Antibodies against human chorionic gonadotropin convert the deglycosylated hormone from an antagonist to an agonist.
Chemical deglycosylation of human chorionic gonadotropin (hCG) produced an antagonist (DG-hCG) that specifically bound to hCG receptors but was no longer able to stimulate adenylate cyclase in the murine Leydig tumor cell line, MLTC-1. DG-hCG was restored to an agonist by incubating cells or membranes having the bound analogue with antibodies against hCG (anti-hCG). In the presence of anti-hCG, cyclic AMP accumulation and adenylate cyclase activity were stimulated over DG-hCG alone. There was no accumulation of cyclic AMP when the cells were exposed to anti-hCG alone or DG-hCG and normal serum or anti-hCG first then DG-hCG. Several different batches of anti-hCG were effective but their activity did not correlate with their affinity for DG-hCG or hCG. The effect of anti-hCG on DG-hCG activity was dose- and time-dependent. Maximal stimulation of cyclic AMP was achieved with antisera dilutions of 1:200 or less. When DG-hCG-treated cells were exposed to anti-hCG at 37 degrees C, there was a 10-min lag. The lag was eliminated when the cells were exposed to the antibodies at 4 degrees C for 3 h and then warmed to 37 degrees C. Adenylate cyclase was also activated when Fab fragments prepared by papain digestion of anti-hCG were used, whereas Fc fragments were not effective. Thus, the divalency of the anti-hCG is not the critical factor in the mechanism of antibody action. Our results suggest that anti-hCG converts DG-hCG from an antagonist to an agonist possibly by altering the conformation of the modified hormone.


Dose-response studies in carcinogenesis by nitroso-N-methyl-N-(2-phenyl)ethylamine in rats and the effects of deuterium substitution.
A dose-response study of the carcinogenicity of nitroso-N-methyl-N-(2-phenyl)ethylamine was carried out in male Fischer 344 rats. The compound was given in drinking water at concentrations of 115, 28, 9.5, 3.2, 1.1 and 0.4 mg/litre. The highest concentration proved toxic leading to the early death of several animals; the remainder of this group were treated for 21 wk. All of the other concentrations were given for 33 wk, except the 28 mg/litre treatment which ceased at 30 wk. An additional group of rats was given 0.4 mg/litre for 104 wk. In all groups of animals, except those in the high-dose group that died early and those given 0.4 mg/litre for 33 wk, 50% or more of the animals had tumours of the oesophagus or forestomach or both when they died. In several groups the number of rats with these tumours approached 100%. The total dose of carcinogen received by the rats in the lowest dose group was 1.3 mg and 45% of them had tumours of the upper gastro-intestinal tract. The effect on carcinogenicity of labelling the nitrosamine with deuterium in either the methyl group or the alpha-methylene of the phenylethyl group was determined by treating groups of rats with equimolar concentrations of the deuterium-labelled and unlabelled nitrosamine. A very significant increase in carcinogenic effectiveness was observed with the compound containing deuterium in the alpha-methylene of the phenylethyl group, suggesting that methylation might not be the important event in carcinogenesis by this compound in rats.


Incidence and mortality from breast and cervical cancer in a Brazilian town.
To analyze the magnitude of changes in the incidence and mortality from cervical cancer (CC) and breast cancer (BC) in Campinas, São Paulo State, between the five-year periods of 1991-1995 and 2010-2014. data on cancer were obtained from the Campinas Population-Based Cancer Registry and data on deaths from the Mortality Information System of the Computing Department of the Unified Health System. Age-standardized incidence and mortality rates were calculated by the direct method, with the respective 95% confidence intervals. The magnitude of the changes was measured by the rate ratio (rate ratio; 95%CI). among the periods studied, there was a threefold increase in the detection rate of in situ CC (3.03; 95%CI: 2.64-3.47) and fivefold increase for in situ BC (5.23; 95%CI: 4.98-5.50). The proportion of cases of in situ BC in relation to the total number of cases of BC increased from 3.31% to 11.05%. The incidence rate of invasive CC decreased by 57% (0.43; 95%CI: 0.40-0.47), and the incidence rate of invasive BC increased by 40% (1.40; 95%CI: 1.33-1.47). The mortality rate of the CC decreased by 58% (0.42; 95%CI: 0.32-0.56), and that of BC by 15% (0.85; 95%CI: 0.82-0.89). the incidence of in situ carcinomas of CC and BC increased in almost two decades. The rate of invasive carcinoma of CC decreased, and that of BC increased. Mortality from both cancers decreased. Observing these changes is useful for assessing the impact of the actions carried out in the period and for planning future actions.


Docosahexaenoic acid induces apoptosis in colorectal carcinoma cells by modulating the PI3 kinase and p38 MAPK pathways.
Numerous studies have shown that long-chain polyunsaturated fatty acids can kill cancer cells in vitro as well as in vivo, while normal cells remain unaffected. Unfortunately, the cellular and molecular mechanisms responsible for this phenomenon are still poorly understood. The aim of this study was to investigate the potential chemopreventative/antiproliferative potential of docosahexaenoic acid (DHA) in an adenocarcinoma cell line (CaCo2 cells) and to evaluate the signalling pathways modulated by it. DHA (5-50 microM) significantly inhibited cell viability in a dose-dependent manner in CaCo2 cells, while the viability of normal colon cells (NCM460 cells) was not compromised. DHA also induced apoptosis in CaCo2 cells, as indicated by increases in caspase-3 activation and poly-ADP-ribose polymerase cleavage. Signalling proteins, which include extracellular signal-regulated kinase, p38 mitogen-activated protein kinase (MAPK), Akt and p53 were analysed by Western blotting using phosphospecific and total antibodies. The protein inhibitors wortmannin (phosphoinositide 3 kinase inhibitor), PD 98059 (MEK inhibitor) and SB 203580 (p38 inhibitor) as well as silencing RNA [small interfering RNA (siRNA)] of the p38 MAPK protein, were used to investigate cross-talk between signalling pathways. DHA supplementation significantly suppressed Akt phosphorylation, which also correlated with decreased cell viability and increased apoptosis in CaCo2 cells. Furthermore, siRNA experiments suggested a possible role for p38 MAPK in the phosphorylation of p53 at Ser15, a site which is associated with DNA damage. DHA might thus exert its beneficial effects by means of increased apoptosis and suppression of the important survival-related kinase, Akt.


Childhood burns in Zaria, Nigeria.
From 1971 to 1980, 429 children with burn injuries were admitted to the Ahmadu Bello University Hospital, Zaria. These were major burns in 275 patients, moderate in 82 and minor in 72. Fourteen of the patients were neonates, 102 infants, 228 were 5 years old or younger and 85 were older. Socioeconomic factors contributing to the injuries included the use of firewood for cooking at ground-level and for warming the house and body during the cold season; loose indigenous garments; thatch-roofed huts and the post-partum rituals of mud-bed heating and hot baths. Flame burns exceeded scalds with a seasonal frequency which peaked during the harmattan. In the absence of a 'burn's unit', burned children were nursed on the general ward together with other sick children by the same nursing personnel supervised by general surgeons. Complications included wound infection, respiratory distress, measles, malnutrition and tetanus. One-fifth of the patients absconded. Overall mortality was 13 per cent but 29 per cent of the neonates died. Preventive strategy should include public information, nursery school supervision, economic development and architectural improvements.


An autopsy case of a cystic variant of thymic carcinoma mimicking a thymic cyst.
An autopsy case of thymic carcinoma is reported. The surgically excised cystic tumour from a 38-year-old Japanese male mimicked a thymic cyst pathologically. After a clinical course of 6 years, postmortem examination disclosed extensive metastases, including cystic lesions lined by benign-looking squamous epithelium. This evidence suggested that the present tumour was not of the specific variants of thymic carcinoma and not a thymic cyst with malignant transformation.


The pituitary cleft of the rat: an electron microscopic study.
The epithelium of the pituitary cleft and its colloid have been studied at the ultrastructural level in normal, adrenalectomized, castrated, dehydrated and lactating adult rats. Both control and experimental animals showed cells in different stages of degradation inside the cleft and mixed with the colloid. These exfoliated cells seems to have originated from the cleft's epithelium of the adjacent granular cells. In adrenalectomized and castrated rats the rostral epithelium of the cleft had large intercellular spaces that in some instances appeared to open directly into the cleft. Occasionally, the adenohypophysial canaliculi of the adrenalectomized rats were also seen connecting with the cleft. In lactating and castrated animals dark cells appeared more frequently in the rostral and caudal epithelium of the cleft. The results obtained suggest that the colloids is originated at least in part by involuted pituitary cells. There is also evidence that the follicular cavities of the Pars distalis and the cleft are continuous structures.


Putting cyaphide in its place: determining the donor/acceptor properties of the κC-cyaphido ligand.
The synthesis of group 9 pyridine-diimine complexes M(DippPDI)X and [M(DippPDI)L]+ (M = Co, Rh; DippPDI = 1,1'-(pyridine-2,6-diyl)bis(N-(2,6-diisopropylphenyl)ethan-1-imine); X = CP-, CCH-; L = CO, t BuNC) bearing a series of strong-field ligands, including the cyaphide ion (C[triple bond, length as m-dash]P-), is reported. A combined experimental and computational comparative study of the group 9 PDI cyaphide complexes Co(DippPDI)(CP) and Rh(DippPDI)(CP), as well as the N-heterocyclic carbene (NHC) gold(i) cyaphide complex Au(IDipp)(CP) (IDipp = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene), reveals the σ donor and π acceptor properties of the κC-cyaphido ligand, and allow us to suggest a position for this ion in the spectrochemical series.


Commensal Escherichia coli Strains of Bovine Origin Competitively Mitigated Escherichia coli O157:H7 in a Gnotobiotic Murine Intestinal Colonization Model with or without Physiological Stress.
Cattle are a primary reservoir of enterohemorrhagic Escherichia coli (EHEC) O157:H7. Currently, there are no effective methods of eliminating this important zoonotic pathogen from cattle, and colonization resistance in relation to EHEC O157:H7 in cattle is poorly understood. We developed a gnotobiotic EHEC O157:H7 murine model to examine aspects of the cattle pathogen-microbiota interaction, and to investigate competitive suppression of EHEC O157:H7 by 18 phylogenetically distinct commensal E. coli strains of bovine origin. As stress has been suggested to influence enteric colonization by EHEC O157:H7 in cattle, corticosterone administration (±) to incite a physiological stress response was included as an experimental variable. Colonization of the intestinal tract (IT) of mice by the bovine EHEC O157:H7 strain, FRIK-2001, mimicked characteristics of bovine IT colonization. In this regard, FRIK-2001 successfully colonized the IT and temporally incited minimal impacts on the host relative to other EHEC O157:H7 strains, including on the renal metabolome. The presence of the commensal E. coli strains decreased EHEC O157:H7 densities in the cecum, proximal colon, and distal colon. Moreover, histopathologic changes and inflammation markers were reduced in the distal colon of mice inoculated with commensal E. coli strains (both propagated separately and communally). Although stress induction affected the behavior of mice, it did not influence EHEC O157:H7 densities or disease. These findings support the use of a gnotobiotic murine model of enteric bovine EHEC O157:H7 colonization to better understand pathogen-host-microbiota interactions toward the development of effective on-farm mitigations for EHEC O157:H7 in cattle, including the identification of bacteria capable of competitively colonizing the IT.


