[Concentration enhancement for retaining daily living competence in dementia].
Dementia is characterized by reduced memory and concentration abilities leading to a decrease in activities of daily living. Various studies have shown that various forms of physical exercise have a positive therapeutic effect at an early stage of dementia. In the present study the effects of an exercise-based Brain-Gym concept on the concentration and routine daily competences were evaluated in dementia patients. During a 4-month intervention period specially trained nursing staff and healthcare students put this exercise program into practice. Using an intervention and control group design, the concentration abilities of the dementia patients were tested on a monthly base. Additionally, the routine daily competence of the patients was evaluated by the nursing staff. Even though no significant differences could be detected, the intervention group achieved higher scores in concentration abilities than the control group on all four testing dates. Furthermore, the routine daily competence was improved in the intervention group throughout the intervention period. This concept can be used for dementia patients. Due to the low requirements concerning coordination and condition Brain-Gym is suitable for the target group and can easily be implemented by caregivers; however, significant evidence of positive impacts on concentration and everyday life competence could not yet be found in this study.


RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1.
RASSF1A, one of the two major isoforms of the putative tumor suppressor gene RASSF1, located at 3p21.3, is inactivated in a variety of human cancers including lung, breast, bladder and renal cell carcinomas. We have isolated and cloned two human homologues of this gene, RASSF3 and NORE1, located at 12q14.1 and 1q32.1, respectively. Both RASSF3 and NORE1 share almost 60% homology, at the amino acid level, with RASSF1. The RASSF3 gene contains five exons and encodes a 247 amino acid protein (MW of 28.6 kDa) with a highly conserved Ras association (RalGDS/AF-6) (RA) domain at the C-terminus. RASSF3 is ubiquitously expressed in all normal tissues and cancer cell lines analysed. NORE1, which is homologous to the previously described mouse Nore1 gene, exists in at least two spliced isoforms, A and B. Transcript A encodes a protein of 418 amino acids (MW or 47 kDa) while transcript B contains an ORF of 265 aa (MW of 30.5 kDa). Both share a RA domain, encoded by exons 3 through 6. NORE1A and NORE1B are expressed in most of the normal tissues analysed but they appear to be down-regulated in several cancer cell lines. However, contrary to RASSF1A, gene silencing by methylation of the CpG islands at which the two NORE1 transcripts initiate is not a common event in human primary tumors. RASSF3 and NORE1B are very similar, at the N-terminus, to the splice variant C of RASSF1 (RASSF1C), which does not seem to be involved in tumorigenesis. NORE1A is most closely related to RASSF1A, for sequence homology and genomic organization. However, aberrations in tumors have so far not been found. The presence of a Ras association domain common to NORE1, RASSF1, and RASSF3 suggests their possible involvement in Ras-like signaling pathways.


Determination of betaxolol and its metabolites in blood and urine by high-performance liquid chromatography with fluorimetric detection.
Analytical methods for the determination of betaxolol and two of its metabolites in blood and urine are described. Betaxolol, alpha-hydroxybetaxolol, and the acid metabolite were extracted, with over 65% efficiency, from biological samples by liquid-liquid extraction methods. Analysis was performed using reversed-phase high-performance liquid chromatography with fluorimetric detection. N,N-Dimethyloctylamine (0.005 M) was used to improve the chromatography of betaxolol and alpha-hydroxybetaxolol, while acetic acid (1%) was used for the acid metabolite. An excitation wavelength of 200 nm was found to produce the best detector response. Linear standard curves were obtained for all three compounds with detection limits (signal-to-noise ratio = 3) varying between 1 and 10 ng/ml. The coefficients of variation of the determination for all three compounds in blood and urine varied between 3.0 and 8.7%. The metabolism of betaxolol was studied in twelve healthy male subjects. The amounts (mean +/- S.D.) of betaxolol, alpha-hydroxybetaxolol and the acid metabolite renally excreted in the first 48 h after intravenous administration of 10 mg of betaxolol hydrochloride are 17.1 +/- 6.2, 0.4 +/- 0.1 and 14.5 +/- 3.7%, respectively, of the administered dose.


Immunological comparison of recombinant shrimp allergen Pen m 4, produced in Pichia pastoris and Escherichia coli.
Shellfish are a leading cause of allergies worldwide, affecting about one-tenth of the general population. The sarcoplasmic calcium-binding protein, also known as allergen Pen m 4, is an important factor in shrimp allergies. Our objective was to assess the most effective techniques for producing a recombinant Pen m 4 protein as a potential tool for diagnosing shrimp allergies. In this study, for the first time, we produced a functional recombinant Pen m 4 protein in a eukaryotic system, Pichia pastoris, and analyzed it against Escherichia coli-produced equivalents in enzyme-linked immunosorbent and reverse-phase protein microarray assays. A dual tag system based on the maltose-binding protein was successfully used to increase the yield of Pen m 4 by 1.3-2.3-fold in both bacteria and yeast, respectively. Immunological characterization showed that N-glycosylation is neither crucial for the folding of Pen m 4 nor its recognition by specific IgE. However, the Ca2+-depletion assay indicated a dependence on calcium ion presence in blood samples. Results demonstrate how a comparative analysis can elucidate essential allergen manufacturing points. In conclusion, E. coli-produced Pen m 4 protein fused with the maltose-binding protein should be the preferred option for further studies in Penaeus monodon allergy diagnostics.


Hemodialysis Access Outcomes for Patients with Unstable Housing.
End-stage renal disease has traditionally been noted to disproportionately affect patients with fewer resources. Our goal was to assess practice patterns and outcomes in patients with unstable housing undergoing permanent hemodialysis access creation. A retrospective, single-center review of patients with unstable housing was conducted. Perioperative and long-term outcomes were assessed. Univariable and multivariable analysis as well as Kaplan-Meier analysis were performed. There were 144 patients (63% male) identified with a mean age of 57 years. Thirty-three percent of patients had no current permanent residence, and 81% had at least 3 addresses the year before operation. Access type included brachiocephalic (48%), brachiobasilic (19%), radiocephalic fistulas (11%), and prosthetic grafts (19%). Thirty-day readmission was seen in 27.8% of patients. Kaplan-Meier analysis showed that 1-year and 4-year patient survival were 94.4% and 80.6%, respectively. Multivariable analysis demonstrated that newly formed access (odds ratio [OR] 3.66, 95% CI 1.02 to 13.16, p = 0.05), absence of a permanent residence (OR 2.92, 95% CI 1.15 to 7.44, p = 0.03), and female gender (OR 2.86, 95% CI, 1.18 to 7.14, p = 0.02) were associated with 90-day readmission. Multivariable analysis of mortality revealed that previous stroke (hazard ratio [HR] 7.15, 95% CI 1.93 to 26.5, p = 0.003), history of alcohol use disorder (HR 4.55, 95% CI 1.22 to 16.99, p = 0.024), and age (HR 1.10, 95% CI, 1.02 to 1.18, p = 0.017) were associated with 4-year mortality; housing instability was not associated with decreased survival. Preoperative tunneled dialysis catheter (HR 1.63, 95% CI 1.02 to 2.61, p = 0.04) was associated with 4-year reintervention and frequent address change (HR 0.47, 95% CI 0.27 to 0.81, p = 0.01) was found to be a protective factor against long-term reintervention. Poor outcomes in patients with unstable housing were primarily driven by comorbidities. Lack of permanent residence was significantly associated with readmission.


Improved Estimates of Host-Guest Interaction Energies for Endohedral Fullerenes Containing Rare Gas Atoms, Small Molecules, and Cations.
Endohedral fullerenes have evinced much interest from the fundamental and applications points of view. However, given the nature of the weak interaction between the guest species and the host cage in these confined systems, the interaction energy values obtained using various theoretical methods, and different basis sets vary over a wide range. For example, the reported interaction energy for the HF@C60 system ranges from -2.5 kcal/mol to -14.9 kcal/mol. In the present manuscript, we report reliable interaction energy values for different endohedral fullerenes (He@C60 , Ne@C60 , Ar@C60 , Kr@C60 , H2 @C60 , HF@C60 , H2 O@C60 , NH3 @C60 , CH4 @C60 , Li+ @C60 , Na+ @C60 , and K+ @C60 ) obtained using the domain-based local pair natural orbital coupled-cluster singles, doubles, and perturbative triples (DLPNO-CCSD(T)) method and the def2-TZVP basis set. We believe that these energy values could be considered as benchmark values, and the performance of other quantum chemical methods could be assessed accordingly. Local energy decomposition analysis within the DLPNO-CCSD(T) framework is used to estimate the electrostatic, exchange, and dispersion components of the interaction energy for some of the endohedral fullerenes.


Predictors of low back pain hospitalization--a prospective follow-up of 57,408 adolescents.
Low back pain (LBP) is common among adolescents and it has been estimated that one-fifth of adolescents suffer from recurrent severe LBP. However, longitudinal studies describing the risk factors of LBP are scarce. The purpose of this study was to investigate whether health, physical activity and other health behaviors, socio-demographic background and school success predict LBP hospitalization until early middle age. A cohort of 72,378 adolescents (57,408 respondents, response rate 79%) aged 14-18 years participating in a population survey between 1979 and 1997 was followed for an average of 11.1 years through the national hospital discharge register. We identified 810 (1.1%) persons with LBP hospitalization, 620 males (1.7% of the whole male cohort) and 190 (0.5%) females (HR 3.2; 95% CI: 2.7-3.7). In multivariate Cox's analysis, the strongest risk factors for LBP hospitalization for the whole cohort were weekly health complaints (HR 1.5; 95% CI: 1.2-1.9), daily smoking (HR 1.4; 95% CI: 1.1-1.7), and poor school success (HR 1.4; 95% CI: 1.1-1.9). Late puberty decreased the risk in males (HR 0.7; 95% CI: 0.5-0.9). Among females, participation in organized sports (HR 1.7; 95% CI: 1.1-2.5) was associated with an increased risk for LBP hospitalization. The associations between the risk factors and LBP hospitalization persisted into adulthood. Efforts to reduce adolescent smoking may decrease LBP-related morbidity in males. Coaches should pay special attention to the nature of physical training and personal exercises in females, and physiotherapists and sports physicians to the prevention of LBP hospitalization.


Brain and serum levels of naloxone following peripheral administration.
Striatal, hypothalamic and serum concentrations of naloxone were measured by a new high-performance liquid chromatographic procedure at various time up to 120 min following subcutaneous administration of 1, 5, and 10 mg naloxone hydrochloride/kg to rats. A dose-concentration relationship was evident throughout. Peak levels were observed at the first measurement time (15 min) and tissue values were consistently higher than concentrations in serum. The correlations between serum and brain naloxone levels suggests that in normal rats central concentrations of the drug can be extrapolated from serum concentrations.


