MMDB: Entrez's 3D structure database.
The three dimensional structures for representatives of nearly half of all protein families are now available in public databases. Thus, no matter which protein one investigates, it is increasingly likely that the 3D structure of a homolog will be known and may reveal unsuspected structure-function relationships. The goal of Entrez's 3D-structure database is to make this information accessible and usable by molecular biologists (http://www.ncbi.nlm.nih.gov/Entrez). To this end Entrez provides two major analysis tools, a search engine based on sequence and structure 'neighboring' and an integrated visualization system for sequence and structure alignments. From a protein's sequence 'neighbors' one may rapidly identify other members of a protein family, including those where 3D structure is known. By comparing aligned sequences and/or structures in detail, using the visualization system, one may identify conserved features and perhaps infer functional properties. Here we describe how these analysis tools may be used to investigate the structure and function of newly discovered proteins, using the PTEN gene product as an example.


Interpretation of the variability of peak flow rates in chronic bronchitis.
Increased diurnal variation of expiratory flow rates has been documented in patients with chronic bronchitis, but this could be secondary to the disease process of bronchitis rather than an associated disease--namely, asthma. Peak expiratory flow was measured twice daily before and after inhalation of 200 micrograms salbutamol in 34 subjects with chronic bronchitis. The FEV1 ranged from 38% to 121% predicted. Diurnal variation (expressed as highest-lowest/highest (%)) was increased in 18 subjects, all but three of whom had airflow obstruction and an increase in methacholine airway responsiveness. There was only a weak correlation between diurnal variation and airway responsiveness (r = -0.54) or the severity of the airflow obstruction. This finding, together with the occurrence of an increase in diurnal variation without an increase in methacholine airway responsiveness in three subjects, suggests that the increased diurnal variation in chronic bronchitis may have a different underlying mechanism from that in asthma.


Enhanced Ca2+ entry due to Orai1 plasma membrane insertion increases IL-8 secretion by cystic fibrosis airways.
Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR). The most common mutation, ΔF508, causes retention of CFTR in the endoplasmic reticulum (ER). Some CF abnormalities can be explained by altered Ca(2+) homeostasis, although it remains unknown how CFTR influences calcium signaling. This study examined the novel hypothesis that store-operated calcium entry (SOCE) through Orai1 is abnormal in CF. The significance of Orai1-mediated SOCE for increased interleukin-8 (IL-8) expression in CF was also investigated. CF and non-CF human airway epithelial cell line and primary cells (obtained at lung transplantation) were used in Ca(2+) imaging, electrophysiology, and fluorescence imaging experiments to explore differences in Orai1 function in CF vs. non-CF cells. Protein expression and localization was assessed by Western blots, cell surface biotinylation, ELISA, and image correlation spectroscopy (ICS). We show here that store-operated Ca(2+) entry (SOCE) is elevated in CF human airway epithelial cells (hAECs; ≈ 1.8- and ≈ 2.5-fold for total Ca(2+)(i) increase and Ca(2+) influx rate, respectively, and ≈ 2-fold increase in the I(CRAC) current) and is caused by increased exocytotic insertion (≈ 2-fold) of Orai1 channels into the plasma membrane, which is normalized by rescue of ΔF508-CFTR trafficking to the cell surface. Augmented SOCE in CF cells is a major factor leading to increased IL-8 secretion (≈ 2-fold). CFTR normally down-regulates the Orai1/stromal interaction molecule 1 (STIM1) complex, and loss of this inhibition due to the absence of CFTR at the plasma membrane helps to explain the potentiated inflammatory response in CF cells.


Uptake of benzoate by Rhodopseudomonas palustris grown anaerobically in light.
The uptake and anaerobic metabolism of benzoate were studied in short-term experiments with phototrophic cells of Rhodopseudomonas palustris. Cells that were preincubated and assayed anaerobically in the presence of 1 mM dithiothreitol accumulated [7-14C]benzoate at a rate of at least 0.5 nmol . min-1 . mg-1 of protein. Cells that were preincubated aerobically, or anaerobically in the absence of a reducing agent or an electron donor such as succinate, took up benzoate at reduced rates. Benzoate was removed from the external medium with remarkably high efficiency; initial uptake rates were independent of substrate concentration, and uptake remained linear down to concentrations of less than 1 microM. Uptake rates were not sensitive to external pH in the range of 6.5 to 8.1, and very little free benzoate was found associated with the cells. By contrast, benzoyl coenzyme A (CoA) was formed rapidly in cells exposed to labeled benzoate. Its appearance in such cells, together with the more gradual accumulation of other compounds tentatively identified as reduction products, is consistent with the identification of benzoyl CoA as an intermediate in the anaerobic reductive metabolism of benzoate. The very effective uptake of external benzoate can be explained by its conversion to benzoyl CoA immediately after its passage across the cell membrane by simple or facilitated diffusion. Such a chemical conversion would serve to maintain a downhill concentration gradient between the cell cytoplasm and the cell surroundings, even at very low external benzoate concentrations.


Plasma concentrations of lipoproteins and risk of lower-limb peripheral artery disease in people with type 2 diabetes: the SURDIAGENE study.
The lipid profile has not been fully investigated in individuals with peripheral artery disease (PAD). We aimed to evaluate the relationship between plasma concentrations of lipoproteins and the prevalence of lower-limb PAD at baseline and its incidence during follow-up in people with type 2 diabetes. Plasma concentrations of total cholesterol, HDL-cholesterol, triacylglycerol and apolipoprotein (Apo) A-I, ApoA-II, ApoB-100 and Apo(a) were measured at baseline using colorimetric or MS methods in the SURDIAGENE cohort. Total cholesterol/HDL-cholesterol ratio, non-HDL-cholesterol and LDL-cholesterol were estimated using computation formulas. Logistic and Cox proportional hazard regression models were fitted to estimate OR or HR, with related 95% CI, for baseline prevalence or incidence of major PAD (lower-limb amputation or requirement of revascularisation) during follow-up by increasing lipoprotein tertiles, after adjustment for key confounders. Among 1468 participants (women 42%, mean ± SD age 65 ± 11 years, duration of diabetes 14 ± 10 years at baseline), 129 (8.8%) had a baseline history of major PAD. Major PAD was less prevalent at baseline in the highest (vs lowest) tertile of HDL-cholesterol (OR 0.42 [95% CI 0.26, 0.71], p = 0.001) and ApoA-I (OR 0.39 [95% CI 0.23, 0.67], p = 0.0007), and more frequent in the highest tertile of total cholesterol/HDL-cholesterol ratio (OR 1.95 [95% CI 1.18, 3.24], p = 0.01). Among 1339 participants without a history of PAD at baseline, incident PAD occurred in 97 (7.2%) during a median (25th-75th percentile) duration of follow-up of 7.1 (4.4-10.7) years, corresponding to 9685 person-years and an incidence rate of 9.8 (95% CI 8.0, 12.0) per 1000 person-years. The risk of incident PAD was lower in the top (vs bottom) tertile of HDL-cholesterol (HR 0.54 [95% CI 0.30, 0.95], p = 0.03) or ApoA-I (HR 0.50 [95% CI 0.28, 0.86], p = 0.01) and higher in the top tertile of total cholesterol/HDL-cholesterol ratio (HR 2.81 [95% CI 1.61, 5.04], p = 0.0002) and non-HDL-cholesterol (HR 1.80 [95% CI 1.06, 3.12], p = 0.03). We reported independent associations between HDL-cholesterol, ApoA-I, total cholesterol/HDL-cholesterol ratio or non-HDL-cholesterol and the prevalence or the incidence of major PAD in people with type 2 diabetes. Our findings provide a picture of lipoprotein profile in people with type 2 diabetes. Graphical abstract.


Postprandial responses of glucose, insulin and triglycerides: influence of the timing of meal intake during night work.
The objective was to study the postprandial responses of glucose, insulin and triglycerides to meal intake at different clock times during night work. Eleven night shift working nurses participated. Identical test meals were ingested at 19:30, 23:30 and 03:30, and contained 440 kcal/1,860 kJ of energy (33 E% fat, 51 E% carbohydrate, 16 E% protein). The food intake was standardized three days before the first test meal. Blood samples were drawn just before the test meals were ingested and thereafter at 30, 60, 90, 120, 180 and 240 minutes. The postprandial responses were estimated as the total area under the curve (AUC) and significance testing was done using repeated measures ANOVA. The highest insulin level was found after meal intake at 23:30, and the lowest after meal intake 03:30. The glucose response showed the same pattern. The insulin response to food intake in night working nurses is more pronounced in the night compared with morning and evening. The results would have implications for metabolic and cardiovascular disorders in night workers.


Neurosarcoidosis: a clinical dilemma.
Sarcoidosis is an inflammatory multisystem disorder of unknown cause. Practically no organ is immune to sarcoidosis; most commonly, in up to 90% of patients, it affects the lungs. The nervous system is involved in 5-15% of patients. Neurosarcoidosis is a serious and commonly devastating complication of sarcoidosis. Clinical diagnosis of neurosarcoidosis depends on the finding of neurological disease in multisystem sarcoidosis. As the disease can present in many different ways without biopsy evidence, solitary nervous-system sarcoidosis is difficult to diagnose. Corticosteroids are the drug of first choice. In addition, several cytotoxic drugs, including methotrexate, have been used to treat sarcoidosis. The value of new drugs such as anti-tumour necrosis factor alpha will be assessed. In this review we describe the clinical manifestations of neurosarcoidosis, diagnostic dilemmas and considerations, and therapy.


[Human Bifidobacterium flora, its normalizing and protective functions].
The paper is concerned with investigation of the normalizing and protective role of the Bifidobacterium flora in humans and its quantitative predomination in intestinal microbiocenosis of children and adults. The data on antagonistic properties of bifidobacteria with respect to pathogenic and facultative pathogenic bacteria, the Bifidobacterium flora influence on the host metabolism and efficiency of bifidobacterin in recovery of the Bifidobacterium flora optimal level are presented.


Histochemical differentiation of complex carbohydrates with variants of the concanavalin A-horseradish peroxidase method.
Various treatments carried out prior to the concanavalin A-horseradish perioxidase (HRP) method have been found to affect the staining and have permitted differentiation of three main classes of complex carbohydrates in the rat alimentary tract. Class I mucosubstances lose and class II and III paradoxically gain concanavalin A-horseradish peroxidase reactivity after periodate oxidation. Class II mucosubstances lose whereas class III retain or increase their reactivity with a reduction step interposed between oxidation and concanavalin A-horseradish peroxidase staining. Mucous neck cells, pyloric glands, Brunner's glands and mast cells exhibit strong class III staining, whereas other sites such as intestinal goblet and salivary gland acini differ widely in their type of staining. Liver glycogen stains like mucosubstances in an unstable subgroup of class III. The paradoxical increase in concanavalin A binding during oxidation correlates with the appearance of Schiff reactivity implicating oxidation of vicinal hydroxyls as the basis for the effect. The periodate-induced staining is therefore, thought to result from an oxidative disruption of linkages between vicinal hydroxyls of neighboring sugars and hydroxyls of mannose required for concanavalin A binding. Staining with the described concanavalin A-horseradish peroxidase variants appears to afford information concerning cytochemical distribution of mannose-rich glycoproteins as well as differences among these substances in the relation of mannose to neighboring sugars.