Dissolved polycyclic aromatic hydrocarbons from the Northwestern Pacific to the Southern Ocean: Surface seawater distribution, source apportionment, and air-seawater exchange.
Polycyclic aromatic hydrocarbons (PAHs) as a group of toxic and carcinogenic compounds are large scale globally emitted anthropogenic pollutants mainly emitted into the atmosphere. However, atmospheric transport cannot fully explain the spatial variability of PAHs in the marine atmosphere and seawater. It is hypothesized that PAHs accumulated in seawater and ocean circulation can also influence PAHs observed in air above the ocean. In order to investigate PAHs in seawater as a potential secondary source to air, we collected paired air and seawater samples during a research cruise from China to the Antarctic in 2018-2019, covering the Pacific Ocean, the Indian Ocean, and the Southern Ocean. Summed concentrations of 28 analyzed PAHs in seawater were highest in the Pacific Ocean (4000 ± 1400 pg/L), followed by the Indian Ocean (2700 ± 1000 pg/L), and the Southern Ocean (2300 ± 520 pg/L). Three-ringed PAHs dominated the composition profile. We found that PAH levels in the Pacific and Indian Oceans were strong inversely correlated with salinity and distance to the coastline. This suggests that riverine inputs and continental discharges are important sources of PAHs to the marine environment. Derived air-seawater fugacity ratios suggest that net fluxes of PAHs were from seawater to the air in the Pacific and Indian Oceans at 9.0-8100 (median: 1600) ng/m2/d and 290-2000 (median: 1300) ng/m2/d, respectively. In the Southern Ocean, the net flow of PAHs was from air to seawater with a flux of -1000-450 (median: -82) ng/m2/d. Source apportionment from two different models suggested that the largest contribution to total PAHs was from petrogenic sources (44-57%), followed by coal/wood combustion (30-31%), fossil fuel combustion (15%), and engine combustion emissions (2.8-9.5%). Higher contributions from petrogenic sources were found at sites close to coastal regions. Both coal/wood combustion and petrogenic sources are responsible for the PAH concentrations detected in the Indian and Southern Oceans.


Analysis of multidimensional factors in attempts to quit using tobacco by Korean adolescents.
This study aims to understand the extent of adolescents' attempts to quit using tobacco and the factors influencing such attempts in Korea, using a descriptive, cross-sectional design and secondary data analysis with the 2019 Youth Health Behavior Survey. The participants were 4028 adolescent tobacco users who had used tobacco for 1 day or more in the past 30 days. The data analysis was performed using IBM SPSS/WIN 26.0 program, and multivariable logistic regression analysis was conducted using the complex sampling method module. A total of 68.2% of the participants attempted to quit using tobacco. We analyzed the factors for adolescents' attempts to quit using tobacco by dividing them into psychological, physical, behavioral, and environmental dimensions. The factors influencing adolescents' attempts to quit using tobacco, identified through multivariable logistic regression analysis, are as follows: participation in sports activities (OR = 1.20, 95% CI 1.01-1.41), vigorous physical activity (OR = 1.24, 95% CI 1.06-1.46), and type of tobacco product used (OR = 1.65, 95% CI 1.24-2.21) in the behavioral dimension; pictorial cigarette pack warnings (perceived smoking as unhealthy) (OR = 1.91, 95% CI 1.56-2.36), and the presence of secondhand smoking at home (OR = 1.18, 95% CI 1.01-1.38) in the environmental dimension. Schools and public healthcare providers must consider multidimensional factors when providing support for successful tobacco cessation in adolescents and focus particularly on elements relating to physical activity and environmental factors.


Dynamic interplay of the SUMO and ERK pathways in regulating Elk-1 transcriptional activity.
The ETS domain transcription factor Elk-1 is a direct target of the MAP kinase pathways. Phosphorylation of the Elk-1 transcriptional activation domain by MAP kinases triggers its activation. However, Elk-1 also contains two domains with repressive activities. One of these, the R motif, appears to function by suppressing the activity of the activation domain. Here, we demonstrate that SUMO modification of the R motif is required for this repressive activity. A dynamic interplay exists between the activating ERK MAP kinase pathway and the repressive SUMO pathway. ERK pathway activation leads to both phosphorylation of Elk-1 and loss of SUMO conjugation and, hence, to the loss of the repressive activity of the R motif. Thus, the reciprocal regulation of the activation and repressive activities are coupled by MAP kinase modification of Elk-1.


Characterisation of a new species of Pythium isolated from a wheat field in northern France and its antagonism towards Botrytis cinerea causing the grey mould disease of the grapevine.
A new species, Pythium bifurcatum, isolated from soil samples taken from a wheat field in Lille in northern France is described here. The oomycete occurred thrice out of 50 samples. The type specimen is F-91, which is a slow-growing saprophyte living on vegetable debris and which can be recognised by its antheridial as well as oogonial characteristics, which are different from other known species of Pythium. When grown together with Botrytis cinerea, the causal agent of the grey mould disease of the grapevine, Pythium bifurcatum shows a pronounced antagonism and suppresses its growth. Morphological features of this new species, its antagonism to B. cinerea, the sequences of the ITS region of its nuclear ribosomal DNA, and its comparison with related species are discussed in this article.


Surface immunoglobulins as targets for anti-immunoglobulin-dependent cell-mediated lysis of B cells.
Human K cells are able to lyse human lymphoblastoid B cells in the presence of specific anti-human immunoglobulin isotype antibodies. The human lymphoblastoid B-cell line DAUDI (surface mu- and kappa-chains positive) was lysed in the presence of anti-mu and anti-kappa antisera, or IgG fraction of these antisera, and B-cell-depleted human lymphocytes. Lysis was not induced by anti-isotypic antisera alone or human lymphocytes alone. Lysis was not induced by antisera directed at isotypes which were not expressed on the DAUDI cells. The human lymphoblastoid B-cell line RAJI, which does not express surface membrane isotypes, could not be lysed by the anti-isotype-dependent cell-mediated mechanism. Lysis of DAUDI cells by this mechanism was mediated by Fc gamma receptor-bearing human non-B lymphocytes and required an intact Fc piece in the inducing anti-isotypic antibody. These observations are discussed as a possible role for K cells in the regulation of immune responses by interaction between anti-idiotypic antibodies and idiotype-bearing cells.


Amniotic fluid concentrations of 3,3',5'-tri-iodothyronine (reverse T3), 3,3'-di-iodothyronine, 3,5,3'-tri-iodothyronine (T3) and thyroxine (T4) in normal and complicated pregnancy.
Amniotic fluid concentrations of 3,3',5'-tri-iodothyronine (rT3), 3,3'-Di-iodothyronine (3,3'-T2), 3,5,3'-tri-iodothyronine (T3) and T4 were studied in 384 women during normal and complicated pregnancy. An inverse correlation was observed between decreasing rT3 and increasing 3,3'-T2 concentrations in amniotic fluid with gestational age. The mean rT3 level in normal pregnancy was 2.81 nmol/1 at 12-20 weeks and decreased significantly to 1.06 nmol/1 at 36-42 weeks of gestation. The mean 3,3'-T2 concentration was 49.1 pmol/1 at12-20 weeks increasing to 119 pmol/1 at 36-42 weeks. The mean T4 value of 3.83 nmol/1 at 12-20 weeks was about half that of later periods. The T3 concentration in a random sample of 45 amniotic fluids ranged from less than 28 to 370 pmol/1 (mean 102 pmol/1). The mean rT3, 3,3'-T2 and T4 values measured in patients with intra-uterine malnutrition, gestation diabetes, tocolysis, placental insufficiency and rhesus incompatibility at 31-40 weeks of gestation were not significantly different from those in uncomplicated pregnancy. Significantly decreased rT3 and T4 concentrations were found in toxaemia. From the results obtained in complicated pregnancy it may be concluded that measurements of iodothyronines, especially rT3, in amniotic fluid have insignificant diagnostic value in the recognition of intra-uterine lesions with the probable exception of fetal hypothyroidism. The analysis of the dependence of iodothyronine concentrations on the gestational age showed a maximum of rT3 and T4 levels between 20 and 30 weeks of pregnancy. This marked rise of iodothyronine concentrations in amniotic fluid at mid-gestation may be due to the onsetting maturation of the hypothalamic-pituitary-thyroid control system of the fetus.


Estimated incidence of hepatitis A virus infection in Catalonia.
Hepatitis A normally is underreported by statutory disease reporting systems. The objective of this study is to estimate the incidence of hepatitis A virus (HAV) infection from prevalence surveys of infection carried out in representative samples of the population in 1989, 1996, and 2002 and the reported disease incidence during 1991 to 2003 in Catalonia. The real incidence of the infection was estimated from the reported incidence adjusted by the prevalence of susceptible individuals and the probability of presenting clinical manifestations. The bootstrap resampling technique was used to calculate 95% confidence intervals (CIs) of reported, clinical, and all infection cases. The infection rate estimated by the bootstrap method was 31.1/100,000 person-years (bootstrap studentized 95% CI, 19.4-56.0), and the rate of clinical hepatitis was 20.0/100,000 person-years (95% CI, 11.8-39.9), rates that were 6.3 and 4.1 times greater than the reported rate during the same period, respectively. In children younger than 5 years, the estimated infection rate was 13.8 times greater than the reported rate. Combined use of reported cases and results of seroprevalence surveys suggest that underreporting of HAV infection is substantial in Catalonia, especially in children younger than 5 years.


Epidemiological investigation and case-control study: a Legionnaires' disease outbreak associated with cooling towers in Warstein, Germany, August-September 2013.
Between 1 August and 6 September 2013, an outbreak of Legionnaires' disease (LD) with 159 suspected cases occurred in Warstein, North Rhine-Westphalia, Germany. The outbreak consisted of 78 laboratory-confirmed cases of LD, including one fatality, with a case fatality rate of 1%. Legionella pneumophila, serogroup 1, subtype Knoxville, sequence type 345, was identified as the epidemic strain. A case-control study was conducted to identify possible sources of infection. In univariable analysis, cases were almost five times more likely to smoke than controls (odds ratio (OR): 4.81; 95% confidence interval (CI): 2.33-9.93; p < 0.0001). Furthermore, cases were twice as likely to live within a 3 km distance from one identified infection source as controls (OR: 2.14; 95% CI: 1.09-4.20; p < 0.027). This is the largest outbreak of LD in Germany to date. Due to a series of uncommon events, this outbreak was most likely caused by multiple sources involving industrial cooling towers. Quick epidemiological assessment, source tracing and shutting down of potential sources as well as rapid laboratory testing and early treatment are necessary to reduce morbidity and mortality. Maintenance of cooling towers must be carried out according to specification to prevent similar LD outbreaks in the future.


