOVA was used to determine changes in cognitive function and ADL over 2 months. The interaction of group and time was significant indicating that the experimental group showed improvement in attention, visuospatial function, verbal memory, and executive function compared to the control group which had a sustained or gradual decrease in test performance. A significant group by time interaction in instrumental ADL was also found between the experimental group with gradual improvement and the control group showing no noticeable change. Findings show that the cognitive training program developed in this study is beneficial in restoring cognitive function and improving ADL in patients following a stroke. Further study is needed to investigate the long-term relationship between cognitive training participation and cognitive improvement and effective functioning in daily living.


Using lod-score differences to determine mode of inheritance: a simple, robust method even in the presence of heterogeneity and reduced penetrance.
Determining the mode of inheritance is often difficult under the best of circumstances, but when segregation analysis is used, the problems of ambiguous ascertainment procedures, reduced penetrance, heterogeneity, and misdiagnosis make mode-of-inheritance determinations even more unreliable. The mode of inheritance can also be determined using a linkage-based method (maximized maximum lod score or mod score) and association-based methods, which can overcome many of these problems. In this work, we determined how much information is necessary to reliably determine the mode of inheritance from linkage data when heterogeneity and reduced penetrance are present in the data set. We generated data sets under both dominant and recessive inheritance with reduced penetrance and with varying fractions of linked and unlinked families. We then analyzed those data sets, assuming reduced penetrance, both dominant and recessive inheritance, and no heterogeneity. We investigated the reliability of two methods for determining the mode of inheritance from the linkage data. The first method examined the difference (delta) between the maximum lod scores calculated under the two mode-of-inheritance assumptions. We found that if delta was > 1.5, then the higher of the two maximum lod scores reflected the correct mode of inheritance with high reliability and that a delta of 2.5 appeared to practically guarantee a correct mode-of-inheritance inference. Furthermore, this reliability appeared to be virtually independent of alpha, the fraction of linked families in the data set, although the reliability decreased slightly as alpha fell below .50.(ABSTRACT TRUNCATED AT 250 WORDS)


Lipopolysaccharides of Salmonella T mutants.
The composition of lipopolysaccharides derived from various Salmonella T forms was studied. All T1-form lipopolysaccharides examined contained 14 to 22% each of both d-galactose and pentose in addition to 4 to 9% each of ketodeoxyoctonic acid, heptose, d-glucosamine, and d-glucose. The pentose was identified as d-ribose. The T2-form lipopolysaccharide examined did not contain a significant amount of pentose, nor more than the usual amounts of d-galactose. Periodate oxidation of T1 (lipo) polysaccharides followed by NaBH(4) reduction revealed that ribose was almost quantitatively protected, galactose was destroyed, and threitol and mannose were newly formed. The latter two products probably originated from 4-linked galactose and heptose, respectively. Ribose and galactose were found in specific precipitates of T1 lipopolysaccharide with anti-T1 antiserum but were not found in specific precipitates of alkali-treated T1 lipopolysaccharide and of Freeman degraded polysaccharide with anti-T1 serum Ribose and galactose are present in these degraded preparations in the form of nondialyzable polymers. The T1-form mutant lipopolysaccharides lacked the O-specific sugars constituting the side-chains in the wild-type antigens. They did not produce the soluble O-specific haptenic polysaccharide known to be accumulated in RI strains. With these properties, T1 lipopolysaccharides resemble RII lipopolysaccharides. Like RII degraded polysaccharides, T1-degraded polysaccharides also contained glucosamine. Furthermore, strong cross-reactions were found to exist between T1 and RII lipopolysaccharides in both hemagglutination inhibition assays and in precipitation tests. It is proposed that T1 lipopolysaccharides represent RII lipopolysaccharides to which polymers consisting of ribose and galactose are attached.


[From GLP1 receptor agonists to triple hormone receptor activation supplemented with glucagon receptor agonism.]
Following the introduction of mono- and then dual hormone (incretin) receptor agonists into therapy, attention was turned to multiple receptor stimulation, with the additional activation of the glucagon receptor, as a new option for the pharmaceutical treatment of type 2 diabetes and obesity. In addition to its role in carbohydrate metabolism, the article reviews the other important physiological tasks of glucagon, especially its participation in intrainsular paracrine regulation, energy expenditure and the shaping of appetite and food consumption. It covers the potential benefits of the triple combination and briefly touches data on the efficacy and safety of the first triple receptor agonist drug, retatrutide, in preclinical human studies. Further confirmation of the promising results may represent progress in the treatment of these forms of disease and their accompanying conditions, such as steatosis hepatis. Orv Hetil. 2023; 164(42): 1656-1664.


Validity of archaeomagnetic field recording: an experimental pottery kiln at Coppengrave, Germany.
Palaeomagnetic data obtained from archaeological materials are used for reconstructions of the Earth's magnetic field of the past millennia. While many studies tested the reliability of this recorder for palaeointensity only a few studies did this for direction. The study presents an archaeomagnetic and rock magnetic investigation applied to an experimental pottery kiln, which was operated in 2003 to produce stone ware. This kind of high-quality pottery needs a temperature of at least 1160 °C. Shortly before heating of the kiln direct absolute measurements of the absolute geomagnetic field vector have been carried out close to it. After cooling of the kiln 24 oriented palaeomagnetic samples have been taken. Although Curie temperatures are about 580 °C, that is the typical temperature for magnetite, thermal as well as alternating field demagnetisations reveal also a considerable amount of hematite as magnetic carrier. This mixture of magnetite and hematite is dominated by pseudo-single domain grains. Demagnetisation removed in some cases weak secondary components, but in most cases the specimens carried a single component thermoremanent magnetisation. The mean characteristic remanent magnetisation direction agrees on 95 per cent confidence level with the directly measured field direction. Archaeointensity was obtained from five specimens with the Thellier-Coe method and with the multiple-specimen palaeointensity domain-state corrected method. Six of these specimens also provided a result of the Dekkers-Böhnel method, which overestimated the archaeointensity by about 9 per cent compared to the direct value, while after correction for fraction the value agrees very well. For the multiple-specimen palaeointensity domain-state corrected method only fractions between 25 and 75 per cent have been used and specimens showing alteration have been excluded. Above 450 °C many specimens showed alteration of the magnetic grains. Because median destructive temperatures were often above this value in most cases the fraction was less than 50 per cent. Nevertheless the obtained intensity (48.48 ± 0.24 μ) is on 95 per cent confidence level in agreement with the direct observation. Behaviour of the specimens during the Thellier-experiments was not ideal because of narrow unblocking temperature spectra and alteration. Nevertheless, the obtained mean archaeointensity is also in agreement with the direct field observation. Here the relative palaeointensity error is about 6 per cent and very high compared the multiple-specimen palaeointensity domain-state corrected method. The investigation demonstrates that a pottery kiln can provide a very precise estimate of the ancient geomagnetic field vector.


Profiling extracellular vesicle surface proteins with 10 µL peripheral plasma within 4 h.
Extracellular vesicle (EV) surface proteins, expressed by primary tumours, are important biomarkers for early cancer diagnosis. However, the detection of these EV proteins is complicated by their low abundance and interference from non-EV components in clinical samples. Herein, we present a MEmbrane-Specific Separation and two-step Cascade AmpLificatioN (MESS2CAN) strategy for direct detection of EV surface proteins within 4 h. MESS2CAN utilises novel lipid probes (long chains linked by PEG2K with biotin at one end, and DSPE at the other end) and streptavidin-coated magnetic beads, permitting a 49.6% EV recovery rate within 1 h. A dual amplification strategy with a primer exchange reaction (PER) cascaded by the Cas12a system then allows sensitive detection of the target protein at 10 EV particles per microliter. Using 4 cell lines and 90 clinical test samples, we demonstrate MESS2CAN for analysing HER2, EpCAM and EGFR expression on EVs derived from cells and patient plasma. MESS2CAN reports the desired specificity and sensitivity of EGFR (AUC = 0.98) and of HER2 (AUC = 1) for discriminating between HER2-positive breast cancer, triple-negative breast cancer and healthy donors. MESS2CAN is a pioneering method for highly sensitive in vitro EV diagnostics, applicable to clinical samples with trace amounts of EVs.


High-throughput cognitive assessment using BrainTest.org: examining cognitive control in a family cohort.
Introduction Understanding the relationship between brain and complex latent behavioral constructs like cognitive control will require an inordinate amount of data. Internet-based methods can rapidly and efficiently refine behavioral measures in very large samples that are needed for genetics and behavioral research. Cognitive control is a multifactorial latent construct that is considered to be an endophenotype in numerous neuropsychiatric disorders, including attention deficit/hyperactivity disorder (ADHD). While previous studies have demonstrated high correlations between Web- and lab-based scores, skepticism remains for its broad implementation. Methods Here, we promote a different approach by characterizing a completely Web-recruited and tested community family sample on measures of cognitive control. We examine the prevalence of attention deficit symptoms in an online community sample of adolescents, demonstrate familial correlations in cognitive control measures, and use construct validation techniques to validate our high-throughput assessment approach. Results A total of 1214 participants performed Web-based tests of cognitive control with over 200 parent-child pairs analyzed as part of the primary study aims. The data show a wide range of "subclinical" symptomatology in a web community sample of adolescents that supports a dimensional view of attention and also provide preliminary narrow-sense heritability estimates for commonly used working memory and response inhibition tests. Conclusions Finally, we show strong face and construct validity for these measures of cognitive control that generally exceeds the evidence required of new lab-based measures. We discuss these results and how broad implementation of this platform may allow us to uncover important brain-behavior relationships quickly and efficiently.