Rapid mineralization of benzo[a]pyrene by a microbial consortium growing on diesel fuel.
A microbial consortium which rapidly mineralized the environmentally persistent pollutant benzo[a]pyrene was recovered from soil. The consortium cometabolically converted [7-(14)C]benzo[a]pyrene to (14)CO(2) when it was grown on diesel fuel, and the extent of benzo[a]pyrene mineralization was dependent on both diesel fuel and benzo[a]pyrene concentrations. Addition of diesel fuel at concentrations ranging from 0.007 to 0.2% (wt/vol) stimulated the mineralization of 10 mg of benzo[a]pyrene per liter 33 to 65% during a 2-week incubation period. When the benzo[a]pyrene concentration was 10 to 100 mg liter(-1) and the diesel fuel concentration was 0.1% (wt/vol), an inoculum containing 1 mg of cell protein per liter (small inoculum) resulted in mineralization of up to 17.2 mg of benzo[a]pyrene per liter in 16 days. This corresponded to 35% of the added radiolabel when the concentration of benzo[a]pyrene was 50 mg liter(-1). A radiocarbon mass balance analysis recovered 25% of the added benzo[a]pyrene solubilized in the culture suspension prior to mineralization. Populations growing on diesel fuel most likely promoted emulsification of benzo[a]pyrene through the production of surface-active compounds. The consortium was also analyzed by PCR-denaturing gradient gel electrophoresis of 16S rRNA gene fragments, and 12 dominant bands, representing different sequence types, were detected during a 19-day incubation period. The onset of benzo[a]pyrene mineralization was compared to changes in the consortium community structure and was found to correlate with the emergence of at least four sequence types. DNA from 10 sequence types were successfully purified and sequenced, and that data revealed that eight of the consortium members were related to the class Proteobacteria but that the consortium also included members which were related to the genera Mycobacterium and Sphingobacterium.


Long-term clinical and radiographic outcome of the PPF system in ceramic-on-polyethylene hip bearings.
From 1990 to 1991 we implanted 176 non-cemented proximal press-fit (PPF) total hip arthroplasties (THA) with ceramic-on-polyethylene articulation in 170 patients. Of these, 119 patients (122 THA) were followed from 104 to 129 months. Four cups have been revised for aseptic loosening, but revealed no radiolucencies of the stem. Two infections and two dislocations occurred. The median postoperative Harris hip score was 91. Ninety-eight per cent of the patients were satisfied with the outcome, 83% were free of pain and 67% walked without a limp. Serial radiographs showed stable fixation with bone ongrowth in nearly all arthroplasties except for four cups. Stem radiolucencies were first seen within 12 months, but were of no clinical relevance. Proximal periprosthetic bone resorption of the stem was seen in 18%. Radiolucencies occurred because of polyethylene debris-induced granulomas. The PPF system yields satisfactory long-term results in patients with primary and secondary hip osteoarthritis and dysplasia.


Poly[[μ-aqua-diaqua-bis-(μ-furan-2,5-dicarboxyl-ato-κ(2) O (2):O (5))bis-(1,10-phenanthroline-κ(2) N,N')dicopper(II)] N,N-dimethyl-formamide monosolvate].
The asymmetric unit of the title compound, {[Cu2(C6H2O5)2(C12H8N2)2(H2O)3]·C3H7NO} n , contains two Cu(II) atoms, two furan-2,5-dicarboxyl-ate (L) ligands, two 1,10-phenanthroline (phen) ligands, three coordinating water mol-ecules and one N,N-dimethyl-formamide solvent mol-ecule. Each Cu(II) atom is coordinated by two N atoms from one phen ligand, two O atoms from two L ligands and two water mol-ecules in a distorted octa-hedral geometry. The main difference between the environments of the two independent Cu atoms is in the Cu-Owater distances, which are 2.415 (2) and 2.639 (2) Å for one Cu(II) atom and 2.3560 (19) and 2.911 (4) Å for the other. Ligands L and one independent water mol-ecule bridge the Cu(II) atoms, forming corrugated polymeric layers parallel to the ab plane. Inter-molecular O-H⋯O and C-H⋯O hydrogen bonds consolidate the crystal packing.


Poly-victimization of autistic adults: An investigation of individual-level correlates.
Autistic people experience high rates of violence and victimization which is largely due to structural injustices, including stigma and social attitudes. Identifying and addressing systemic and structural factors is vitally important, however effecting change in embedded social structures is likely to take some time, even with concerted efforts. In the meantime, it is important to understand whether there are other individual-level factors that may assist in developing preventative and protective strategies for autistic people. The current study investigated the role of individual-level risk factors in the victimization of autistic people. Specifically, we examined whether characteristics that are common among autistic people that is, lower social competence, higher compliance and emotion regulation difficulties or more ADHD features (inattention, impulsiveness and hyperactivity) were associated with poly-victimization in a community sample of 228 adults (118 autistic, 110 non-autistic). Our results show that only ADHD features were predictive of poly-victimization once socio-demographic background variables (age, sexual orientation) were adjusted for. Group status was not a significant predictor in the model and there were no interaction effects between any of the characteristics and group status. These findings suggest that, regardless of whether a person is autistic, ADHD features may place individuals at higher risk of experiencing multiple forms of violence in adulthood. Further research using longitudinal designs and larger, diverse samples is needed. Furthermore, the regression model only accounted for about one-third of the variance in poly-victimization which highlights the importance of looking beyond individual-level risk factors to structural and systemic factors that contribute to disproportionate victimization of autistic people.


[Study of the stability of the alpha-ketoglutarate decarboxylase from the brain of a bull].
Stability of alpha-ketoglutarate decarboxylase (alpha-KGDC) from the bull brain was studied in different temperature regimes. The high-purified preparations of alpha-KGDC are highly unstable both when kept at a temperature of 0 degrees C and as affected by temperature. The least loss of the alpha-KGDC activity is observed in the preparations obtained after lyophilization and stored for a long time as powder. The temperature inactivation may be prevented by adding to the medium Ca2+ (10(-3) M) and TPP (10(-2) M) as well as TPP and Ca2+ and Mg2+ in different combinations. At low temperatures none of the mentioned components and such substances as histidine and serum albumin has no stabilizing effect on alpha-Kgdc preparations show that the inhibitory effect of the latter is more pronounced. It is peculiar to both less purified and highly purified alpha-KGDC preparations. The action of urea is less pronounced and is greatly similar by the inhibitory effect as compared to alpha-KGDC from the pigeon muscles.


Increased visceral adiposity and cortisol to cortisone ratio in adults with congenital lifetime isolated GH deficiency.
Adult-onset GH deficiency (GHD) increases visceral adiposity and the activity of the enzyme 11β-hydroxysteroid dehydrogenase, which converts cortisone (E) to cortisol (F), both linked to insulin resistance and increased cardiovascular risk. Conversely, we reported that adults with congenital isolated GHD (IGHD) have increased insulin sensitivity. To assess the type of fat distribution and the amount of visceral and sc fat and to correlate them to the F/E ratio in adults with untreated IGHD due to a mutation in the GHRH receptor gene. Body composition was assessed by dual-energy x-ray absorptiometry, thickness of sc and visceral fat was measured by sonography, and serum F and E were measured in 23 IGHD subjects and 21 age-matched controls. Waist/hip ratio (WHR), trunk fat, and trunk/extremity fat (TR/EXT) ratio were higher in IGHD subjects. Visceral fat index (VFI) (but not sc fat index [SFI]) was higher in IGHD. F and F/E ratio were also higher in IGHD. In all 44 individuals, WHR correlated with TR/EXT ratio, thickness of visceral fat, VFI/SFI ratio, F, and F/E ratio. TR/EXT ratio correlated with visceral fat thickness, VFI/SFI ratio, and F. Age had a significant effect on VFI and on F/E ratio. Body mass index SD score and WHR have a similar significant effect on TR/EXT ratio and on F/E ratio. Lifetime congenital untreated IGHD causes increased visceral adiposity with a high F/E ratio. However, the increased insulin sensitivity suggests that visceral adiposity needs a minimal GH secretion to translate into increased insulin resistance.


[Information value of computed tomography in diagnosing pericardial diseases].
The authors present the results of examination of 38 patients with various diseases of the pericardium using the CT method. It possesses a high sensitivity and permits one to reveal pericardial effusions as well as tumor lesions of the pericardium. CT has a high resolving power and provides for visualization of of the unchanges pericardium and adjoining structures. It also allows for densitometric measurements of pericardial effusion. The results obtained make it possible to attribute this method to one of the most informative in the diagnosis of pericardial diseases.


Dissociation of human copper-zinc superoxide dismutase dimers using chaotrope and reductant. Insights into the molecular basis for dimer stability.
The dissociation of apo- and metal-bound human copper-zinc superoxide dismutase (SOD1) dimers induced by the chaotrope guanidine hydrochloride (GdnHCl) or the reductant Tris(2-carboxyethyl)phosphine (TCEP) has been analyzed using analytical ultracentrifugation. Global fitting of sedimentation equilibrium data under native solution conditions (without GdnHCl or TCEP) demonstrate that both the apo- and metal-bound forms of SOD1 are stable dimers. Sedimentation velocity experiments show that apo-SOD1 dimers dissociate cooperatively over the range 0.5-1.0 M GdnHCl. In contrast, metal-bound SOD1 dimers possess a more compact shape and dissociate at significantly higher GdnHCl concentrations (2.0-3.0 M). Reduction of the intrasubunit disulfide bond within each SOD1 subunit by 5-10 mM TCEP promotes dissociation of apo-SOD1 dimers, whereas the metal-bound enzyme remains a stable dimer under these conditions. The Cys-57 --> Ser mutant of SOD1, a protein incapable of forming the intrasubunit disulfide bond, sediments as a monomer in the absence of metal ions and as a dimer when metals are bound. Taken together, these data indicate that the stability imparted to the human SOD1 dimer by metal binding and the formation of the intrasubunit disulfide bond are mediated by independent molecular mechanisms. By combining the sedimentation data with previous crystallographic results, a molecular explanation is provided for the existence of different SOD1 macromolecular shapes and multiple SOD1 dimeric species with different stabilities.