Down-regulation of Flt-1 gene expression by the proteasome inhibitor MG262.
The mechanisms involved in the anti-angiogenic actions of the proteasome inhibitors are poorly understood. Here, we report that the gene expression of the VEGF receptor Flt-1 (vascular endothelial growth factor receptor 1) was down-regulated by the reversible proteasome inhibitor MG262 in explant cultures of the developing chicken pecten oculi, a vascular organ consisting of endothelial cells, pericytes, and macrophages. In addition, the inhibitor prevented the induction of Flt-1 by lipopolysaccharide (LPS) in macrophages and down-regulated the expression of Flt-1 after LPS induction. Flt-1 gene expression was also down regulated by MG262 in cultures of human microvascular endothelial cells. Interestingly, a transcript of Flt-1, coding for a soluble form of the receptor (sFlt-1) with anti-angiogenic properties, was not down-regulated in the same extent. Only a small decrease in the expression of VEGF and Ang-2 was detected in the pecten oculi upon inhibition of the proteasome, while no major changes were observed in the expression of other angiogenic molecules, such as KDR or Ang-1. Since recent experiments have demonstrated the importance of anti-Flt-1 therapy in the inhibition of tumor angiogenesis, retinal angiogenesis, arthritis, and atherosclerosis (Luttun et al. [2002]: Nat Med 8:831-840), our observation on down-regulation of Flt-1 in microvascular endothelial cells and macrophages by MG262 supports the postulated role of the proteasome inhibitors as potential candidates for therapeutic modulation of angiogenesis and inflammation.


Determinants of adoption of alternative response to foot and mouth disease: micro-level evidence of smallholder pastoralist in north East District, Botswana.
This paper examines factors influencing the adoption of alternative response to Foot and Mouth Disease (FMD) among smallholder beef producers in the dry lands of Africa, specifically, North East district in Botswana. Principal component analysis was used to categorise FMD responses. Thereafter, a multivariate probit regression model was used to examine the effect of socioeconomic and institutional factors on the adoption of alternative responses to FMD. The study found that household size, opportunity cost incurred, frequency of contact with extension officers, training received on FMD, distance to the nearest market, as well as distance to grazing and water areas had a positive effect on the adoption of alternative responses to the outbreak. We conclude that although producers are aware of the detriments of FMD to their livelihoods, some still choose not to adopt the responses and socioeconomic and institutional characteristics play a role.


Changes in construing and outcome of group therapy for alcoholism.
Consistent changes in the way they construed their drinking problem were found in alcoholics who completed an inpatient group therapy program. Patients who showed most change in construal were the ones most likely to relapse.


The relationship between the lateral cutaneous antebrachial nerve and the superficial branch of the radial nerve and its impact on regional anesthetic and pain blocks of the thumb; What is more important: Nerves or dermatomes?
Innervation of the thumb and radial part of the dorsum of the hand is achieved primarily by the radial nerve, which is usually blocked for hand surgery. Inefficient blocks occur because the lateral antebrachial cutaneous nerve also extends into this area. The question then arises, whether skin innervation and peripheral blocking techniques should be directed at from the innervation by these nerves or more by the dermatome and its spinal segments. In 68 human upper limbs embalmed with Thiel's method, the topography of the lateral antebrachial cutaneous nerve (LACN), the superficial branch of the radial nerve (sbRN) and communicating branch (CB) were investigated by meticulous dissection from the cubital fossa to the most distal macroscopically dissectible branch, and the areas reached by these nerves were compared to the described dermatome. In 52.9% of all specimens, the LACN was found proximal to the rascetta, in 35.3% it extended to the base of the thumb, and in 8 cases (11.8%) it extended distally to the base of the thumb. In 50%, the LACN was anterolateral to the brachioradialis muscle, and in 38.2%, strictly lateral. Only in 8 cases (11.8%) the LACN presented itself running more dorsally and laterally. A CB was observed in 28 specimens (41.2%). Both investigated nerves were found to innervate the dermatomes of C6 and C7. The LACN should be considered for individual targeted blocks for surgical procedures and pain therapy within the wrist and thumb region as all nerves that might contribute to innervation of a targeted dermatome should be blocked.


Structure of UDP-N-acetylglucosamine acyltransferase with a bound antibacterial pentadecapeptide.
UDP-GlcNAc acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the transfer of the R-3-hydroxyacyl chain from R-3-hydroxyacyl acyl carrier protein (ACP) to the glucosamine 3-OH group of UDP-GlcNAc. LpxA is essential for the growth of Escherichia coli and related Gram-negative bacteria. The crystal structure of the E. coli LpxA homotrimer, determined previously at 2.6 A in the absence of substrates or inhibitors, revealed that LpxA contains an unusual, left-handed parallel beta-helix fold. We now present the crystal structure at 1.8 A resolution of E. coli LpxA in a complex with a pentadecapeptide, peptide 920. Three peptides, each of which adopts a beta-hairpin conformation, are bound per LpxA trimer. The peptides are located at the interfaces of adjacent subunits in the vicinity of the three active sites. Each peptide interacts with residues from both adjacent subunits. Peptide 920 is a potent inhibitor of E. coli LpxA (Ki = 50 nM). It is competitive with respect to acyl-ACP but not UDP-GlcNAc. The compact beta-turn structure of peptide 920 bound to LpxA may open previously uncharacterized approaches to the rational design of LpxA inhibitors with antibiotic activity.


Bronchopulmonary dysplasia is not related to neurofilament light for neuroaxonal damage in preterm infants.
Neurofilament light (NfL) has been identified as a biomarker for neuroaxonal damage in preterm infants, but its relation with bronchopulmonary dysplasia (BPD) has not been established. We hypothesized that BPD is associated with increased NfL levels at an early stage, indicative of early neuroaxonal damage. We included preterm infants born <30 weeks of gestation for assessment of NfL levels from cord blood and blood obtained at postnatal days 3, 7, 14, and 28. We used linear regression analysis to compare NfL levels between infants with moderate/severe BPD and infants with no/mild BPD, and linear mixed model analysis to compare the effect of time on NfL levels between groups. Sixty-seven infants with a gestational age (GA) of 27 ± 1.3 weeks were included for analysis, of whom 19 (28%) developed moderate/severe BPD. Although NfL levels were higher at every time point in infants with BPD, statistical significance was lost after adjustment for GA, small for gestational age (SGA) and intraventricular hemorrhage (IVH). Groups did not differ in NfL change over time. The positive association between BPD and NfL in the first weeks of life could be explained by GA, SGA and IVH rather than by development of BPD. Neurofilament light chain (NfL) is a known biomarker for neuroaxonal damage. Biomarkers for brain damage during the first weeks of life in preterm infants developing BPD are lacking. NfL levels obtained during the first weeks of life did not differ between infants with and without BPD in analyses adjusted for GA, SGA, and IVH.


[Current problems in lipomas of the oral mucosa with reference to our experience of 7 cases].
We present a review of the lipomas in the buccal mucosa in relation with our experience in seven cases.


The structural properties and resistant digestibility of maize starch-glyceride monostearate complexes.
This study investigated the effects of pullulanase debranching on the structural properties and digestibility of maize starch (MS)-glyceryl monostearate (GMS) complexes. According to our results, the apparent amylose content of MS increased from 36.34 % to 95.55 % and complex index reached 93.09 % after 16 h of pullulanase debranching. The crystallinity of prepared MS-GMS complexes increased to 33.24 % with a blend of B-type and V-type crystals. The surface of prepared MS-GMS complexes granules emerged more small lamellar crystals tightly adhering to the surface of granules. The Fourier transforms infrared spectroscopy analysis showed that debranching pretreatment MS-GMS complexes exhibited higher levels of short-range orders structure. These results indicated that maize starch was favorable to form more ordered starch-lipid complexes structure after debranching pretreatment, which resulted in the restriction of starch hydrolysis. In vitro digestion data implied that resistant starch (RS) content increased with the extension of the debranching time, and the highest RS content (69.58 %) appeared with 16 h pullulanase debranching. This work suggests that debranching pretreatment could be an efficient way to produce ordered starch-lipid complexes with controllable structure and anti-digestibility.


[Chrono- and inotropic and heterometric regulation of mechanical activity in the heart of atrial fibrillation patients].
The theory of accidental functions was used in the analysis of the heart's mechanical activity. The dependence of right-ventricular pressure on R--R duration and ultimate diastolic pressure was evaluated in 10 patients, using cardiac probe. Cross-correlation and cross-variance functions were used to assess chrono-inotropic relationship and the relationship between ultimate diastolic and systolic pressure values. Poor correlation was shown between ultimate diastolic and systolic pressure in tachycardia. Evidence is presented that mechanical activity is controlled through chrono-inotropic relationship in tachysystolic arrhythmias. In cases of normosystole and bradycardia, the heterometric system makes the principal contribution to the control of the heart mechanical activity.


Grazer control of nutrient availability in the periphyton.
Benthic algal assemblages are regulated by both abiotic (e.g., nutrient) and biotic (e.g., grazing) constraint. The objective of this study was to determine how changes in these two factors affected the structure of an algal assemblage in an ephemeral stream. Coverslips were incubated for 21 days in enclosures containing one of three nutrient environments (ambient, phosphorus-enriched, or phosphorus and nitrogen enriched) and one of four densities of the snail Gonibasis (0, 40, 80, or 120 snails/m2) and examined directly to enumerate the algal assemblage. The effect of grazing on algal biomass was dependent on the nutrient environment. An overstory of diatoms was susceptible to removal by grazing and was not strongly affected by nutrient enrichment. An understory of Stigeoclonium was more resistant to grazing and responded strongly to nutrient enrichment only in the presence of grazers. Snail grazers may mediate nutrient availability to the understory indirectly by removing overlying cells or by direct excretion of nutrients. Multiple interactions occur between benthic herbivores and algae, and, as shown here, some of them are positive and involve modifications of the nutrient environment.