Molecular analysis of noroviruses involved in acute gastroenteritis outbreaks in military units in Israel, 1999-2004.
The study presented here was conducted to determine the genetic properties of noroviruses (NoVs) identified between 1999 and 2004 in army recruits with acute gastroenteritis. Partial sequence analysis of the RNA-dependent RNA polymerase gene revealed the presence of two major sub-genogroups, all of which were related to genogroup II of NoV. Serological analysis using recombinant antigens confirmed this observation. Local strains associated with a 1999 outbreak were closely related to GII-6 strains, while those identified later were very closely related to GII-4 strains. GII-4 strains were also associated with an outbreak in civilian nursing homes in Israel in 2002 and samples from this outbreak were included in this study for comparison. This is the first report describing the molecular properties of NoV strains associated with diarrhea-related morbidity in Israel.


Cardiac arrest due to intracranial hypotension following pseudohypoxic brain swelling induced by negative suction drainage in a cranioplasty patient: a case report.
Pseudohypoxic brain swelling (PHBS) is known to be an uncommon event that may occur during and following an uneventful brain surgery, when negative suction drainage is used. The cerebrospinal fluid loss related to suction drainage can evoke intracranial hypotension that progress to PHBS. The main presentations of PHBS are sudden unexpected circulatory collapses, such as severe bradycardia, hypotension, cardiac arrest, consciousness deterioration and diffuse brain swelling as seen with brain computerized tomography (CT). We present a stuporous 22-year-old patient who underwent cranioplasty under general anesthesia. The entire course of the general anesthesia and operation progressed favorably. However, the time of scalp suture completion, sudden bradycardia and hypotension occurred, followed by cardiac arrest immediately after initiation of subgaleal and epidural suction drainage. After successful resuscitation, the comatose patient was transferred to the neurosurgical intensive care unit and PHBS was confirmed using brain CT.


The Link between Refractoriness and Neuroprogression in Treatment-Resistant Bipolar Disorder.
Treatment refractoriness remains one of the biggest challenges in the field of bipolar disorder (BD) as treatments are often suboptimal or unsatisfactory. Recent evidence points towards a potential link between the progressively evolving nature of BD, increased inflammation, and reduced treatment response. There are several medications and other somatic treatments available, but remission rates are low, and medication compliance is still problematic. Psychotherapeutic techniques appear to be promising in several disease states and in relapse prevention, but additional research is needed to determine who will benefit from what strategy the most. Current knowledge on the link between neuroprogression in BD and poor treatment response promotes the use of anti-inflammatory and neuroprotective strategies in the early phases of BD. In the later stages of BD, mood stabilization and medication adherence would be essential in preventing additional brain changes and loss of cognitive reserve. Additional large-scale, longitudinal, and methodologically robust studies are urgently needed to develop effective therapeutic interventions for treatment-resistant BD.


Receptor glycosylation regulates Ly-49 binding to MHC class I.
Murine NK cells express the Ly-49 family of class I MHC-binding receptors that control their ability to lyse tumor or virally infected host target cells. X-ray crystallography studies have identified two predominant contact sites (sites 1 and 2) that are involved in the binding of the inhibitory receptor, Ly-49A, to H-2D(d). Ly-49G2 (inhibitory) and Ly-49D (activating) are highly homologous to Ly-49A and also recognize H-2D(d). However, the binding of Ly-49D and G(2) to H-2D(d) is of lower affinity than Ly-49A. All Ly-49s contain N-glycosylation motifs; however, the importance of receptor glycosylation in Ly-49-class I interactions has not been determined. Ly-49D and G(2) contain a glycosylation motif (NTT (221-223)), absent in Ly-49A, adjacent to one of the proposed binding sites for H-2D(d) (site 2). The presence of a complex carbohydrate group at this critical site could interfere with class I binding. In this study, we are able to demonstrate for the first time that Ly-49D binds H-2D(d) in the presence of mouse beta(2)-microglobulin. We also demonstrate that glycosylation of the NTT (221-23) motif of Ly-49D inteferes with recognition of H-2D(d). Alteration of the Ly-49D-NTT (221-23) motif to abolish glycosylation at this site resulted in enhanced H-2D(d) binding and receptor activation. Furthermore, glycosylation of Ly-49G2 at NTT (221-23) also reduces receptor binding to H-2D(d) tetramers. Therefore, the addition of complex carbohydrates to the Ly-49 family of receptors may represent a mechanism by which NK cells regulate affinity for host class I ligands.


Calorie intake during mammary development influences cancer risk: lasting inhibition of C3H/HeOu mammary tumorigenesis by peripubertal calorie restriction.
To test for a relationship between peripubertal calorie intake, mammary development, and tumorigenesis, weanling C3H/HeOu mice were separated into 3 groups: fed diet either ad libitum (AL) and designated group AL (n = 60); fed a similar, calorie-restricted (CR) diet only during mammary development when 4-12 weeks old and then subsequently fed ad libitum when > or = 13 weeks old (group CR4-12, n = 24); or continuously calorie restricted (group CR, n = 60). Eight weeks of peripubertal calorie restriction provided CR4-12 mice with lasting protection from mammary tumorigenesis (P = 0.004) and lowered cumulative tumor incidence by 33% compared to AL mice. Sustained calorie restriction of group CR mice further reduced mammary tumor incidence compared to both AL (P = 0.000001) and CR4-12 mice (P = 0.009). Calorie intake significantly influenced mammary development and cellular proliferation. Compared to the mammary development of AL mice, calorie restriction reduced the diameter of ductal end buds (189 microns compared to 146 microns; P < 0.01), lowered the end bud [3H]thymidine labeling index from > or = 20 to < or = 13% (P < 0.001), delayed end bud migration and mammary glandular growth (P < 0.01), reduced alveolar budding (P < 0.001), reduced the proportion of alveoli containing at least one [3H]thymidine labeled cell from > or = 50 to < or = 22% (P < 0.001), and lowered the alveolar [3H]thymidine labeling index of labeled alveoli from > or = 14 to < or = 7% (P < 0.001). These findings link peripubertal calorie intake, mammary development, and carcinogenic risk, and show that the abrogation of mammary tumorigenesis by calorie restriction is partially attributable to influences on mammary development.


Investigation of the axonal transport of three acidic, soluble proteins (14-3-2, 14-3-3, and S-100) in the rabbit visual system.
The question of whether three acidic, water-soluble proteins (14-3-2, 14-3-3, and S-100, the first and last known to be brain-specific) are axonally transported was investigated in the rabbit visual system. The water-soluble proteins were obtained from individual optic nerves, combined optic tracts and lateral geniculate bodies, superior colliculi, and, in some instances, retinas at various times (1--56 days) after monocular injections of [3H]leucine. These proteins were separated by a two-step polyacrylamide gel electrophoresis procedure that isolated 14-3-2, 14-3-3, and S-100 almost uncontaminated by other radioactivity. The isolated 14-3-2 and S-100 were demonstrated to be approx. 90% pure by a new method based on retarding the migration of these proteins by immunoadsorption during the first step of electrophoresis. An analysis of the radioactive labeling of the total soluble proteins (TSP) and the isolated acidic proteins revealed that: (1) S-100 was not axonally transported; (2) both 14-3-2 and 14-3-3 were part of one of the slow components of axonal transport (2--4 mm/day); (3) the radioactivity of 14-3-2 and 14-3-3 represented about 2.7% and 3.2%, respectively, of the radioactivity incorporated into the axonally transported TSP; (4) the ultimate distributions of the radioactively labeled 14-3-2 and 14-3-3 were the same (about 70% of each destined for the superior colliculus) and differed from that of the TSP; and (5) the rates of catabolism of the axonally transported 14-3-2 and 14-3-3 were slightly greater than that of the TSP, with half-lives for 14-3-2 and 14-3-3 estimated to be 11 and 10 days, respectively.


POPULATION STRUCTURE, LOCAL MATE COMPETITION, AND SEX-ALLOCATION PATTERN IN THE ANT MESSOR ACICULATUS.
Population-genetic structure and sex-allocation ratios were investigated for the ant Messor aciculatus, a species that conducts mass nuptial flights. An electrophoretic survey on two polymorphic loci revealed excessive homozygosities in two populations. Because inbreeding inside nests does not occur, the heterozygote deficiency may result from population subdivision rather than assortative inbreeding during nuptial flights. Assuming no inbreeding, a simulation based on the observed genotype distribution in the study site suggested that, on average, a breeding swarm consists of alates from only 1.7 colonies. This population genetic structure seems to cause local mate competition (LMC), a factor that can shift population sex ratio toward females. The sex-allocation ratio to males in the population (0.166 ± 0.030; mean ± SE) was significantly female biased and lower than the expected optima for queens (0.5) and for workers (0.25) without LMC. Sex-ratio variability among colonies was explained by a pattern of constant male investment, which is predictable assuming LMC. Thus, the study provides the first evidence of LMC in ants with mass nuptial flights and contradicts previous assumptions about breeding structure in swarming ants. The results suggest that LMC can affect sex-allocation patterns for ant colonies and populations.


Analysis of the epidemiological burden of acne vulgaris in China based on the data of global burden of disease 2019.
Acne vulgaris is a chronic, inflammatory skin disease, which has brought an increasing disease burden to patients and society. But there is no systematic study on the disease burden and social development of acne vulgaris in China. This study aimed to analyze the epidemiological burden and trend of acne vulgaris in China from 1990 to 2019 based on the data in the global burden of disease 2019 (GBD 2019). The number of incidences/illnesses, age-standardized incidence/prevalence rates, disability-adjusted life years (DALYs), and DALY rate of acne vulgaris in China from 1990 to 2019 were obtained from the GBD 2019 to evaluate the epidemiological trends and age-period-cohort trends. The associations between disease burden and social development degrees were analyzed using a sociodemographic index. In 2019, the age-standardized prevalence and incidence of acne vulgaris in China were both at low levels in the world. From 1990 to 2019, the prevalent cases and incident cases of acne vulgaris in China rose firstly and then fell (peaked in 2005 and 2003, respectively), and the age-standardized prevalence/incidence/DALY rates showed growth trends continuously. The prevalence of acne vulgaris peaked in the 15-19 age group while the incidence peak age was 10-14 years old and there was an obvious gender difference, females were higher than males. With the increase of sociodemographic index (SDI) value, the morbidity of acne vulgaris showed a linear growth trend (P < 0.05). From 1990 to 2019, the disease burden of acne vulgaris is increasing in China, which is correlated with social and medical development. Active research on the epidemiological data of acne vulgaris and its relationship with the level of social development is important for both the diagnosis and treatment of acne vulgaris and for the development of health policies.