Protonation of the dinitrogen-reduction catalyst [HIPTN3N]Mo(III) investigated by ENDOR spectroscopy.
Dinitrogen is reduced to ammonia by the molybdenum complex of L = [HIPTN3N](3-) [Mo; HIPT = 3,5-(2,4,6-iPr3C6H2)2C6H3]. The mechanism by which this occurs involves the stepwise addition of proton/electron pairs, but how the first pair converts MoN2 to MoN ═ NH remains uncertain. The first proton of reduction might bind either at Nβ of N2 or at one of the three amido nitrogen (N(am)) ligands. Treatment of MoCO with [2,4,6-Me3C5H3N]BAr'4 [Ar' = 2,3-(CF3)2C6H3] in the absence of reductant generates HMoCO(+), whose electron paramagnetic resonance spectrum has greatly reduced g anisotropy relative to MoCO. (2)H Mims pulsed electron nuclear double-resonance spectroscopy of (2)HMoCO(+) shows a signal that simulations show to have a hyperfine tensor with an isotropic coupling, aiso((2)H) = -0.22 MHz, and a roughly dipolar anisotropic interaction, T((2)H) = [-0.48, -0.93, 1.42] MHz. The simulations show that the deuteron is bound to N(am), near the Mo equatorial plane, not along the normal, and at a distance of 2.6 Å from Mo, which is nearly identical with the (Nam)(2)H(+)-Mo distance predicted by density functional theory computations.


Enhancing Healthcare Access-Smartphone Apps in Arrhythmia Screening: Viewpoint.
Atrial fibrillation is the most commonly reported arrhythmia and, if undiagnosed or untreated, may lead to thromboembolic events. It is therefore desirable to provide screening to patients in order to detect atrial arrhythmias. Specific mobile apps and accessory devices, such as smartphones and smartwatches, may play a significant role in monitoring heart rhythm in populations at high risk of arrhythmia. These apps are becoming increasingly common among patients and professionals as a part of mobile health. The rapid development of mobile health solutions may revolutionize approaches to arrhythmia screening. In this viewpoint paper, we assess the availability of smartphone and smartwatch apps and evaluate their efficacy for monitoring heart rhythm and arrhythmia detection. The findings obtained so far suggest they are on the right track to improving the efficacy of early detection of atrial fibrillation, thus lowering the risk of stroke and reducing the economic burden placed on public health.


Failure to demonstrate transmission of enzootic bovine leukemia virus infection from cows to sheep by use of common injection needles.
Four bovine leukemia virus (BLV)-seropositive and 2 BLV-seronegative cows were used as donors in a study to provide evidence whether IM injection with common needles is a means of spreading bovine leukemia. Sheep were used as recipients. Of the 4 BLV-seropositive cows, 2 had high virus expression (VE; 43% and 28% of their lymphocyte thin sections had associated BLV-particles), whereas the other 2 cows did not have observed VE. After each of the 4 cows was given an injection of a 5-antigen Leptospira bacterin, a BLV-seronegative sheep was immediately given an injection of the same bacterin with the same needle. None of these sheep seroconverted, nor did either of 2 sheep given only the bacterin (with a previously unused needle). Sheep inoculated IM with 0.2 ml of whole blood from both of the cows with high VE and from 1 of the 2 BLV-seropositive cows that did not have observed VE did seroconvert. In contrast, the sheep inoculated with 0.2 ml of blood from the remaining BLV-seropositive (0% VE) cow and from the 2 BLV-seronegative cows remained seronegative. These results were interpreted to indicate that the quantity of infective lymphocytes passed during injection with common needles is too small to induce infection.


Regional, racial, and gender differences in colorectal cancer screening in middle-aged African-Americans and Whites.
African-Americans have higher incidence and mortality from colorectal cancer than non-African-Americans. Early detection with colorectal cancer (CRC) screening reduces untimely death because the test can detect abnormalities and precancerous polyps in the colon and rectum. However, African-Americans aged 50 and older continue to have low CRC screening adherence. A retrospective analysis was conducted on data from the 2010 National Health Interview Survey to examine trends in self-reported CRC screening by geographic region, race, and gender. African-Americans, particularly men, were less likely to have been screened for colon cancer compared to all races and genders in this study. Individuals in the south were more likely to receive CRC screening than other regions. Colon cancer education and interventions are needed among low-adherent groups to promote the benefits of early detection with CRC screening.


Roles of the AMP-activated and cyclic-AMP-dependent protein kinases in the adrenaline-induced inactivation of acetyl-CoA carboxylase in rat adipocytes.
1. In isolated rat adipocytes, acetyl-CoA carboxylase is inactivated by treatment of the cells with adrenaline or the beta-agonist isoproterenol, but not by the alpha-agonist phenylephrine. The inactivation is stable during purification in the presence of protein phosphatase inhibitors, and is associated with a 30-40% increase in the labelling of enzyme isolated from 32P-labelled cells. 2. Increased phosphorylation occurs within peptide T1, which was identified by sequencing to be the peptide Ser-Ser77-Met-Ser79-Gly-Leu-His-Leu-Val-Lys, containing Ser-77 (phosphorylated by cyclic-AMP-dependent protein kinase) and Ser-79 (phosphorylated by the AMP-activated protein kinase). Analysis of the release of radioactivity as free phosphate during Edman degradation of peptide T1 revealed that all of the phosphate was in Ser-79 in both basal and hormone- or agonist-stimulated cells. Treatment of adipocytes with various agents which activate cyclic-AMP-dependent protein kinase by receptor-independent mechanisms (forskolin, cyclic AMP analogues, isobutylmethylxanthine) also produced inactivation of acetyl-CoA carboxylase and increased phosphorylation at Ser-79. 3. The (Rp)-[thio]phosphate analogue of cyclic AMP, which is an antagonist of binding of cyclic AMP to the regulatory subunit of cyclic-AMP-dependent protein kinase, opposes the effect of adrenaline on phosphorylation and inactivation of acetyl-CoA carboxylase. Together with the effects of isobutylmethylxanthine and the stimulatory cyclic AMP analogues, this strongly indicates that cyclic-AMP-dependent protein kinase is an essential component of the signal transduction pathway, although clearly it does not directly phosphorylate acetyl-CoA carboxylase. 4. As shown by okadaic acid inhibition, greater than 95% of the acetyl-CoA carboxylase phosphatase activity in extracts of rat adipocytes or liver is accounted for by protein phosphatase-2A, with less than 5% attributable to protein phosphatase-1. Inhibition of protein phosphatase-1 via phosphorylation of inhibitor-1 is therefore unlikely to be the mechanism by which cyclic-AMP-dependent protein kinase indirectly increases phosphorylation of acetyl-CoA carboxylase. Various other potential mechanisms are discussed.


Relation of biventricular strain and dyssynchrony in repaired tetralogy of fallot measured by cardiac magnetic resonance to death and sustained ventricular tachycardia.
Ventricular strain and dyssynchrony can be measured in patients with repaired tetralogy of Fallot (TOF), but their effect on clinical outcomes is poorly understood. The purpose of this study was to investigate if ventricular strain and dyssynchrony measured by cardiac magnetic resonance feature tracking are associated with death and sustained ventricular tachycardia. Patients with TOF who died or had ventricular tachycardia (TOF case, n = 16) were compared with age-matched patients with TOF with no adverse outcome (TOF control, n = 32). For each patient, midventricular short-axis and 4-chamber cine steady-state free precession images were analyzed using cardiac magnetic resonance feature-tracking software. Peak left ventricular (LV) and right ventricular (RV) global circumferential and longitudinal strain and indexes of dyssynchrony were compared between groups. Compared with the TOF control group, median strain values were significantly lower for the TOF case group for both the LV (circumferential: 17% vs 23%, p = 0.003; longitudinal: 13% vs 18%, p <0.001) and the RV (circumferential: 10% vs 16%, p = 0.001; longitudinal: 11% vs 18%, p <0.001). In a multivariate model including strain and dyssynchrony parameters, RV and LV longitudinal strain were strongly associated with the adverse outcome (p = 0.003 and 0.04, respectively; area under the curve = 0.92). No differences in ventricular dyssynchrony were identified between the groups. In conclusion, patients with TOF in this cohort who experienced adverse outcomes had lower values of all strain parameters than those who did not, and impaired longitudinal strain of both ventricles was strongly associated with adverse clinical outcomes.


Muscarinic cholinergic receptor-mediated control of cyclic AMP metabolism. Agonist-induced changes in nucleotide synthesis and degradation.
Activation of muscarinic cholinergic receptors on 1321N1 human astrocytoma cells results in a 40-70% inhibition of isoproterenol- or prostaglandin E1 (PGE1)-stimulated accumulation of cyclic AMP. Previous investigations have demonstrated that this effect is due to a Ca2+-dependent activation of phosphodiesterase in the presence of muscarinic receptor agonists. However, during prolonged exposure of 1321N1 cells to a cholinergic agonist, a series of adaptive changes occurs which culminates in a complete loss of the muscarinic receptor-mediated inhibition of cyclic AMP accumulation. These alterations include: (a) A 50-100% increase in the capacity of isoproterenol and PGE1 to stimulate cyclic AMP accumulation. This phenomenon was rapid in onset, reached a maximum in 15-20 min, and disappeared over the next 2 hr even in the continued presence of carbachol. (b) A loss of the effects of muscarinic receptor stimulation on cyclic AMP accumulation. This phenomenon was apparent within 15 min after addition of carbachol, and complete desensitization was observed after 75 min. The loss of muscarinic receptor-mediated effects on cyclic AMP levels was due to a loss of the Ca2+-dependent stimulation of phosphodiesterase activity by muscarinic receptor agonists. (c) A loss of muscarinic receptors as assessed by [3H]quinuclidinyl benzilate binding. This effect was apparent after 90 min in the presence of carbachol. More than 80% of the receptors were lost after 24 hr, with no change occurring in the KD of [3H]quinuclidinyl benzilate. The concentration-effect curve for carbachol-induced changes in agonist responsiveness of the cyclic AMP system was similar to that for carbachol-induced reductions in cyclic AMP levels. Coincubation of carbachol with a saturating concentration of atropine prevented these adaptive changes from occurring. Although incubation of cells in Ca2+-free buffer or in the presence of 20 mM Co2+ prevented the inhibitory effects of muscarinic receptor stimulation on cyclic AMP accumulation, carbachol preincubations under these conditions still produced the adaptive changes in agonist responsiveness. The divalent cation ionophore, A23187, mimics the effects of muscarinic receptor stimulation on cyclic AMP levels by activating phosphodiesterase. Following complete carbachol-induced loss of responsiveness to muscarinic receptor agonists, A23187 was still capable of inhibiting cyclic AMP accumulation.