Falls and Associated Factors among Adolescents and Young Adults with Arthrogryposis Multiplex Congenita.
Falls research among individuals with arthrogryposis multiplex congenita (AMC), a group of congenital conditions characterized by joint contractures in two or more body regions, is sparse. The primary objectives of this study were to estimate the prevalence of single, multiple, and injurious falls among adolescents and adults with AMC and identify factors associated with multiple and injurious falls. Individuals, aged 10-50 years, with a diagnosis of AMC completed questionnaires obtaining demographic and AMC-specific information, falls history (e.g., number, injurious/non-injurious), markers of bone health, orthopedic surgical history, and mobility aid use, as well as the Gillette Functional Assessment Questionnaire and the Saltin-Grimby Physical Activity Level Scale. Falls were defined as "any body part above the ankle coming to rest on the ground, floor, or a lower level". Falling was defined as ≥ 1 fall, while multiple falls were defined as ≥ 2 falls in the past year.Differences in falling, multiple falls, and injurious falls rates between adolescents (10-17 years) and adults (aged 18-50 years) were evaluated. Using univariate binary logistic regression models, associations between participant characteristics and multiple falls, as well as injurious falls, were evaluated, while considering age as a covariate (p ≤ 0.050); odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Adolescents (N = 28; median age = 14 years) and adults (N = 40; median age = 32 years) with AMC had similar falling, i.e., 89.3% versus 70.0%, and injurious fall rates, i.e., 32.1% versus 27.5%, respectively (p > 0.050).Adolescents with AMC, however, were more likely to report multiple falls in the past year, i.e., 89.3%, when compared to adults with AMC, i.e., 57.5% (p = 0.005). Beyond age, multiple falls were associated with a greater number of lower-limb surgeries [p = 0.036, OR (95%CI): 1.18 (1.01-1.39)], ability to transfer floor-to-stand with support [p = 0.002, OR (95%CI): 8.98 (2.30-35.06)], and increased mobility per the Gillette Functional Assessment Questionnaire [p = 0.004, OR (95%CI): 1.48 (1.13-1.92)]. Factors associated with a reduced odds of multiple falls were spinal involvement [p = 0.025, OR (95%CI): 0.23 (0.07-0.84)], history of spinal surgery [p = 0.018, OR (95%CI: 0.18 (0.04-0.74)], greater upper extremity involvement [OR (95%CI): 0.65 (0.44-0.95)], home assistive device use [p = 0.010, OR (95%CI): 0.15 (0.03-0.63)], and community wheelchair use [p = 0.006, OR (95%CI): 0.16 (0.04-0.59)]. None of the explored characteristics were associated with injurious falls in the past year (p > 0.050). Falls are exceedingly common among adolescents and adults with AMC; potential risk and protective factors for multiple falls are identified for future prospective falls research.


Person-centered Feeding Care: A Protocol to Re-introduce Oral Feeding for Nursing Home Patients with Tube Feeding.
Although the literature on nursing home (NH) patients with tube feeding (TF) has focused primarily on the continuation vs. discontinuation of TF, the reassessment of these patients for oral feeding has been understudied. Re-assessing patients for oral feeding may be better received by families and NH staff than approaches focused on stopping TF, and may provide an opportunity to address TF in less cognitively impaired patients as well as those with end-stage conditions. However, the literature contains little guidance on a systematic interdisciplinary team approach to the oral feeding reassessment of patients with TF, who are admitted to NHs. This project had two parts that were conducted in one 170-bed intermediate/skilled, Medicare-certified NH in Honolulu, Hawai'i. Part 1 consisted of a retrospective observational study of characteristics of TF patients versus non-tube fed patients at NH admission (2003-2006) and longitudinal follow-up (through death or 6/30/2011) with usual care of the TF patients for outcomes of: feeding and swallowing reassessment, goals of care reassessment, feeding status (TF and/or per oral (PO) feedings), and hospice status. Part 2 involved the development of an interdisciplinary TF reassessment protocol through working group discussions and a pilot test of the protocol on a new set of patients admitted with TF from 2011-2014. Part 1: Of 238 admitted patients, 13.4% (32/238) had TF. Prior stroke and lack of DNR status was associated with increased likelihood of TF. Of the 32 patients with TF at NH admission, 15 could communicate and interact (mild, moderate or no cognitive impairment with prior stroke or pneumonia); while 17 were nonverbal and/or bedbound patients (advanced cognitive impairment or terminal disease). In the more cognitively intact group, 9/15 (60%) were never reassessed for tolerance of oral diets and 10/15 (66.7%) remained with TF without any oral feeding until death. Of the end-stage group, 13/17 (76.5%) did not have goals of care reassessed and remained with TF without oral feeding until death. Part 2: The protocol pilot project included all TF patients admitted to the facility in 2011-2014 (N=33). Of those who were more cognitively intact (n=22), 21/22 (95.5%) had swallowing reassessed, 11/22 (50%) resumed oral feedings but 11 (50%) failed reassessment and continued exclusive TF. Of those with end-stage disease (n=11), 100% had goals of care reassessed and 9 (81.8%) families elected individualized oral feeding (with or without TF). Using findings from our retrospective study of usual care, our NH's interdisciplinary team developed and pilot-tested a protocol that successfully reintroduced oral feedings to tube-fed NH patients who previously would not have resumed oral feeding.


The social determinants of substance use associated with deaths of despair: Individual risks and population impacts.
As the incidence of deaths from external causes including poisonings, suicide, and alcohol-related liver disease, increases in countries such as the United States and Canada, a better understanding of the fundamental social determinants of the substance use underlying these so-called "deaths of despair", at the population level, is needed. Using data from the nationally representative data from the Canadian Community Health Survey (2003, 2015-2016, 2018 cycles) (N = 30,729), the independent associations between age, sex, marital status, immigrant status, race/ethnicity, education, income, rurality, affective health and the use of illicit substances, opioids (without distinction for prescription status), problematic levels of alcohol, and combined past-year use (≥2) of substances, were explored using multivariate logistic regression, marginal risk, and population attributable fraction estimation, with propensity score-adjusted sensitivity analyses. Males, those who were under 29 years, without a partner, born in Canada, White, or had an affective disorder reported both higher use of individual substances and multiple substances in the past year. Social determinants appear to explain a substantial proportion of substance use patterns overall. Between 10% and 45% of illicit substance, problematic alcohol, and polysubstance use prevalence was attributable to non-partnered marital status, non-immigrant status, and White race/ethnicity. Of opioid use prevalence, 25% was attributable to White race/ethnicity, 13% to affective disorder status and 4% to lower-income. Though not all substance use will result in substance-related morbidity or mortality, these findings highlight the role of social determinants in shaping the intermediary behavioural outcomes that shape population-level risk of "deaths of despair".


Chondrolysis of the glenohumeral joint following a color test using gentian violet.
Two patients developed chondrolysis following injection of 0.4% aqueous gentian violet into the glenohumeral joint to visualize a rotator cuff tear during surgery. In both cases, conventional radiographs revealed joint space narrowing 10-12 months after surgery. Histological examination of the humeral heads revealed loss of the articular cartilage.


[Coverage in the management of loss of skin substances on the lower third of the leg: about 9 cases].
Coverage of loss of skin substances on the lower third of the leg is a challenging problem. This is due to adjacent soft tissues impairment, shortage of local vascularization and bone exposure. We conducted a retrospective study of a series of 9 cases of skin coverage of the lower third of the leg treated at the University Hospital Hassan II of Fez from 2016 to 2018. This study aims to highlight the characteristic of the loss of skin substances on the lower third of the leg, while emphasizing the difficulty of management.


Perception of sweetness and bitterness in different vehicles.
In the present study, we investigated taste-taste, taste-vehicle, and simultaneous taste-vehicle-taste mixtures. Subjects made estimates of the sweetness and bitterness of 27 stimuli. Sucrose (292, 585, and 1170 mM), caffeine (13, 26, and 52 mM), and binary mixtures of low (292-13 mM), middle (585-26 mM), and high (1170-52 mM) levels of both components were dispersed in water, carboxymethylcellulose (CMC) 1% w/v, and gelatin 6% w/v. The sweetness and bitterness of the sucrose-vehicle-caffeine combinations were significantly weaker than the respective sucrose-vehicle and caffeine-vehicle combinations. The emerged mutual suppressive effects were asymmetrical and persisted when both tastants were presented in CMC and gelatin. Moreover, the increase in vehicle consistency and the simultaneous addition of another taste reduced the perceived intensity of a taste either presented alone or dissolved in water. For both sweetness and bitterness, the total taste suppression observed was always significant.


Toriello-Carey syndrome associated with respiratory failure and non-mechanical ileus.
Toriello-Carey syndrome comprises agenesis of the corpus callosum, telecanthus, small palpebral fissures, Pierre Robin sequence, abnormal ears, and cardiac defects. We report a boy who has some additional findings, including a severe respiratory failure and intestinal dysmotility. The boy died of these two disorders at age 13 months. Histological examination revealed pulmonary immaturity and a defect of smooth muscle cells in the longitudinal muscle coat of the intestinal musculature, both of which might explain some aspects of the pathophysiology of the patient.


Molecular cloning and linkage analysis of the Japanese medaka fish complement Bf/C2 gene.
Evolutionary studies of complement factor B (Bf) and C2 in lower vertebrates have revealed the presence of the Bf/C2 common ancestor-like molecule in lamprey (cyclostome) and the Bf molecule encoded by the duplicated genes closely linked to the major histocompatibility complex (MHC) in Xenopus (amphibian). To further define when Bf/C2 gene duplication occurred and when linkage between the Bf/C2 gene and the MHC was established, we amplified the Bf/C2 sequences in teleost, the Japanese medaka (Oryzias latipes), by reverse transcription - polymerase chain reaction with primers corresponding to the common amino acid sequences shared by mammalian Bf and C2. Only a single molecular species has been amplified, and the corresponding cDNA clones were isolated from the liver cDNA library. The longest insert contained 2384 nucleotides with an open reading frame of 754 residues. The deduced amino acid sequence showed 33.6% and 34.1% overall identity with the human Bf and C2 sequences, respectively, hence this clone was named medaka Bf/C2. The single-copy medaka Bf/C2 gene had exactly the same exon-intron organization as the mammalian Bf and C2 genes, and spanned about 8 kilobases. The Bf/C2 locus was mapped to the close proximity (2.9 cM) of the superoxide dismutase locus on the linkage group XX by the use of a restriction site polymorphism between two inbred strains of the medaka.


Stabilized oral nanostructured lipid carriers of Adefovir Dipivoxil as a potential liver targeting: Estimation of liver function panel and uptake following intravenous injection of radioiodinated indicator.
Adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor is effective against Hepatitis B virus. Its poor oral bioavailability leads to frequent administration causing severe adverse effects. Thereby the entrapment of AD within lipid nanoparticulate systems is a way of increasing AD oral bioavailability as a result of improving intestinal permeability with efficient liver-targeted delivery together with higher drug stability during storage. AD-loaded nanostructured lipid carriers (AD-NLCs) were prepared via solvent emulsification diffusion technique adopting 24 full factorial design to study the effect of lipid percentage, presence of egg yolk lecithin, surfactant type and percentage on entrapment efficiency (E.E.%), particle size and percent in-vitro drug released after 8 h (Q8hrs). Formula (F12) showed E.E.% of 90.5 ± 0.2%, vesicle size of 240.2 ± 2.5 nm and Q8hrs of 58.55 ± 9.4% was selected as the optimum formula with desirability value of 0.757 based on highest EE%, lowest P.S. and Q8hrs. Further evaluation of the optimized formula using radioiodinated rose bengal (RIRB) in thioacetamide induced liver damage in Swiss Albino mice revealed a higher liver uptake of 22 ± 0.01% ID/g (percent injected dose/g organ) and liver uptake/Blood (T/B) ratio of 2.22 ± 0.067 post 2 h of I.V injection of RIRB compared to 9 ± 0.01% ID/g and 0.64 ± 0.017 in untreated group, respectively. NLCs could be successfully used as oral drug delivery carriers of the antiviral drug Adefovir Dipivoxil to the liver with higher stability and oral bioavailability. Graphical abstract.