Influence of Intraoperative Medial Collateral Ligament Bony Avulsion Injury on the Outcome of Primary Total Knee Arthroplasty.
The purpose of this study is (1) to find the clinical and radiological outcome of intraoperative bony avulsion of medial collateral ligament (MCL) treated with screw and washer construct and (2) to predict the preoperative factors which may contribute to the avulsion-type MCL injury during primary total knee arthroplasty (TKA). Intraoperative MCL avulsion injury occurred in 46 (0.8%) of the 4916 consecutive primary TKA from January 2011 to December 2015. After exclusion, the 41 knees were matched 1:2 with controls without MCL injury and compared for the various clinical, radiological, and functional parameters. The clinical parameters analyzed were age, gender, body mass index, preoperative diagnosis like osteoarthritis or rheumatoid arthritis, range of motion, sagittal deformity, and vitamin D levels. The radiological parameters calculated were coronal deformity, proximal tibial varus angle, distal femur valgus angle, joint line congruence angle, posterior tibial slope, "cup and saucer" morphology, presence or absence of knee subluxation, tibia vara, and femoral bowing. The preoperative and postoperative Knee Society Score and Knee Society Functional Score were analyzed. Complications or revisions, if any, were noted during the follow-up. Multivariate logistic regression analysis was used to predict the preoperative risk factors for MCL avulsion injury. At a mean follow-up of 58.4 ± 19.3 months, there were no radiological or physical examination findings of instability. Compared to the preoperative disability, there was a statistically significant improvement in clinical scores (Knee Society Score and Knee Society Functional Score) in the final follow-up (P < .001) in both cases and the control group. The mean preoperative coronal deformity was 170.6 ± 6.96 in the study group and 167.7 ± 4.3 in the control group (P = .021). The mean preoperative tibial slope was 10.5 ± 4.9 in the study group and 7.91 ± 4.15 in the control group (P = .003). The preoperative knee subluxation was present in 48.8% knees (P < .001) and "cup and saucer" morphology in 68.3 knees (P < .001) in the study group. The adjusted odds of MCL avulsion injury were greater for severe varus deformity (odds ratio [OR] 1.462, 95% confidence interval [CI] 1.15-1.86), knee subluxation (OR 39.78, 95% CI 3.78-418.86), and "cup and saucer" morphology (OR 33.11, 95% CI 5.69-192.66). Intraoperative MCL bony avulsion injury can be managed successfully with screw and washer construct without the need for increased prosthetic constraint in primary TKA. The presence of severe varus deformity, knee subluxation, and "cup and saucer" morphology tend to have an increased chance of MCL avulsion injury.


Concluding remarks: Harnessing non-covalent interactions for synthesis and catalysis.
An overview of the Faraday Discussion meeting on harnessing non-covalent interactions for synthesis and catalysis, is presented. This covers progress in the field across chemical biology, bioinspired catalysis using homogeneous coordination complexes, supramolecular approaches for catalysis, advanced diffraction and spectroscopic methods for the measurement of structure and the influence of non-covalent interactions, and how computational tools inform and start to predict the role of non-covalent interactions.


Long-term efficacy of percutaneous mitral commissurotomy for restenosis after previous mitral commissurotomy.
We analysed long-term results of percutaneous mitral commissurotomy (PMC) performed because of mitral restenosis after previous commissurotomy. Follow-up of a prospective cohort. Tertiary university hospital. We studied 163 consecutive patients who underwent PMC because of restenosis occurring 16 ± 8 years after previous commissurotomy (closed-heart in 121, open-heart in 30 and PMC in 12). Mean age was 48 ± 14 years; 62 patients (38%) had valve calcification. Restenosis was due to bicommissural fusion in all cases. PMC using a single or double balloon in 80 patients and the Inoue balloon in 83. Good immediate results (IR) (valve area ≥ 1.5 cm2 with MR ≤ 2/4) were obtained in 135 pts (83%). 20-year rates were 27.9 ± 4.7% for cardiovascular survival without mitral surgery and 14.8 ± 3.9% for good functional results (cardiovascular survival without reintervention on the mitral valve and in New York Heart Association (NYHA) class I or II). After good IR, 20-year rates were 33.2 ± 5.5% for cardiovascular survival without surgery and 17.9 ± 4.7% for good functional results. After good IR, multivariate predictive factors of poor late functional results were higher NYHA class (p = 0.01), atrial fibrillation (p = 0.0002) and higher mean mitral gradient after PMC (p = 0.004). In patients with restenosis after mitral commissurotomy, PMC provides good IR in most cases. After good IR, one patient out of three remains free from surgery and one out of five has good functional results at 20 years. These findings support the use of PMC after previous commissurotomy, particularly in selected patients with few symptoms and in sinus rhythm.


A novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse.
Lobeline, an alkaloidal constituent of Lobelia inflata LINN., has a long history of therapeutic usage ranging from emetic and respiratory stimulant to tobacco smoking cessation agent. Although classified as both an agonist and an antagonist at nicotinic receptors, lobeline has no structural resemblance to nicotine, and structure--function relationships do not suggest a common pharmacophore. Lobeline inhibits nicotine-evoked dopamine release and [3H]nicotine binding, thus acting as a potent antagonist at both alpha3beta2(*) and alpha4beta2(*) neuronal nicotinic receptor subtypes. However, lobeline does not release dopamine from its presynaptic terminal, but appears to induce the metabolism of dopamine intraneuronally. Reevaluation of the mechanism by which lobeline alters dopamine function reveals that its primary mechanism is inhibition of dopamine uptake and promotion of dopamine release from the storage vesicles within the presynaptic terminal, via an interaction with the tetrabenazine-binding site on the vesicular monoamine transporter (VMAT2). Thus, lobeline appears to perturb the fundamental mechanisms of dopamine storage and release. Based on its neurochemical mechanism, the ability of lobeline to functionally antagonize the neurochemical and behavioral effects of the psychostimulants amphetamine and methamphetamine was examined. Lobeline was found to inhibit the amphetamine-induced release of dopamine in vitro, and amphetamine-induced hyperactivity, drug discrimination, and self-administration. However, lobeline does not support self-administration in rats, suggesting a lack of addiction liability. Thus, lobeline may reduce the abuse liability of these psychostimulants. The development of lobeline and lobeline analogs with targeted selectivity at VMAT2 represents a novel class of therapeutic agents having good potential as efficacious treatments for methamphetamine abuse.


Maternal effects in fish populations.
Recently, the importance of the female to population dynamics-especially her non-genetic contribution to offspring fitness or maternal effect-has received much attention in studies of a diverse collection of animal and plant taxa. Of particular interest to fisheries scientists and managers is the role of the demographic structure of the adult component of fish populations in the formation of future year classes. Traditionally, fisheries managers tended to assess whole populations without regard to variation between the individuals within the population. In doing so, they overlooked the variation in spawning production between individual females as a source of variation to recruitment magnitude and fluctuation. Indeed, intensive and/or selective harvesting of larger and older females, those that may produce more-and higher quality-offspring, has been implicated in the collapse of a number of important fish stocks. In a fisheries resource management context, whether capture fisheries or aquaculture, female demographics and inter-female differences warrant serious consideration in developing harvesting and breeding strategies, and in understanding general population dynamics. Here I review the range of female traits and environmental conditions females encounter which may influence the number or quality of their offspring via a maternal effect.


Bipolar disorder predicted shorter and borderline personality disorder symptoms longer time to remission - A prospective cohort study of major depressive patients.
Major depressive episodes (MDEs) of major depressive (MDD) or bipolar disorders (BD) are frequently complicated by features of borderline personality disorder (BPD). Mixed features are a hallmark of BD and affective lability of BPD, and both may markedly influence illness course. However, direct comparisons of outcome of depression in MDD, BD, and BPD are scarce. In a cohort study based on stratified sampling, we diagnosed psychiatric MDE patients with SCID-I/P and SCID-II interviews and examined mixed symptoms using the Mix-MDE scale and borderline symptoms using the Borderline Personality Disorder Severity Index. During a six-month prospective follow-up, the MDE patients with MDD (n = 39), BD (n = 33), or BPD (n = 23) completed biweekly online assessments. Using life chart methodology, we divided the follow-up period into qualitatively different mood state periods. We investigated durations of mood episodes, times to first full symptomatic remission, and their predictors. Remission rates were similar in MDD, MDE/BD, and MDE/BPD patients. MDE/BD patients experienced more numerous and shorter distinct mood state periods during follow-up than the others. MDE/BD was associated with shorter (HR = 2.44, 95 % CI = 1.27-4.67) and dimensionally assessed BPD severity with longer time to first remission (HR = 0.95, 95 % CI = 0.91-1.00). Moderate sample size and follow-up duration. Course of illness over six months differs between the three depressive groups. Bipolar depressive patients have the most alternating course and the shortest time to first period of remission. Dimensionally assessed severity of BPD may predict longer time to remission from depression.


Transfer of pathogenic and nonpathogenic cytosolic proteins between spinal cord motor neurons in vivo in chimeric mice.
Recent studies have reported spread of pathogenic proteins in the mammalian nervous system, but whether nonpathogenic ones spread is unknown. We initially investigated whether spread of a mutant amyotrophic lateral sclerosis-associated cytosolic superoxide dismutase 1 (SOD1) protein between motor neurons could be detected in intact chimeric mice. Eight-cell embryos from G85R SOD1YFP and G85R SOD1CFP mice were aggregated, and spinal cords of adult chimeric progeny were examined for motor neurons with cytosolic double fluorescence. By 3 mo of age, we observed extensive double fluorescence, including in amyotrophic lateral sclerosis-affected cranial nerve motor nuclei but not in the relatively spared extraocular nuclei. Chimeras of nonpathogenic wtSOD1YFP and G85R SOD1CFP also exhibited double fluorescence. In a third chimera, mitochondrial mCherry did not transfer to G85R SOD1YFP motor neurons, suggesting that neither RNA nor organelles transfer, but mito-mCherry neurons received G85R SOD1YFP. In a chimera of ChAT promoter-EGFP and mito-mCherry, EGFP efficiently transferred to mito-mCherry+ cells. Thus, nonpathogenic cytosolic proteins appear capable of transfer. During study of both the SOD1FP and EGFP chimeras, we observed fluorescence also in small cells neighboring the motor neurons, identified as mature gray matter oligodendrocytes. Double fluorescence in the G85R SOD1FP chimera and observation of the temporal development of fluorescence first in motor neurons and then in these oligodendrocytes suggest that they may be mediators of transfer of cytosolic proteins between motor neurons.