[Research on liposoluble ingredients of Quchiling].
To study the liposoluble ingredients of Quchiling (LQ), which enter the blood and the brain,and to confirm the active ingredients of LQ in vivo. Serum pharmacochemistry and gas chromatography mass spectroscopy were used to analyze ingredients of LQ entering the blood and the brain. There were eleven ingredients of LQ to enter the blood and six ingredients of LQ to enter the brain. It is confirmed that eleven ingredients of LQ entered the blood, which are beta-asarone, schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B, schisantherrin A, schisantherrin B, schisantherrin C, delta-cadinene, delta-cadinol and calamendiol in the blood, and that six ingredients are beta-asarone, schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B and calamendiol in the brain.


Repellent effect of microencapsulated essential oil in lotion formulation against mosquito bites.
Many essential oils have been reported as natural sources of insect repellents; however, due to high volatility, they present low repellent effect. Formulation technique by using microencapsulation enables to control the volatility of essential oil and thereby extends the duration of repellency. In this study, the effectiveness of microencapsulated essential oils of Alpinia galanga, Citrus grandis and C. aurantifolia in the lotion formulations were evaluated against mosquito bites. Essential oils and N,N-Diethyl-3-methylbenzamide (DEET) were encapsulated by using interfacial pre- cipitation techniques before incorporation into lotion base to form microencapsulated (ME) formulation. The pure essential oil and DEET were also prepared into lotion base to produce non-encapsulated (NE) formulation. All the prepared formulations were assessed for their repellent activity against Culex quinquefasciatus under laboratory condition. Field evaluations also were conducted in three different study sites in Peninsular Malaysia. In addi- tion, Citriodiol® (Mosiquard®) and citronella-based repellents (KAPS®, MozAway® and BioZ Natural®) were also included for comparison. In laboratory conditions, the ME formulations of the essential oils showed no significant difference with regard to the duration of repellent effect compared to the microencapsulated DEET used at the highest con- centration (20%). It exhibited >98% repellent effect for duration of 4 h (p = 0.06). In the field conditions, these formulations demonstrated comparable repellent effect (100% for a duration of 3 h) to Citriodiol® based repellent (Mosiguard®) (p = 0.07). In both test conditions, the ME formulations of the essential oils presented longer duration of 100% repellent effect (between 1 and 2 h) compared to NE formulations. The findings of the study demonstrate that the application of the microencapsulation technique during the preparation of the formulations significantly increases the duration of the repellent effect of the essential oils, suggesting that the ME formulation of essential oils have potential to be commercialized as an alternative plant-based repellent in the market against the mosquitoes.


Effect of knowledge of informal poultry drug prescribers on their attitude and practice toward antimicrobial use, residues, and resistance in Bangladesh.
Informal prescribers (IPs) significantly contribute to the development of antimicrobial resistance and in disseminating pathogens from poultry to humans and other animals through the food chain, posing a serious global health threat. Therefore, this study aimed to assess whether the knowledge of IPs has an impact on their attitude and practice toward antimicrobial use, antibiotic residues, and antimicrobial resistance. In this cross-sectional study, we conducted a pre-tested and questionnaire-based survey to investigate the knowledge, attitude, and practice of IPs in selected parts of the Mymensingh division, Bangladesh. Then, we used the linear regression model test with R-squared (R2) to measure the association between the study variables. Our investigation revealed that 70% of the IPs knew about antibiotics and 75% had good knowledge about antibiotic resistance, whereas only 50% were aware of withdrawal periods. Informal prescribers also displayed good attitudes toward the use and sale of antibiotics with withdrawal periods and completion of medication (50%). Analysis of their practice on the sale and prescription of antibiotics showed that 70% and 30% of IPs use antibiotics against bacterial infections and other conditions, respectively. Most of them do not consult a veterinarian before selling or prescribing antibiotics, although 80% claim to do so. This is because 75% of IPs gave other options regarding their consultations. However, 95% of IPs uses antibiotics only for therapeutic purposes. Furthermore, only 10% sell antibiotics based on a veterinarian's recommendation. Approximately 45% of IPs use single antibiotics at a time, while the rest use multiple antibiotics, individually or combined. Approximately 15% use antibiotics monthly, while 85% use them whenever the need arises. The knowledge and attitude of IPs are significantly affected by their age (p ≤ 0.025). The district of domicile also impacted their knowledge. Surprisingly, IPs from Jamalpur had significantly better knowledge compared to those from Mymensingh and Sherpur (p ≤ 0.01). The attitude of IPs from Jamalpur and Netrokona also differed significantly (p ≤ 0.001) from that of Mymensingh and Sherpur. The knowledge of IPs influenced their attitude up to 80.5% (r2 = 0.628) and their practice up to 75.4% (r2 = 0.545). The knowledge of IPs greatly influenced their attitude and practice, while sociodemographics also influenced their knowledge and attitude toward antimicrobial use, antibiotic residues, and antimicrobial resistance.


Molecular characterization and spatial expression of the sunflower ABP1 gene.
We have used RT-PCR and low-stringency cDNA library screening to isolate the coding sequence of the sunflower auxin-binding protein (ABP1). All the clones analysed contained the same nucleotide sequence, suggesting that ABP1 is encoded by a single-copy gene in sunflower. The deduced amino acid sequence shows a high degree of similarity with ABP1 proteins from other plant species. Most remarkably, the sunflower protein lacks two cysteine residues present in all other plant ABPs known to date and shown to be involved in a disulfide bridge in the maize protein. Genomic Southern hybridization data support the existence of a single copy of the ABP1 gene in the sunflower genome. Northern hybridization corroborated earlier observations indicating that the steady-state level of ABP1 transcript is higher in actively dividing and growing organs than in the rest of the plant: it is more abundant in the shoot apex, floral buds and immature embryos than in mature leaves, stem, roots and ray flowers. To characterize the tissular ABP1 transcript distribution in sunflower, various organ sections were analysed upon in situ hybridization. Localized accumulation of the ABP1 transcript suggests that its spatial expression is highly regulated at the tissue level. In addition, the transcript preferentially accumulates in tissues having a high rate of cellular division, such as shoot and root apical meristems, leaf primordia and pro-vascular tissues. The ABP1 expression pattern was also studied at a temporal scale during lateral root formation. Real time PCR showed an elevation of the steady state level of the ABP1 transcript in root axes after 36 h of seed germination. In situ hybridization revealed that this global increase is the result of local accumulation of the ABP1 transcript in lateral root primordia, which are known to develop under auxin action. The possibility that a high ABP1 expression level correlates with a high cellular sensitivity to auxin is discussed.


Disentangling the effects of modality, interval length and task difficulty on the accuracy and precision of older adults in a rhythmic reproduction task.
Studies on the functional quality of the internal clock that governs the temporal processing of older adults have demonstrated mixed results as to whether they perceive and produce time slower, faster, or equally well as younger adults. These mixed results are due to a multitude of methodologies applied to study temporal processing: many tasks demand different levels of cognitive ability. To investigate the temporal accuracy and precision of older adults, in Experiment 1, we explored the age-related differences in rhythmic continuation task taking into consideration the effects of attentional resources required by the stimulus (auditory vs. visual; length of intervals). In Experiment 2, we added a dual task to explore the effect of attentional resources required by the task. Our findings indicate that (1) even in an inherently automatic rhythmic task, where older and younger adult's general accuracy is comparable, accuracy but not precision is altered by the stimulus properties and (2) an increase in task load can magnify age-related differences in both accuracy and precision.


For Those Who Fight, Fall and Raise Again - Impact of COVID-19 Pandemic on Mental Health of Health Care Providers.
During the COVID-19 pandemic health care providers found themselves under increased demands in the work environment and in their professional and personal lives which created both physical and mental health challenges. Thus, we aim to provide an integrative review that identifies and summarizes the research published regarding mental health functioning in health care providers, in Serbia, since the beginning of the pandemic. A search of the published literature was conducted using Medline and SCIndex databases, applying key words "COVID-19" and "Serbia". The search was limited to papers published since the beginning of the COVID-19 pandemic until January 2022. Two reviewers independently screened the retrieved papers. The study used pre-defined inclusion and exclusion criteria. We identified eight papers on the subject of mental health functioning in health care providers. The studies were all original research papers with predominantly cross-sectional study design, using online assessments. Sample size varied in number of participants and profile of medical providers (physicians, nurses and medical technicians, community pharmacists). Dominantly, focus of interests of researchers were exploration of levels of anxiety, depression, sleep disturbances, burnout, as well as behavioural changes and environmental influences. The studies related to mental health of medical professionals show the importance of recognizing the psychological challenges posed by health crises caused by COVID-19. They raise awareness of recognizing differences and difficulties between wide range of medical sectors, and appeal for necessity for accessible and professional psychological support. Further studies should address the detailed exploration of the mental health of this specific population, as well as propose strategies needed to balance the challenges posed by the pandemic.