Automatic detection of immature platelets for decision making regarding platelet transfusion indications for pediatric patients.
Immature or reticulated platelets are known as a clinical marker of thrombopoiesis. Recently, an automatic method was established to detect reticulated platelets as immature platelet fraction (IPF) by means of hematology analyzer XE-2100. We assessed the effects of IPF detection after chemotherapy for various pediatric malignant disorders of 16 patients. Our results indicate that IPF should be considered a useful marker of imminent platelet recovery so that unnecessary platelet transfusion can be avoided.


A solitary cardiac metastasis involving the tricuspid valve ring.
An unique case of solitary metastasis to the region of the tricuspid valve is described. The mechanisms of formation and symptomatology of cardiac neoplasms are discussed. Tumour spread in this case was probably embolic.


Individualized alignment in total knee arthroplasty using image-based robotic assistance : Video article.
Over the past decades many innovations were introduced in total knee arthroplasty (TKA) focusing on implant longevity and higher procedural precision; however, there are still a high number of dissatisfied patients. It was reported that better anatomical alignment may result in improved patient outcome; however, current technologies have limitations to achieve this. The aim of this video article is to describe the technique of individualized alignment in TKA with the use of image-based robotic assistance. The technology is based on an individual patient knee model computed from segmented computed tomography (CT) scans. A preoperative planning of prosthesis position is conducted following the principle of kinematic alignment. Intraoperatively the soft tissue envelope is recorded and the computer predicts the gap balance based on the virtual planning. The prosthesis position is then adapted to achieve balanced gaps and to avoid soft tissue release. This technique is shown in a cadaver operation and clinical examples of two patients are described. With the combination of anatomically oriented prosthesis positioning and minor adaptations with respect to the soft tissue, an individualized alignment is achieved with reduced need of soft tissue release. The robotic-assisted surgery guarantees a precise implementation of the planning. The initial experience showed a promising outcome in short-term follow-up.


Neuropeptide Y-like immunoreactivity in perivascular nerve fibres of the guinea-pig.
The distribution of perivascular nerve fibres displaying neuropeptide Y-like immunoreactivity was studied in the guinea-pig. Generally, neuropeptide Y fibres were numerous around arteries and moderate in number around veins. In the heart, immunoreactive fibres were numerous in the auricles and the atria (epi- and endocardium) whereas the ventricles had a more scarce supply. The coronary vessels were richly supplied with fibres. Around large elastic and muscular arteries the fibres formed well developed plexuses. Small arteries in the respiratory tract, the gastrointestinal tract and the genito-urinary tract received a particularly rich supply. In the liver, spleen and kidney only few perivascular fibres were seen. Since immunoreactive fibres around blood vessels disappeared upon surgical or chemical sympathectomy, and sequential immunostaining with antisera against dopamine-beta-hydroxylase (a marker for adrenergic neurons) and against neuropeptide Y revealed their co-existence, it is concluded that neuropeptide Y fibres around blood vessels are sympathetic and adrenergic.


Accumulation of triclosan from diet and its neuroendocrine effects in Atlantic croaker (Micropogonias undulatus) under two temperature Regimes.
Rising water temperatures due to climate change may increase the uptake and effects of triclosan in aquatic organisms. Our objectives were to investigate the accumulation of dietary triclosan and its neuroendocrine effects in Atlantic croaker, an estuarine fish, under two temperatures and during depuration. A pilot study was used to select a dietary exposure of 50 mg/kg. For 10 days, fish were exposed to one of four diet/temperature treatments (n = 16/treatment): normal diet at 26 °C and 29 °C and triclosan-treated diet at 26 °C and 29 °C. Fish exposed to triclosan at 26 °C accumulated 2.6 mg/kg wet weight on average versus 5.6 mg/kg wet weight at 29 °C. Triclosan exposure significantly impacted reflexes, resulting in the loss of the dorsal fin reflex (DS) in 53% of fish, while temperature and triclosan-temperature interactions were not significant. Triclosan body burden did not significantly predict DS loss. There were no significant differences in thyroid hormone levels among groups. Triclosan-treated fish at 26 °C were fed untreated pellets for 5 additional weeks. Two fish lost the DS during the first depuration week, and no affected fish recovered the reflex. These results have important implications for fish and their predators, as the DS may be important for swimming performance and social patterning.


An improved model for the population dynamics of cattle gastrointestinal nematodes on pasture: parameterisation and field validation for Ostertagia ostertagi and Cooperia oncophora in northern temperate zones.
Gastrointestinal nematodes (GIN) are amongst the most important pathogens of grazing ruminants worldwide, resulting in negative impacts on cattle health and production. The dynamics of infection are driven in large part by the influence of climate and weather on free-living stages on pasture, and computer models have been developed to predict infective larval abundance and guide management strategies. Significant uncertainties around key model parameters limits effective application of these models to GIN in cattle, however, and these parameters are difficult to estimate in natural populations of mixed GIN species. In this paper, recent advances in molecular biology, specifically ITS-2 rDNA 'nemabiome' metabarcoding, are synthesised with a modern population dynamic model, GLOWORM-FL, to overcome this limitation. Experiments under controlled conditions were used to estimate rainfall constraints on migration of infective L3 larvae out of faeces, and their survival in faeces and soil across a temperature gradient, with nemabiome metabarcoding data permitting species-specific estimates for Ostertagia ostertagi and Cooperia oncophora in mixed natural populations. Results showed that L3 of both species survived well in faeces and soil between 0 and 30 °C, and required at least 5 mm of rainfall daily to migrate out of faeces, with the proportion migrating increasing with the amount of rainfall. These estimates were applied within the model using weather and grazing data and use to predict patterns of larval availability on pasture on three commercial beef farms in western Canada. The model performed well overall in predicting the observed seasonal patterns but some discrepancies were evident which should guide further iterative improvements in model development and field methods. The model was also applied to illustrate its use in exploring differences in predicted seasonal transmission patterns in different regions. Such predictive modelling can help inform evidence-based parasite control strategies which are increasingly needed due climate change and drug resistance. The work presented here also illustrates the added value of combining molecular biology and population dynamics to advance predictive understanding of parasite infections.


Electroencephalography characteristics of patients with supratentorial glioma in different consciousness states induced by propofol.
Gliomas are the most common primary intracranial malignant tumors. Some of these patients exhibit previously clinically undetected neurological deficits after sedation. The absence of neurophysiological evidence for this phenomenon limits the use of time-sensitive monitoring methods. The study aims to compare differences between glioma patients under sedation and those without intracranial lesions by comparing their EEG features. Twenty-one patients without intracranial tumors and 21 with frontal lobe supratentorial gliomas were enrolled. The EEG power spectrum of the glioma group was comparable to that of the control group for both sides of the brain (P > 0.05 for all frequencies). Compared with those without intracranial lesions, the weighted phase lag index (wPLI) in the alpha and beta bands on the non-occupied side decreased. Glioma patients had weaker functional connectivity during sedation than patients without intracranial lesions, manifesting as reduced functional connectivity on the non-occupied side.


Lentivirus carrying the NeuroD1 gene promotes the conversion from glial cells into neurons in a spinal cord injury model.
In this study, we aimed to reprogram reactive glial cells into neural stem cells and neurons in vivo, by up-regulating NeuroD1. 60 rats were randomly divided into three groups with equal numbers. All rats received a spinal cord injury. Group A received only normal saline injection. Group B received unloaded lentivirus injection. Group C received NeuroD1 recombinant lentivirus injection. The BBB scores of the animals were documented at 3, 7, 14, 21days after SCI. 5 random rats of each group were removed at those timings after SCI and sacrificed. In the spinal cord slices, the numbers and morphology of neural stem cells, immature neurons and mature neurons were examined after immunohistochemical staining. Except day 3 after SCI, the BBB scores of group C on days 7, 14 and 21 were significantly higher than the other two groups (P<0.05). Compared with the group A and B, a remarkable increase was noticed in the number of positive cells in the group C (P<0.05). These findings suggest that NeuroD1 up-regulated cells can be reprogrammed into neural stem cells, immature and functional neurons. It may be possible to replace neurons after injury by endogenous means, as a first step toward spinal cord repair.


Vena Caval Filter Utilization and Outcomes in Pulmonary Embolism: Medicare Hospitalizations From 1999 to 2010.
Inferior vena caval filters (IVCFs) may prevent recurrent pulmonary embolism (PE). Despite uncertainty about their net benefit, patterns of use and outcomes of these devices in contemporary practice are unknown. The authors determined the trends in utilization rates and outcomes of IVCF placement in patients with PE and explored regional variations in use in the United States. In a national cohort study of all Medicare fee-for-service beneficiaries ≥65 years of age with principal discharge diagnoses of PE between 1999 and 2010, rates of IVCF placement per 100,000 beneficiary-years and per 1,000 patients with PE were determined. The 30-day and 1-year mortality rates after IVCF placement were also investigated. Among 556,658 patients hospitalized with PE, 94,427 underwent IVCF placement. Between 1999 and 2010, the number of PE hospitalizations with IVCF placement increased from 5,003 to 8,928, representing an increase in the rate per 100,000 beneficiary-years from 19.0 to 32.5 (p < 0.001 for both). As the total number of PE hospitalizations increased (from 31,746 in 1999 to 54,392 in 2010), the rate of IVCF placement per 1,000 PE hospitalizations did not change significantly (from 157.6 to 164.1, p = 0.11). Results were consistent across demographic subgroups, although IVCF use was higher in blacks and patients ≥85 years of age. IVCF utilization varied widely across regions, with the highest rate in the South Atlantic region and the lowest rate in the Mountain region. In a period of increasing PE hospitalizations among Medicare fee-for-service beneficiaries, IVCF placement increased as utilization rates in patients with PE remained greater than 15%. Mortality associated with PE hospitalizations is declining, regardless of IVCF use.


Mitf-D, a newly identified isoform, expressed in the retinal pigment epithelium and monocyte-lineage cells affected by Mitf mutations.
Microphthalmia-associated transcription factor (Mitf) regulates the differentiation of melanocytes, optic cup-derived retinal pigment epithelium (RPE), and some types of bone marrow-derived cells. Mitf consists of at least five isoforms with different N-termini, each of which is encoded by a separate exon 1. Here we identified a novel isoform, termed mouse Mitf-D/human MITF-D, that is expressed in RPE, macrophages, and osteoclasts affected by the Mitf mutations, but not expressed in other Mitf target cells, including melanocyte-lineage cells and natural killer cells. The initiation Met of MITF-D is located in the downstream domain (B1b domain) that is shared by other MITF isoforms. The 5'-untranslated region of MITF-D mRNA is encoded by the newly identified first exon of the MITF gene, termed exon 1D, which is located 3 kb upstream of the exon encoding the B1b domain. Thus, the MITF gene generates multiple isoforms with different expression patterns by using the alternative promoters in a cell-dependent manner, thereby providing the molecular basis for the phenotypic variability seen in the MITF/Mitf mutants.