[Possible causes of thrombus-related hazard of a distal splenorenal venous anastomosis].
A distal splenorenal venous anastomosis (DSRVA) is used as a method to decompress the portal system in hypertension and as a method to treat type 1 diabetes mellitus. The essence of the operation consists in establishing an «end-to-side» anastomosis between the distal end of the transected close to the ostium splenic vein with the left renal vein. Possible shortcomings of this operation include but are not limited to high thrombus-related hazard both in case of using it in portal hypertension and in diabetes mellitus. In the latter, thrombosis of the anastomosis is observed to develop in 27% of diabetic patients within 7-8 postoperative months. The causes of this complication were not studied. The present communication presents the findings of studying the natural pattern of confluence of the portal-system veins performed on a total of 111 cadavers and in 50 patients suffering from chronic hepatitis and undergoing surgery in order to form a left-sided renoportal venous anastomosis. It was demonstrated that DSRVA is associated with impaired natural confluence of the veins and the width of the two veins forming an anastomosis exceeds the width of the blood-outflowing vein more than 1.5-fold. This is followed by analysing the results of studying removability of the pancreas and left kidney in the vertical position by means of excretory urography and probe-assisted duodenography in 54 patients with chronic hepatitis. Removability of the pancreas in 57.4% of cases was greater than that of the left kidney, which is the condition for kinking of the splenic vein in the DSRVA zone. In order to choose an optimal anastomosis and to prevent DSRVA thrombosis it is advisable to preoperatively examine the venous pressure in the left renal vein, removability of the pancreas relative to the left kidney, and during establishing the anastomosis to observe the natural pattern of confluence of veins by the width.


Methylophilus glucosoxydans sp. nov., a restricted facultative methylotroph from rice rhizosphere.
Two restricted facultatively methylotrophic strains, designed B(T) and P, were isolated from rice roots. The isolates were strictly aerobic, Gram-negative, asporogenous, mesophilic, neutrophilic, motile rods that multiplied by binary fission and were able to synthesize indole-3-acetate. The cellular fatty acid profiles of the two strains were dominated by C(16:0), C(16:1)ω7c and C(16:0) 2-OH. The major ubiquinone was Q-8. The predominant phospholipids were phosphatidylethanolamine and phosphatidylglycerol. Cardiolipin (diphosphatidylglycerol) was absent. The two strains assimilated methanol carbon at the level of formaldehyde via the ribulose monophosphate cycle (2-keto-3-deoxy-6-phosphogluconate variant). They lacked α-ketoglutarate dehydrogenase and glutamate dehydrogenase. They assimilated ammonium via the glutamate cycle enzymes glutamine synthetase and glutamate synthase. The DNA G+C contents of strains B(T) and P were 52.5 and 51.5 mol% (T(m)), respectively. The level of DNA-DNA reassociation between these strains was 78%, indicating that they belong to one species. Phylogenetic analysis of strain B(T) based on 16S rRNA and methanol dehydrogenase (mxaF) gene sequences showed a high level of similarity to members of the genus Methylophilus. As the two isolates were clearly distinct from all recognized members of the genus Methylophilus based on phenotypic data and levels of DNA-DNA relatedness (30-46%), they are considered to represent a novel species, for which the name Methylophilus glucosoxydans sp. nov. is proposed; the type strain is B(T) (=VKM B-1607(T)=CCUG 59685(T)=DSM 5898(T)).


Predicting intrinsic disorder from amino acid sequence.
Blind predictions of intrinsic order and disorder were made on 42 proteins subsequently revealed to contain 9,044 ordered residues, 284 disordered residues in 26 segments of length 30 residues or less, and 281 disordered residues in 2 disordered segments of length greater than 30 residues. The accuracies of the six predictors used in this experiment ranged from 77% to 91% for the ordered regions and from 56% to 78% for the disordered segments. The average of the order and disorder predictions ranged from 73% to 77%. The prediction of disorder in the shorter segments was poor, from 25% to 66% correct, while the prediction of disorder in the longer segments was better, from 75% to 95% correct. Four of the predictors were composed of ensembles of neural networks. This enabled them to deal more efficiently with the large asymmetry in the training data through diversified sampling from the significantly larger ordered set and achieve better accuracy on ordered and long disordered regions. The exclusive use of long disordered regions for predictor training likely contributed to the disparity of the predictions on long versus short disordered regions, while averaging the output values over 61-residue windows to eliminate short predictions of order or disorder probably contributed to the even greater disparity for three of the predictors. This experiment supports the predictability of intrinsic disorder from amino acid sequence.


Recognition and treatment of osteochondritis dissecans of the femoral condyles.
Osteochondritis dissecans (OD) of the femoral condyles is a vague and often confusing diagnostic entity encountered by many clinicians. Unfortunately, there are several factors that add to this confusion. Chief among these is the proper recognition and understanding of the disease process, which is not well-documented. In addition, OD is often generically grouped together with other femoral condylar lesions that require differing diagnostic and treatment methods for proper care. OD is commonly divided into two categories, juvenile and adult forms. Each requires different methods of correction and rehabilitation. This paper describes the disease process of OD, explains the differences between the juvenile and adult forms (including common symptoms and diagnostic techniques), describes several of the pathologies that OD is mistakenly grouped with, and gives a brief review of the common arthroscopic and surgical techniques used to treat this pathology. In addition, rehabilitation guidelines and suggestions are offered to aid the athlete's return to functional activities.


The economic consequences of immigration.
Available research supports several major conclusions about the economic consequences of immigration. (i) The aggregate impacts of foreign workers on the earnings and employment of native workers are quite small, but differ for selected population subgroups and high ethnic density labor markets. (ii) Immigrants who arrived during the 1970s are less skilled than earlier arrivals, and their earnings will remain substantially below those of natives throughout their working lives. (iii) The evidence on immigrants' receipt of public assistance income is inconclusive.


Diagnostic accuracy of an in-house ELISA using the intermediate species Leptospira fainei as antigen for diagnosis of acute leptospirosis in dogs.
Diagnosis of animal leptospirosis is still challenging. The microscopic agglutination test, is the current method for diagnosing leptospirosis. However, this technique requires specific equipment, highly trained staff and the maintenance of live cultures of several reference strains of Leptospira for use as antigens. Recently, an ELISA (enzyme-linked immunosorbent assay) employing a Leptospira fainei serovar Hurstbridge based antigen for the early diagnostic of human leptospirosis was developed. In this study we estimate the diagnostic sensitivity and specificity of this test in identifying acute canine leptospirosis. A total of 271 serum samples divided into five panels and tested by MAT as a reference test, were used to evaluate the ELISA. Comparing acutely and non-acutely infected dogs, ELISA-Hb showed 95.6% sensitivity and 93% specificity. L. fainei-based ELISA is adequate for diagnosing acute canine leptospirosis, with high sensitivity and specificity and presenting practical advantages when compared to current techniques.


Cancer mortality in Europe, 2000-2004, and an overview of trends since 1975.
To update the pattern of cancer mortality in Europe. We analysed cancer mortality in 34 European countries during 2000-2004, with an overview of trends in 1975-2004 using data from the World Health Organization. From 1990-1994 to 2000-2004, overall cancer mortality in the European Union declined from 185.2 to 168.0/100 000 (world standard, -9%) in men and from 104.8 to 96.9 (-8%) in women, with larger falls in middle age. Total cancer mortality trends were favourable, though to a variable degree, in all major European countries, including Russia, but not in Romania. The major determinants of these favourable trends were the decline of lung (-16%) and other tobacco-related cancers in men, together with the persistent falls in gastric cancer, and the recent appreciable falls in colorectal cancer. In women, relevant contributions came from the persistent decline in cervical cancer and the recent falls in breast cancer mortality, particularly in northern and western Europe. Favourable trends were also observed for testicular cancer, Hodgkin lymphomas, leukaemias, and other neoplasms amenable to treatment, though the reductions were still appreciably smaller in eastern Europe. This updated analysis of cancer mortality in Europe showed a persistent favourable trend over the last years.


Inhibition of prostate cancer metastasis by administration of a tissue vaccine.
Immunotherapy by vaccination represents a novel method for treatment of cancer. In this regard, vaccines with the broadest possible menu of relevant antigens stand the greatest chance of success. Tissue vaccines are composed of material harvested directly from tumors and contain not only antigens associated with neoplastic epithelium, but also those that may be unique to in vivo growth and antigens associated with the tumor stroma. To test the hypothesis that a tissue vaccine, produced by glutaraldehyde fixation of harvested syngeneic prostate tumors (GFT vaccine), could be used for treatment of prostate cancer, male Lobund-Wistar (LW) rats were treated with methylnitrosourea (MNU) and testosterone propionate to induce autochthonous prostate tumors. Tumor-bearing rats were randomly assigned to one of three treatment groups: no treatment (11 rats); vaccination with media (10 rats); or vaccination with the GFT vaccine (19 rats). Vaccination was given initially with Freund's complete adjuvant and booster doses were given with incomplete Freund's adjuvant every week until the time of euthanasia. There were no significant differences in mean tumor weight between groups; however, GFT-vaccinated rats had a prolonged survival time; and 4/19 (21%) GFT-vaccinated rats were found to be tumor-free compared to none of the untreated or media-treated controls. Further, pulmonary metastasis occurred in only 5/15 (33%) of GFT-vaccinated rats compared to 10/11 (91%) and 10/10 (100%) of untreated and media-vaccinated controls, respectively. Supernatants of cultured splenocytes from similarly media- and GFT-vaccinated rats demonstrated significant (P < 0.001) increases in IFN-gamma and TNF-alpha from splenocytes of GFT-vaccinated rats, suggesting that GFT vaccination stimulates a Th1 response. In summary, treatment of tumor-bearing rats with a tissue vaccine stimulated a protective immune response that resulted in complete tumor regression in 21% of animals and reduced the number of animals with any evidence of metastasis by nearly 70%. These results suggest that tissue vaccines may be useful for the treatment of prostate cancer.


