Neurobehavioural effects of exposure to fluoride in the earliest stages of rat development.
It is known that exposure to high concentrations of Fluoride (F) produces deleterious health effects in human population. However, in the last years it has been concluded that low concentrations of F may have adverse health effects as well. Transplacental passage of F and its incorporation into foetal tissues has been demonstrated. Therefore, the purpose of the present work was to study the effects of the exposure to low levels of F during pregnancy and lactation on the central nervous system functionality. Wistar rats were exposed to low F concentrations (5 and 10 mg/l) during pregnancy and lactation. Sensorimotor reflexes in the each pup were analysed and the postnatal day on which both eyes and auditory canals were opened was recorded. Locomotor activity and anxiety were subsequently analysed in 45- and 90-day-old offspring by an open field test and plus maze test, respectively. A significant delay in the development of eye opening was observed in all offspring whose mothers had been exposed to the two F concentrations tested. Exposure to 5 and 10 mg/l F was also found to significantly decrease locomotor activity only in 90-day-old male and female offspring. A low index of anxiety in the young females and in all adult offspring exposed to the two F concentrations tested was also detected. Taken together, findings from the present study show that exposure to low F concentrations during pregnancy and lactation produces dysfunction in the central nervous system mechanisms which regulate motor and sensitive development, locomotor activity and anxiety


Association of Sex With Neurobehavioral Markers of Executive Function in 2-Year-Olds at High and Low Likelihood of Autism.
Children with autism and their siblings exhibit executive function (EF) deficits early in development, but associations between EF and biological sex or early brain alterations in this population are largely unexplored. To investigate the interaction of sex, autism likelihood group, and structural magnetic resonance imaging alterations on EF in 2-year-old children at high familial likelihood (HL) and low familial likelihood (LL) of autism, based on having an older sibling with autism or no family history of autism in first-degree relatives. This prospective cohort study assessed 165 toddlers at HL (n = 110) and LL (n = 55) of autism at 4 university-based research centers. Data were collected from January 1, 2007, to December 31, 2013, and analyzed between August 2021 and June 2022 as part of the Infant Brain Imaging Study. Direct assessments of EF and acquired structural magnetic resonance imaging were performed to determine frontal lobe, parietal lobe, and total cerebral brain volume. A total of 165 toddlers (mean [SD] age, 24.61 [0.95] months; 90 [54%] male, 137 [83%] White) at HL for autism (n = 110; 17 diagnosed with ASD) and LL for autism (n = 55) were studied. The toddlers at HL for autism scored lower than the toddlers at LL for autism on EF tests regardless of sex (mean [SE] B = -8.77 [4.21]; 95% CI, -17.09 to -0.45; η2p = 0.03). With the exclusion of toddlers with autism, no group (HL vs LL) difference in EF was found in boys (mean [SE] difference, -7.18 [4.26]; 95% CI, 1.24-15.59), but EF was lower in HL girls than LL girls (mean [SE] difference, -9.75 [4.34]; 95% CI, -18.32 to -1.18). Brain-behavior associations were examined, controlling for overall cerebral volume and developmental level. Sex differences in EF-frontal (B [SE] = 16.51 [7.43]; 95% CI, 1.36-31.67; η2p = 0.14) and EF-parietal (B [SE] = 17.68 [6.99]; 95% CI, 3.43-31.94; η2p = 0.17) associations were found in the LL group but not the HL group (EF-frontal: B [SE] = -1.36 [3.87]; 95% CI, -9.07 to 6.35; η2p = 0.00; EF-parietal: B [SE] = -2.81 [4.09]; 95% CI, -10.96 to 5.34; η2p = 0.01). Autism likelihood group differences in EF-frontal (B [SE] = -9.93 [4.88]; 95% CI, -19.73 to -0.12; η2p = 0.08) and EF-parietal (B [SE] = -15.44 [5.18]; 95% CI, -25.86 to -5.02; η2p = 0.16) associations were found in girls not boys (EF-frontal: B [SE] = 6.51 [5.88]; 95% CI, -5.26 to 18.27; η2p = 0.02; EF-parietal: B [SE] = 4.18 [5.48]; 95% CI, -6.78 to 15.15; η2p = 0.01). This cohort study of toddlers at HL and LL of autism suggests that there is an association between sex and EF and that brain-behavior associations in EF may be altered in children at HL of autism. Furthermore, EF deficits may aggregate in families, particularly in girls.