Impact of artificial intelligence on radiology: a EuroAIM survey among members of the European Society of Radiology.
We report the results of a survey conducted among ESR members in November and December 2018, asking for expectations about artificial intelligence (AI) in 5-10 years. Of 24,000 ESR members contacted, 675 (2.8%) completed the survey, 454 males (67%), 555 (82%) working at academic/public hospitals. AI impact was mostly expected (≥ 30% of responders) on breast, oncologic, thoracic, and neuro imaging, mainly involving mammography, computed tomography, and magnetic resonance. Responders foresee AI impact on: job opportunities (375/675, 56%), 218/375 (58%) expecting increase, 157/375 (42%) reduction; reporting workload (504/675, 75%), 256/504 (51%) expecting reduction, 248/504 (49%) increase; radiologist's profile, becoming more clinical (364/675, 54%) and more subspecialised (283/675, 42%). For 374/675 responders (55%) AI-only reports would be not accepted by patients, for 79/675 (12%) accepted, for 222/675 (33%) it is too early to answer. For 275/675 responders (41%) AI will make the radiologist-patient relation more interactive, for 140/675 (21%) more impersonal, for 259/675 (38%) unchanged. If AI allows time saving, radiologists should interact more with clinicians (437/675, 65%) and/or patients (322/675, 48%). For all responders, involvement in AI-projects is welcome, with different roles: supervision (434/675, 64%), task definition (359/675, 53%), image labelling (197/675, 29%). Of 675 responders, 321 (48%) do not currently use AI, 138 (20%) use AI, 205 (30%) are planning to do it. According to 277/675 responders (41%), radiologists will take responsibility for AI outcome, while 277/675 (41%) suggest shared responsibility with other professionals. To summarise, responders showed a general favourable attitude towards AI.


Parental occupational exposure to metals and risk of cancer in the offspring: A register-based case-control study from Sweden.
Cancer risks in the offspring of mothers and fathers exposed to metals are unknown. We estimated the relative risks of childhood cancer, overall and by type, associated with parental occupational exposure to arsenic, cadmium, chromium, nickel, and lead. We conducted a nested case-control study (1960-2015) of children born in Sweden aged 0-19 years diagnosed with cancer (National Cancer Register) matched 25:1 to controls on birth year and sex. We obtained parental occupational data around their birth from censuses and a nationwide register and identified exposure to each metal (yes/no, or higher/lower/no exposure) using the Swedish job-exposure matrix (SWEJEM). Adjusted odds ratios (OR) and 95% confidence intervals (CIs) were estimated separately for maternal and paternal exposures using conditional logistic regression. We compared 9653 cases to 1,72,194 controls in maternal and 12,521 cases to 2,74,434 controls in paternal analyses, respectively. We found a 38% increased risk of cancer associated with maternal occupational exposure to arsenic (OR 1.38 [95% CI 1.06, 1.82]), likely driven by higher risks for lymphoma (OR 1.52 [0.73, 3.15]), central nervous system (CNS) (OR 1.49 [0.88, 2.54]) and other solid malignancies (OR 1.74 [1.14, 2.65]). There were also indications of higher risks of lymphoma in children of mothers exposed to nickel and iron, and of CNS tumours due to chromium exposure. No associations were observed from paternal occupational exposure to any of the metals. We found evidence of increased risks of cancer in children of mothers but not fathers occupationally exposed to arsenic and potentially other metals.


An ELISA for quantifying quail IgY and characterizing maternal IgY transfer to egg yolk in several quail strains.
In avian species, maternal blood immunoglobulin Y (IgY) is transferred to the egg yolks of maturing oocytes, but the mechanism underlying this transfer is unknown. To gain insight into the mechanism of maternal IgY transfer in quail, we established an enzyme-linked immunosorbent assay (ELISA) for the quantitation of quail IgY. We characterized strain differences in blood and egg yolk IgY concentrations and exogenously injected IgY-Fc uptakes into egg yolks. A specific rabbit polyclonal antibody to quail IgY was raised for the ELISA. Blood and egg yolk IgY concentrations were determined in six quail strains (one inbred strain, L; four closed population strains, AWE, DB, PS, WE; one commercial strain, Commercial). The birds were also injected with digoxigenin-labeled quail IgY-Fc, and its uptakes into laid eggs were compared. The strain difference in blood and egg yolk IgY concentrations was at most 2.5-fold, between PS and AWE. The rank order of IgY concentrations was AWE, Commercial, DB, L≥WE≥PS. A significant positive correlation (|R|=0.786) between individual blood IgY and egg yolk IgY and the concentrated egg yolk IgY (1.5-2-fold) against blood IgY was observed. Interestingly, there was a significant inverse correlation (|R|=0.452) between injected IgY-Fc uptakes and the blood IgY concentration, implying competition of the injected IgY-Fc and blood IgY in the process of IgY uptake into egg yolks. In conclusion, we successfully determined blood and egg yolk IgY concentrations in various quail strains by a quail IgY-specific ELISA. The concentrated egg yolk IgY against the blood IgY and the inverse relationship of exogenous IgY-Fc uptake against the blood IgY supports the existence of a selective IgY transport mechanism in avian maturing oocytes.


Conservative approach: Intentional retention of the placenta.
Intentional retention of the placenta (IRP), or 'conservative' treatment or management, entails opening the uterus, delivering the baby, tying and cutting the umbilical cord at its placental insertion site, leaving the placenta in the uterus and waiting for its complete spontaneous resorption in women with placenta accreta spectrum (PAS). The uterine preservation rate with this approach is about 78%, and severe maternal morbidity about 6%; these rates are respectively lower and higher in subgroups of women with placenta percreta. IRP has become a recommended option for women with PAS reluctant to undergo caesarean-hysterectomy and wanting to preserve their fertility, after appropriate information about the uterine preservation rate, but also the risk of a subsequent emergency hysterectomy due to unpredictable haemorrhage and/or infection, and the need for follow-up with regular visits for several months. Some authorities also recommend IRP when hysterectomy is at very high risk of surgical complications.


Inflammatory mediator profiles in tears accompanying keratoconjunctival responses induced by nasal allergy.
The allergic reaction taking place in the nasal mucosa can induce a secondary ocular (keratoconjunctival) response of an immediate (SIOR), late (SLOR) or delayed (SDYOR) type in some patients with keratoconjunctivitis (KC). To investigate the concentration changes of histamine, tryptase, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), eosinophilic peroxidase (EPO), leucotrienes (LTB₄, LTC₄, LTE₄), prostaglandins (PGD₂, PGE₂ and PGF₂α), thromboxane B₂ (TXB₂), myeloperoxidase (MPO), interferon-γ (IFN-γ) and interleukins (IL-2, IL-4 and IL-5) in tears during the SIOR, SLOR and SDYOR. 19 SIORs (p<0.001), 28 SLORs (p<0.001) and 10 SDYORs (p<0.05) recorded in 57 KC patients following nasal challenges with allergens (NPT) and 57 phosphate-buffered saline (PBS) control tests were repeated and supplemented with determination of the mediators in tears. The ocular response types were associated with significant changes (p<0.05) of mediators in tears as follows: (1) SIORs: histamine, tryptase, ECP, LTC₄, PGD₂, PGF₂α, IL-4 and IL-5; (2) SLORs: histamine, ECP, EDN, LTB₄, LTC₄, PGE₂, MPO, IL-4 and IL-5; (3) SDYORs: LTB4, TXB₂, MPO, IFN-γ and IL-2. No significant changes of these factors were measured in tears during the 57 PBS controls (p>0.1). These results demonstrate a causal involvement of nasal allergy in some KC patients, inducing a secondary keratoconjunctival response of an immediate (SIOR), late (SLOR) or delayed (SDYOR) type, associated with different inflammatory mediator profiles in the tears, suggesting participation of different hypersensitivity mechanisms. These results also emphasise the diagnostic value of nasal challenge with allergen combined with monitoring of ocular response in KC patients, responding insufficiently to the usual ophthalmologic therapy.


Domestic violence and perinatal mental disorders: a systematic review and meta-analysis.
Domestic violence in the perinatal period is associated with adverse obstetric outcomes, but evidence is limited on its association with perinatal mental disorders. We aimed to estimate the prevalence and odds of having experienced domestic violence among women with antenatal and postnatal mental disorders (depression and anxiety disorders including post-traumatic stress disorder [PTSD], eating disorders, and psychoses). We conducted a systematic review and meta-analysis (PROSPERO reference CRD42012002048). Data sources included searches of electronic databases (to 15 February 2013), hand searches, citation tracking, update of a review on victimisation and mental disorder, and expert recommendations. Included studies were peer-reviewed experimental or observational studies that reported on women aged 16 y or older, that assessed the prevalence and/or odds of having experienced domestic violence, and that assessed symptoms of perinatal mental disorder using a validated instrument. Two reviewers screened 1,125 full-text papers, extracted data, and independently appraised study quality. Odds ratios were pooled using meta-analysis. Sixty-seven papers were included. Pooled estimates from longitudinal studies suggest a 3-fold increase in the odds of high levels of depressive symptoms in the postnatal period after having experienced partner violence during pregnancy (odds ratio 3.1, 95% CI 2.7-3.6). Increased odds of having experienced domestic violence among women with high levels of depressive, anxiety, and PTSD symptoms in the antenatal and postnatal periods were consistently reported in cross-sectional studies. No studies were identified on eating disorders or puerperal psychosis. Analyses were limited because of study heterogeneity and lack of data on baseline symptoms, preventing clear findings on causal directionality. High levels of symptoms of perinatal depression, anxiety, and PTSD are significantly associated with having experienced domestic violence. High-quality evidence is now needed on how maternity and mental health services should address domestic violence and improve health outcomes for women and their infants in the perinatal period.