Dietary Iron Intake and Anemia Are Weakly Associated, Limiting Effective Iron Fortification Strategies in India.
Anemia prevalence in India remains high despite preventive iron supplementation programs. Consequently, concurrent national policies of iron fortification of staple foods have been initiated. This study evaluated the relation between dietary iron intake and anemia (hemoglobin <12 g/dL) in women of reproductive age (WRA; 15-49 y) with respect to iron fortification in India. Data from 2 national surveys were used. Data on hemoglobin in WRA were sourced from the National Family Health Survey-4, whereas dietary intakes were sourced from the National Sample Survey. Adjusted odds for anemia with increasing iron intake were estimated, along with the effect of modulating nutrients such as vitamins B-12 and C, from statistically matched household data from the 2 surveys. The risks of inadequate (less than the Estimated Average Requirement for WRA) and excess (more than the tolerable upper limit for WRA) intakes of iron were estimated by the probability approach. The relation between iron intake and the odds of anemia was weak (OR: 0.992; 95% CI: 0.991, 0.994); increasing iron intake by 10 mg/d reduced the odds of anemia by 8%. Phytate and vitamin B-12 and C intakes modified this relation by reducing the odds by 1.5% when vitamin B-12 and C intakes were set at 2 μg/d and 40 mg/d, respectively. The additional intake of 10 mg/d of fortified iron reduced the risk of dietary iron inadequacy from 24-94% to 9-39% across states, with no risk of excess iron intake. Approximately doubling this additional iron intake reduced the risk of inadequacy to 2-12%, but the risk of excess intake reached 22%. Providing fortified iron alone may not result in substantial anemia reduction among WRA in India and could have variable benefits and risks across states. Geographically nuanced dietary strategies that include limited fortification and the intake of other beneficial nutrients should be carefully considered.


Consensus Statement on Analgo-sedation in Neurocritical Care and Review of Literature.
Our main objective in developing this consensus is to bring together a set of most agreed-upon statements from a panel of global experts that would act as a guide for clinicians working in neurocritical care units (NCCUs). Given the physiological benefits of analgo-sedation in the NCCU, there is little information on their tailoring in the NCCU. This lack of evidence and guidelines on the use of sedation and analgesia in patients with neurological injury leads to a variation in clinical care based on patient requirements and institutional protocols. Thirty-nine international experts agreed to be a member of this consensus panel. A Delphi method based on a Web-based questionnaire developed with Google Forms on a secure institute server was used to seek opinions of experts. Questions were related to sedation and analgesia in the neurocritical care unit. A predefined threshold of agreement was established as 70% to support any recommendation, strong, moderate, or weak. No recommendations were made below this threshold. Responses were collected from all the experts, summated, and expressed as percentage (%). After three rounds, consensus could be reached for 6 statements related to analgesia and 5 statements related to sedation. Consensus could not be reached for 10 statements related to analgesia and 5 statements related to sedation. This global consensus statement may help in guiding practitioners in clinical decision-making regarding analgo-sedation in the NCCUs, thereby helping in improving patient recovery profiles. In the lack of high-level evidence, the recommendations may be seen as the current best clinical practice. Prabhakar H, Tripathy S, Gupta N, Singhal V, Mahajan C, Kapoor I, et al. Consensus Statement on Analgo-sedation in Neurocritical Care and Review of Literature. Indian J Crit Care Med 2021;25(2):126-133.


Effect of clopidogrel premedication in off-pump cardiac surgery: are we forfeiting the benefits of reduced hemorrhagic sequelae?
Premedication with clopidogrel has reduced thrombotic complications after percutaneous coronary revascularization procedures. However, because of the enhanced and irreversible platelet inhibition by clopidogrel, patients requiring surgical revascularization have a higher risk of bleeding complications and transfusion requirements. A principal benefit of surgical coronary revascularization without cardiopulmonary bypass is its lower hemorrhagic sequelae. The purpose of this study was to evaluate the effect of preoperative clopidogrel administration in the incidence of hemostatic reexploration, blood product transfusion rates, morbidity, and mortality in patients undergoing off-pump coronary artery bypass graft surgery using a large patient sample and a risk-adjusted approach. Two hundred eighty-one patients (17.9%) did and 1291 (82.1%) did not receive clopidogrel before their surgery, for a total of 1572 patients undergoing isolated off-pump coronary artery bypass graft surgery between January 2000 and June 2002. Risk-adjusted logistic regression analyses and a matched pair analyses by propensity scores were used to assess the association between clopidogrel administration and reoperation as a result of bleeding, intraoperative and postoperative blood transfusions received, and the need for multiple transfusions. Hemorrhage-related preoperative risk factors identified in the literature and those found significant in a univariate model were used. The clopidogrel group had a higher likelihood of hemostatic reoperations (odds ratio [OR], 5.1; 95% confidence interval [CI], 2.47 to 10.47; P<0.01) and an increased need in overall packed red blood cell (OR, 2.6; 95% CI, 1.94 to 3.60; P<0.01), multiple unit (OR, 1.6; 95% CI, 1.07 to 2.48; P=0.02), and platelet (OR, 2.5; 95% CI, 1.77 to 3.66; P<0.01) transfusions. Surgical outcomes and operative mortality (1.4% versus 1.4%; P=1.00) were not statistically different. Clopidogrel administration in the cardiology suite increases the risk for hemostatic reoperation and the requirements for blood product transfusions during and after off-pump coronary artery bypass graft surgery.


Use of Urban Residential Community Parks for Stress Management During the COVID-19 Lockdown Period in China.
During the pandemic lockdown period, residents had to stay at home and increased stress and other mental health problems have been associated with the lockdown period. Since most public parks were closed, community parks within gated residential areas became the most important green space in Chinese cities, and the use of such space might help to reduce the residents' stress levels. This study aimed to investigate to what extent urban residents in China used community parks, engaged in outdoor activity during the lockdown period (23 January-8 April 2020) and if the use of such spaces helped to reduce their stress levels. An online questionnaire survey (n = 1342) was carried out from 23 March to 23 April 2020. Ordinary Least Squares regression was used to analyse the association between community park use, outdoor activity, willingness to engage in outdoor activity, and stress level. All results have been further analysed by two-sampled t-test to explore the difference between young and old age groups. We found that the overall self-reported stress level of the respondents was relatively moderate during the lockdown period. Respondents had generally reduced their use of community parks and engagement in outdoor activity. There was no significant association between stress level and the use of community parks or the engagement in outdoor activities. However, we found that older people showed much lower stress levels, used community parks more frequently, and engaged in more outdoor activities than younger adults. The findings suggest that outdoor activities and spatial characteristics in urban China differ from Western studies and advance the need to integrate the stress management role of community parks with urban green space policy to optimise the use of community parks blended in with everyday life, particularly during the lockdown period.


Subsequent cancers after in situ and invasive squamous cell carcinoma of the skin.
To compare cancer risks after in situ and invasive squamous cell carcinoma (SCC) of the skin and to determine whether these 2 forms of cancer differ in prognostic significance. Subsequent events after in situ and invasive SCC were studied in the Swedish Family-Cancer Database, in which cancer data were obtained from the Swedish Cancer Registry from 1958 to 1996. Among 22293 patients with in situ SCC, 3940 had first invasive cancer; among 17637 patients with invasive SCC, 3624 had a second occurrence of cancer. Standardized incidence ratios (SIRs), ratios of the observed to expected number of cases, served as a measure of relative risk. For overall risks, cases diagnosed within the first year of follow-up were omitted. The median age of onset was 72 to 73 years for in situ and invasive SCC, respectively. Standardized incidence ratios of all cancers were increased after in situ SCC (men-women, 1.5:1.3) and invasive SCC (men-women, 1.9:1.5). The subsequent occurrences of cancer and their SIRs were similar after in situ and invasive SCC, with skin cancer showing the highest SIR of 6.4:10.0. Among discordant cancers, increased SIRs were recorded for melanoma and a group of malignant neoplasms observed in patients with immunosuppression, including lymphoma and oral cancers. Subsequent cancers in the salivary glands and nasal cavity also showed increased SIRs, particularly after invasive SCC. Risks of subsequent cancers, including skin cancer, melanoma, and internal cancers, showed similar patterns in patients with in situ and invasive SCC, suggesting that the 2 groups have a similar susceptibility to cancer.


Genetic relation of lobular carcinoma in situ, ductal carcinoma in situ, and associated invasive carcinoma of the breast.
The mutual relation of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS) of the breast, as accepted precursor lesions of invasive breast cancer, is controversial. Because they display genetic heterogeneity, it is not clear how genetically advanced these entities are and what causes the transition to an invasive carcinoma. Six cases of LCIS, four of them with associated lobular invasive carcinoma, four cases of intermediately differentiated DCIS with an associated invasive lobular carcinoma, and nine cases of intermediately and poorly differentiated DCIS with associated ductal invasive carcinoma were investigated by means of comparative genomic hybridisation (CGH) after microdissection and immunohistochemical staining of E-cadherin. LCIS was characterised by a low average rate of copy number changes, no evidence of amplifications, and a high rate of gains and losses of chromosomal material at 1q and 16q, respectively. A high degree of genetic homology with well differentiated DCIS was obvious, as reported previously. The cases of intermediately differentiated DCIS with associated lobular invasive components and lobular differentiation revealed striking homologies, and a significant difference of E-cadherin expression. The comparison of preinvasive and invasive breast lesions, irrespective of differentiation within the same patient, revealed no specific alteration that might be associated with invasion. Genetic alterations seen in invasive carcinoma were not necessarily seen in the adjacent precursor lesions. These results provide strong evidence that invasive breast cancer is a disease with multiple cytogenetic subclones already present in preinvasive lesions. Moreover, specific CGH alterations associated with invasion were not observed. Furthermore, the close genetic association between well differentiated and a subgroup of intermediately differentiated DCIS and LCIS led to the hypothesis that LCIS and a subgroup of DCIS are different phenotypic forms of a common genotype.


Neural correlates of personally familiar faces: parents, partner and own faces.
Investigations of the neural correlates of face recognition have typically used old/new paradigms where subjects learn to recognize new faces or identify famous faces. Familiar faces, however, include one's own face, partner's and parents' faces. Using event-related fMRI, we examined the neural correlates of these personally familiar faces. Ten participants were presented with photographs of own, partner, parents, famous and unfamiliar faces and responded to a distinct target. Whole brain, two regions of interest (fusiform gyrus and cingulate gyrus), and multiple linear regression analyses were conducted. Compared with baseline, all familiar faces activated the fusiform gyrus; own faces also activated occipital regions and the precuneus; partner faces activated similar areas, but in addition, the parahippocampal gyrus, middle superior temporal gyri and middle frontal gyrus. Compared with unfamiliar faces, only personally familiar faces activated the cingulate gyrus and the extent of activation varied with face category. Partner faces also activated the insula, amygdala and thalamus. Regions of interest analyses and laterality indices showed anatomical distinctions of processing the personally familiar faces within the fusiform and cingulate gyri. Famous faces were right lateralized whereas personally familiar faces, particularly partner and own faces, elicited bilateral activations. Regression analyses show experiential predictors modulated with neural activity related to own and partner faces. Thus, personally familiar faces activated the core visual areas and extended frontal regions, related to semantic and person knowledge and the extent and areas of activation varied with face type.