IL-2Rα-biased agonist enhances antitumor immunity by invigorating tumor-infiltrating CD25+CD8+ T cells.
To avoid regulatory T cell promotion and vascular toxicity, the interleukin-2 receptor-β/interleukin-2 receptor-γ (IL-2Rβγ)-biased approach is used by most IL-2 analogs in immuno-oncology. However, recent clinical disappointments in these IL-2 agonists have questioned this strategy. Here we show that both wild-type (IL-2wt) and IL-2Rβγ-attenuated (IL-2α-bias) agonists that preserve IL-2Rα (CD25) activities can effectively expand tumor-specific CD8+ T cells (TSTs) and exhibit better antitumor efficacy and safety than the 'non-α' counterpart (IL-2nα). Mechanistically, TSTs coexpress elevated CD25 and PD-1 and are more susceptible to stimulation by IL-2Rα-proficient agonists. Moreover, the antitumor efficacy of anti-PD-1 depends on activation of PD-1+CD25+ TSTs through autocrine IL-2-CD25 signaling. In individuals with cancer, a low IL-2 signature correlates with non-responsiveness to anti-PD-1 treatment. In mouse models, IL-2α-bias, but not IL-2nα, restores the IL-2 signature and synergizes with anti-PD-1 to eradicate large established tumors. These findings underscore the indispensable function of CD25 in IL-2-based immunotherapy and provide rationales for evaluating IL-2Rα-biased agonists in individuals with cancer.


Reliability of clinical temporomandibular disorder diagnoses.
Temporomandibular disorders (TMD) diagnoses can be viewed as the most useful clinical summary for classifying subtypes of TMD. The Research Diagnostic Criteria for TMD (RDC/TMD) is the most widely used TMD diagnostic system for conducting clinical research. It has been translated into 18 languages and is used by a consortium of 45 RDC/TMD-based international researchers. While reliability of RDC/TMD signs and symptoms of TMD has been amply reported, the reliability of RDC/TMD diagnoses has not. The aim of the study was to determine the reliability of clinical TMD diagnoses using standardized methods and operational definitions contained in the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Data came from reliability assessment trials conducted at 10 international clinical centers, involving 30 clinical examiners assessing 230 subjects. Intraclass correlation coefficients (ICC) were calculated to characterize the reliability. The reliability of the diagnoses was fair to good. Median ICCs for the diagnoses myofascial pain with and without limited opening were 0.51 and 0.60, respectively. Median ICC for arthralgia was 0.47 and 0.61 for disc displacement with reduction. RDC/TMD diagnoses of disc displacement without reduction, osteoarthritis and osteoarthrosis were not prevalent enough to calculate ICC's, but percent agreement was always >95%. The reliability of diagnostic classification improved when diagnoses were grouped into pain versus non-pain diagnoses (ICC=0.72) and for detecting any diagnosis versus no diagnosis (ICC=0.78). In clinical decision-making and research, arriving at a reliable diagnosis is critical in establishing a clinical condition and a rational approach to treatment. The RDC/TMD demonstrates sufficiently high reliability for the most common TMD diagnoses, supporting its use in clinical research and decision making.