DNA histochemical analysis in oral squamous cell carcinoma.
Recent years have witnessed an increasing emphasis on the role of nuclear DNA and its application in experimental pathological diagnosis to predict prognosis and management of certain neoplasm. to establish objective criteria for the degree of differentiation and histochemical quantitative of nuclear DNA of oral squamous cell carcinoma (OSCC) using microspectrophotometric analysis. The study was conducted on histologic materials from patient with OSCC. Two histological grading systems were used; Broder's and invasive front grading system were recorded. Microspectrophotometry was applied on Feulgen-stained sections to determine the quality of tumour nuclear DNA content in two different histological grading systems of OSCC. Nuclear DNA content increased significantly with decreasing tissue differentiation as well with increasing tumour size. The grading system and DNA content provides more objective and accurate criteria which relate the morphologic finding to biologic activity and growth patterns of oral cancer as compared to histologic differentiation alone.


Marker-assisted selection of a neuro-behavioural trait related to behavioural inhibition in the SHR strain, an animal model of ADHD.
The search for the molecular bases of neuro-behavioural traits in Spontaneously Hypertensive Rats (SHR), an animal model of Attention Deficit Hyperactivity Disorder (ADHD), led to the discovery of two quantitative trait loci related to the locomotor activity in the centre of the open field. In the present study, rats from an F2 intercross between the SHR and Lewis strains were selected with markers on the basis of their genotype at these two loci. We obtained a 'high line' in which rats have the alleles increasing the trait, and a 'low line' with the lowering alleles. In activity cages with a dim light, the low line was more active than the high line. The reverse was found in the open field, and the inhibition of locomotor activity in the low line (as compared to the high line) was directly related to the aversiveness of the situation (larger in the centre than in the periphery, and in high light than in low light), and was more intense in males than in females. This inhibition is not attributable to a classical 'anxiety' factor as measured in the elevated plus maze, in which the open arms behaviours were not different between the lines. The high line also showed a deficit in prepulse inhibition of the acoustic startle reflex. The present data show that the two loci previously described in a SHR x Lewis intercross as related to the activity in the centre of the open field are indeed involved in a behavioural inhibition trait. The marker-based selected lines described here are unique tools for the study of the neurobiological bases of this trait and the molecular foundations of its variability of genetic origin.


Scanning Acoustic Microscopy-A Novel Noninvasive Method to Determine Tumor Interstitial Fluid Pressure in a Xenograft Tumor Model.
Elevated tumor interstitial fluid pressure (TIFP) is a prominent feature of solid tumors and hampers the transmigration of therapeutic macromolecules, for example, large monoclonal antibodies, from tumor-supplying vessels into the tumor interstitium. TIFP values of up to 40 mm Hg have been measured in experimental solid tumors using two conventional invasive techniques: the wick-in-needle and the micropuncture technique. We propose a novel noninvasive method of determining TIFP via ultrasonic investigation with scanning acoustic microscopy at 30-MHz frequency. In our experimental setup, we observed for the impedance fluctuations in the outer tumor hull of A431-vulva carcinoma-derived tumor xenograft mice. The gain dependence of signal strength was quantified, and the relaxation of tissue was calibrated with simultaneous hydrostatic pressure measurements. Signal patterns from the acoustical images were translated into TIFP curves, and a putative saturation effect was found for tumor pressures larger than 3 mm Hg. This is the first noninvasive approach to determine TIFP values in tumors. This technique can provide a potentially promising noninvasive assessment of TIFP and, therefore, can be used to determine the TIFP before treatment approach as well to measure therapeutic efficacy highlighted by lowered TFP values.


The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with in utero SARS-CoV-2.
While pregnancy increases the risk for severe COVID-19, the clinical and immunological implications of COVID-19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID-19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1,400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation. Pregnant women with severe COVID-19 show increased inflammation and unique IFN-λ antiviral signaling, with elevated levels of IFNL1 and IFNLR1. Furthermore, SARS-CoV-2 infection re-shapes maternal immunity at delivery, altering the expression of pregnancy complication-associated cytokines, inducing MMP7, MDK, and ESM1 and reducing BGN and CD209. Finally, COVID-19-exposed infants exhibit induction of T cell-associated cytokines (IL33, NFATC3, and CCL21), while some undergo IL-1β/IL-18/CASP1 axis-driven neonatal respiratory distress despite birth at term. Our findings demonstrate COVID-19-induced immune rewiring in both mothers and neonates, warranting long-term clinical follow-up to mitigate potential health risks.


Food limitation and demography of a migratory antelope, the white-eared kob.
Although it is commonly presumed that many populations of large-herbivores are limited by food availability, supporting evidence is scarce. This hypothesis was investigated in a population of over 800,000 white-eared kob in the Boma National Park region of the southern Sudan. Food availability, body condition, and mortality rates of adults and calves were measured during the dry seasons of 1982 and 1983. Sampled age distributions from both the live population and carcasses were used to calculate age-specific rates of mortality. In 1982, food supplies during the dry season were augmented by substantial rainfall, which produced regrowth of grass in areas that ordinarily had little green forage. As a result, fat reserves declined little, and rates of adult mortality showed no increasing trend. Total adult mortality was 5%. In 1983, there was no rainfall during the dry season and food intake was insufficient to meet the estimated energy requirements of kob. As a result, fat reserves declined and adult mortality rates increased fourfold. Total adult mortality was 10% (equivalent to the recruitment rate of yearling into the population). Calf mortality during the dry season was similar in both years (50%), based on field estimates of mortality rates and calf/female ratios. Lactation throughout the dry season possibly provided a buffer for calves against variations in food availability. The age structure of the live population in 1983 suggests that a drought in 1980 reduced kob numbers by 40%. These results suggest that adult survival is influenced strongly by the availability of food during the dry season. However, the duration of the dry season also plays an important role. During the dry season, declining fat reserves make an increasing proportion of the population vulnerable to mortality. As a result, even moderate droughts may lead to substantial changes in population numbers.


Factors influencing mothers' reactions to intrafamily sexual abuse.
A mother's question of whether to believe her child's disclosure of intrafamily child sexual abuse is complex, with many factors influencing her conclusion. Variables related to the abuse and to the family's functioning are examined to determine if particular circumstances are too threatening to mothers, resulting in their disbelief. The findings indicate that the age of the victim, nature of the abuse, presence of the mother in the home during the abuse, relationship of the victim to the offender, prior physical abuse of the child, and alcohol abuse by the offender all contribute to mother's conclusion regarding the reported abuse. The majority of mothers do believe their child, with difficult situations and other family stressors occasionally detracting from a mother's willingness to accept the report.


Caffeine challenge and breath-holding duration in patients with panic disorder.
Breath-holding (BH) has been used as a simple probe to increase endogenous carbon dioxide (CO2). In patients with Panic Disorder (PD), lower baseline BH duration is associated with caffeine-induced panic attacks. In this paper, we assessed BH duration in PD patients in relation to panic attacks induced by caffeine intake. BH duration and state anxiety were assessed in 40 PD patients (12 males), both at baseline and after a 400-mg caffeine challenge test. Patients panicking after caffeine administration (14 patients, 4 males) exhibited a significant reduction of their post-challenge BH duration, while no change of the BH duration was observed in non-panicking patients (26 patients, 8 males). Reduction in post-challenge BH duration was not related to higher anxiety levels--as reflected in the State-Trait Anxiety Inventory-State Form scores--independently of the occurrence of a panic attack. Panickers exhibited significantly lower baseline BH duration, compared to non-panickers. Our findings indicate that in PD patients, caffeine-induced panic attacks are strongly associated with a significant reduction of BH duration at both pre- and post-challenge. Jointly, these findings suggest that in a subgroup of PD patients, sensitivity to endogenous CO2 accumulation may underlie both the lower BH durations and the caffeine-induced panic attacks. In this subgroup of PD patients, caffeine might exert its panicogenic properties through the exacerbation of patients' already pathological hypersensitivity to CO2 accumulation, as indicated by both the significant decrease of their BH duration at post-challenge and by their significantly lower baseline BH duration respectively.


Sonochemical and photosonochemical degradation of 4-chlorophenol in aqueous media.
The degradation of 4-chlorophenol (4-CP) in aqueous media by 516 kHz ultrasonic irradiation was investigated in order to clarify the degradation mechanism. The degradation of concentrated 4-CP solution by means of ultrasound, UV irradiation and their combined application was also studied. The obtained results indicate that *OH radical are the primary reactive species responsible for 4-CP ultrasonic degradation. Very little 4-CP degradation occurs if the sonolysis is carried out in the presence of the *OH radical scavenger tert-butyl alcohol, also indicating that little or no pyrolysis of the compound occurs. The dominant degradation mechanism is the reaction of substrate with *OH radicals at the gas bubble-liquid interface rather than high temperature direct pyrolysis in ultrasonic cavities. This mechanism can explain the lower degradation rate of the ionic form of 4-CP that is partly due to the rapid dissociation of *OH radicals in alkaline solutions. The sonochemical destruction of concentrated 4-CP aqueous solution is obtained with low rate. Coupling photolysis with ultrasound irradiation results in increased efficiency compared to the individual processes operating at common conditions. Interestingly, the photosonochemical decomposition rate constant is greater than the additive rate constants of the two processes. This may be the result of three different oxidative processes direct photochemical action, high frequency sonochemistry and reaction with ozone produced by UV irradiation of air, dissolved in liquid phase because of the geyser effect of ultrasound streaming. Additionally, the photodecomposition, at 254 nm, of hydrogen peroxide produced by ultrasound generating *OH radical can partly explain the destruction enhancement.


Benign cysts of the parotid gland.
Benign cysts of the parotid gland are not frequently diagnosed. They occur in any portion of the parotid gland and may be difficult to diagnose. They present with considerable histological variation in their linings. Three cases are presented of unilocular benign cystic lesions of the parotid gland that have been treated by superficial parotidectomy. Two of them were lined by a single or pseudostratified layer of cuboidal epithelium and were diagnosed as retention cysts. The third was a lympho-epithelial cyst and was lined by stratified squamous and partially by pseudostratified ciliated columnar epithelium. A review of the relevant literature is also presented.