Anatomical and topographical variations in the distribution of brain metastases based on primary cancer origin and molecular subtypes: a systematic review.
While it has been suspected that different primary cancers have varying predilections for metastasis in certain brain regions, recent advances in neuroimaging and spatial modeling analytics have facilitated further exploration into this field. A systematic electronic database search for studies analyzing the distribution of brain metastases (BMs) from any primary systematic cancer published between January 1990 and July 2020 was conducted using PRISMA guidelines. Two authors independently reviewed 1957 abstracts, 46 of which underwent full-text analysis. A third author arbitrated both lists; 13 studies met inclusion/exclusion criteria. All were retrospective single- or multi-institution database reviews analyzing over 8227 BMs from 2599 patients with breast (8 studies), lung (7 studies), melanoma (5 studies), gastrointestinal (4 studies), renal (3 studies), and prostate (1 study) cancers. Breast, lung, and colorectal cancers tended to metastasize to more posterior/caudal topographic and vascular neuroanatomical regions, particularly the cerebellum, with notable differences based on subtype and receptor expression. HER-2-positive breast cancers were less likely to arise in the frontal lobes or subcortical region, while ER-positive and PR-positive breast metastases were less likely to arise in the occipital lobe or cerebellum. BM from lung adenocarcinoma tended to arise in the frontal lobes and squamous cell carcinoma in the cerebellum. Melanoma metastasized more to the frontal and temporal lobes. The observed topographical distribution of BM likely develops based on primary cancer type, molecular subtype, and genetic profile. Further studies analyzing this association and relationships to vascular distribution are merited to potentially improve patient treatment and outcomes.


New Opportunities for Targeting the Androgen Receptor in Prostate Cancer.
Recent genomic analyses of metastatic prostate cancer have provided important insight into adaptive changes in androgen receptor (AR) signaling that underpin resistance to androgen deprivation therapies. Novel strategies are required to circumvent these AR-mediated resistance mechanisms and thereby improve prostate cancer survival. In this review, we present a summary of AR structure and function and discuss mechanisms of AR-mediated therapy resistance that represent important areas of focus for the development of new therapies.


Emergence of a Neisseria gonorrhoeae clone showing decreased susceptibility to cefixime in England and Wales.
The third-generation cephalosporins recommended in national guidelines are amongst the last remaining effective agents for treatment of gonorrhoea. This study characterizes gonococcal isolates with decreased cefixime susceptibility from England and Wales. A total of 96 isolates of Neisseria gonorrhoeae exhibiting cefixime MICs of ≥0.125 mg/L, either collected as part of the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) between 2005 and 2008 (54 from a total of 4649 isolates) or referred to the national reference laboratory in 2008 and 2009 (42 isolates), were tested for susceptibility to a range of antimicrobial agents and were typed using N. gonorrhoeae multiantigen sequence typing (NG-MAST). All 96 isolates were also resistant to tetracycline (MIC ≥2 mg/L) and ciprofloxacin (MIC ≥16 mg/L) and 56% showed low-level chromosomal resistance to penicillin. Where data were available, the mean patient age was 31 years, and 88% (83/94) of patients were men. Isolates referred through GRASP were predominantly from men who have sex with men (MSM; 29/44, 66%) and from patients of white British ethnicity (25/43, 58%). The majority of isolates belonged either to sequence type (ST) 1407 (71/96, 74%) or to a highly related ST that shares the tpbB allele (allele 110), but with a different por allele (20/96, 21%). ST1407 was found in both MSM (22/29, 76%) and heterosexual patients (12/15, 80%) and among all eight isolates from patients reporting sex abroad. The emergence of a clonal group of gonococci showing decreased susceptibility to cefixime in England and Wales highlights the need for continued surveillance.


Homozygous loss of DIAPH1 is a novel cause of microcephaly in humans.
The combination of family-based linkage analysis with high-throughput sequencing is a powerful approach to identifying rare genetic variants that contribute to genetically heterogeneous syndromes. Using parametric multipoint linkage analysis and whole exome sequencing, we have identified a gene responsible for microcephaly (MCP), severe visual impairment, intellectual disability, and short stature through the mapping of a homozygous nonsense alteration in a multiply-affected consanguineous family. This gene, DIAPH1, encodes the mammalian Diaphanous-related formin (mDia1), a member of the diaphanous-related formin family of Rho effector proteins. Upon the activation of GTP-bound Rho, mDia1 generates linear actin filaments in the maintenance of polarity during adhesion, migration, and division in immune cells and neuroepithelial cells, and in driving tangential migration of cortical interneurons in the rodent. Here, we show that patients with a homozygous nonsense DIAPH1 alteration (p.Gln778*) have MCP as well as reduced height and weight. diap1 (mDia1 knockout (KO))-deficient mice have grossly normal body and brain size. However, our histological analysis of diap1 KO mouse coronal brain sections at early and postnatal stages shows unilateral ventricular enlargement, indicating that this mutant mouse shows both important similarities as well as differences with human pathology. We also found that mDia1 protein is expressed in human neuronal precursor cells during mitotic cell division and has a major impact in the regulation of spindle formation and cell division.


[Surgical treatment of rectal cancer in middle-aged and elderly patients].
This article presents results of surgical treatment of 439 patients with cancer of the rectum, including 310 (70.6%) patients older than 60. The transabdominoperineal extirpation of the rectum was made in 48.1% of the elderly and senile patients, the anterior (transabdominal) resection--in 33.6%, Gartman's operation--in 12.6%, transanal excision of the tumor--in 11 patients. Lethal outcomes after the surgical interventions was 4.8%.


Platelet-derived transforming growth factor-β1 promotes keratinocyte proliferation in cutaneous wound healing.
Platelets are a recognised potent source of transforming growth factor-β1 (TGFβ1), a cytokine known to promote wound healing and regeneration by stimulating dermal fibroblast proliferation and extracellular matrix deposition. Platelet lysate has been advocated as a novel personalised therapeutic to treat persistent wounds, although the precise platelet-derived growth factors responsible for these beneficial effects have not been fully elucidated. The aim of this study was to investigate the specific role of platelet-derived TGFβ1 in cutaneous wound healing. Using a transgenic mouse with a targeted deletion of TGFβ1 in megakaryocytes and platelets (TGFβ1fl/fl .PF4-Cre), we show for the first time that platelet-derived TGFβ1 contributes to epidermal and dermal thickening and cellular turnover after excisional skin wounding. In vitro studies demonstrate that human dermal fibroblasts stimulated with platelet lysate containing high levels of platelet-derived TGFβ1 did not exhibit enhanced collagen deposition or proliferation, suggesting that platelet-derived TGFβ1 is not a key promoter of these wound healing processes. Interestingly, human keratinocytes displayed enhanced TGFβ1-driven proliferation in response to platelet lysate, reminiscent of our in vivo findings. In summary, our novel findings define and emphasise an important role of platelet-derived TGFβ1 in epidermal remodelling and regeneration processes during cutaneous wound healing.


Dual-component synaptic potentials in the lamprey mediated by excitatory amino acid receptors.
The synaptic mechanisms underlying amino acid-mediated excitation in the lamprey spinal cord have been investigated. Fine stimulating electrodes were used to stimulate single axons in the spinal cord and evoke unitary EPSPs in lamprey motoneurons and one type of premotor interneuron, the CC interneuron. Three types of EPSP, distinguished by their time course and sensitivity to amino acid antagonists, were seen. Fast EPSPs had a fast rise time (mean, 6.5 msec) and a short half-decay time (mean, 22.5 msec). Slow EPSPs lasted at least 200 msec, had a slow rise time (mean, 28 msec), and a long half-decay time (mean, 109 msec). The third type of unitary potential, called "mixed" EPSP, also lasted at least 200 msec, had a fast rise time (mean, 12 msec), and a long half-decay time (mean, 105 msec). Lamprey neurons were found to possess 3 types of excitatory amino acid receptor: N-methyl-D-aspartate (NMDA), kainate, and quisqualate receptors. 2-Amino-5-phosphonovaleric acid (APV) or Mg2+ blocked the depolarizations caused by N-methyl-D,L-aspartate (NMA) but not those of kainate or quisqualate. Cis-2, 3-piperidine dicarboxylic acid (PDA) blocked the depolarizations caused by NMA and kainate but not those of quisqualate. Fast EPSPs were unaffected by the bath application of APV or Mg2+ but were greatly reduced by PDA, suggesting that these EPSPs were mediated by non-NMDA, possibly kainate receptors. Both APV and Mg2+ blocked the slow EPSPs, suggesting that they were mediated by NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Health behavior changes after a cancer diagnosis: what do we know and where do we go from here?
Survival rates for certain types of cancer have improved over the past few decades. Changing unhealthy behaviors such as smoking, poor diet, and sedentary life-style among individuals who have been diagnosed with cancer may help to reduce cancer treatment sequelae, possibly reduce risk of recurrence for specific types of cancer, and reduce risk for other common diseases such as cardiovascular disease, obesity, and hypertension. This article reports the prevalence of each of these behaviors among those diagnosed with cancer and reviews interventions that have targeted these risk behaviors. There is considerable variation in the type of research questions asked, the methodologic quality of the research, sample sizes, and the outcomes observed across studies focusing on changing the three health risk behaviors. In the final section, we provide guidelines for researchers in developing health behavior interventions for individuals diagnosed with cancer and highlight challenges that should be addressed.


Nurse Practitioner Care Compared with Primary Care or Nephrologist Care in Early CKD.
Early interventions in CKD have been shown to improve health outcomes; however, gaps in access to nephrology care remain common. Nurse practitioners can improve access to care; however, the quality and outcomes of nurse practitioner care for CKD are uncertain. In this propensity score-matched cohort study, patients with CKD meeting criteria for nurse practitioner care were matched 1:1 on their propensity scores for ( 1 ) nurse practitioner care versus primary care alone and ( 2 ) nurse practitioner versus nephrologist care. Processes of care were measured within 1 year after cohort entry, and clinical outcomes were measured over 5 years of follow-up and compared between propensity score-matched groups. A total of 961 (99%) patients from the nurse practitioner clinic were matched on their propensity score to 961 (1%) patients receiving primary care only while 969 (100%) patients from the nurse practitioner clinic were matched to 969 (7%) patients receiving nephrologist care. After matching to patients receiving primary care alone, those receiving nurse practitioner care had greater use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (82% versus 79%; absolute differences [ADs] 3.4% [95% confidence interval, 0.0% to 6.9%]) and statins (75% versus 66%; AD 9.7% [5.8% to 13.6%]), fewer prescriptions of nonsteroidal anti-inflammatory drugs (10% versus 17%; AD -7.2% [-10.4% to -4.2%]), greater eGFR and albuminuria monitoring, and lower rates of all-cause hospitalization (34.1 versus 43.3; rate difference -9.2 [-14.7 to -3.8] per 100 person-years) and all-cause mortality (3.3 versus 6.0; rate difference -2.7 [-3.6 to -1.7] per 100 person-years). When matched to patients receiving nephrologist care, those receiving nurse practitioner care were also more likely to be prescribed angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and statins, with no difference in the risks of experiencing adverse clinical outcomes. Nurse practitioner care for patients with CKD was associated with better guideline-concordant care than primary care alone or nephrologist care, with clinical outcomes that were better than or equivalent to primary care alone and similar to those with care by nephrologists. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_12_08_CJN0000000000000305.mp3.