Gender differences in burns: A study from emergency centres in the Western Cape, South Africa.
Little is known about gender differences in aetiology and management of acute burns in resource-constrained settings in South Africa. This cross-sectional study is based on burn case reports (n=1915) from eight emergency centres in Western Cape, South Africa (June 2012-May 2013). Male/female rate ratios by age group and age-specific incidence rates were compiled for urban and rural areas along with gender differences in proportions between children and adults for injury aetiology, burn severity, length of stay and patient disposition. Children 0-4 years in urban areas had the highest burn incidence but only among adults did male rates surpass females, with fire burns more common among men 20-39 years and hot liquid burns among men 55+ years. Men had a higher proportion of burns during weekends, from interpersonal violence and suspected use of alcohol/other substances, with more pronounced differences for hot liquid burns. Despite similar Abbreviated Injury Scale (AIS) scores, men were more often transferred to higher levels of care and women more often treated and discharged. Burns were far more common among children although gender differences arose only among adults. Men sustained more injuries of somewhat different aetiology and were referred to higher levels of care more often for comparable wound severity. The results suggest different disposition between men and women despite similar AIS scores. However, further studies with more comprehensive information on severity level and other care- and patient-related factors are needed to explore these results further.


Screening for Impaired Visual Acuity in Older Adults: US Preventive Services Task Force Recommendation Statement.
Update of the US Preventive Services Task Force (USPSTF) recommendation on screening for impaired visual acuity in older adults. The USPSTF reviewed the evidence on screening for visual acuity impairment associated with uncorrected refractive error, cataracts, and age-related macular degeneration among adults 65 years or older in the primary care setting; the benefits and harms of screening; the accuracy of screening; and the benefits and harms of treatment of early vision impairment due to uncorrected refractive error, cataracts, and age-related macular degeneration. This recommendation applies to asymptomatic adults 65 years or older who do not present to their primary care clinician with vision problems. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in older adults. (I statement).


Structural basis for activation of CB1 by an endocannabinoid analog.
Endocannabinoids (eCBs) are endogenous ligands of the cannabinoid receptor 1 (CB1), a G protein-coupled receptor that regulates a number of therapeutically relevant physiological responses. Hence, understanding the structural and functional consequences of eCB-CB1 interactions has important implications for designing effective drugs targeting this receptor. To characterize the molecular details of eCB interaction with CB1, we utilized AMG315, an analog of the eCB anandamide to determine the structure of the AMG315-bound CB1 signaling complex. Compared to previous structures, the ligand binding pocket shows some differences. Using docking, molecular dynamics simulations, and signaling assays we investigated the functional consequences of ligand interactions with the "toggle switch" residues F2003.36 and W3566.48. Further, we show that ligand-TM2 interactions drive changes to residues on the intracellular side of TM2 and are a determinant of efficacy in activating G protein. These intracellular TM2 rearrangements are unique to CB1 and are exploited by a CB1-specific allosteric modulator.


Severe fever with thrombocytopenia syndrome with myocardial dysfunction and encephalopathy: A case report.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China, Korea and Japan caused by a novel bunyavirus, SFTS virus (SFTSV). Although central nervous system manifestations are common in SFTS patients, the pathogenesis has not been elucidated; and there are few reports of myocardial dysfunction. Here we report an elderly Japanese patient with reversible myocardial dysfunction and encephalopathy. A previously healthy 65-year-old male engaged in forestry got a tick bite and developed fever and fatigue in 3 days. Three days after onset, he presented to a local hospital where the diagnosis of SFTS with hemophagocytotic syndrome was made. The blood test showed leukopenia and thrombocytopenia as well as elevated levels of alanine aminotransferase and aspartate aminotransferase. Marked hemophagocytosis was found on bone marrow smear. Peripheral blood was positive for SFTSV gene by reverse-transcription polymerase chain reaction. On day 7, the patient was transferred to our hospital. We observed disturbance of consciousness, Kernig sign and myoclonus to face and limbs. Decreased blood flow of whole cerebral cortex was detected by single photon emission computed tomography (SPECT). Chest X-ray revealed cardiomegaly and electrocardiography (ECG) showed abnormal T waves. These data suggested acute encephalopathy and myocardial dysfunction. We treated him with corticosteroid and blood transfusion, which resulted in the complete recovery of the above abnormal symptoms and laboratory data including the findings in SPECT and ECG in about a month. This case demonstrated transient myocardial dysfunction and encephalopathy can occur in addition to typical clinical manifestation of SFTS.