The persistence of humoral and cellular immunities more than three decades after smallpox vaccination.
This study assessed the persistence of humoral (neutralising antibody titre to vaccinia virus) and cellular (immediate vaccinia-specific interferon (IFN)-gamma-producing T-cell) immunities to smallpox in a Korean population. Individuals who were vaccinated 25-60 years previously had higher neutralising antibody titres (geometric mean titre (GMT) 13.7; 95% CI 11.0-17.2) than vaccinia-naive individuals (GMT 6.7; 95% CI 5.5-8.0; p <0.001). However, there was no significant difference in cellular immunity between individuals vaccinated previously and vaccinia-naive individuals, and only 15% of the individuals vaccinated previously displayed an immediate IFN-gamma-producing effector-memory response in ELISPOT assays.


Childbirth: management of labour through the ages.
This paper examines the management of labour through the ages, and looks particularly at the emergence of invasive techniques in childbirth and the development of pain management. Obstetric practices throughout the 17th and 18th centuries are explored.


Influence of Concurrent and Adjuvant Temozolomide on Health-Related Quality of Life of Patients with Grade III Gliomas: A Secondary Analysis of a Randomized Clinical Trial (KNOG-1101 Study).
The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL). In this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B). Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33). The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.


Methods of rapid diagnosis for the etiology of meningitis in adults.
Infectious meningitis may be due to bacterial, mycobacterial, fungal or viral agents. Diagnosis of meningitis must take into account numerous items of patient history and symptomatology along with regional epidemiology and basic cerebrospinal fluid testing (protein, etc.) to allow the clinician to stratify the likelihood of etiology possibilities and rationally select additional diagnostic tests. Culture is the mainstay for diagnosis in many cases, but technology is evolving to provide more rapid, reliable diagnosis. The cryptococcal antigen lateral flow assay (Immuno-Mycologics) has revolutionized diagnosis of cryptococcosis and automated nucleic acid amplification assays hold promise for improving diagnosis of bacterial and mycobacterial meningitis. This review will focus on a holistic approach to diagnosis of meningitis as well as recent technological advances.


[Styrylquinolines-type synthetic compounds with leishmanicidal and cytotoxic activities].
Leishmaniasis is a major public health problem faced by many countries, including Colombia. Its treatment has limitations such as the toxicity of the drugs used, the emergence of resistant strains, and prolonged and expensive treatments. Thus, there is an urgent need to find alternative solutions. To evaluate the leishmanicidal and cytotoxic activities of three 2-styrylquinolines type compounds: 2-[(E)-2-(2,3-diacetyloxyphenyl)ethenyl]quinolin-8-yl-acetate, E1; 2-[(E)-2-(4-acetyloxy-3-methoxyphenyl)ethenyl] quinoline, E2, and 2-[(E)-2-(2,3-diacetyloxyphenyl)ethenyl] quinoline, E3. The 2-styrylquinolines were obtained by organic synthesis using Perkin-type condensation reaction from 8-hydroxy quinaldine or quinaldine and aromatic aldehydes. The leishmanicidal activity was evaluated on intracellular amastigotes of Leishmania (Viannia) panamensis by flow cytometry. The results were expressed as lethal concentration 50 (LC 50 ) for cytotoxicity and effective concentration 50 (EC 50 ) for leishmanicidal activity, calculated by the Probit method. E3 showed high activity against L. (V) panamensis with a calculated EC 50 value of 1.4 µg/ml, and a selectivity index of 3.9; E1 and E2 showed higher EC 50 values of 5.6 and 68.1 µg/ml, respectively. For cytotoxicity, LC 50 values ranging from 5.4 to 68.1 µg/ml were calculated. E2 was moderately toxic, showing an LC 50 very similar to that of amphotericin B, a substance used as cytotoxic control. The styrylquinoline E3 is a promising compound against L. (V) panamensis , as it was able to significantly inhibit amastigotes inside the cell, reducing infection despite its toxicity.


Complement activation requirements for histamine release from human leukocytes: influence of purified C3ahu and C5ahu on histamine release.
The activation of human sera for histamine release by zymosan and anti-BSA-BSA complexes at equivalence was dose dependent and associated with a marked fall in CH50, C3 and C5 hemolytic activities. Heat-aggregated IgG, though able to fix greater than 90% of human CH50 activity and produce a lesser fall in C3 and C5 activities than zymosan and BSA-anti-BSA complexes, was unable to induce basophil histamine release. Chemically purified human C3a and C5a each caused histamine release from human basophils; C5a was more potent than C3a. In addition, neither zymosan nor BSA-anti-BSA complexes released histamine when incubated with homozygous C3-deficient serum. The addition of C3a and C5a at suboptimal concentrations produced an additive effect of histamine release.


Wavy membranes and the growth rate of a planar chemical garden: Enhanced diffusion and bioenergetics.
To model ion transport across protocell membranes in Hadean hydrothermal vents, we consider both theoretically and experimentally the planar growth of a precipitate membrane formed at the interface between two parallel fluid streams in a 2D microfluidic reactor. The growth rate of the precipitate is found to be proportional to the square root of time, which is characteristic of diffusive transport. However, the dependence of the growth rate on the concentrations of hydroxide and metal ions is approximately linear and quadratic, respectively. We show that such a difference in ionic transport dynamics arises from the enhanced transport of metal ions across a thin gel layer present at the surface of the precipitate. The fluctuations in transverse velocity in this wavy porous gel layer allow an enhanced transport of the cation, so that the effective diffusivity is about one order of magnitude higher than that expected from molecular diffusion alone. Our theoretical predictions are in excellent agreement with our laboratory measurements of the growth of a manganese hydroxide membrane in a microfluidic channel, and this enhanced transport is thought to have been needed to account for the bioenergetics of the first single-celled organisms.


Assessing the impact of innovative training of family physicians for the patient-centered medical home.
New approaches to enhance access in primary care necessitate change in the model for residency education. To describe instrument design, development and testing, and data collection strategies for residency programs, continuity clinics, residents, and program graduates participating in the Preparing the Personal Physician for Practice (P(4)) project. We developed and pilot-tested surveys to assess demographic characteristics of residents, clinical and operational features of the continuity clinics and educational programs, and attitudes about and implementation status of Patient Centered Medical Home (PCMH) characteristics. Surveys were administered annually to P(4) residency programs since the project started in 2007. Descriptive statistics were used to profile data from the P(4) baseline year. Most P(4) residents were non-Hispanic white women (60.7%), married or partnered, attended medical school in the United States and were the first physicians in their families to attend medical school. Nearly 85% of residency continuity clinics were family health centers, and about 8% were federally qualified health centers. The most likely PCMH features in continuity clinics were having an electronic health record and having fully secure remote access available; both of which were found in more than 50% of continuity clinics. Approximately one-half of continuity clinics used the electronic health record for safety projects, and nearly 60% used it for quality-improvement projects. We created a collaborative evaluation model in all 14 P(4) residencies. Successful implementation of new surveys revealed important baseline features of residencies and residents that are pertinent to studying the effects of new training models for the PCMH.


Diffusion ability of endotoxin through dentinal tubules.
The aim of this study was to evaluate the ability of endotoxin to diffuse through dentinal tubules towards the cement and to observe the period of time needed for it to reach the external root surface. Thirty single-rooted human teeth had their crowns and apices removed in order to standardize the root length to 15 mm. Teeth were instrumented until #30 K-file and made externally impermeable with epoxy adhesive, leaving 10 mm of the exposed root (middle third). The specimens were placed in plastic vials and irradiated (60Co gamma-rays). Then, they were divided into 2 groups (n = 15): G1) Escherichia coli endotoxin was inoculated into the root canal of the specimens and 1 ml of pyrogen-free water was put in the tubes; G2) (control): pyrogen-free water was inoculated into the root canals and 1 ml of pyrogen-free water was put in each tube. After 30 min, 2 h, 6 h, 12 h, 24 h, 48 h, 72 h and 7 days, the water of the tubes was removed and replaced. The removed aliquot was tested for the presence of endotoxin. Considering that the endotoxin is a B-lymphocyte polyclonal activator, at each experimental period, B-lymphocyte culture was stimulated with a sample of water removed from each tube and antibody (IgM) production was detected by ELISA technique. The results of IgM production were higher in groups of 24 h, 48 h, 72 h and 7 days in relation to the other studied groups, with statistically significant differences (ANOVA and Tukey's test p < 0.05). Endotoxin was able to diffuse through the dentinal tubules towards the cement, reaching the external root surface after the period of 24 h.


Restoration of deoxycholate-disrupted membrane oxidases of Micrococcus lysodeikticus.
Membrane-associated l-malate and reduced nicotinamide adenine dinucleotide (NADH) oxidase complexes of Micrococcus lysodeikticus were inactivated with deoxycholate. Reactivation of NADH oxidase by addition of Mg(2+) occurred in these detergent-membrane mixtures, but reactivation of l-malate oxidase did not occur in the presence of deoxycholate. Removal of detergent by gel filtration allowed Mg(2+)-dependent restoration of both l-malate and NADH oxidases. Maximal NADH and l-malate oxidase restoration required 10 min and 40 min, respectively, at 30 mm MgSO(4). Maximal restoration of both oxidases required at least 12 mm MgSO(4) in an incubation period of 1 hr. Reduced-minus-oxidized difference spectra of Mg(2+)-restored membrane oxidases showed participation of cytochromes b, c, and a when either l-malate or NADH served as reductant; addition of dithionite did not increase the alpha- and beta-region absorbancy maxima of these hemoproteins when restored membranes were first reduced with the physiological substrates l-malate or NADH. Not all divalent cations tested were equally effective for reactivation of both oxidases. l-Malate oxidase was restored by both Mn(2+) and Ca(2+). NADH oxidase was not activated by Mn(2+) and only slightly stimulated by Ca(2+). Separation of deoxycholate-disrupted membranes (detergent removed) into soluble and particulate fractions showed that both fractions were required for Mg(2+)-dependent oxidase activities. Electron micrographs indicated conditions of detergent treatment did not destroy the vesicular nature of protoplast ghost membranes.