Ultrasonically improved semi-hydrogenation of alkynes to (Z-)alkenes over novel lead-free Pd/Boehmite catalysts.
This paper reports the application of ultrasound in the semi-hydrogenation of alkynes over two novel Pd/Boehmite catalysts. The semi-hydrogenations of phenylacetylene, diphenylacetylene and 2-butyne-1,4-diol have either been investigated in an ultrasonic bath under atmospheric hydrogen pressure, or in an ultrasonic horn reactor under 0.1-0.5MPa hydrogen pressure. Alkyne hydrogenation was suppressed by sonication under atmospheric hydrogen pressure, but promoted by sonication under 0.1MPa of hydrogen pressure. Sonication increased selectivity towards the semi-hydrogenated products in both cases. Catalyst loading, hydrogen pressure, temperature and the presence of quinoline, all impacted on hydrogenation rate, activity and selectivity to semi-hydrogenated products. Palladium leaching from the catalyst was evaluated in ethanol and hexane both under plain stirring and sonication.


In vitro inhibition effect of some chalcones on erythrocyte carbonic anhydrase I and II.
In this study, 4'-(phenylurenyl/thiourenyl)chalcones (14-25) were prepared from 4'-(phenylurenyl/thiourenyl)acetophenones and benzaldehyde derivatives by Claisen-Schmidt condensation. In vitro inhibition effects of chalcone derivatives on purified carbonic anhydrase I and carbonic anhydrase II were investigated by using the CO2 hydration method of Maren. The result showed that all the synthesized compounds inhibited the CA isoenzymes activity. 18 and 19 were found to be most active (IC50 = 25.41 μM and 23.06 μM) for hCA I, respectively. For hCA II, 24 is the most active compound (IC50 = 14.40 μM).


The chemical and enzymatic interaction of glutathione with the fungal metabolite, fusarin C.
Glutathione (GSH) interacts both chemically and enzymatically with fusarin C, a mutagenic metabolite produced by Fusarium moniliforme. The chemical reaction, which is pH-dependent, results in the formation of both fusarin A and a compound that lacks the 2-pyrrolidone moiety thereby suggesting an interaction at the C-13-C-14 epoxide. Enzymatic interaction of fusarin C with GSH also appears to occur at this site as fusarins A and D, which lack the epoxide, do not serve as substrates for GSH-S-transferases. The interaction of GSH with fusarin C appears to be an important deactivation step which could explain the lack of carcinogenicity observed for fusarin C in rats.


Synthesis and anticancer activities of novel 8-azapurine carbocyclic nucleoside hydrazones.
A series of novel 8-azapurine carbocyclic nucleoside hydrazones were synthesized through a useful procedure starting from amino alcohol and pyrimido dichloride. All the products were characterized by (1)H NMR, (13)C NMR and HRMS spectral analysis and the stereochemical structure of key intermediate was also confirmed by a single crystal X-ray diffraction crystallographic analysis. Moreover, the anticancer activities were evaluated in vitro against human liver cancer Huh-7 cell line and human breast cancer A549 cell line.


The effect of ghrelin on the fibrosis of chicken bursa of fabricius infected with infectious bursal disease virus.
The present study aimed to investigate the effect of ghrelin on the degree of bursa of Fabricius (BF) fibrosis in infectious bursal disease virus-infected chickens. Specific pathogen free (SPF) chicks were divided into four groups. One group was used as the control ("C"). The other three groups were inoculated with IBDV on the 19th day, of which two were injected intraperitoneally with 0.5 nmol ("LG") or 1.0 nmol ("HG") ghrelin/100 g weight from the 18th day to the 22nd day, and one was injected intraperitoneally with PBS ("I"). Hematoxylin-eosin staining, Masson's staining, and quantitative real-time PCR were used to determine the effects of ghrelin on the degree of inflammatory cell infiltration, the bursal fibrosis degree, and the expression of TGF-β and MMP-9 mRNA in IBDV-infected SPF chicks. The results showed that ghrelin administration reduced the number of infiltrated inflammatory cells in BF from 5 dpi and significantly attenuated the degree of fibrosis induced by IBDV from 2 dpi to 7 dpi (P < 0.05). Moreover, the TGF-β expression in the LG and HG groups were significantly or highly significantly lower (P < 0.05 or P < 0.01) than those of I group from 2 dpi to 5 dpi. In addition, ghrelin administration downregulated MMP-9 expression evoked by IBDV from 2 dpi to 7 dpi (P < 0.05 or P < 0.01). These results suggested that ghrelin attenuated the bursal fibrosis degree of IBDV-infected SPF chicks by reducing the number of inflammatory cells and by decreasing the expression of TGF-β and MMP-9, which shortened the process of bursa recovery.


Spectrofluorimetric determination of 2-chloro-2'-deoxyadenosine (cladribine) in human plasma by photochemical reaction and chloroacetaldehyde derivatization.
A quantitative fluorescence assay for 2-chloro-2'-deoxyadenosine (cladribine, leustatin, 2-CdA) in human plasma is described. The drug was isolated from plasma by ethyl acetate extraction and derivatized by a two-step procedure in which 2'-deoxyisoguanosine (2'-diG) was first prepared by UV irradiation of 2-CdA and was then treated with chloroacetaldehyde to form the fluorescent derivative, 1,N6-etheno-2'-deoxyisoguanosine. Fluorescence intensity of the solutions was measured using an excitation wavelength of 275 nm and emission of 397 nm. The analytical measuring range of the method extends from about 1 microgram/l to at least 100 micrograms/l.


Neurofibrillary tangles induced by a sclerosing angioma.
A sclerosing angioma in the frontal cortex of a 40 year old woman produced local pressure, with resulting alteration of the blood-brain barrier. In the narrow cortical zone affected by chronic pressure, the level of aluminum was significantly elevated; and all neurons had neurofibrillary tangles of the Alzheimer type.


The kynurenine pathway and bipolar disorder: intersection of the monoaminergic and glutamatergic systems and immune response.
Dysfunction in a wide array of systems-including the immune, monoaminergic, and glutamatergic systems-is implicated in the pathophysiology of depression. One potential intersection point for these three systems is the kynurenine (KYN) pathway. This study explored the impact of the prototypic glutamatergic modulator ketamine on the endogenous KYN pathway in individuals with bipolar depression (BD), as well as the relationship between response to ketamine and depression-related behavioral and peripheral inflammatory markers. Thirty-nine participants with treatment-resistant BD (23 F, ages 18-65) received a single ketamine infusion (0.5 mg/kg) over 40 min. KYN pathway analytes-including plasma concentrations of indoleamine 2,3-dioxygenase (IDO), KYN, kynurenic acid (KynA), and quinolinic acid (QA)-were assessed at baseline (pre-infusion), 230 min, day 1, and day 3 post-ketamine. General linear models with restricted maximum likelihood estimation and robust sandwich variance estimators were implemented. A repeated effect of time was used to model the covariance of the residuals with an unstructured matrix. After controlling for age, sex, and body mass index (BMI), post-ketamine IDO levels were significantly lower than baseline at all three time points. Conversely, ketamine treatment significantly increased KYN and KynA levels at days 1 and 3 versus baseline. No change in QA levels was observed post-ketamine. A lower post-ketamine ratio of QA/KYN was observed at day 1. In addition, baseline levels of proinflammatory cytokines and behavioral measures predicted KYN pathway changes post ketamine. The results suggest that, in addition to having rapid and sustained antidepressant effects in BD participants, ketamine also impacts key components of the KYN pathway.


[What prosthodontic therapy should we select for periodontally compromised patients? Part 2: Review of the literature focusing on conventional prosthodontic therapy for periodontally compromised patients and clinical implication (RPD vs FPD vs implant)].
To review the clinical literature on fixed partial denture (FPD) and removable partial denture (RPD)treatment for periodontally compromised patients with partial dentate. In addition, prosthodontic management in periodontitis-susceptible subjects was evaluated from the results of Part 1 and Part 2. Clinical studies that documented survival rates of FPD in periodontally compromised patients were selected and reviewed. There was no RPD study that fulfilled the criteria of this review paper. On the other hand, 8 reports that were reviewed in this study showed good survival rate of FPD in long-term clinical results. Since the number of reports on RPD is very few, it was difficult to evaluate the RPD treatment for periodontally compromised patients. From the results of some long-term follow-up retrospective studies, however, it was suggested that FPD of high-risk design showed excellent results. Regarding management in periodontits- susceptible subjects, it should be discussed whether positive prosthodontic treatment is necessary. Strict plaque control by both doctors and patients before/after treatment is indispensable for prosthodontic management in periodontally compromised patients.


Accessory function of human leukemic cell lines: properties of B and B-K562 hybrid cell lines.
The accessory function (AF) of various B cell lines has been investigated by studying their ability to replace monocytes inducing the proliferation of highly purified T lymphocytes in the presence of phytohemagglutinin. AF could be exerted by B cells from different origin, including Epstein-Barr virus (EBV) transformed lymphoblastoid cell lines (LCL), Burkitt's lymphoma (BL)-derived lines, either EBV-positive or not, pre-B and B leukemias and lymphomas. The EBV-converted BJAB-B95 BL cells could exert an AF as efficient as BJAB cells, their EBV-negative counterparts, which demonstrates that EBV itself does not play any role in this function. The HLA-DR antigen-negative BL-K562 hybrids PUTKO and DUTKO, T220.127.116.11 cells which derived from an HLA-DR-negative variant of the T51 LCL and 721.84.5 cells from a mutagenically dissected HLA-DR-negative clone of the 721 LCL, also exerted very efficient AF. 721 LCL, PUTKO and DUTKO hybrids could produce interleukin 1 activity when triggered with 12-O-tetradecanoyl-phorbol 13-acetate (TPA). Furthermore, addition of anti-DR monoclonal antibodies which blocked completely the AF of the B cell lines in mixed lymphocyte-tumor cell reaction did not affect the mitogen-triggered AF exerted by the same B cell lines. The induction of cellular differentiation with TPA markedly reduced the AF exerted by all B cell lines studied as well as by the hybrid cells DUTKO. By contrast, the PUTKO hybrid was unsensitive to sodium butyrate and TPA treatments, which were unable to abrogate its AF. Taken together, these data indicate that the AF in mitogen-induced T lymphocyte responses is dependent upon some precise maturational stages of accessory cells and HLA-DR antigen expression is not required for AF in mitogen-induced proliferation assays.


Extensive metastasectomy for a single lesion with cardiac invasion.
Cardiac metastases are rare and considered a sign of end-stage oncologic disease. A lack of telltale clinical symptoms leads to late detection, thus usually limiting surgical options. Modern diagnostic tools such as fluorodeoxyglucose positron emission tomography, single-photon emission computed tomography, or cardiac magnetic resonance imaging could allow for timely detection and open up new therapeutic options. Highly selected oligometastatic patients may benefit from extensive surgical procedures including transmyocardial resection.