Genetic structure of Pseudococcus microcirculus (Hemiptera: Pseudococcidae) populations on epiphytic orchids in south Florida.
In 2012, the orchid mealy bug Pseudococcus microcirculus was first detected in situ in North America's more diverse orchid region, the Big Cypress Basin (Collier Co FL). A follow-up survey showed that the mealy bug is more widespread and found on epiphytic orchids in two locations, in both the Fakahatchee Strand State Preserve (sites B and F) and the Florida Panther National Wildlife Refuge (sites M and C). There, we collected mealy bugs (n = 54) from 35 orchid individuals and screened allelic variation at seven microsatellite loci. We estimated genetic diversity and differentiation among all sites and compared the variation among individuals collected on the same plant. Genetic differentiation between sites M and C (FST = 0.03, P < 0.01) and,Mand B (FST = 0.04, P < 0.01) was detected.We also detected significantly lower mean pairwise relatedness among individuals from site B compared to all the other locations, and this population had the lowest inbreeding coefficient. Genetic diversity and mean pairwise relatedness were highly variable among plants with multiple individuals; however, plants from sites F and M tend to have collections of individuals with higher mean pairwise relatedness compared to sites B and C. Our results indicate that there is genetic diversity and differentiation among mealy bugs in these locations, and that collections of individuals on the same plant are genetically diverse. As such, the mealy bugs throughout these areas are likely to be genetically diverse and exist in multiple distinct populations.


On the interactions of catalase with subcellular structure.
The interaction of mouse liver catalase with subcellular membranes was studied, and an ionic interaction with a variety of membranes, including those derived from the microsomes, was observed. The interaction with microsomal membranes was found to be abolished by pre-treatment of catalase with neuraminidase, indicating a functional significance for catalase-bound sialic acid. Catalase activity was found to be enhanced when bound to membranes, and evidence for a weak association of catalase with peroxisomal structure in mouse liver was also obtained. It is concluded that mouse liver catalase has a capacity to bind to a variety of subcellular membranes in vivo and that this interaction may be consistent with a general protective role for the enzyme, as well as being compatible with a model of peroxisomal biogenesis which involves the interaction of catalase with microsomal membranes.


The Hancock pericardial xenograft: incidence of early mechanical failures at a medium-term follow-up.
The Hancock pericardial xenograft has been used in our Institution since August 1981 as an alternative to porcine bioprostheses. Up to July 1984, 97 Hancock pericardial xenografts have been implanted in 84 patients; of 76 operative survivors with a mean age of 55.2 +/- 13 years (range 13-75 years), 50 had undergone aortic valve replacement, 16 mitral valve replacement and 10 mitral-aortic valve replacement. Follow-up ranged from 0.5 to 5.2 years with a cumulative duration of 239 patient/years and is 99% complete. Actuarial survival is 92% +/- 4% for patients with aortic valve replacement and 84% +/- 10% for patients with mitral valve replacement at 5 years, and 77% +/- 14% for those with mitral-aortic valve replacement at 4 years. Thromboembolic episodes occurred in 2 patients (1 after aortic and 1 after mitral valve replacement). The actuarial freedom from emboli is 100% for patients with mitral-aortic valve replacement at 4 years, and 96% +/- 3% for patients with aortic and 93% +/- 6% for patients with mitral valve replacement at 5 years. Reoperation was performed in 13 patients (9 aortic, 2 mitral and 2 mitral-aortic valve replacements), because of endocarditis in 3 (2 aortic and 1 mitral valve replacement), paravalvular leak in 1 (aortic valve replacement), and primary tissue failure in 9 (6 aortic, 1 mitral and 2 mitral-aortic valve replacements). Actuarial freedom from primary tissue failure is 72% +/- 9% for aortic and 83% +/- 8% for mitral Hancock pericardial xenografts at 5 years. Eleven xenografts explanted because of primary tissue failure were studied pathologically.(ABSTRACT TRUNCATED AT 250 WORDS)