Mortality differences in pulmonary fibrosis among the most populated states in the United States.
Recent studies suggest that the mortality rate of pulmonary fibrosis (PF) in the U.S. is decreasing. However, the mortality trends and demographic differences of PF among the states have not been evaluated. To evaluate PF-related mortality rates and trends in the nine most populated states in the U.S. Population-based study using the Multiple Cause of Death Database available through the Centers for Disease Control and Prevention website. PF-related deaths were identified using ICD codes. From 2004 to 2018, average annual mortality rates ranged from being the lowest in New York (110.8 per 1,000,000) to the highest in North Carolina (195.3 per 1,000,000). The mortality rates showed a decline in the majority of the states and were stable in the other states. The most significant declines were in California and Michigan. The average mortality rates in males were higher than females in all the states (rate ratio ranged from 1.56 in Texas to 1.81 in New York) and the decline in the mortality rates was more pronounced compared to males in most states. The mortality rates in Blacks were lower compared to Whites in all the states (rate ratio ranged from 0.47 in New York to 0.69 in Ohio) and the decline in the mortality rates over the period was more significant than in Whites. There is substantial variation in mortality rates and mortality trends between states and different demographics. Further studies are needed to evaluate the environmental factors, diagnostic accuracy, and coding practices contributing to these differences.


Antidepressant-Like Effect of 1α-Hydroxyvitamin D3 on Mice in the Forced Swimming Test.
We examined the effect of 1α-hydroxyvitamin D3 [1α(OH)D3] on mice in the forced swimming test. Intragastric administration of 1.0 μg/kg of 1α(OH)D3 reduced immobility time in the forced swimming test. At all concentrations tested (0.5, 1.0, 2.0 μg/kg), 1α(OH)D3 had no effect on locomotor activity, compared with controls. These results suggest that 1α(OH)D3 may have antidepressant-like activity.


Interconnection: A qualitative analysis of adjusting to living with renal cell carcinoma.
ABSTRACTObjective:Adjusting to cancer is an ongoing process, yet few studies explore this adjustment from a qualitative perspective. The aim of our qualitative study was to understand how patients construct their experience of adjusting to living with cancer. Qualitative analysis was conducted of written narratives collected from four separate writing sessions as part of a larger expressive writing clinical trial with renal cell carcinoma patients. Thematic analysis and constant comparison were employed to code the primary patterns in the data into themes until thematic saturation was reached at 37 participants. A social constructivist perspective informed data interpretation. Interconnection described the overarching theme underlying the process of adjusting to cancer and involved four interrelated themes: (1) discontinuity-feelings of disconnection and loss following diagnosis; (2) reorientation-to the reality of cancer psychologically and physically; (3) rebuilding-struggling through existential distress to reconnect; and (4) expansion-finding meaning in interconnections with others. Participants related a dialectical movement in which disruption and loss catalyzed an ongoing process of finding meaning. Our findings suggest that adjusting to living with cancer is an ongoing, iterative, nonlinear process. The dynamic interactions between the different themes in this process describe the transformation of meaning as participants move through and revisit prior themes in response to fluctuating symptoms and medical news. It is important that clinicians recognize the dynamic and ongoing process of adjusting to cancer to support patients in addressing their unmet psychosocial needs throughout the changing illness trajectory.


Multicenter study of brucellosis in Egypt.
Brucellosis causes appreciable economic losses in livestock. Examination of milk and tissues from animals in Egypt for Brucella spp. showed increased prevalence rates of serologically reactive animals. All isolates were B. melitensis biovar 3. One Brucella sp. was isolated from milk of serologically nonreactive buffaloes.


Encoding details: positive emotion leads to memory broadening.
In the current experiment we tested the hypothesis that unlike negative arousal, which leads to memory narrowing effects whereby an increase in memory for the central details is accompanied by a decrease in memory for the peripheral details, positive arousing events might lead to a memory broadening effect such that positive arousal would increase memory for both central and peripheral details. This was assessed by testing recognition for central and peripheral details of pictures that were selected to vary in a continuous manner across a wide range of arousal for both positive and negative items. The results indicated that increases in both positive and negative stimulus arousal levels led to gradual increases in memory for the central aspects of the photos. In contrast, negative arousal first increased then decreased memory for peripheral detail as arousal levels increased, whereas positive arousal led to a continuous increase in memory for peripheral details. Thus, arousing negative materials lead to memory narrowing, whereas arousing positive materials can lead to memory broadening.


Coronavirus disease-2019: A review on the disease exacerbation via cytokine storm and concurrent management.
Setting up treatment strategies is the highest concern today to reduce the fatality of COVID-19. Due to a very new kind of virus attack, no specific treatment has been discovered to date. The most crucial way to dominate the disease severity is now the repurposing of drugs. In this review, we focused on the current treatment approaches targeting the crucial causative factors for the disease burden through cytokine storm or cytokine release syndrome. Several vaccines have been developed and have been applied already for prevention purposes, and several are on the way to be developed, although the effects and side effects are under observation. Presently, regulation of the immune response through intervention treatment methods has been adjusted on the basis of the COVID-19 severity stage and generally includes vaccines, immunotherapies including convalescent plasma and immunoglobulin treatment, monoclonal antibodies, cytokine therapy, complement inhibition, regenerative medicine, and repurposed anti-inflammatory and immune-regulatory drugs. Combination therapy is not acceptable in all respects because there is no concrete evidence in clinical trials or in vivo data. Target-specific drug therapies, such as inhibition of cytokine-producing signaling pathways, could be an excellent solution and thus reduce the severity of inflammation and disease severity. Therefore, gathering information about the mechanism of disease progression, possible goals, and drug efficacy of immune-based approaches to combat COVID-19 in the context of orderly review analysis is consequential.


Antimicrobial and Antibiofilm Activity of Chitosan on the Oral Pathogen Candida albicans.
Oral candidiasis is particularly evident, not only in cancer patients receiving chemotherapy, but also in elderly people with xerostomy. In general, Candida is an opportunistic pathogen, causing infections in immunocompromised people and, in some cases, when the natural microbiota is altered. Chitosan, a natural derivative of chitin, is a polysaccharide that has been proven to possess a broad spectrum of antimicrobial activity that encompasses action against fungi, yeast and bacteria. While recent studies have revealed a significant antibiofilm activity upon several microorganisms, including C. albicans, little is known regarding the impact of chitosan upon the adhesive process or mature biofilms. With that in mind, the purpose of this work was to evaluate, in vitro, the capability of chitosan to inhibit C. albicans growth and biofilm formation. The results obtained showed that chitosan is capable of inhibiting C. albicans planktonic growth (HMW, 1 mg/mL; LMW, 3 mg/mL). Regarding biofilm growth, chitosan inhibited C. albicans adhesion (ca. 95%), biofilm formation (percentages above 90%) and reduced mature biofilms by ca. 65% and dual species biofilms (C. albicans and S. mutans) by ca. 70%. These results display the potential of this molecule to be used as an effective anti-Candida agent capable of acting upon C. albicans infections.


Resistance to flow of arterial Y-grafts 6 months after coronary artery bypass surgery.
The use of both internal thoracic arteries (ITAs) as a Y-graft configuration has been proposed as a technique allowing complete arterial revascularization. Controversy remains, however, about the capacity of this Y-graft configuration to provide sufficient blood flow to the whole left coronary system and about possible steal phenomenon occurring during periods of maximal myocardial blood flow demand. To evaluate graft conductance 6 months after Y-graft revascularization of the left coronary system with both ITAs, 11 consecutive patients were studied during cardiac catheterization. In all of the cases, the left ITA had been connected to the left anterior descending coronary artery (LAD) territory (mean, 1.3 anastomoses), and the free right ITA was anastomosed proximally to the left ITA and distally to the left circumflex (LCX) territory (mean, 1.9 anastomoses). Pressure and fractional flow reserve (FFR) were recorded using a 0.014-inch pressure wire advanced distally in the left ITA main stem close to the proximal anastomosis of the free right ITA (ITA-stem) and in the distal part of each ITA branch at the site of their implantation to the LAD (ITA-LAD) or LCX (ITA-LCX) system. At each of these sites, the pressure gradient between aorta and the graft was measured in basal condition and during maximal hyperemia induced by intragraft bolus injection of 40 microg of adenosine. In basal conditions, the pressure gradient was minimal between the aorta and the ITA-stem (2+/-2 mm Hg), the ITA-LAD (3+/-3 mm Hg), and the ITA-LCX (3+/-2 mm Hg; P value was not significant versus ITA-LAD). During maximal hyperemia, the pressure gradient increased to 7+/-2 mm Hg in the ITA-stem, to 9+/-5 mm Hg in the ITA-LAD, and to 9+/-3 in the ITA-LCX (P value not significant versus ITA-LAD). The fractional flow reserve was 0.93+/-0.03 in the ITA-stem, 0.91+/-0.04 in the ITA-LAD, and 0.91+/-0.03 in the ITA-LCX. A Y-graft configuration with a free right ITA attached to a pedicled left ITA allows an adequate revascularization of the whole left coronary system with an even distribution of perfusion pressure in both distal branches and minimal resistance to maximal blood flow.