The value of Jamshidi core needle bone biopsy in predicting postoperative osteomyelitis in grade IV pressure ulcer patients.
We present a retrospective review of 108 patients with spinal cord injury who underwent reconstruction of grade IV pressure ulcers between 1989 and 1994. Complications of reconstruction secondary to undetected osteomyelitis, namely, deep abscess and sinus tract formation, and their effect on hospital course after the flap reconstruction were quantitatively evaluated. Specifically, this study assesses whether the use of Jamshidi core needle bone biopsy allows for the accurate diagnosis, and therefore treatment, of osteomyelitis before pressure ulcer closure. Early diagnosis and treatment of osteomyelitis would presumably reduce the complication rate of reconstruction. The 108 patients in the study all underwent intraoperative Jamshidi core needle bone biopsy, and postoperative complications were evaluated by reviewers blinded to results of the biopsies. Of the 25 (23 percent) postoperative complications noted, 14 (13 percent) were attributed to underlying osteomyelitis. Patients with pressure ulcer complicated by osteomyelitis were hospitalized significantly longer than those with no osteomyelitis. On average, the former group stayed for 57 days and the latter 21 days (p < 0.001). All 14 patients who developed complications because of deep abscess and sinus tract formation had intraoperative Jamshidi core needle bone biopsy abnormality consistent with osteomyelitis (positive Jamshidi core needle bone biopsy results). The Jamshidi core needle bone biopsy compares favorably with other published modalities used to diagnose osteomyelitis, including white blood cell count, erythrocyte sedimentation rate, radiologic study, and bone biopsy culture. We propose an algorithm for the management of spinal cord injury patients with grade IV pressure ulcers. This algorithm incorporates the use of preoperative Jamshidi core needle bone biopsy to allow for the diagnosis and treatment of osteomyelitis before the flap reconstruction and to prevent complications of undiagnosed osteomyelitis after reconstruction.


Preimplantation embryo programming: transcription, epigenetics, and culture environment.
Preimplantation development directs the formation of an implantation- or attachment-competent embryo so that metabolic interactions with the uterus can occur, pregnancy can be initiated, and fetal development can be sustained. The preimplantation embryo exhibits a form of autonomous development fueled by products provided by the oocyte and also from activation of the embryo's genome. Despite this autonomy, the preimplantation embryo is highly influenced by factors in the external environment and in extreme situations, such as those presented by embryo culture or nuclear transfer, the ability of the embryo to adapt to the changing environmental conditions or chromatin to become reprogrammed can exceed its own adaptive capacity, resulting in aberrant embryonic development. Nuclear transfer or embryo culture-induced influences not only affect implantation and establishment of pregnancy but also can extend to fetal and postnatal development and affect susceptibility to disease in later life. It is therefore critical to define the basic program controlling preimplantation development, and also to utilize nuclear transfer and embryo culture models so that we may design healthier environments for preimplantation embryos to thrive in and also minimize the potential for negative consequences during pregnancy and post-gestational life. In addition, it is necessary to couple gene expression analysis with the investigation of gene function so that effects on gene expression can be fully understood. The purpose of this short review is to highlight our knowledge of the mechanisms controlling preimplantation development and report how those mechanisms may be influenced by nuclear transfer and embryo culture.


Endophenotypes, dimensions, risks: is psychosis analogous to common inherited medical illnesses?
Psychiatric illnesses are perceived as fundamentally different from common medical disorders, a view arising from the mind-body problem and difficulties relating the brain's emergent properties to its physiological substrates. However, schizophrenia and many common medical illnesses are heritable and result from the influence of both genetic and environmental sources. Unlike illnesses such as Huntington's disease, which are caused by a fully penetrant dominant mutation, no single "schizophrenia gene" has been identified. Instead, schizophrenia is likely caused by common variants of many genes, each contributing a subtle effect. Schizophrenia genetically resembles common medical illnesses such as type 2 diabetes, ischemic heart disease, and familial hypercholesterolemia, that have an associated genetic variant, but that are also influenced by other factors such as diet, culture and habits. Just as these illnesses operate through complex gene/environment interaction, schizophrenia is likely caused by several gene variants, neurodevelopmental processes, and learned behavioral response biases. These clinical diseases, however, represent severe forms of the phenotype for both psychiatric and medical illnesses. From a dimensional perspective, individuals possessing the same genotype could express milder forms of the clinical disorder along a spectrum of related traits. We discuss this perspective in the context of an endophenotypic and biological marker approach to understanding schizophrenia and present a research strategy to compare schizophrenia endophenotypes to risk for common medical illnesses.


Disclosure of genetic research results to members of a founder population.
There is currently extensive discussion and debate in the literature on how, when, and to whom genetic research results should be returned (see Genetics in Medicine, April 2012 issue). Here, we describe our experience in disclosing genetic information on Mendelian disorders discovered during the course of our research in the Hutterites. We first assessed attitudes toward the disclosure of carrier results, which revealed that many individuals wanted carrier information and that many intended to use the information in family planning. Based on this information, we developed a pilot study to test and disclose cystic fibrosis (CF) carrier status. Next, a larger scale project was developed in order to disclose genetic research results for 14 diseases to those interested in receiving the information. We developed brochures, offered a live interactive educational program, conducted a consent process, and disclosed results in letters mailed to the consented individuals. Overall, ~80% of individuals who participated in the educational program signed consent forms for the release of their results for 14 diseases. We describe our experience with returning individual genetic research results to participants in a population-based research study.


Refractory urticaria and the importance of diagnosing Schnitzler's syndrome.
A 52-year-old man presented with chronic urticaria that was refractory to standard chronic spontaneous urticaria (CSU) treatment. Over time, he developed systemic symptoms including fatigue, weight loss, arthralgia and bone pain. His laboratory investigations also became significant for microcytic anaemia, neutrophilia and elevated C reactive protein, erythrocyte sedimentation rate and IgE levels, in addition to an IgM monoclonal protein. He achieved only partial remission with typical medications for CSU including omalizumab, cyclosporine and cetirizine. After 6 years, his worsening symptoms and abnormal investigations led to a rare diagnosis of Schnitzler's syndrome and a trial of the interleukin 1 receptor antagonist, anakinra, which caused a rapid and complete resolution of his symptoms.


Observations of sharp oxalate reductions in stratocumulus clouds at variable altitudes: organic acid and metal measurements during the 2011 E-PEACE campaign.
This work examines organic acid and metal concentrations in northeastern Pacific Ocean stratocumulus cloudwater samples collected by the CIRPAS Twin Otter between July and August 2011. Correlations between a suite of various monocarboxylic and dicarboxylic acid concentrations are consistent with documented aqueous-phase mechanistic relationships leading up to oxalate production. Monocarboxylic and dicarboxylic acids exhibited contrasting spatial profiles reflecting their different sources; the former were higher in concentration near the continent due to fresh organic emissions. Concentrations of sea salt crustal tracer species, oxalate, and malonate were positively correlated with low-level wind speed suggesting that an important route for oxalate and malonate entry in cloudwater is via some combination of association with coarse particles and gaseous precursors emitted from the ocean surface. Three case flights show that oxalate (and no other organic acid) concentrations drop by nearly an order of magnitude relative to samples in the same vicinity. A consistent feature in these cases was an inverse relationship between oxalate and several metals (Fe, Mn, K, Na, Mg, Ca), especially Fe. By means of box model studies we show that the loss of oxalate due to the photolysis of iron oxalato complexes is likely a significant oxalate sink in the study region due to the ubiquity of oxalate precursors, clouds, and metal emissions from ships, the ocean, and continental sources.


Simultaneous imaging of neural activity in three dimensions.
We introduce a scanless optical method to image neuronal activity in three dimensions simultaneously. Using a spatial light modulator and a custom-designed phase mask, we illuminate and collect light simultaneously from different focal planes and perform calcium imaging of neuronal activity in vitro and in vivo. This method, combining structured illumination with volume projection imaging, could be used as a technological platform for brain activity mapping.


[Effect of the position of the body in space on the dynamics of tendon reflexes in stroke patients during the rehabilitation period].
Chronometry of Achilles reflexes in 40 healthy subjects and 25 patients in the recovery period after cerebral stroke with regard to body posture showed that in normal subjects the vertical position was associated with a reduced time of the reflectory response whereas in the patients it was increased. It is assumed that a change in the speed of tendon reflexes in different postures is related to the readjustment of suprasegmental and afferent influences on the segmental apparatus of the spinal cord.


Recurrent Chromosomal Abnormalities in Tissues Involved by Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
Prognostically relevant chromosomal abnormalities in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are routinely identified by fluorescence in situ hybridization (FISH) on peripheral blood or bone marrow specimens. We studied the prevalence of chromosomal abnormalities on extramedullary tissues involved by CLL/SLL and evaluated their association with prominent proliferation centers (PPCs). FISH for recurrent abnormalities in CLL/SLL was performed on formalin-fixed, paraffin-embedded biopsy sections. PPCs were identified on H&E-stained sections. Available FISH results on peripheral blood or bone marrow specimens were also reviewed. Recurrent FISH abnormalities were detected in 69% of 320 CLL/SLL biopsy specimens studied, including +12 (35%), 13q- (24%), 11q- (15%), 17p- (6%), 6q- (2%), and IGH/BCL2 (0.9%). Forty-three patients had abnormal blood or bone marrow FISH analyses, of whom 7 (16%) had discordant +12 and/or 13q-, and 3 (7%) had discordant 17p- or 11q-. Morphology was positive (17%), negative (78%), or equivocal (6%) for PPCs on 247 evaluable biopsy specimens, a finding not significantly associated with FISH results (P = .7). Trisomy 12 is overrepresented in tumoral CLL/SLL involvement, compared with the known predominance of 13q- in blood. Discrepancies between leukemic and tissue FISH findings are occasionally encountered. FISH results do not correlate with the presence of PPCs.