Protein C levels in infancy and early childhood. Influence of breast feeding.
Protein C antigen levels were measured in the plasma of healthy full term infants by electroimmunoassay. During the first three months of life (on day four, at one month, two months and three months of age) protein C antigen levels were compared in breast-fed and bottle-fed infants. None of the two groups of infants received vitamin K at birth. Only at the age of three months there was a significant difference between the groups. Unexpectedly infants, who were breast-fed, had a higher protein C level at three months of age. Levels were also measured in 15 healthy children between one and three years of age. The antigen levels increase with age to reach adult values at about three years of age.


Deep learning-based dynamic PET parametric Ki image generation from lung static PET.
PET/CT is a first-line tool for the diagnosis of lung cancer. The accuracy of quantification may suffer from various factors throughout the acquisition process. The dynamic PET parametric Ki provides better quantification and improve specificity for cancer detection. However, parametric imaging is difficult to implement clinically due to the long acquisition time (~ 1 h). We propose a dynamic parametric imaging method based on conventional static PET using deep learning. Based on the imaging data of 203 participants, an improved cycle generative adversarial network incorporated with squeeze-and-excitation attention block was introduced to learn the potential mapping relationship between static PET and Ki parametric images. The image quality of the synthesized images was qualitatively and quantitatively evaluated by using several physical and clinical metrics. Statistical analysis of correlation and consistency was also performed on the synthetic images. Compared with those of other networks, the images synthesized by our proposed network exhibited superior performance in both qualitative and quantitative evaluation, statistical analysis, and clinical scoring. Our synthesized Ki images had significant correlation (Pearson correlation coefficient, 0.93), consistency, and excellent quantitative evaluation results with the Ki images obtained in standard dynamic PET practice. Our proposed deep learning method can be used to synthesize highly correlated and consistent dynamic parametric images obtained from static lung PET. • Compared with conventional static PET, dynamic PET parametric Ki imaging has been shown to provide better quantification and improved specificity for cancer detection. • The purpose of this work was to develop a dynamic parametric imaging method based on static PET images using deep learning. • Our proposed network can synthesize highly correlated and consistent dynamic parametric images, providing an additional quantitative diagnostic reference for clinicians.


Maternal mortality in the covid-19 pandemic: findings from a rapid systematic review.
The COVID-19 pandemic is having significant direct and associated effects on many health outcomes, including maternal mortality. As a useful marker of healthcare system functionality, trends in maternal mortality provide a lens to gauge impact and inform mitigation strategies. To report the findings of a rapid systematic review of studies on levels of maternal mortality before and during the COVID-19 pandemic. We systematically searched for studies on the 1st March 2021 in MEDLINE and Embase, with additional studies identified through MedRxiv and searches of key websites. We included studies that reported levels of mortality in pregnant and postpartum women in time-periods pre- and during the COVID-19 pandemic. The maternal mortality ratio was calculated for each study as well as the excess mortality. The search yielded 3411 references, of which five studies were included in the review alongside two studies identified from grey literature searches. Five studies used data from national health information systems or death registries (Mexico, Peru, Uganda, South Africa, and Kenya), and two studies from India were record reviews from health facilities. There were increased levels of maternal mortality documented in all studies; however, there was only statistical evidence for a difference in maternal mortality in the COVID-19 era for four of these. Excess maternal mortality ranged from 8.5% in Kenya to 61.5% in Uganda. Measuring maternal mortality in pandemics presents many challenges, but also essential opportunities to understand and ameliorate adverse impact both for women and their newborns. Our systematic review shows a dearth of studies giving reliable information on levels of maternal mortality, and we call for increased and more systematic reporting of this largely preventable outcome. The findings help to highlight four measurement-related issues which are priorities for continuing research and development.