A Survey on the Journal of the Korean Academy of Child and Adolescent Psychiatry: Implications for Growth and Development.
This study aimed to assess the status of the Journal of the Korean Academy of Child and Adolescent Psychiatry (JKACAP) and propose measures for its growth and development. The study was conducted using a questionnaire survey targeting members of the Korean Academy of Child and Adolescent Psychiatry. The six key elements analyzed were Access to the journal, Convenience following conversion to English, Recognition as an international journal and institutional achievements, Author perspectives on manuscript submission,Transition to an online-only journal, and Content and identity of the journal. The survey revealed that email notification was highly effective for Journal Accessibility, with the website and search engines also frequently being used by members. Conversion to English in 2018 initially impacted readability and submission rates, but these concerns have decreased over time. However, the Recognition of JKACAP as an international academic journal was still not on par with SCIE journals, highlighting the need for further efforts towards SCIE inclusion. Despite these challenges and limited research opportunities, there was an active intention among members to submit manuscripts. Respondents showed a notable preference for the Transition to an online-only journal. Regarding content and identity of the JKACAP, members predominantly favored review articles and perceived the journal as a research and communication platform for Korean child and adolescent psychiatrists. The results indicate the need for JKACAP to enhance its digital accessibility, provide more support for domestic and international authors, and actively seek SCIE indexing. Addressing the varied content preferences of its members, improving the submission process, and transitioning to an online-only format could further its growth and solidify its position as an internationally recognized academic journal in the field of child and adolescent psychiatry.


Penile syringoma: reports and review of patients with syringoma located on the penis.
Syringoma of the penis is rare. This paper describes two men with syringoma of the penis and summarizes the clinical features of previously reported men with this condition. A 25-year-old African man presented with a nonpruritic flesh-colored papule on the right side of his proximal dorsal penile shaft and a 22-year-old Caucasian man presented with multiple asymptomatic flesh-colored papules on his ventral and lateral penis. Neither man had similar lesions elsewhere or a family member with this condition. Reports of patients with penile syringoma were identified using a medical search engine (PubMed Central) and references included in the published papers on this subject. Microscopic examination of both men's papules showed syringoma. Including these individuals, syringoma exclusively localized to the penis has only been reported in 11 men. It usually presents as multiple asymptomatic flesh-colored papules on the dorsal penile shaft of men less than 30 years of age. Epithelial-lined cystic spaces containing homogenous eosinophilic material are noted in the fibrotic upper dermis. The papules do not recur following excisional biopsy. Syringoma exclusively located on the penis is extraordinary and has only been reported in 11 men. It presents as a solitary papule or multiple asymptomatic papules on the penile shaft. Microscopic examination shows epithelial structures and eccrine ducts with comma-like tails resembling tadpoles in the fibrotic upper dermis; amorphous pink secretion is often present in the epithelial-lined spaces. Excision of the penile papules not only provides the diagnosis, but also successfully removes the individual lesion without recurrence.


Cell-free Biosynthesis of Chlorogenic Acid Using a Mixture of Chassis Cell Extracts and Purified Spy-Cyclized Enzymes.
A novel cell-free biosynthesis system based on a mixture of chassis cell extracts and purified Spy-cyclized enzymes (CFBS-mixture) was developed. As a demonstration, the CFBS-mixture was applied to chlorogenic acid (CGA) biosynthesis. The mix-and-match and Plackett-Burman experiments demonstrated that Lonicera japonica hydroxycinnamate-CoA quinate transferase and p-hydroxyphenylacetate 3-hydroxylase were the key enzymes for the production of CGA. After optimization of the concentrations of the biosynthetic enzymes in the CFBS-mixture reaction using the Plackett-Burman experimental design and the path of the steepest ascent, 711.26 ± 15.63 mg/L CGA was produced after 16 h, which is 71.1-fold the yield obtained using the conventional crude extract-based CFBS and 9.1-fold the reported yield obtained using the living cells. Based on the CFBS-mixture results, the production of CGA was further enhanced in engineered Escherichia coli. The CFBS-mixture strategy is highly effective and will be useful for high-level CFBS of natural products.


Ultrafine Betulin Formulation with Biocompatible Carriers Exhibiting Improved Dissolution Rate.
The purpose of this research was to develop new methods of increasing dissolution rate and solubility of betulin extracted from birch bark. The ultrafine formulation of betulin with polyethylene glycol and β-glycine was obtained by freeze-drying. The rate of release of betulin from the formulation into water was significantly higher in comparison with the initial betulin sample and its composite with polyethylene glycol obtained by ball-milling.


Theoretical and experimental studies of the spin trapping of inorganic radicals by 5,5-dimethyl-1-pyrroline N-oxide (DMPO). 3. Sulfur dioxide, sulfite, and sulfate radical anions.
Radical forms of sulfur dioxide (SO(2)), sulfite (SO(3)(2-)), sulfate (SO(4)(2-)), and their conjugate acids are known to be generated in vivo through various chemical and biochemical pathways. Oxides of sulfur are environmentally pervasive compounds and are associated with a number of health problems. There is growing evidence that their toxicity may be mediated by their radical forms. Electron paramagnetic resonance (EPR) spin trapping using the commonly used spin trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), has been employed in the detection of SO(3)(•-) and SO(4)(•-). The thermochemistries of SO(2)(•-), SO(3)(•-), SO(4)(•-), and their respective conjugate acids addition to DMPO were predicted using density functional theory (DFT) at the PCM/B3LYP/6-31+G**//B3LYP/6-31G* level. No spin adduct was observed for SO(2)(•-) by EPR, but an S-centered adduct was observed for SO(3)(•-)and an O-centered adduct for SO(4)(•-). Determination of adducts as S- or O-centered was made via comparison based on qualitative trends of experimental hfcc's with theoretical values. The thermodynamics of the nonradical addition of SO(3)(2-) and HSO(3)(-) to DMPO followed by conversion to the corresponding radical adduct via the Forrester-Hepburn mechanism was also calculated. Adduct acidities and decomposition pathways were investigated as well, including an EPR experiment using H(2)(17)O to determine the site of hydrolysis of O-centered adducts. The mode of radical addition to DMPO is predicted to be governed by several factors, including spin population density, and geometries stabilized by hydrogen bonds. The thermodynamic data supports evidence for the radical addition pathway over the nucleophilic addition mechanism.


Two distinct proton binding sites in the ATP synthase family.
The F1F0 ATP synthase utilizes energy stored in an electrochemical gradient of protons (or Na+ ions) across the membrane to synthesize ATP from ADP and phosphate. Current models predict that the protonation/deprotonation of specific acidic c ring residues is at the core of the proton translocation mechanism by this enzyme. To probe the mode of proton binding, we measured the covalent modification of the acidic c ring residues with the inhibitor dicyclohexylcarbodiimide (DCCD) over the pH range from 5 to 11. With the H+-translocating ATP synthase from the archaeum Halobacterium salinarium or the Na+-translocating ATP synthase from Ilyobacter tartaricus, the pH profile of DCCD labeling followed a titration curve with a pKa around neutral, reflecting protonation of the acidic c ring residues. However, with the ATP synthases from Escherichia coli, mitochondria, or chloroplasts, a clearly different, bell-shaped pH profile for DCCD labeling was observed which is not compatible with carboxylate protonation but might be explained by the coordination of a hydronium ion as proposed earlier [Boyer, P. D. (1988) Trends Biochem. Sci. 13, 5-7]. Upon site-directed mutagenesis of single binding site residues of the structurally resolved c ring, the sigmoidal pH profile for DCCD labeling could be converted to a more bell-shaped one, demonstrating that the different ion binding modes are based on subtle changes in the amino acid sequence of the protein. The concept of two different binding sites in the ATP synthase family is supported by the ATP hydrolysis pH profiles of the investigated enzymes.


Decreased expression of the satiety signal receptor CCKAR is responsible for increased growth and body weight during the domestication of chickens.
Animal domestication has resulted in changes in growth and size. It has been suggested that this may have involved selection for differences in appetite. Divergent growth between chickens selected for egg laying or meat production is one such example. The neurons expressing AGRP and POMC in the basal hypothalamus are important components of appetite regulation, as are the satiety feedback pathways that carry information from the intestine, including CCK and its receptor CCKAR (CCK1 receptor). Using 16 generations of a cross between a fast and a relatively slow growing strain of chicken has identified a region on chromosome 4 downstream of the CCKAR gene, which is responsible for up to a 19% difference in body weight at 12 wk of age. Animals possessing the high-growth haplotype at the locus have lower expression of mRNA and immunoreactive CCKAR in the brain, intestine, and exocrine organs, which is correlated with increased levels of orexigenic AGRP in the hypothalamus. Animals with the high-growth haplotype are resistant to the anorectic effect of exogenously administered CCK, suggesting that their satiety set point has been altered. Comparison with traditional breeds shows that the high-growth haplotype has been present in the founders of modern meat-type strains and may have been selected early in domestication. This is the first dissection of the physiological consequences of a genetic locus for a quantitative trait that alters appetite and gives us an insight into the domestication of animals. This will allow elucidation of how differences in appetite occur in birds and also mammals.


Radiomics modelling in rectal cancer to predict disease-free survival: evaluation of different approaches.
Radiomics may be useful in rectal cancer management. The aim of this study was to assess and compare different radiomics approaches over qualitative evaluation to predict disease-free survival (DFS) in patients with locally advanced rectal cancer treated with neoadjuvant therapy. Patients from a phase II, multicentre, randomized study (GRECCAR4; NCT01333709) were included retrospectively as a training set. An independent cohort of patients comprised the independent test set. For both time points and both sets, radiomic features were extracted from two-dimensional manual segmentation (MS), three-dimensional (3D) MS, and from bounding boxes. Radiomics predictive models of DFS were built using a hyperparameters-tuned random forests classifier. Additionally, radiomics models were compared with qualitative parameters, including sphincter invasion, extramural vascular invasion as determined by MRI (mrEMVI) at baseline, and tumour regression grade evaluated by MRI (mrTRG) after chemoradiotherapy (CRT). In the training cohort of 98 patients, all three models showed good performance with mean(s.d.) area under the curve (AUC) values ranging from 0.77(0.09) to 0.89(0.09) for prediction of DFS. The 3D radiomics model outperformed qualitative analysis based on mrEMVI and sphincter invasion at baseline (P = 0.038 and P = 0.027 respectively), and mrTRG after CRT (P = 0.017). In the independent test cohort of 48 patients, at baseline and after CRT the AUC ranged from 0.67(0.09) to 0.76(0.06). All three models showed no difference compared with qualitative analysis in the independent set. Radiomics models can predict DFS in patients with locally advanced rectal cancer.


LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway.
Highly upregulated in liver cancer (HULC), a lncRNA that is considered a key molecule in human liver cancer, has recently been revealed to be involved in hepatocellular carcinoma (HCC) development and progression [1, 2]. It has been reported that HULC can promote tumor invasion and metastasis of HCC, but its function and mechanism of action in HCC have not been elucidated. In this study, we found that HULC was aberrantly up-regulated in HCC tissues and associated with TNM stage, intrahepatic metastases, HCC recurrence, and postoperative survival. HULC depletion inhibited the growth and metastasis of HCC cell lines in vitro and in vivo. Moreover, HULC contributes to ZEB1-induced epithelial-mesenchymal transition (EMT), a requirement for tumor invasion and metastasis that plays a key role in cancer progression. This effect of ZEB1 was inhibited by HULC siRNA. We conclude that the HULC functioned as a competing endogenous RNA (ceRNA) to mediate EMT via up-regulating ZEB1. In this way, it sequesters the miR-200a-3p signaling pathway to facilitate HCC metastasis. HULC comes into play as an oncogene in HCC, acting mechanistically by inducing HCC cells to activate EMT. Such an effect promotes tumor progression and metastasis through the miR-200a-3p/ZEB1 signaling pathway. The identification of this novel pathway that links high expression levels of HULC with EMT in HCC cells may serve as the foundation for the development of novel anti-tumor therapeutics.


Does intraperitoneal injection of propofol prior to detorsion improve testes weight and histopathological findings in a rat model?
To determine the long-term preventive effects of intraperitoneal propofol on testicular ischemia-reperfusion injury in a rat model. Forty adult male albino Wistar rats were divided randomly into the following four groups according to the planned treatment (n=10 per group): group I, control; group II, sham-operated; group III, torsion/detorsion (T/D); and group IV, T/D plus propofol. Testicular ischemia was achieved by twisting the left testis 720° clockwise (ie, applying torsion) for 1 h. In the T/D plus propofol group (group IV), 50 mg/kg propofol was administered intraperitoneally 30 minutes before detorsion. Ipsilateral orchiectomy was performed under general anesthesia to determine the mean testicular weight and to enable histopathological examination of the testes using Johnsen's mean testicular biopsy score 30 days after the surgical procedure in all groups. The testicular weights in groups I, II, III, and IV were 1.65±0.32, 1.59±0.33, 1.11±0.56, and 1.08±0.50 g (mean ± SD), respectively. Testicular weight was significantly lower in the T/D groups (III and IV) than in both the control and sham-operated groups (I and II), but there was no improvement in testicular weight as a result of propofol administration. Similarly, Johnsen's mean testicular biopsy score was lower in groups III and IV than in groups I and II, but no positive effect was conferred by the administration of propofol in group IV. The use of propofol in the treatment of testicular ischemia-reperfusion injury caused by testis torsion has no significant long-term therapeutic potential.


Specificity of alkaline elastase Bacillus on the oxidized insulin A- and B-chains.
The substrate specificity of alkaline elastase Bacillus from alkalophilic Bacillus sp. Ya-B was investigated using oxidized insulin A- and B-chains. Under time-limited cleavage, the initial cleavage site of the enzyme on the oxidized insulin A-chain and B-chain was at the leucine13-tyrosine14 bond and the leucine15-tyrosine16 bond, respectively. When the cleavage was completed, three major cleavage sites and three minor cleavage sites on the A-chain, and five major cleavage sites and four minor cleavage sites on the B-chain were found. However, most of the peptides produced after complete hydrolysis of the A- or B-chain by the enzyme were composed of four to six amino acid residues. The results suggest that this enzyme cleaves the oxidized insulin A- and B-chains in a block-cutting manner.


Exploring second professional year pharmacy student reflections after an interprofessional shadowing experience with nursing students in critical care units: a qualitative study.
Accreditation standards for pharmacy and nursing education require interprofessional education (IPE) as a key component in both curricula. There is increasing evidence for using interprofessional shadowing as a learning modality for IPE; reflection can be used to enhance learning from these experiences. We explored pharmacy student-reported reflections from an interprofessional shadowing experience with nursing students through qualitative content analysis of reflective statements. We found that pharmacy students gained knowledge of nursing roles and areas of expertise, awareness of how the team provides care, and awareness of the importance of communication and mutual respect to improve both team performance and patient safety. Additionally, we were able to assess interprofessional sub-competencies that were met as a result of the interprofessional shadowing experience, specifically, pharmacy students gained knowledge and skills across all four IPEC Core Competencies. Interprofessional shadowing combined with reflection can enhance learning, and thematic analysis of these reflections can be utilized to assess IPE outcomes.


Liver abscess as a first manifestation of colonic tumor.
Male, 72-year-old, morbidly obese, diabetic, admitted for abdominal pain, prostration and fever that started last 3 days. Abdominal ultrasound and abdominal computed tomography scan showed liver injury in the transition of V and VI segments measuring 8.4 cm. Due to the possibility of liver abscess, initiate empirical antibiotic therapy with ampicillin and sulbactam and metronidazole and performed ultrasound-guided percutaneous drainage of liver injury. Negative for malignant cells, with the presence of leukocytes and negative culture. After 2 weeks of treatment, take control image without changing the lesion dimension. New percutaneous drainage with the same results. We opted for performing endoscopic ultrasound (EUS) with fine-needle aspiration (FNA). FNA pathology: Moderately differentiated adenocarcinoma. Immunohistochemistry suggestive of metastasis of the lower gastrointestinal tract. Due this finding, realized colonoscopy, which revealed a vegetating lesion with central ulceration, bleeding, filling almost the entire cecum. Patient was referred for surgical resection of the bowel tumor, which showed moderately differentiated adenocarcinoma infiltrating vegetative and possibly originated from villous adenoma with high-grade dysplasia. The finding of metastatic liver abscess of colonic neoplasia is not common. In most cases, the material from the abscess drainage allows the diagnosis, but in this case, even after two ultrasound-guided percutaneous drainage was not obtained conclusive bacteriological or histopathological. Opted for new puncture through EUS, which allowed definitive diagnosis of the condition. Metastatic colon neoplasm should be considered in cases of differential diagnosis of liver abscess.


Stacking classifier to improve the classification of shoulder motion in transhumeral amputees.
In recent years surface electromyography signals-based machine learning models are rapidly establishing. The efficacy of prosthetic arm growth for transhumeral amputees is aided by efficient classifiers. The paper aims to propose a stacking classifier-based classification system for sEMG shoulder movements. It presents the possibility of various shoulder motions classification of transhumeral amputees. To improve the system performance, adaptive threshold method and wavelet transformation have been applied for features extraction. Six different classifiers Support Vector Machines (SVM), Tree, Random Forest (RF), K-Nearest Neighbour (KNN), AdaBoost and Naïve Bayes (NB) are designed to extract the sEMG data classification accuracy. With cross-validation, the accuracy of RF, Tree and Ada Boost is 97%, 92% and 92% respectively. Stacking classifiers provides an accuracy as 99.4% after combining the best predicted multiple classifiers.


[Radionuclide evaluation of myocardial perfusion in intensive physical training in patients with a history of myocardial infarct].
Forty patients who had had myocardial infarction six months before their entry into the study were examined using perfusion scintigraphy of the myocardium with 201TI. The patients were divided into the test and the control group. The patients of the test group trained intensively for 12 months according to the special programme which contributed to an improvement of myocardial perfusion at rest irrespective of the nature of the previous myocardial infarction and the clinical severity of coronary insufficiency. A considerable enhancement of tolerance to exercise as a result of the training leads to prevention of the ischemic response to the exercise whose earlier level proved to be the threshold.


Risk Factors for Early- and Late-Onset Cholecystitis after Y-Configured Metal Stent Placement in Patients with Malignant Hilar Biliary Obstruction: A Single-Center Study.
This study evaluated the prevalence and risk factors of early- (within 7 days of placement) and late-onset (after 7 days of placement) cholecystitis after Y-configured metal stent placement. Between June 2005 and August 2020, 109 patients who had been treated with Y-configured metal stents for malignant hilar obstruction were enrolled in the study. We retrospectively analyzed the potential risk factors for post-stent cholecystitis. The presence of diabetes (p = 0.042), the length of the common part of the Y-stent (p = 0.017), filling of the gallbladder with contrast medium during the procedure (p = 0.040), and tumor invasion of the cystic duct accompanied by filling the gallbladder with contrast medium during metal stent placement (p = 0.001) were identified as important risk factors. In cases of late-onset cholecystitis, stent obstruction (p = 0.004) and repeated endoscopic procedures due to stent malfunction (p = 0.024) were significant risk factors. In the multivariate logistic regression analysis, significant risk factors were the length of the common part of the Y-stent (p = 0.032) in early-onset cholecystitis and stent obstruction (p = 0.007) in late-onset cholecystitis. This study demonstrated that early-onset cholecystitis may occur in patients according to the length of the common portion of the Y-stent. In contrast, late-onset cholecystitis may occur in patients with stent obstruction.