Effect of Zn2+ and temperature on the conformational equilibrium of single-stranded polyA in neutral solutions.
Effect of Zn(2+) ions on the conformation of polyA in cacodilic buffer at pH 7 was investigated by differential UV spectroscopy (DUV) and by thermal denaturation. The shapes of the DUV spectra and melting curves suggest a transition of polyA into a more ordered "metallized", possibly double-helical conformation at Zn(2+) concentrations above 3×10(-5) M. A phase diagram of polyA complexes with Zn(2+) was constructed for the temperature range from 20 °C to 95 °C and Zn(2+) concentrations between 10(-5) M and 5×10(-4) M. It was found that the transition of a single strand into the "metallized" form is possible only if the length of the disordered single-stranded region becomes larger than a certain critical value, ranging between 98% and 78% as the metal concentration increases from 3×10(-5) to 5×10(-4) M.


The relationship between nutrition, infection, and immunity.
The importance of nutrition in every aspect of human physiology slowly is being appreciated clinically. However, it is clear that immune function is highly dependent on the nutritional status of the individual. That status, in turn, is dependent on the nutritional intake and the metabolic machinery of the individual.


Leptopilina heterotoma and L. boulardi: strategies to avoid cellular defense responses of Drosophila melanogaster.
Eggs of three strains of the cynipid parasitoid Leptopilina heterotoma and a Tunisian strain (G317) of L. boulardi are not encapsulated by hemocytes of Drosophila melanogaster hosts, but the eggs of a Congolese strain (L104) of L. boulardi are encapsulated. To determine the reason for the difference in host response against the parasitoid eggs, lamellocytes (hemocytes that encapsulate foreign objects and form capsules around endogenous tissues in melanotic tumor mutants) were examined in host larvae parasitized by the five Leptopilina strains. Parasitization by the three L. heterotoma strains affected the morphology of host lamellocytes and suppressed endogenous melanotic capsule formation in melanotic tumor hosts. L104 did not alter the morphology of host lamellocytes nor block tumor formation in melanotic tumor mutant hosts. The morphology of some lamellocytes was affected by G317 parasitization but host lamellocytes were still capable of forming melanotic tumors and encapsulating dead supernumerary parasitoid larvae. Therefore, the eggs of strains affecting lamellocyte morphology are protected from encapsulation by the host's blood cells. L. heterotoma eggs float freely in the host hemocoel but L. boulardi eggs are attached to host tissue surfaces. Lamellocytes cannot infiltrate the attachment site so the capsule around the L104 egg remains incomplete. The wasp larva uses this gap in the capsule as an escape hatch for emergence.


Does endocytosis occur in fungal hyphae?
The evidence and arguments for and against the occurrence of endocytosis in fungal hyphae are summarized. The balance of evidence is in favour of the existence of endocytosis. This is supported by an analysis of the recently sequenced Neurospora genome which strongly suggests that this fungus possesses the complex protein machinery required to conduct endocytosis.


Effect of moist heat sterilisation on the pyrogenicity of cell wall components from Staphylococcus aureus.
As opposed to endotoxins very little is known about the heat resistance of Gram positive pyrogens. The aim of this study is to examine the pyrogenic activity of the cell wall components lipoteichoic acid and peptidoglycan from Staphylococcus aureus after moist heat sterilisation. The pyrogenic activity is determined as the ability of the substances to induce interleukin-6 secretion in Mono Mac 6 cells. The standard terminal moist heat sterilisation procedures (121 degrees C for 15min and 134 degrees C for 3min) are not able to inactivate the pyrogenic activity of S. aureus lipoteichoic acid and peptidoglycan. However after longer treatment times the pyrogenic activity of lipoteichoic acid is removed at both 121 degrees C and 134 degrees C. In contrast the activity of peptidoglycan is not removed after 160min at neither 121 degrees C nor 134 degrees C where only a 2-log reduction is obtained. In conclusion the terminal moist heat sterilisation procedures described by the European Pharmacopoeia are not able to inactivate the interleukin-6 inducing activity of S. aureus lipoteichoic acid and peptidoglycan.


Obligate bacterial endosymbionts limit thermal tolerance of insect host species.
The thermal tolerance of an organism limits its ecological and geographic ranges and is potentially affected by dependence on temperature-sensitive symbiotic partners. Aphid species vary widely in heat sensitivity, but almost all aphids are dependent on the nutrient-provisioning intracellular bacterium Buchnera, which has evolved with aphids for 100 million years and which has a reduced genome potentially limiting heat tolerance. We addressed whether heat sensitivity of Buchnera underlies variation in thermal tolerance among 5 aphid species. We measured how heat exposure of juvenile aphids affects later survival, maturation time, and fecundity. At one extreme, heat exposure of Aphis gossypii enhanced fecundity and had no effect on the Buchnera titer. In contrast, heat suppressed Buchnera populations in Aphis fabae, which suffered elevated mortality, delayed development and reduced fecundity. Likewise, in Acyrthosiphon kondoi and Acyrthosiphon pisum, heat caused rapid declines in Buchnera numbers, as well as reduced survivorship, development rate, and fecundity. Fecundity following heat exposure is severely decreased by a Buchnera mutation that suppresses the transcriptional response of a gene encoding a small heat shock protein. Similarly, absence of this Buchnera heat shock gene may explain the heat sensitivity of Ap. fabae Fluorescent in situ hybridization revealed heat-induced deformation and shrinkage of bacteriocytes in heat-sensitive species but not in heat-tolerant species. Sensitive and tolerant species also differed in numbers and transcriptional responses of heat shock genes. These results show that shifts in Buchnera heat sensitivity contribute to host variation in heat tolerance.


Emergency laparoscopic intervention for fibrous band-induced intestinal obstruction and ischemia associated with Meckel's diverticulum: A case report.
Meckel's diverticulum (MD) is a common congenital malformation of the digestive tract, often asymptomatic but occasionally leading to complications such as bowel obstruction and ischemia. Timely recognition and treatment of these complications are crucial. We report the case of a 27-year-old male patient presenting with complete intestinal obstruction and ischemia of the ileum due to a fibrous band associated with MD. The patient presented with severe abdominal pain lasting for 10 h. Physical examination revealed a distended abdomen, antalgic position, and positive decompression. Laboratory tests showed leukocytosis and elevated lactic acid levels. Computed tomography revealed dilated small bowel loops with signs of intestinal ischemia. Emergency exploratory laparoscopy confirmed a complete ileum with ischemia and identified a fibrous band originating from the mesentery, strangulating the affected loop. The fibrous band was dissected and sectioned, confirming its association with the MD, which was resected with subsequent recovery of peristalsis and vascularization of the compromised segment. The patient had a favorable postoperative recovery without complications. MD is a rare cause of bowel obstruction, requiring a high index of suspicion for diagnosis. Despite the challenges in preoperative identification, early surgical intervention is crucial to prevent adverse outcomes. This case emphasizes the importance of promptly recognizing and managing MD-related complications to optimize patient outcomes. MD should be considered in cases of acute occlusive abdomen, despite its infrequent occurrence. Early diagnosis and timely surgical intervention are essential to minimize morbidity and mortality associated with MD-related complications.


Gangliosides suppression of murine lymphoproliferation and interleukin 1 production.
Studies were carried out to determine whether inhibition of gangliosides on lymphoproliferation was related to interleukin (IL)-1. The results showed that gangliosides, GM1 and GT1b were able to inhibit the proliferation of spleen lymphocytes from C57BL/6J mice in dose-dependent fashion, whereas asialo-GM1 was not inhibitory. However, gangliosides, GM1 and asialo-GM1 did not suppress the production of IL-1 in Salmonella typhosa lipopolysaccharide (LPS)-induced peritoneal adherent cells. Various types of LPS including S. enteritidis, S. minnesota and Escherichia coli 055:B5 were used to stimulate the production of IL-1 in adherent cell cultures. The IL-1 production was not affected by gangliosides, GD1a and GD1b. Although GT1b suppressed IL-1 production of human monocytes to 82% of control level it did not, however, affect the IL-1 production of murine adherent cells. Thus, the inhibitory mechanism of gangliosides on murine immune cells remains unclear, and warrants further study.


Management for a patient of moyamoya disease presenting with ischemic stroke in the first trimester of pregnancy.
We report an extremely rare case of a 27-year-old woman presenting with ischemic stroke as an initial manifestation of moyamoya disease in the first trimester of pregnancy. We conducted an artificial abortion when her neurological symptoms rapidly became refractory to optimal antithrombotic treatments. The progression of neurologic deficits stopped immediately after abortion, resulting in recovery to independence, with slight motor aphasia and right hemiparesis due to improved cerebral flow. We highlight rapid artificial abortion combined with antithrombotic treatment for patients of moyamoya disease with pregnancy-associated ischemic stroke as an appropriate treatment to correct hemodynamic instability and suppress the progression of neurological symptoms.


Hybrid quantum and classical methods for computing kinetic isotope effects of chemical reactions in solutions and in enzymes.
A method for incorporating quantum mechanics into enzyme kinetics modeling is presented. Three aspects are emphasized: 1) combined quantum mechanical and molecular mechanical methods are used to represent the potential energy surface for modeling bond forming and breaking processes, 2) instantaneous normal mode analyses are used to incorporate quantum vibrational free energies to the classical potential of mean force, and 3) multidimensional tunneling methods are used to estimate quantum effects on the reaction coordinate motion. Centroid path integral simulations are described to make quantum corrections to the classical potential of mean force. In this method, the nuclear quantum vibrational and tunneling contributions are not separable. An integrated centroid path integral-free energy perturbation and umbrella sampling (PI-FEP/UM) method along with a bisection sampling procedure was summarized, which provides an accurate, easily convergent method for computing kinetic isotope effects for chemical reactions in solution and in enzymes. In the ensemble-averaged variational transition state theory with multidimensional tunneling (EA-VTST/MT), these three aspects of quantum mechanical effects can be individually treated, providing useful insights into the mechanism of enzymatic reactions. These methods are illustrated by applications to a model process in the gas phase, the decarboxylation reaction of N-methyl picolinate in water, and the proton abstraction and reprotonation process catalyzed by alanine racemase. These examples show that the incorporation of quantum mechanical effects is essential for enzyme kinetics simulations.