Chromosomal variation in pocket gophers (Geomys) detected by sequential G-, R-, and C-band analyses.
The chromosomes of six taxa, representing five species of Geomys (G. attwateri, G. breviceps, G. personatus, G. texensis, G. bursarius) were analysed for variation in G-band, R-band, sequential R-/DAPI-AMD, and sequential R-/C-band patterns. Eleven chromosomes had structural rearrangements resulting from deletion/addition events. Fission/fusion rearrangements occurred in two chromosomes, and a pericentric inversion was confirmed in only one chromosome. Eighteen of 34 autosomes had constitutive heterochromatin, with variation in its presence or absence, position, and quantity. The heterochromatic differences were seen both among species and between two subspecies of G. personatus. Chromomycin A3 fluorescent staining identified G-C rich regions in 31 of the autosomes with 29 showing variation in their presence or absence, position, and quantity, and identified a high degree of cryptic variation. The X chromosome was highly variable, with differences attributable to structural rearrangements and variation in chromomycin bright-staining regions.


Stomach perforation-induced general occlusion/occlusion-like syndrome and stable gastric pentadecapeptide BPC 157 therapy effect.
Using rat stomach perforation as a prototypic direct lesion applied in cytoprotection research, we focused on the first demonstration of the severe occlusion/ occlusion-like syndrome induced by stomach perforation. The revealed stomach-induced occlusion/occlusion-like syndrome corresponds to the previously described occlusion/occlusion-like syndromes in rats suffering multicausal pathology and shared severe vascular and multiorgan failure. This general point was particularly reviewed. As in all the described occlusion/occlusion-like syndromes with permanent occlusion of major vessels, peripheral and central, and other similar noxious procedures that severely affect endothelium function, the stable gastric pentadecapeptide BPC 157 was resolving therapy. To reveal the stomach perforation-induced general occlusion/occlusion-like syndrome and BPC 157 therapy effect. The procedure included deeply anesthetized rats, complete calvariectomy, laparotomy at 15 min thereafter, and stomach perforation to rapidly induce vascular and multiorgan failure occlusion/occlusion-like syndrome. At 5 min post-perforation time, rats received therapy [BPC 157 (10 µg or 10 ng/kg) or saline (5 mL/kg, 1 mL/rat) (controls)] into the perforated defect in the stomach). Sacrifice was at 15 min or 60 min post-perforation time. Assessment (gross and microscopy; volume) included: Brain swelling, peripheral vessels (azygos vein, superior mesenteric vein, portal vein, inferior caval vein) and heart, other organs lesions (i.e., stomach, defect closing or widening); superior sagittal sinus, and peripherally the portal vein, inferior caval vein, and abdominal aorta blood pressures and clots; electrocardiograms; and bleeding time from the perforation(s). BPC 157 beneficial effects accord with those noted before in the healing of the perforated defect (raised vessel presentation; less bleeding, defect contraction) and occlusion/occlusion-like syndromes counteraction. BPC 157 therapy (into the perforated defect), induced immediate shrinking and contraction of the whole stomach (unlike considerable enlargement by saline application). Accordingly, BPC 157 therapy induced direct blood delivery via the azygos vein, and attenuated/eliminated the intracranial (superior sagittal sinus), portal and caval hypertension, and aortal hypotension. Thrombosis, peripherally (inferior caval vein, portal vein, abdominal aorta) and centrally (superior sagittal sinus) BPC 157 therapy markedly reduced/annihilated. Severe lesions in the brain (swelling, hemorrhage), heart (congestion and arrhythmias), lung (hemorrhage and congestion), and marked congestion in the liver, kidney, and gastrointestinal tract were markedly reduced. We revealed stomach perforation as a severe occlusion/occlusion-like syndrome, peripherally and centrally, and rapid counteraction by BPC 157 therapy. Thereby, further BPC 157 therapy may be warranted.