Magnetic resonance imaging findings in piriformis syndrome: a case report.
Piriformis syndrome (PS) is an unusual cause of sciatica that, because of the lack of strict diagnostic criteria, remains a controversial clinical entity. The diagnosis of PS is still primarily clinical because no diagnostic tests have proven to be definitive. We report the case of a 30-year-old woman, affected by a severe scoliosis, who developed a persistent buttock pain resembling that of PS. The clinical suspicion was confirmed by magnetic resonance imaging (MRI) of the pelvis, which showed an enlargement of the left piriformis muscle with an anterior isplacement of the sciatic nerve. The role of MRI in the diagnosis, clinical definition, and therapeutic approach to PS is discussed.


[Approaches for formation of the large bowel anastomoses for prophylaxis of their sutures insufficiency].
The results of surgical treatment of 424 patients, in whom the postponed and elective surgery was done for the large bowel malignancies, were analyzed. Advantages of a one-layer suture while formation of a large-bowel anastomoses in comparison with a two-layer suture were noted: minimal rate of the sutures insufficiency--(4.9 +/- 0.8)%, and (7.9 +/- 1.7)%, accordingly (p<0.001). Mostly often insufficience of the colorectal anastomosis sutures was observed after anterior rectal resection--in (9.7 +/- 1.9)% and (7.2 +/- 1.5)% patients. Postoperative lethality was 2.6%, for majority of the patients the reasons of the death were pulmonary thromboembolism and an acute cardio-vascu- lar insufficiency.


Core excitations of biphenyl.
High-resolution C(1s) near-edge X-ray absorption and X-ray photoionization spectra of the free biphenyl molecule are presented and theoretically analyzed in order to allow an assignment of the observed spectral features. Finite lifetime broadening, a high density of vibrational states, and a strong overlap of contributions from chemically different carbon atom sites only partially allow resolving the vibrational fine structure. However, the shape and width of the spectral profiles are strongly determined by both chemical shifts and vibronic effects. In particular, different from photoionization of valence levels, both types of core level spectra do not contain contributions from dihedral modes which are related to the twisting motion of the two phenyl rings. Contrary to naphthalene, C-H stretching modes are significantly enhanced in the core excitation spectra of biphenyl while the contributions from C-C stretching modes are reduced.


Results for patients with sarcoma not otherwise specified and other diagnoses than Ewing sarcoma treated according to the Euro-EWING 99 trial.
Euro-EWING 99 trial of the European Ewing tumor Working Initiative of National Groups (EE99) was an international phase III study in patients with Ewing sarcoma. The German Society of Pediatric Oncology and Hematology (GPOH) data center registered and followed patients with other diagnoses than Ewing sarcoma who were treated according to the EE99 protocol in an additional non-Ewing database. Data of 27 patients with other diagnoses than Ewing sarcoma treated according to the EE99 protocol were analyzed. Patients had miscellaneous histologic diagnoses, the majority were diagnosed with sarcoma not otherwise specified (NOS) arising in bone and soft tissue (63%). The median age at diagnosis was 16.9 years (range 4.5-41.4). Localized disease was diagnosed in 61.5% of the patients and 38.5% had distant metastases at time of primary diagnosis. The median follow-up time was 3.7 years (range 0.5-9.5). Patients with localized disease showed a 3-year event-free survival (EFS) of 68%, compared to 3-year EFS of 20% in patients with metastases (P = 0.042). Three-year EFS for patients with sarcoma NOS was 52%, patients with localized and metastatic disease showed 3-year EFS of 66 and 20%, respectively. EFS in patients with other diagnoses than Ewing sarcoma treated according to EE99 was significantly higher in patients with localized than metastatic disease. Sarcomas of soft tissue and bone that cannot be classified to current diagnostic categories constitute a therapeutic challenge.


Jaw Opening Decreases Window to the Deep Parotid Lobe.
To describe the relationship between jaw opening and access to the deep parotid window, we identified the following distances in 10 human skulls: symphysis to angle of mandible, mastoid tip to angle of mandible, angle of mandible to condylar process, and mastoid tip to condylar process. With the jaw closed and open, these distances were measured with 1 to 3 wooden blocks, each measuring 1 cm, between the upper and lower incisors. The triangular deep parotid area formed by the last 3 distances was calculated. A repeated measures analysis of variance showed a significant decrease in the deep parotid area with increasing interincisal distance ( P < .01). A generalized estimating equation model demonstrated a statistically significant decreasing area of the deep parotid window with increasing interincisal distance. These results suggest that nasal intubation may improve access to the parotid window.


Performance evaluation of child safety seats in far-side lateral sled tests at varying speeds.
Protection of children in Child Safety Seats (CSS) in side impact crashes has been a topic of recent studies. The objective of this study was to evaluate the performance of CSS in far-side impacts through a series of sled tests conducted at varying test speeds. Forty eight sled tests were conducted at three speeds (24 km/h, 29 km/h and 36 km/h), under two different CSS attachment conditions (LATCH and seat belt attached), using rear facing and forward facing CSS from four different manufacturers. Analyses were conducted to examine head retention within the CSS, velocity of the head as it passes an imaginary plane (cross over into other occupant space or door), lateral trajectory of the head and knee; head, chest and pelvis accelerations; neck and lumbar loads and moments. In addition to these parameters, the CSS were visually inspected for structural integrity after each test. Results from these sled tests highlighted the differential performance of CSS in far-side impacts. During the tests, all CSS experienced significant lateral movement irrespective of attachment type. In rear facing CSS tests, one of the designs failed as the seat disengaged from its base. In forward facing CSS tests, it was observed that the seat belt attached CSS experienced less rotational motion than the LATCH attached CSS. ATD head retention within the seat was not achieved with either CSS attachments at any speed. The findings from this study augment the current efforts to define regulatory sled setup procedure for far-side impact crashes involving children in CSS, which currently does not exist and will eventually further the protection of children in automobiles.


A survey of orofacial injuries among basketball players.
To determine the prevalence of orofacial injuries among basketball players in Benin City, Nigeria and to survey the athletes' awareness, attitude and use of mouthguards. A cross-sectional survey of basketball players in the standard basketball arena in Benin City was conducted between November 2009 and January 2010. A self-administered questionnaire elicited information on demography, the prevalence of oral and facial injuries, distribution of site and cause of orofacial injuries, athletes' knowledge, attitudes and usage of mouthguards. Data were subjected to descriptive statistics and Chi square test. The response rate was 78%. Of the 156 respondents, 79.5% were male and 20.5% female, with a mean age of 23.1 years. The distributions was amateurs (61.5%) professionals (38.5%). The mean number of injuries in previous 12 months was 3.7 ± 1.8. The prevalence of both facial and oral injuries among the respondents was 62.8% with the lip and gingiva most commonly involved respectively. The common causes of the orofacial injury reported were from elbows of opponents, falling and collisions with other players. The prevalence of injury was not significantly associated with demography, category, competition and duration of participation. More than half had heard and seen mouthguards and the coach was the leading source of information. The reasons for non-use of mouthguard were mostly ignorance, non-availability and non-affordability. The high prevalence of orofacial injury among basketball players reported in this study justifies the need for multidisciplinary injury prevention interventional approach with emphasis on the rules of the games.


Antiproliferative and Antimicrobial Activities of Selected Bryophytes.
One-hundred and sixty-eight aqueous and organic extracts of 42 selected bryophyte species were screened in vitro for antiproliferative activity on a panel of human gynecological cancer cell lines containing HeLa (cervix epithelial adenocarcinoma), A2780 (ovarian carcinoma), and T47D (invasive ductal breast carcinoma) cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and for antibacterial activity on 11 strains using the disc-diffusion method. A total of 99 extracts derived from 41 species exerted ≥25% inhibition of proliferation of at least one of the cancer cell lines at 10 μg/mL. In the cases of Brachythecium rutabulum, Encalypta streptocarpa, Climacium dendroides, Neckera besseri, Pleurozium schreberi, and Pseudoleskeella nervosa, more than one extract was active in the antiproliferative assay, whereas the highest activity was observed in the case of Paraleucobryum longifolium. From the tested families, Brachytheciaceae and Amblystegiaceae provided the highest number of antiproliferative extracts. Only 19 samples of 15 taxa showed moderate antibacterial activity, including the most active Plagiomnium cuspidatum, being active on 8 tested strains. Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus were the most susceptible to the assayed species. This is the first report on the bioactivities of these 14 species.


Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy.
The exclusion of pregnant women from initial COVID-19 messenger RNA vaccine trials raised hesitancy regarding the benefits of vaccination for pregnant women, hence little is known about vaccines' efficacy in this population. To determine the maternal-neonatal transplacental transfer of SARS-CoV-2 antibodies among vaccinated parturient women. A control group of COVID-19-recovered patients was included to compare the immunoglobulin G levels between vaccinated and recovered patients. This is a prospective cohort study conducted in a single tertiary medical center in Israel between February and March 2021; parturient women vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy were included and compared with COVID-19-recovered parturient women. SARS-CoV-2 immunoglobulin G antibodies were measured in maternal and cord sera, dried blood spot samples taken from newborns, and breast milk samples. The primary aim was to determine whether neonatal cord and dried blood spot samples were positive for SARS-CoV-2 antibodies and to evaluate the transfer ratio, defined as cord blood immunoglobulin G divided by maternal immunoglobulin G levels. The study included 64 vaccinated parturient women and 11 parturient women who had COVID-19 during pregnancy. All maternal blood sera samples and 98.3% of the cord blood sera samples were positive for SARS-Cov-2 immunoglobulin G with median concentrations of 26.1 (interquartile range, 22.0-39.7) and 20.2 (interquartile range, 12.7-29.0), respectively. Similarly, 96.4% of neonatal blood spot samples and all breast milk samples were positive for SARS-CoV-2 immunoglobulin G with median concentrations of 11.0 (interquartile range, 7.2-12.8) and 4.9 (interquartile range, 3.8-6.0), respectively. There was a significant positive correlation between maternal serum levels of SARS-CoV-2 immunoglobulin G and cord blood (r=0.483; P=.0001), neonatal blood spot (r=0.515; P=.004), and breast milk levels (r=0.396; P=.005) of SARS-CoV-2 immunoglobulin G. The median placental transfer ratio of SARS-COV-2 immunoglobulin G was 0.77. Comparison of vaccinated and recovered COVID-19 patients revealed significantly higher SARS-CoV-2 immunoglobulin G levels in maternal serum and cord blood among vaccinated women (P<.0001). Our study demonstrated the efficient transfer of SARS-CoV-2 immunoglobulin G across the placenta in women, vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy, to their neonates, with a positive correlation between maternal serum and cord blood antibody concentrations. In addition to maternal protection against COVID-19, the vaccine may also provide neonatal humoral immunity.