General anesthesia in early childhood and possible association with autism: a population-based matched cohort study.
In experimental animal studies, exposure to general anesthesia in early childhood may results in changes in infant brain morphology and behavior, potentially leading to the development of autistic behaviors in the long-term. However, in clinical studies the role of exposure to general anesthesia in early childhood and the risk of autism is unknown. This is a population-based cohort study including all children aged 0-5 years of age exposed to general anesthesia between 2001 and 2014 and a corresponding matched population without such an exposure. Propensity score calculation was based on 49 variables (including age of parents, malformations, APGAR Score, and family income, among others). Quasi-Poisson regression was used to estimate risk ratios (RRs) with 95% confidence intervals (CIs) for the association between exposure to general anesthesia and autism or autism spectrum disorder. In total, 401,750 children exposed to general anesthesia were compared with 1,187,796 unexposed individuals. Autism or autism spectrum disorder were more common in the children exposed to general anesthesia as compared to unexposed children (1.65% and 0.98%, respectively, P<0.01). There was a statistically significant higher risk of autism or autism spectrum disorder in children exposed to general anesthesia as compared to unexposed children also after propensity score adjustment (RR 1.62, 95% CI: 1.57-1.67). Exposure to general anesthesia in early childhood was associated with an increased risk of autism or autism spectrum disorder. Future studies are needed to asses if general anesthesia may cause autism or if the association is due to other factors.


Circulating ficolin-2 and ficolin-3 in normal pregnancy and pre-eclampsia.
Ficolins are soluble molecules of the innate immune system that recognize carbohydrate molecules on microbial pathogens, apoptotic and necrotic cells. They act through two distinct routes: initiating the lectin pathway of complement activation and mediating a primitive opsonophagocytosis. In this study, we measured plasma levels of ficolin-2 and ficolin-3 in 60 pre-eclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women by enzyme-linked immunosorbent assay (ELISA). Circulating levels of complement activation products (C4d, C3a, SC5b9), angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor) and markers of endothelial activation (von Willebrand factor antigen), endothelial injury (fibronectin) and trophoblast debris (cell-free fetal DNA) were also determined. Plasma levels of ficolin-2 were significantly lower in healthy pregnant than in healthy non-pregnant women, while ficolin-3 levels did not differ significantly between the two groups. Furthermore, pre-eclamptic patients had significantly lower ficolin-2 and ficolin-3 concentrations than healthy non-pregnant and pregnant women. In the pre-eclamptic group, plasma ficolin-2 levels showed a significant positive correlation with serum placental growth factor (PlGF) concentrations and significant inverse correlations with serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1), blood urea nitrogen and creatinine, serum lactate dehydrogenase activities, as well as with plasma VWF:antigen, fibronectin and cell-free fetal DNA concentrations. In conclusion, circulating levels of ficolin-2 are decreased in the third trimester of normal pregnancy. There is a further decrease in plasma ficolin-2 concentrations in pre-eclampsia, which might contribute to the development of the maternal syndrome of the disease through impaired removal of the trophoblast-derived material released into the maternal circulation by the hypoxic and oxidatively stressed pre-eclamptic placenta.


Treatment of leachate from a solid waste landfill site using a two-stage anaerobic filter.
Raw leachate was treated using a two-stage upflow anaerobic filter process. Leachate from a solid waste landfill site, which received both municipal and industrial wastes, contained high organic matter (17-21 g/L COD, 13-14 g/L BOD, and 3.5-4.6 g/L volatile acids), and low metal (Zn and Fe) concentrations. Depending on sampling time, leachate composition and characteristics varied considerably. At an organic loading up to 4 g COD/day(2) media area, the BOD and COD removal percentages were 98 and 91%, respectively. The biofilters were also effective for metal removal. However, the filter effluent contained a high concentration of ammonia. System overloading was characterized by the accumulation of large quantities of volatile acids and by a now ratio of alkalinity/volatile acids, resulting in low COD removal and reduced gas production. Once the first filter was upset, the second stage could only partially respond to the volatile acids accumulated in the effluent of first filter.


Automaticity in Mahaim fibers.
Automatic rhythms associated with Mahaim fibers usually occur during radiofrequency catheter ablation. The incidence and significance of spontaneous automaticity in Mahaim fibers are unknown. Spontaneous automatic rhythms were observed in 5 (12.5%) of 40 patients with Mahaim fibers referred for nonpharmacologic therapy because of recurrent episodes of symptomatic tachyarrhythmias, usually antidromic circus movement tachycardia (33/40 patients). Three were female and two were male. Their mean age was 15 +/- 7 years compared to 26 +/- 13 years of the patients without automaticity (P = 0.09). Three patients had both antidromic tachycardia and asymptomatic spontaneous automatic rhythms recorded during ambulatory ECG (1 patient) or electrophysiologic study (2 patients). In 2 patients, the automatic rhythm triggered antidromic tachycardia. Two other patients had nonsustained repetitive episodes of wide QRS tachycardia due to automaticity arising in the Mahaim fiber, without antidromic tachycardia. All automatic rhythms were abolished by successful catheter ablation of the Mahaim fibers. Spontaneous automaticity occurred in 12.5% of our Mahaim patients and may trigger antidromic tachycardia. Spontaneous automaticity, which is not seen in rapidly conducting accessory pathways, is another argument for the presence of an AV nodal-like structure in Mahaim fibers.


Effect of perforations in burr hole covers on cranial bone regeneration in rabbits.
The reconstruction of bone defects is a significant problem in cranio-maxillofacial surgery. In an effort to avoid the known disadvantages of autogenous bone grafting, alternatives have been investigated. Bone substitute materials, degradable or nondegradable, aim at facilitating bone regeneration, while they take over load-bearing functions for a period of time. In this study, the healing of cranial defects in rabbits was assessed using polylactide guiding covers with and without perforations. Bilateral circular cranial defects were produced in 16 New Zealand white rabbits. The defects were covered with extruded and laser cut polylactide burr hole covers, each animal receiving a perforated burr hole cover on one side and a nonperforated one on the contralateral side. Bone seeking fluorochromes were administered at regular intervals. After an observation period of 8 weeks the amount of bone regeneration in the area of the defects was quantified from contact radiographs, and the dynamics of bone formation were assessed by fluorescence microscopy. Stained sections were used to analyze morphologic differences. No signs of adverse tissue reactions or osteolysis were observed. A bone-guiding function was observed for both covers with or without perforations. Intracranial tissue herniation into the defect hindered the regeneration process. Wide intraindividual and interindividual variation became apparent and average defect filling was only 40% within the 8-week observation period. In this model the perforated covers offered no advantage over nonperforated covers. It can be concluded from this study, that the use of external burr hole covers alone does not guarantee a full thickness regeneration of the cranial defect, but it provides a guiding function for promotion of structured bone regeneration.


Non-lethal sampling for the detection of Renibacterium salmoninarum by qPCR for diagnosis of bacterial kidney disease.
Bacterial kidney disease (BKD), caused by Renibacterium salmoninarum (Rs), can be transmitted both horizontally and vertically and there is no available cure or prophylaxis. The control of BKD requires continuous surveillance, which is challenging in aquaculture as well as in programs for conservation and restoration of salmonid fish strains. BKD is a notifiable disease in Sweden and is monitored through the mandatory health control program using a polyclonal ELISA for detection of the Rs p57 protein in kidney. Fish must be killed for sampling, an obvious disadvantage especially regarding valuable broodfish. The present study shows that gill-/cloacal swabs collected in vivo for real-time PCR (qPCRgc ), allow a sensitive and specific detection of Rs. The sensitivity of qPCRgc was estimated to 97.8% (credible interval (ci) 93.8%-100%) compared to 98.3% (ci 92.7%-100%) and 48.8% (ci 38.8%-58.8%) of kidney samples for qPCR (qPCRk ) and ELISA (ELISAk ) respectively, by use of the Bayesian Latent Class Analysis (BLCA). Since the goal of the program is eradication of BKD the most sensitive test is preferrable. Using qPCRgc instead of ELISAk will result in a lower false negative rate and can be useful for surveillance in aquaculture and in breeding programs with valuable fish. However, a higher false positive rate warrants confirmatory lethal testing before a previously Rs negative farm is subject to restrictions.


The influence of age and sex on blood levels of calcium-regulating hormones in dogs.
In order to study age- and sex-related changes in calcium-regulating hormones, serum levels of parathormone (PTH), calcitonin (CT), and vitamin D metabolites were determined in 20 young dogs and 11 old dogs. A highly significant increase in serum levels of PTH was observed in old dogs (1.65 +/- 0.09 ng/ml versus 1.05 +/- 0.09 ng/ml in young animals) (p less than 0.001). Serum levels of 25-(OH)-D were significantly decreased in old dogs (11.24 +/- 2.03 ng/ml compared to 20.59 +/- 1.57 ng/ml in young dogs) (p less than 0.001). No significant differences in serum levels of 1,25-(OH)2-D, 24,25-(OH)2-D, and CT were found between young and old dogs. Serum CT levels were higher in males, especially in old animals. Young females had significantly higher serum levels of 25-(OH)-D than males. It seems that for some reason old dogs are in a relative state of vitamin D deficiency and hyperparathyroidism, which suggests the cause of skeletal alterations related to aging. A similar situation is observed in human geriatric patients.


The significance of small erythrocytes.
Small erythrocytes (mean corpuscular volume less than 80 mu-3 by the Coulter Model S) were found in 222 (2.75%) of 8,086 consecutive patients admitted to a large suburban general hospital. Forty-five (20.3%) of these 222 patients had laboratory findings consistent with thalassemia. Seventy-six (31.2%) were found to be iron deficient. Patients whose hemoglobin values were below 9.0 Gm. per 100 ml. were more likely to be iron deficient. The hemoglobin A2 values were significantly lower in iron-deficient than in non-iron-deficient patients. Although the mean corpuscular volume is much lower and the erythrocyte count is higher in thalassemia than in iron deficiency, hematologic values obtainable from the Counlter S (such as MCV, erythrocyte count, and hemoglobin) alone are not valuable in differentiating thalassemia from iron deficiency.