Assessment of CA1 injury after global ischemia using supervised 2D analyses of nuclear pyknosis.
Selective neuronal vulnerability is a common theme in both acute and chronic diseases affecting the nervous system. This phenomenon is particularly conspicuous after global cerebral ischemia wherein CA1 pyramidal neurons undergo delayed death while surrounding hippocampal regions are relatively spared. While injury in this model can be easily demonstrated using either histological or immunological stains, current methods used to assess the cellular injury present in these biological images lack the precision required to adequately compare treatment effects. To address this shortcoming, we devised a supervised work-flow that can be used to quantify ischemia-induced nuclear condensation using microscopic images. And while we demonstrate the utility of this technique using models of ischemic brain injury, the approach can be readily applied to other paradigms in which programmed cell death is a major component.


Reproducibility of electrical sensory testing in lower urinary tract at weekly intervals in healthy volunteers and women with non-neurogenic detrusor overactivity.
To evaluate the reproducibility of a standardized technique of current perception threshold measurements with square wave and sine wave current, with monopolar and bipolar electrodes in a cohort of patients with overactive bladder (OAB) and healthy volunteers. We enrolled 6 female nulliparous healthy volunteers and 11 female patients with OAB. Current perception threshold measurements of the bladder were performed using several techniques. The same sequence was used for all 3 measurements performed at weekly intervals to assess the reproducibility. An intraclass correlation coefficient >0.75 was considered as very good reproducibility. All the different stimulation forms were well tolerated by all participants and all experienced stimulation at 2.5-Hz and 95-Hz square wave current. The results with sine wave current showed less uniform results. The intraclass correlation showed the greatest reproducibility with bipolar stimulation at a current of 95 Hz. Sine wave current at 5 Hz and 250 Hz showed low reproducibility. Bipolar stimulation had significantly lower thresholds than monopolar stimulation (P < .0001). No significant differences were found between the healthy subjects and the patients with OAB for the 4 settings. In the healthy volunteers and patients with OAB, the determination of the current perception threshold in the bladder using a standardized method is feasible and well tolerated, with both bipolar and monopolar stimulation. In our study, square wave current showed strong reproducibility at weekly intervals at 2.5 Hz and 95 Hz. However, sinusoid current gave weak reproducibility.


Two pairs of farnesyl phenolic enantiomers as natural nitric oxide inhibitors from Ganoderma sinense.
Four new farnesyl phenolic compounds, ganosinensols A-D (1-4) were isolated from the 95% EtOH extract of the fruiting bodies of Ganoderma sinense. Two pairs of enantiomers, 1/2, and 3/4 were isolated by HPLC using a Daicel Chiralpak IE column. Their structures were elucidated from extensive spectroscopic analyses and comparison with literature data. The absolute configurations of 1-4 were assigned by ECD spectra. All of these isolated compounds showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values from 1.15 to 2.26μM.


Facile All-Optical Method for In Situ Detection of Low Amounts of Ammonia.
As a key precursor for nitrogenous compounds and fertilizer, ammonia affects our lives in numerous ways. Rapid and sensitive detection of ammonia is essential, both in environmental monitoring and in process control for industrial production. Here we report a novel and nonperturbative method that allows rapid detection of ammonia at low concentrations, based on the all-optical detection of surface-enhanced Raman signals. We show that this simple and affordable approach enables ammonia probing at selected regions of interest with high spatial resolution, making in situ and operando observations possible.


Fermentation of araticum, baru, and pequi by-products by probiotic strains: effects on microorganisms, short-chain fatty acids, and bioactive compounds.
Fruit by-products, due to their unique chemical composition containing dietary fibers and bioactive compounds, may favor the growth of probiotic strains. This study evaluated the fermentation of araticum, baru, and pequi by-products using Lactobacillus acidophilus (La-5, LA3, and NCFM) and Bifidobacterium animalis subsp. lactis (Bb-12) probiotic strains. We assessed probiotic viability, short-chain fatty acid levels, and bioactive compound levels after 48 h of fermentation. Araticum and pequi by-products led to counts higher than 6 log CFU/mL after 48-h fermentation for all Lactobacillus strains, but only the araticum by-product supported the growth of the Bb-12 strain. Fermentation of araticum by-product resulted in greater amounts of acetate (39.97 mM for LA3 and 39.08 mM for NCFM) and propionate (0.20 mM for NCFM), while baru by-product showed greater amounts of butyrate (0.20 mM for La-5 and Bb-12). Fermentation of araticum and baru by-products resulted in an increase in bioactive compounds, with the latter showing total phenolic compounds and antioxidant activity from 1.4 to 1.7 and from 1.3 to 3.1 times higher, respectively, than the negative control treatment. Araticum by-product exhibited a higher potential for prebiotic effects, and fermentation by the tested probiotic strains is essential to increase bioactive compound levels.


Does the fish-infecting Trypanosoma micropteri belong to Trypanosoma carassii?
Recently, based on a limited morphological characterisation and partial 18S rRNA gene sequence, Jiang et al. (2019) described Trypanosoma micropteri Jiang, Lu, Du, Wang, Hu, Su et Li, 2019 as a new pathogen of farmed fish. Here we provide evidence based on the expanded sequence dataset, morphology and experimental infections that this trypanosome does not warrant the establishment as a new species, because it is conspecific with the long-term known Trypanosoma carassii Mitrophanow, 1883, a common haemoflagellate parasite of freshwater fish. The former taxon thus becomes a new junior synonym of T. carassii.


Alfa2-adrenoblockers attenuate the elevated plasma cholesterol, anxiety levels and restore impaired spatial memory of rats under the chronic noise exposure.
Noise is considered one of the environmental hazards that negatively affect health. It can cause damage to the auditory, neurological, hormonal and cardiovascular systems, in addition to impairing psychological and cognitive functions. Considering the significance of vascular disturbances and oxidative stress in the development of the aforementioned negative effects, the purpose of our investigation was to study the level of high density lipoprotein-cholesterol (HDL-Cl), low density lipoprotein-cholesterol (LDL-Cl), and total cholesterol (TCl) in plasma, in addition to the behavioral characteristics of white rats, and the effects of the α2-adrenoblockers beditin and mesedin to reveal their antiatherogenic effect during noise exposure. The "Open field" and "Y-maze" tests were used in order to evaluate the behavioral states of the rats. Investigations were carried out on albino rats divided into 4 groups. The 1st group of rats served as a control. The 2nd, 3rd and 4th groups were exposed to 91 dBA of noise; the duration of exposure was 8 h per day for 60 days. The 3rd group was injected with beditin and the 4th group with mesedin, both intraperitoneally and repeatedly. According to our results, the chronic exposure to high-volume noise leads to the increase of plasma TCl and LDL-Cl concentrations and the decrease of HDL-Cl levels, resulting in increase of the atherogenic coefficient, which is estimated to be one of the main cardiovascular disease risk factors. The "Open field" and "Y-maze" tests revealed that chronic noise exposure caused disturbances in the behavioral activity, a noise duration-dependent delay in movement and orientation, increased anxiety and deficit in the animals' spatial memory. The administration of α2-adrenoblockers to the noise-exposed animals had a regulatoryeffects of varying intensities, depending on the medication used and the studied parameters under the conditions of chronic acoustic stress.


Elastic fibers: building bridges between cells and their matrix.
Extracellular elastic fibers confer resilience and flexibility to tissues. Recent studies have identified a protein, fibulin-5, that connects these fibers to cells and regulates their assembly and organization.


Ontogeny of substance P-containing structures in the ocular tissue of the rat: an immunohistochemical analysis.
The ontogeny of the substance P-like immunoreactivity (SPI) containing system in the ocular tissue of the rat was examined by means of the indirect immunofluorescence method. SPI-containing amacrine cells first appeared at postnatal day 4 and displaced SPI-containing amacrine cells at postnatal day 5. After this time, they developed markedly reaching their maximum content and distribution at postnatal day 14. On the other hand, SPI-containing cells in the trigeminal ganglion were first seen at gestational day 17 and reached their maximum content at birth. SPI-containing fibers in the cornea and uvea were first observed at gestational days 17-19. The SPI-containing fibers in the iris reached their maximum content at birth, while those in the cornea, choroid and ciliary body were fully developed at postnatal day 3. In the adult rats, numerous SPI structures were still seen in the ocular tissue, retina, cornea and uvea. These findings suggest that SPI might play some role in the developing ocular tissue in addition to its neurotransmitter or neuromodulator role in the adult, because SPI structures appear in the retina before establishment of synaptogenesis and in the cornea and uvea during the fetal stage.


Ecological and Evolutionary Consequences of Anticancer Adaptations.
Cellular cheating leading to cancers exists in all branches of multicellular life, favoring the evolution of adaptations to avoid or suppress malignant progression, and/or to alleviate its fitness consequences. Ecologists have until recently largely neglected the importance of cancer cells for animal ecology, presumably because they did not consider either the potential ecological or evolutionary consequences of anticancer adaptations. Here, we review the diverse ways in which the evolution of anticancer adaptations has significantly constrained several aspects of the evolutionary ecology of multicellular organisms at the cell, individual, population, species, and ecosystem levels and suggest some avenues for future research.


Effect of the amount of thickness reduction on color and translucency of dental monolithic zirconia ceramics.
This study investigated the effect of amount of thickness reduction on color and translucency of dental monolithic zirconia ceramics. One-hundred sixty-five monolithic zirconia specimens (16.3 mm × 16.3 mm × 2.0 mm) were divided into 5 groups (Group I to V) according to the number of A2-coloring liquid applications. Each group was then divided into 11 subgroups by reducing the thickness up to 1.0 mm in 0.1-mm increments (Subgroup 0 to 10, n=3). Colors and spectral distributions were measured according to CIELAB on a reflection spectrophotometer. All measurements were performed on five different areas of each specimen. Color difference (ΔE(*) ab) and translucency parameter (TP) were calculated. Data were analyzed using one-way ANOVA and multiple comparison Scheffé test (α=.05). There were significant differences in CIE L(*) between Subgroup 0 and other subgroups in all groups. CIE a(*) increased (0.52<R(2)<0.73), while CIE b(*) decreased (0.00<R(2)<0.74) in all groups with increasing thickness reduction. Perceptible color differences (ΔE(*) ab>3.7) were obtained between Subgroup 0 and other subgroups. TP values generally increased as the thickness reduction increased in all groups (R(2)>0.89, P<.001). Increasing thickness reduction reduces lightness and increases a reddish, bluish appearance, and translucency of monolithic zirconia ceramics.