Foster care during the COVID-19 pandemic: A qualitative analysis of caregiver and professional experiences.
Research is needed to facilitate better understanding of how different groups have been impacted by COVID-19, especially those in already strained service systems such as foster care. These inquiries will support further response, recovery and preparedness efforts. This qualitative study addressed how professionals and caregivers in foster care described being affected by COVID-19 in order to support future research and planning for foster care systems in this pandemic context. A sample of foster parents and foster care professionals (N = 357) from a mostly rural, southeastern state in the U.S. participated in the study. Qualitative analysis was conducted of 357 open-ended responses regarding the impact of COVID-19 from a survey distributed in August 2020. The coding process resulted in the identification of 15 distinct themes: Isolation & Loss of Social Support, Work Changes/Stressors, School Issues, Childcare Issues, No Impact/Positive Changes, Financial Problems, Fear of Contagion, Negative Child Welfare Impacts, Mental Health Problems/Stress, Loss of Faith/Trust & Societal Frustrations, Health & Mental Healthcare Access Issues, PPE & Testing Issues, Grief & Loss, and Marital Problems. Secondary impacts rather than direct physiologic effects of the virus were primarily reported. This study underscores the various challenges facing foster care systems, and how the pandemic context is exacerbating many of these issues. Further research is needed to ensure the implementation of adequately complex and nuanced responses that target needs and avoid creating further problems for foster care.


Effects of probiotics on the content and bioaccessibility of phenolic compounds in red pitaya pulp.
This study assessed the effects of the incorporation of Lactobacillus acidophilus LA-05 or Bifidobacterium animalis ssp. lactis BB-12 in the content and bioaccessibility of phenolics in red pitaya pulp. The oxygen radical absorbance capacity (ORAC) of the dialyzed (bioaccessible) fraction of red pitaya pulp fermented by these probiotics was also assessed. After 48 h of cultivation in red pitaya pulp, the pH and sugar contents decreased, while organic acids and viable counts of the tested probiotics increased (p < 0.05). After exposure to simulated gastrointestinal conditions the viable counts of L. acidophilus LA-05 and B. lactis BB-12 in fermented red pitaya pulp were close to 8 and 7 log CFU/mL, respectively. Fermentation with probiotics decreased (p < 0.05) the contents of phenolic acids and flavonoids in red pitaya pulp. Both, L. acidophilus LA-05 and B. lactis BB-12 increased the presence of phenolics in the non dialyzed fraction of the red pitaya pulp. The bioaccessibility of catechin, epigallocatechin gallate, and procyanidin B2 increased (p < 0.05) in red pitaya pulp fermented by L. acidophilus LA-05 or B. lactis BB-12. The bioaccessible fraction of red pitaya pulp fermented by L. acidophilus LA-05 or B. lactis BB-12 showed higher antioxidant activity than that of the non-fermented red pitaya pulp. These findings indicate the fermentation of red pitaya by probiotics as an alternative to increase the bioaccessibility of specific phenolics, as well as the antioxidant activity in this fruit.


Primary chondrosarcoma of the breast: a case presentation and review of the literature.
Mammary sarcomas are uncommon tumors. When tumors like malignant cystosarcomaphyllodes and metaplastic carcinoma, where malignant cartilaginous areas may be present, are excluded, only nine cases have been reported to date.We report another case of primary chondrosarcoma of the breast here. A 24-year-old Mediterranean woman presented with a painful mass in the right breast and a physical examination revealed a palpable mass. An incisional biopsy was performed and primary chondrosarcoma was diagnosed based on histological examination. Our patient underwent a mastectomy. A preoperative clinical and cytological diagnosis of chondrosarcoma, even though possible in a few cases, is usually not attained due to its similar clinical behavior with other breast tumors.


Safety and efficacy of autologous endothelial progenitor cells transplantation in children with idiopathic pulmonary arterial hypertension: open-label pilot study.
Experimental data suggest that transplantation of EPCs attenuates monocrotaline-induced pulmonary hypertension in rats and dogs. In addition, our previous studies suggested that autologous EPC transplantation was feasible, safe, and might have beneficial effects on exercise capacity and pulmonary hemodynamics in adults with IPAH. Thus, we hypothesized that transplantation of EPCs would improve exercise capacity and pulmonary hemodynamics in children with IPAH. Thirteen children with IPAH received intravenous infusion of autologous EPCs. The right-sided heart catheterization and 6-MWD test were performed at baseline and at the time of 12 wk after cell infusion. At the time of 12 wk, mPAP decreased by 6.4 mmHg from 70.3 +/- 19.0 to 63.9 +/- 19.3 mmHg (p = 0.015). PVR decreased by approximately 19% from 1118 +/- 537 to 906 +/- 377 dyn s/cm(5) (p = 0.047). CO increased from 3.39 +/- 0.79 to 3.85 +/- 0.42 L/min (p = 0.048). The 6-MWD increased by 39 m from 359 +/- 82 to 399 +/- 74 m (p = 0.012). NYHA functional class also improved. There were no severe adverse events with cell infusion. The small pilot study suggested that intravenous infusion of autologous EPCs was feasible, safe, and associated with significant improvements in exercise capacity, NYHA functional class, and pulmonary hemodynamics in children with IPAH. Confirmation of these results in a randomized controlled trial are essential.


Life cycle assessment of biogas upgrading technologies.
This article evaluates the life cycle assessment (LCA) of three biogas upgrading technologies. An in-depth study and evaluation was conducted on high pressure water scrubbing (HPWS), as well as alkaline with regeneration (AwR) and bottom ash upgrading (BABIU), which additionally offer carbon storage. AwR and BABIU are two novel technologies that utilize waste from municipal solid waste incinerators - namely bottom ash (BA) and air pollution control residues (APC) - and are able to store CO(2) from biogas through accelerated carbonation processes. These are compared to high pressure water scrubbing (HPWS) which is a widely used technology in Europe. The AwR uses an alkaline solution to remove the CO(2) and then the solution - rich in carbonate and bicarbonate ions - is regenerated through carbonation of APC. The BABIU process directly exposes the gas to the BA to remove and immediately store the CO(2), again by carbonation. It was determined that the AwR process had an 84% higher impact in all LCA categories largely due to the energy intensive production of the alkaline reactants. The BABIU process had the lowest impact in most categories even when compared to five other CO(2) capture technologies on the market. AwR and BABIU have a particularly low impact in the global warming potential category as a result of the immediate storage of the CO(2). For AwR, it was determined that using NaOH instead of KOH improves its environmental performance by 34%. For the BABIU process the use of renewable energies would improve its impact since accounts for 55% of the impact.


Monte Carlo simulation studies on the prediction of protein folding types from amino acid composition. II. Correlative effect.
A number of methods to predicting the folding type of a protein based on its amino acid composition have been developed during the past few years. In order to perform an objective and fair comparison of different prediction methods, a Monte Carlo simulation method was proposed to calculate the asymptotic limit of the prediction accuracy [Zhang and Chou (1992), Biophys. J. 63, 1523-1529, referred to as simulation method I]. However, simulation method I was based on an oversimplified assumption, i.e., there are no correlations between the compositions of different amino acids. By taking into account such correlations, a new method, referred to as simulation method II, has been proposed to recalculate the objective accuracy of prediction for the least Euclidean distance method [Nakashima et al. (1986), J. Bochem. 99, 152-162] and the least Minkowski distance method [Chou (1989), Prediction in Protein Structure and the Principles of Protein Conformation, Plenum Press, New York, pp. 549-586], respectively. The results show that the prediction accuracy of the former is still better than that of the latter, as found by simulation method I; however, after incorporating the correlative effect, the objective prediction accuracies become lower for both methods. The reason for this phenomenon is discussed in detail. The simulation method and the idea developed in this paper can be applied to examine any other statistical prediction method, including the computer-simulated neural network method.


Idiopathic bleeding during the second half of pregnancy as a risk factor for adverse perinatal outcome.
To investigate pregnancy outcome in women suffering from idiopathic vaginal bleeding (IVB) during the second half of pregnancy. A comparison between patients admitted to the hospital due to bleeding during the second half of pregnancy and patients without bleeding was performed. Patients lacking prenatal care as well as multiple gestations were excluded from the analysis. Stratified analyses using the Mantel-Haenszel technique and a multiple logistic regression model were performed to control for confounders. During the study period, 173,621 singleton deliveries occurred at our institute. Of these, 2077 (1.19%) were complicated with bleeding upon admission during the second half of pregnancy. After excluding cases with bleeding due to placental abruption, placenta previa, cervical problems, etc., 67 patients were classified as having IVB (0.038%). Independent risk factors associated with IVB, using a backward, stepwise multivariable analysis were oligohydramnios (OR=6.2; 95% CI 3.1-12.7; p < 0.001), premature rupture of membranes (OR=3.4; 95% CI 1.8-6.2; p < 0.001), intrauterine growth restriction (IUGR, OR 5.6; 95% CI 2.5-12.2; p < 0.001), and Jewish ethnicity (OR=1.9; 95% CI 1.0-3.5; p=0.036). These patients subsequently were more likely to deliver preterm (<37 weeks, 56.7% vs. 7.3%; mean gestational age of 33.6+/-5.7 weeks vs. 39.2+/-2.1 weeks; p < 0.001) and by cesarean delivery (CD, 35.8% vs. 12.1%, OR=4.0; 95% CI 2.4-6.6; p < 0.001). Higher rates of low Apgar scores (<7) at 1 and 5 minutes were noted in these patients (OR=10.3; 95% CI 5.9-17.8; p < 0.001 and OR=17.8; 95% CI 7.1-44.5; p < 0.001, respectively). Moreover, perinatal mortality rate among patients admitted due to idiopathic bleeding was significantly higher as compared to patients without bleeding (9.6% vs. 1.2%, OR=8.4; 95% CI 3.3-21.2; p < 0.001). However, when controlling for preterm delivery, using the Mantel-Haenszel technique, the association lost its significance. Idiopathic vaginal bleeding during the second half of pregnancy is a risk factor for adverse perinatal outcome, mostly due to its significant association with preterm delivery. Careful surveillance, including fetal monitoring, is suggested in these cases in order to reduce the adverse perinatal outcome.


A preliminary account of the properties of recombinant human Glyoxylate reductase (GRHPR), LDHA and LDHB with glyoxylate, and their potential roles in its metabolism.
Human lactate dehydrogenase (LDH) is thought to contribute to the oxidation of glyoxylate to oxalate and thus to the pathogenesis of disorders of endogenous oxalate overproduction. Glyoxylate reductase (GRHPR) has a potentially protective role metabolising glyoxylate to the less reactive glycolate. In this paper, the kinetic parameters of recombinant human LDHA, LDHB and GR have been compared with respect to their affinity for glyoxylate and related substrates. The Km values and specificity constants (Kcat/K(M)) of purified recombinant human LDHA, LDHB and GRHPR were determined for the reduction of glyoxylate and hydroxypyruvate. K(M) values with glyoxylate were 29.3 mM for LDHA, 9.9 mM for LDHB and 1.0 mM for GRHPR. For the oxidation of glyoxylate, K(M) values were 0.18 mM and 0.26 mM for LDHA and LDHB respectively with NAD+ as cofactor. Overall, under the same reaction conditions, the specificity constants suggest there is a fine balance between the reduction and oxidation reactions of these substrates, suggesting that control is most likely dictated by the ambient concentrations of the respective intracellular cofactors. Neither LDHA nor LDHB utilised glycolate as substrate and NADPH was a poor cofactor with a relative activity less than 3% that of NADH. GRHPR had a higher affinity for NADPH than NADH (K(M) 0.011 mM vs. 2.42 mM). The potential roles of LDH isoforms and GRHPR in oxalate synthesis are discussed.