Risk factors for severe acute kidney injury among patients with rhabdomyolysis.
Acute kidney injury (AKI) is a life-threatening complication of rhabdomyolysis (RM). The aim of the present study was to assess patients at high risk for the occurrence of severe AKI defined as stage II or III of KDIGO classification and in-hospital mortality of AKI following RM. We performed a retrospective study of patients with creatine kinase levels > 1000 U/L, who were admitted to the West China Hospital of Sichuan University between January 2011 and March 2019. The sociodemographic, clinical and laboratory data of these patients were obtained from an electronic medical records database, and univariate and multivariate regression analyses were subsequently conducted. For the 329 patients included in our study, the incidence of AKI was 61.4% and the proportion of stage I, stage II, stage III were 18.8, 14.9 and 66.3%, respectively. The overall mortality rate was 19.8%; furthermore, patients with AKI tended to have higher mortality rates than those without AKI (24.8% vs. 11.8%; P < 0.01). The clinical conditions most frequently associated with RM were trauma (28.3%), sepsis (14.6%), bee sting (12.8%), thoracic and abdominal surgery (11.2%) and exercise (7.0%). Furthermore, patients with RM resulting from sepsis, bee sting and acute alcoholism were more susceptible to severe AKI. The risk factors for the occurrence of stage II-III AKI among RM patients included hypertension (OR = 2.702), high levels of white blood cell count (OR = 1.054), increased triglycerides (OR = 1.260), low level of high-density lipoprotein cholesterol (OR = 0.318), elevated serum phosphorus (OR = 5.727), 5000<CK ≤ 10,000 U/L (OR = 2.617) and CK>10,000 U/L (OR = 8.093). Age ≥ 60 years (OR = 2.946), sepsis (OR = 3.206) and elevated prothrombin time (OR = 1.079) were independent risk factors for in-hospital mortality in RM patients with AKI. AKI is independently associated with mortality in patients with RM, and several risk factors were found to be associated with the occurrence of severe AKI and in-hospital mortality. These findings suggest that, to improve the quality of medical care, the early prevention of AKI should focus on high-risk patients and more effective management.


The patterns of brain gangliosides of Rana catesbeiana during metamorphosis and in the adult.
Ganglioside patterns were quantitated for brains of bullfrog (Rana catesbeiana) at three stages of metamorphosis and adult. At each stage nine gangliosides were identified by mobility on silica gel thin-layer chromatograms, and quantitated on the basis of sialic acid content. A single band with chromatographic mobility close to that of GD2, and doublets close to GT1b and GQ were quantitatively the major ones (over 16% each). Doublets close to GM1 and GD1b and a single band slightly behind GD1a made up 5-10% each. A doublet comigrating with GM3, and bands close to GM2 (trace) and GD3 were present in smaller amounts. The only developmental trend was a slight increase in the proportion of the band close to GD3 from 2.4% (early prometamorphic phase) to 9.1% (adult). This suggests that changes in the regenerative capacity of frog nervous tissues during metamorphosis are due to changes other than ganglioside composition.


Food Marketing to - and Research on - Children: New Directions for Regulation in the United States.
As countries around the world work to restrict unhealthy food and beverage marketing to children, the U.S. remains reliant on industry-self regulation. The First Amendment's protection for commercial speech and previous gutting of the Federal Trade Commission's authority pose barriers to restricting food marketing to children. However, false, unfair, and deceptive acts and practices remain subject to regulation and provide an avenue to address marketing to young children, modern practices that have evaded regulation, and gaps in the food and beverage industry's self-regulatory approach.


Tolerance and accumulation of copper in the salt-marsh shrub Halimione portulacoides.
The present study evaluated the tolerance and accumulation potential in the salt-marsh shrub Halimione portulacoides under moderate and high external Cu levels. A greenhouse experiment was conducted in order to investigate the effects of a range of external Cu concentrations (0 to 60 mmol l(-1)) on growth and photosynthetic performance by measuring gas exchange, chlorophyll fluorescence parameters and photosynthetic pigments. We also determined total copper, nitrogen, phosphorus and sulfur concentrations in the plant tissues. H. portulacoides survived with external Cu concentrations of up to 35 mmol Cu l(-1), although the excess of metal resulted in a biomass reduction of 48%. The effects of Cu on growth were linked to a drastic reduction in net photosynthesis. However, H. portulacoides tolerated Cu levels of up to 15 mmol Cu l(-1) without suffering adverse physiological effects. Our results indicate that this species could play an important role in the restoration of Cu-contaminated soils.


Prospective randomized comparison of quality of regenerate in distraction osteogenesis of ring versus monolateral fixator in patients with infected nonunion of the tibia using digital radiographs and CT.
In this randomized study, we aimed to compare quality of regenerate in monolateral versus circular frame fixation in 30 patients with infected nonunion of tibia. Both groups were comparable in demographic and injury characteristics. A phantom (aluminium step wedge of increasing thickness) was designed to compare the density of regenerate on radiographs. A CT scan was performed at three and six months postoperatively to assess regenerate density. A total of 30 patients (29 male, one female; mean age 32.54 years (18 to 60)) with an infected nonunion of a tibial fracture presenting to our tertiary institute between June 2011 and April 2016 were included in the study. The regenerate mineralization on radiographs was comparable in both groups at two, four, six, and ten months' follow-up but the rail fixator group had statistically significant higher grades of mineralization when compared with the circular frame group at eight and 12 months' follow-up. The regenerate mineralization was also higher in the rail fixator group than in the circular frame group on CT at three and six months, although this difference was not statistically significant. Overall, the regenerate mineralization was higher in the monolateral than the circular frame group. A monolateral fixator may be preferred in patients with infected nonunion of the tibia with bone defects up to 7 cm. Cite this article: Bone Joint J 2019;101-B:1416-1422.


Water solubility enhancement effects of some polychlorinated organic pollutants by dissolved organic carbon from a soil with a higher organic carbon content.
To elucidate the role of a soil humic acid (HA) in the transport of polychlorinated organic pollutants (PCOPs), such as polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and coplanar-polychlorinated biphenyls, their partition coefficients (Kdoc) into an HA were compared with their adsorption coefficients (KOC) for a soil with a higher organic carbon (OC) content. The soil sample (ando soil) used in the present study was collected in the same location as the HA. The log Kdoc values were positively correlated with logarithm of octanol-water partition coefficients (log KOW) of the PCOPs, indicating that the partitioning of PCOPs into the HA was mainly due to hydrophobic interactions. However, the correlation between log Kdoc and log KOC was negative. This can be attributed to the enhanced water solubility of the PCOPs as the result of the dissolved organic matter from the soil. That is, when the more hydrophobic PCOPs with higher log KOW values are partitioned into the HA, then the larger quantities of PCOPs that are partitioned into the HA are able to dissolve in the aqueous phase. These results suggest that, in a soil with a higher OC content, the HA can serve as more effective carrier of PCOPs from the soil to an aquatic environment.


Postural adaptations to repeated optic flow stimulation in older adults.
The purpose of this study is to understand the processes of adaptation (changes in within-trial postural responses) and habituation (reductions in between-trial postural responses) to visual cues in older and young adults. Of particular interest were responses to sudden increases in optic flow magnitude. The postural sway of 25 healthy young adults and 24 healthy older adults was measured while subjects viewed anterior-posterior 0.4 Hz sinusoidal optic flow for 45 s. Three trials for each of three conditions were performed: (1) constant 12 cm optic flow amplitude (24 cm peak-to-peak), (2) constant 4 cm amplitude (8 cm p-t-p), and (3) a transition in amplitude from 4 to 12 cm. The average power of head sway velocity (P(vel)) was calculated for consecutive 5s intervals during the trial to examine the changes in sway within and between trials. A mixed factor repeated measures ANOVA was performed to examine the effects of subject Group, Trial, and Interval on the P(vel). P(vel) was greater in older adults in all conditions (p<0.001). During the 12 cm constant amplitude trials, within-trial adaptation occurred for all subjects, but there were differences in the between-trial habituation. P(vel) of the older adults decreased significantly between all 3 trials, but decreased only between Trials 1 and 2 in young adults. While the responses of the young adults to the transition in optic flow from 4 to 12 cm did not significantly change, older adults had an increase in P(vel) following the transition, ranging from 6.5 dB for the first trial to 3.4 dB for the third trial. These results show that older adults can habituate to repeated visual perturbation exposures; however, this habituation requires a greater number of exposures than young adults. This suggests aging impacts the ability to quickly modify the relative weighting of the sensory feedback for postural stabilization.


Application of office ultrasound in the management of the spinal cord injury patient.
The effectiveness of office ultrasonography of the bladder and kidneys to provide routine urological followup was assessed in the outpatient spinal cord injury clinic. A total of 86 asymptomatic spinal cord injury patients underwent office ultrasonography of the kidneys and bladder as part of the routine urological followup. There were 106 ultrasound scans performed. Of the patients 68 had a blinded excretory urogram for comparison, including 20 who underwent additional studies (computerized tomography scans of the abdomen and pelvis, and/or radiologist-performed ultrasound examinations of the kidneys and bladder). All 18 patients who underwent office ultrasound but not excretory urography each underwent computerized tomography scans of the abdomen and pelvis and/or radiologist-performed ultrasound examinations of the kidneys and bladder. Office ultrasound detected 5 of 6 kidney stones, 6 of 6 hydronephrotic kidneys, 5 of 7 renal masses (4 of 6 cysts and 1 of 1 renal tumor), 3 of 3 bladder stones and 3 of 3 bladder diverticula. Subtle changes of chronic renal infection noted on excretory urography in 4 patients were not detected on corresponding ultrasound scans but voiding cystourethrograms revealed no reflux, and comparison to prior studies confirmed that these renal units were stable. Outpatient ultrasonography performed by the urologist proved to be a cost-effective and sensitive screening examination for urological disorders in the spinal cord injury population. The technique is easily learned, well tolerated and indicated when further urological evaluation is required.


Accuracy of infection reporting in US nursing home ratings.
To assess the accuracy of nursing home-reported data on urinary tract infections (UTIs), which are publicly reported on Nursing Home Care Compare, and pneumonia, which are not publicly reported. We used secondary data for 100% of Medicare fee-for-service beneficiaries in the United States between 2011 and 2017. We identified Medicare fee-for-service beneficiaries who were nursing home residents between 2011 and 2017 and admitted to a hospital with a primary diagnosis of UTI or pneumonia. After linking these hospital claims to resident-level nursing home-reported assessment data in the Minimum Data Set, we calculated the percentages of infections that were appropriately reported and assessed variation by resident- and nursing home-level characteristics. We developed a claims-based nursing home-level measure of hospitalized infections and estimated correlations between this and publicly reported ratings. Medicare fee-for-service beneficiaries who were nursing home residents and hospitalized for UTI or pneumonia during the study period were included. Reporting rates were low for both infections (UTI: short-stay residents 29.1% and long-stay residents 19.2%; pneumonia: short-stay residents 66.0% and long-stay residents 70.6%). UTI reporting rates increased when counting additional assessments, but it is unclear whether these reports are for the same versus a newly developed UTI. Black residents had slightly lower reporting rates, as did nursing homes with more Black residents. Correlations between our claims-based measure and publicly reported ratings were poor. UTI and pneumonia were substantially underreported in data used for national public reporting. Alternative approaches are needed to improve surveillance of nursing home quality.


Total homocysteine levels in plasma: high-performance liquid chromatographic determination with electrochemical detection and glassy carbon electrode.
An isocratic high-performance liquid chromatography with electrochemical detection (HPLC-ED) method for the determination of total plasma homocysteine [H(e)] has been developed. The electrochemical detection is performed using a glassy-carbon electrode that is not specific for thiol groups. We have tried to solve the problem of specificity focusing our work on chromatographic resolution and have obtained good results without coelution of other thiol compounds or any substances mentioned as common interferences for carbon electrode methods: uric acid, ascorbic acid and salicylates. Thirty samples a day can be assayed for total homocysteine with a lower limit of detection of 2 pmol, and a limit of quantification of 1.0 micromol/l, with a coefficient of variation (C.V.) <20%. For a concentration of total plasma homocysteine of 9.36 micromol/l, the intra- and inter-assay C.V.s were of 3.86% and 5.55% respectively. The analytical recovery achieved in the preparation of the samples ranged from 85.0% to 98.3% and the electrochemical response was linear up to 100 micromol/l.


Peritoneovenous shunt for intractable malignant ascites. A single case report of metastatic peritoneal mesothelioma implanted via LeVeen shunt.
A patient with malignant ascites refractory to conservative and conventional therapy underwent peritoneovenous shunt. The shunt provided palliation for 7 months with relief of nausea, vomiting, and anorexia and with decrease of weight and abdominal girth. There was no need for repeated paracenteses, which had been required before shunting. The patient's strength increased. However, increasing shortness of breath developed approximately 6 to 7 months after insertion of the shunt. The shunt was associated with extensive metastatic dissemination of peritoneal mesothelioma to both lungs. It is suggested that peritoneal mesothelioma is a contraindication for peritoneovenous shunt.


Successful management of severe bronchial asthma exacerbated by anti-PD-L1 treatment: A report of two cases.
Immune checkpoint inhibitors (ICIs) have been used for various carcinomas. However, immune-related adverse events have been observed. There have been few reports of treatment with biologics for severe bronchial asthma induced by ICI; therefore, their efficacy is unknown. We report two cases of severe bronchial asthma requiring systemic steroid administration while using anti-programmed death-ligand 1 (PD-L1) antibody for advanced non-small-cell lung cancer. The anti-interleukin-5 antibody, mepolizumab, was introduced, resulting in the discontinuation of systemic prednisolone and good asthma control. These reports suggest that treatment with biologics may be effective in severe cases of poorly controlled bronchial asthma during ICI therapy.


Reinforcement of the abdominal wall with acellular dermal matrix or synthetic mesh after breast reconstruction with the pedicled transverse rectus abdominis musculocutaneous flap. A prospective double-blind randomized study.
The pedicled transverse rectus abdominis musculocutaneous flap (p-TRAM) is a well-established option for autologous breast reconstruction (BR) but donor-site morbidity is still reported. The aim of the present study was to compare donor-site morbidity after reinforcement of the abdominal wall regarding development of bulging or hernia, abdominal muscle strength, complications, and abdominal pain hypothesizing, that reinforcement with acellular dermal matrix (Strattice™) is superior to reinforcement with synthetic mesh (Prolene®). A randomized, prospective, double-blind study was conducted with 29 patients admitted for BR with the p-TRAM flap at Department of Plastic Surgery, AUH, Denmark, 2014-2016. Allocation rate 1:1. Follow-up at 4, 12, and 24 months. 24 months postoperatively the computerized tomography verified bulging frequency was 35.7% in the ADM group and 6.7% in the synthetic mesh group (p = 0.11). Two patients (14.3%) in the ADM group and no patients in the synthetic mesh group developed hernia. No significant difference between baseline and 2-year measurement of abdominal muscle strength was observed. The present study did not demonstrate any statistically significant differences between treatment groups regarding risk of bulging or hernia, abdominal muscle strength, complications, pain or pain related QoL within two years of follow-up. Although the small sample size sets limitations for drawing wide conclusions the hypothesis that reinforcement with ADM is superior to synthetic mesh cannot be confirmed. Further research into methods for decreasing donor-side morbidity related to the TRAM flap or other rectus abdominis muscle-based flaps is needed.


Substance P inhibits the action potentials in bullfrog sympathetic ganglion cells.
Substance P (0.5-5 microM) depressed the spike peak and after-hyperpolarization of action potentials of bullfrog sympathetic ganglion cells. It also depressed the after-hyperpolarization and prolonged the falling phase in Ca2+ spikes. The voltage-dependent K+ currents, both the delayed rectifier K+ current (Ik1) and the M current (Ik2), were suppressed by substance P, suggesting that the depression of the after-hyperpolarization may be due to suppression of these K+ currents.


Dual functions of angiopoietin-like protein 2 signaling in tumor progression and anti-tumor immunity.
Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein homologous to angiopoietins. Previous studies suggest that tumor cell-derived ANGPTL2 has tumor-promoting function. Here, we conducted mechanistic analysis comparing ANGPTL2 function in cancer progression in a murine syngeneic model of melanoma and a mouse model of translocation renal cell carcinoma (tRCC). ANGPTL2 deficiency in tumor cells slowed tRCC progression, supporting a tumor-promoting role. However, systemic ablation of ANGPTL2 accelerated tRCC progression, supporting a tumor-suppressing role. The syngeneic model also demonstrated a tumor-suppressing role of ANGPTL2 in host tumor microenvironmental cells. Furthermore, the syngeneic model showed that PDGFRα+ fibroblasts in the tumor microenvironment express abundant ANGPTL2 and contribute to tumor suppression. Moreover, host ANGPTL2 facilitates CD8+ T-cell cross-priming and enhances anti-tumor immune responses. Importantly, ANGPTL2 activates dendritic cells through PIR-B-NOTCH signaling and enhances tumor vaccine efficacy. Our study provides strong evidence that ANGPTL2 can function in either tumor promotion or suppression, depending on what cell type it is expressed in.


Hot Hydrocarbon-Solvent Slot-Die Coating Enables High-Efficiency Organic Solar Cells with Temperature-Dependent Aggregation Behavior.
Organic solar cells (OSCs) have made rapid progress in terms of their development as a sustainable energy source. However, record-breaking devices have not shown compatibility with large-scale production via solution processing in particular due to the use of halogenated environment-threatening solvents. Here, slot-die fabrication with processing involving hydrocarbon-based solvents is used to realize highly efficient and environmentally friendly OSCs. Highly compatible slot-die coating with roll-to-roll processing using halogenated (chlorobenzene (CB)) and hydrocarbon solvents (1,2,4-trimethylbenzene (TMB) and ortho-xylene (o-XY)) is used to fabricate photoactive films. Controlled solution and substrate temperatures enable similar aggregation states in the solution and similar kinetics processes during film formation. The optimized blend film nanostructures for different solvents in the highly efficient PM6:Y6 blend is adopted to show a similar morphology, which results in device efficiencies of 15.2%, 15.4%, and 15.6% for CB, TMB, and o-XY solvents. This approach is successfully extended to other donor-acceptor combinations to demonstrate the excellent universality of this method. The results combine a method to optimize the aggregation state and film formation kinetics with the fabrication of OSCs with environmentally friendly solvents by slot-die coating, which is a critical finding for the future development of OSCs in terms of their scalable production and high-performance.


The hydroxylation of the salicylate anion by a Fenton reaction and T-radiolysis: a consideration of the respective mechanisms.
The yield of 2,3- and 2,5-dihydroxybenzoates (dHB's) from the reaction of .OH radicals with salicylate (SA) ions has been measured as a function of pH and in the presence of oxidants. Under steady-state radiolysis conditions, the production of these products occurs via the reactions .OH + SA----HO-SA. (radical adduct) HO-SA. H+.OH+----2-carboxyphenoxyl radical (SA.) + H2O HO-SA. + SA.----2,3-/2,5-dHB + SA The addition of the oxidants O2, Fe3+ edta, or Fe(CN)63- increases the relative yield of 2,5-dHB/2,3-dHB from about 0.2 to 1. A model to account for this effect is presented. Steady-state radiolyses of 3- and 4-hydroxybenzoate give dihydroxybenzoate products consistent with the phenol group being an ortho-para director in the electrophilic attack of the hydroxyl radical on the aromatic ring. A comparison of product distributions from the reaction of ferrous edta with hydrogen peroxide using salicylate as a scavenger strongly suggests that the same hydroxyl radical adducts are formed as in the radiation experiments.


Empty colon: a pitfall in the assessment of colonic transit time.
We report a misleading outcome of colonic transit time (CTT) assessment in an adolescent girl with functional constipation. We found prolonged total and right segmental CTT despite high doses of oral polyethylene glycol 4000 and repeated treatment with polyethylene glycol-electrolyte solution (Klean-Prep®) by nasogastric tube. A colonoscopy aiming at disimpaction of a possible faecal mass revealed an empty colon with dozens of radio-opaque markers adhered to the colonic wall. This report shows that the result of a CTT cannot be accepted blindly. Especially the clustering of many markers within narrow margins might point at entrapment of markers in mucus against the colonic wall.


The in situ detection of smoking in public area by laser-induced breakdown spectroscopy.
The cigarette smoke in public area could be harmful to the non-smokers. In this paper, laser-induced breakdown spectroscopy (LIBS) is applied to the in situ detection of the cigarette smoke in public area, and the single particles aerosol mass spectrometer (SPAMS) is utilized to aid the elemental analysis as well as realize the isotope detection. According to the obtained emission spectra, the smoke consists of Mg, Ca, Sr, Na, K elements which are absent in air, and the concentrations of H2O and CO2 in smoke increase obviously. Moreover, the cigarette ash after burning is taken as the sample for off-line detection and several heavy metal elements are detected. The comparison between the spectra of cigarette smoke and ash shows that these two kinds of detection are greatly different in terms of constituent and plasma status. In addition, the molecular emission of Carbon-Nitrogen was observed in smoke spectrum, and the molecular vibrational and rotational temperature of CN molecule was calculated. Finally, the LIBS and SPAMS were applied to the semi-quantitative detection and isotope analysis of Pb in the smoke.