Effect of coping on endocrinoimmune functions in different stress situations.
The objective of this study was to examine the effects of coping strategies on the endocrine and immune functions in different stress situations. Thirty-eight medical students were enrolled in this study. Cell-mediated immune function was measured using the lymphocyte proliferative response to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production during the nonexamination period and during the preexamination period. Endocrine functions were assessed by measuring the plasma levels of norepinephrine, adrenocorticotropic hormone (ACTH) and cortisol. The Global Assessment of Recent Stress (GARS) scale, the Stress Response Inventory, the anxiety, depression, and somatization subscales of the Symptom Checklist-90-revised, the Way of Coping-revised, the Toronto Alexithymia Scale and the Anger Expression Scale were used as psychometric measures. The subjects with higher levels of total GARS scores showed significantly higher IL-2 production during the nonexam period than those with lower levels of total GARS scores. During the same period, IL-2 production in the less positive reappraisal group was significantly higher than in the more positive reappraisal group. Lymphocyte proliferation in the group seeking less social support was also significantly higher than in the group seeking more social support. However, no significant association was found between the coping strategies and each of the hormone levels. These results suggest that positive reappraisal and seeking social support can be associated with the alteration of immune function during a chronic stress period. In particular, positive reappraisal is likely to reverse the stress-induced immune responses. This study did not find that neuroendocrine function such as the sympathetic-adrenal medullary axis or the hypothalamic-pituitary-adrenal axis is playing a mediating role in the relationship between coping and immunity.


[Finite elemental analysis of the influence of mandibular plane angle on the stress distribution of implant tooth].
Finite elemental analysis of the mechanical characteristics of a first mandibular implant molar under different mandibular plane angles determines the load conditions on the implant, thereby providing guidance for clinical application. CT data of three mandibular plane angles (low, average, high) were collected. A finite elemental combination model of a dental implant was constructed. The orthogonal experimental research was designed. Results followed data collection and analysis. The optimal combination was a low angle, 4.8 mm, and type Ⅱ bone. The relations among diameter of the implant, angle of mandibular bone, and bone density were determined. Mandibular plane angle influences the stability of a dental implant. Under constant biting force, dental implants bear the stress proportional to the angle, high angles cause high stress, average angles cause average stress, and low angles cause the least stress.


The benefits of exercise for outcome improvement following traumatic brain injury: Evidence, pitfalls and future perspectives.
Traumatic brain injury (TBI), also known as a silent epidemic, is currently a substantial public health problem worldwide. Given the increased energy demands following brain injury, relevant guidelines tend to recommend absolute physical and cognitive rest for patients post-TBI. Nevertheless, recent evidence suggests that strict rest does not provide additional benefits to patients' recovery. By contrast, as a cost-effective non-pharmacological therapy, exercise has shown promise for enhancing functional outcomes after injury. This article summarizes the most recent evidence supporting the beneficial effects of exercise on TBI outcomes, focusing on the efficacy of exercise for cognitive recovery after injury and its potential mechanisms. Available evidence demonstrates the potential of exercise in improving cognitive impairment, mood disorders, and post-concussion syndrome following TBI. However, the clinical application for exercise rehabilitation in TBI remains challenging, particularly due to the inadequacy of the existing clinical evaluation system. Also, a better understanding of the underlying mechanisms whereby exercise promotes its most beneficial effects post-TBI will aid in the development of new clinical strategies to best benefit of these patients.


Polycystic ovary syndrome in patients with focal epilepsy: a study in 93 women.
A prospective cohort analysis of premenopausal women with focal epilepsy was conducted in order to determine whether polycystic ovary syndrome (PCOS) is a common finding in women treated with antiepileptic drugs (AED). This study was carried out in 93 of 150 women (aged between 20 and 53 years; mean, 34.3 years) with chronic focal epilepsy consecutively cared for at the Department of Epileptology, University of Bonn: 38 were receiving one AED (18 valproate, 20 carbamazepine), 36 more than one drug, and 19 were without medication. Patients were followed-up for 6 months. PCOS was defined as hyperandrogenism (testosterone concentration, > 0.7 ng/ml) combined with oligomenorrhoea (cycle length, > 35 days) or amenorrhoea. PCOS was identified in two out of 19 (10.5%) patients receiving no medication; in four of 38 (10.5%) of patients receiving monotherapy, and in none of the patients receiving more than one AED. The incidence of PCOS in patients treated with valproate monotherapy (11.1%) was similar to that in patients treated with carbamazepine (10%) and also to that in patients not treated with AEDs. The results of this study suggest that the manifestation of PCOS in women with focal epilepsy is not related to the administration of valproate or carbamazepine.


Hierarchical organization from self-assembling disulfide macrocycles.
We report cystine-based macrocyclic compounds showing very unique self-assembling behavior. 24-membered disulfide macrocycle 3 shows a helical and tubular organization and also forms an insoluble plaque that is birefringent with congo red dye. 48-membered macrocycle 4 shows a vesicle-like assembly with capability for encapsulation, as demonstrated by rhodamine B encapsulation.


Assessment of gelatin-supplemented BACTEC blood culture medium in a pediatric hospital.
Sodium polyanetheolesulfonate (SPS), an anticoagulant used in blood culture media, adversely affects the isolation of Neisseria meningitidis. The addition of gelatin appears to counteract this effect. Studies using the radiometric BACTEC system, however, have noted a lower isolation rate of other bacteria from gelatin-supplemented media. We wished to evaluate the effect of the addition of gelatin (1.2%) to a nonradiometric BACTEC aerobic medium (NR6A) on the recovery of N. meningitidis and other pathogens. The NR6A medium with gelatin (NR6A analogue) also contained a lower concentration of SPS (0.025% vs 0.035%). We did 6045 paired comparisons of blood cultured in routine NR6A medium and the NR6A analogue. Eight isolates of N. meningitidis were recovered, five only from the gelatin-supplemented medium and three from both bottles. There was no statistically significant difference in total recovery of aerobic and facultative bacteria or Candida species from both bottles. Haemophilus influenzae was detected earlier in the nonsupplemented NR6A medium. We conclude that the use of the NR6A analogue medium appeared to increase the yield of N. meningitidis without adversely affecting the recovery of other common pathogens, although the recovery of H. influenzae was slightly delayed.


Delirium during clozapine treatment: incidence and associated risk factors.
Incidence and risk factors for delirium during clozapine treatment require further clarification. We used computerized pharmacy records to identify all adult psychiatric inpatients treated with clozapine (1995-96), reviewed their medical records to score incidence and severity of delirium, and tested associations with potential risk factors. Subjects (n = 139) were 72 women and 67 men, aged 40.8 +/- 12.1 years, hospitalized for 24.9 +/- 23.3 days, and given clozapine, gradually increased to an average daily dose of 282 +/- 203 mg (3.45 +/- 2.45 mg/kg) for 18.9 +/- 16.4 days. Delirium was diagnosed in 14 (10.1 % incidence, or 1.48 cases/person-years of exposure); 71.4 % of cases were moderate or severe. Associated factors were co-treatment with other centrally antimuscarinic agents, poor clinical outcome, older age, and longer hospitalization (by 17.5 days, increasing cost); sex, diagnosis or medical co-morbidity, and daily clozapine dose, which fell with age, were unrelated. Delirium was found in 10 % of clozapine-treated inpatients, particularly in older patients exposed to other central anticholinergics. Delirium was inconsistently recognized clinically in milder cases and was associated with increased length-of-stay and higher costs, and inferior clinical outcome.


Impact of the MCP-1-2518A>G polymorphism on COVID-19 severity in the Iranian population: A case-control study.
As a result of SARS-CoV-2 infection, the host's immune system is disrupted, and chemokines and cytokines are intensified to eliminate the virus, resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19 have been observed to have elevated levels of MCP-1, a chemokine associated with the severity of the disease. In some diseases, polymorphisms in the regulatory region of the MCP-1 gene correspond to serum levels and disease severity. An attempt was made in this study to assess the relationship between MCP-1 G-2518A and serum MCP-1 levels in Iranian COVID-19 patients and the severity of the disease. In this study, patients were randomly sampled from outpatients on the first day of diagnosis and from inpatients on the first day of their hospitalization. Patients were classified into the outpatient (without symptoms or with mild symptoms) and inpatient (with moderate, severe, and critical symptoms) groups. The serum level of MCP-1 was measured by ELISA and the frequency of MCP-1 G-2518A gene polymorphism genotypes in COVID-19 patients was checked by the RFLP-PCR method. Participants with COVID-19 infection had a higher rate of underlying diseases, such as diabetes, high blood pressure, kidney disease, and cardiovascular disease than the control group (P-value < 0.001). Also, the frequency of these factors in inpatients was significantly higher compared to outpatients (P-value < 0.001). Additionally, the level of MCP-1 in serum was significantly different with an average of 11.90 in comparison to 2.98 in the control group (P-value, 0.05), which is attributed to elevated serum levels among patients in hospitals with an average of 11.72 in comparison to 2.98 in the control group. Compared with outpatients, inpatients had a higher frequency of the G allele of the MCP-1-2518 polymorphism (P-value < 0.05), while a notable difference was observed in the serum level of MCP-1 in COVID-19 patients with the MCP-1-2518 AA genotype in the whole group in comparison to the control group (P-value: 0.024). Totally, the results showed that a high frequency of the G allele is related to hospitalization and poor outcome in COVID-19 cases.


Ovarian malignancy unmasked by venous gangrene in a patient on warfarin therapy: a case report.
Venous gangrene complicating deep vein thrombosis in the context of anticoagulation use in patients with gynecologic malignancy is rarely reported. We report an unusual presentation of venous gangrene of the lower limbs associated with warfarin therapy in a 53-year-old woman from the Cook Islands with an occult ovarian cancer. A 53-year-old woman of Cook Islands origin presented with exertional dyspnea, rapid atrial fibrillation, bilateral lower limb edema, and painful digital ischemia of her hallux. She was on warfarin therapy for atrial fibrillation and had a stable therapeutic international normalized ratio. Bilateral proximal lower limb deep vein thrombosis and digital gangrene subsequently developed in the setting of a supratherapeutic international normalized ratio and platelet count depletion. Her warfarin was reversed and heparin therapy was commenced with resulting correction of her thrombocytopenia. We would like to attract the attention of the reader to the potential hazard of the use of warfarin in patients with malignancy. In our case, we also demonstrated a predictive value of supratherapeutic international normalized ratio and platelet count depletion that could herald massive thrombosis and gangrene in a patient who was previously stable on warfarin therapy. Early recognition and prompt reversal of warfarin in these circumstances is essential to correct the unbalanced prothrombotic process that leads to extensive thrombosis and gangrene. The outlook of such cases remains dismal and results in extensive morbidity and mortality.