Confirmation of ethnopharmacological anti-inflammatory properties of Ocotea odorifera and determination of its main active compounds.
Ocotea odorifera (Vell.) Rohwer has been used in traditional medicine in the south of Brazil for the treatment of inflammatory-related conditions, such as rheumatism. However, there is not any scientific evidence for popular use. To investigate the O. odorifera anti-inflammatory potential and identification of the main active compounds through metabolomic approaches. In order to in vivo evaluate the inhibition of the main inflammatory pathways, the leaf decoction, leaf extract, its fractions and the essential oils from leaves and branches were submitted to the ear oedema and the neutrophils recruitment assays. The samples were chemically investigated by UHPLC-HRMS or GC-MS. The multivariate statistical analysis (PLS-DA) was used to determine the substances correlated with the anti-inflammatory properties. The in vivo studies indicated a promissory anti-inflammatory effect on both oedema and neutrophil recruitment for some samples including the decoction; hydroethanolic, ethyl acetate, and chloroform fractions; and the essential oils. According to the PLS-DA, the S-(+)-reticuline was evidenced as one of the three compounds of the plant most correlated with both anti-inflammatory mechanisms. Thus, S-(+)-reticuline was isolated and the anti-inflammatory activity was confirmed. Moreover, for the first time, the dual inhibition of oedema and neutrophil recruitment was uncovered and reported. Another compound positively correlated with the anti-inflammatory activity is likely to be a new compound since zero hit on the comprehensive mass database were encountered. The compounds found in the essential oils also showed significant anti-inflammatory activity, and thus indeed the plant has different classes of active substances. The decoction of O. odorifera and different fractions from its ethanolic extract demonstrated anti-inflammatory activity through dual inhibition of oedema and neutrophil recruitment. Thus, corroborating the popular medicinal use of the decoction of leaves from O. odorifera as an anti-inflammatory medicine. Besides, reticuline, one of the main active compounds, was isolated and proved to display the dual mechanism of action, indicating the O. odorifera as a promising source of active compounds for the treatment of inflammatory conditions.


Consequences of stress: a multiplicative function of health status.
We hypothesized that an individual's state of health affects its response to stress. To test this, we used the natural history of inherited heart disease in hamsters as a sliding scale of organ vulnerability on which we superimposed a constant set of stressors. When the animal was stressed at an early point in its disease, heart failure did not develop. Later, after cardiac compensatory changes had developed, stress precipitated overt heart failure. Finally, stress administered when the animal was in overt heart failure further amplified the medical consequences of stress, and some animals succumbed.


Advances in the pathology of COPD.
Chronic obstructive pulmonary disease encompasses alterations in the parenchyma, airways and vascular compartments. This review is designed to help surgical pathologists evaluate the lungs of subjects who have clinical manifestations of airflow obstruction so that appropriate clinical-pathological correlations can be performed.


Increased sensitivity to platinum drugs of cancer cells with acquired resistance to trabectedin.
In order to investigate the mechanisms of acquired resistance to trabectedin, trabectedin-resistant human myxoid liposarcoma (402-91/T) and ovarian carcinoma (A2780/T) cell lines were derived and characterised in vitro and in vivo. Resistant cell lines were obtained by repeated exposures to trabectedin. Characterisation was performed by evaluating drug sensitivity, cell cycle perturbations, DNA damage and DNA repair protein expression. In vivo experiments were performed on A2780 and A2780/T xenografts. 402-91/T and A2780/T cells were six-fold resistant to trabectedin compared with parental cells. Resistant cells were found to be hypersensitive to UV light and did not express specific proteins involved in the nucleotide excision repair (NER) pathway: XPF and ERCC1 in 402-91/T and XPG in A2780/T. NER deficiency in trabectedin-resistant cells was associated with the absence of a G2/M arrest induced by trabectedin and with enhanced sensitivity (two-fold) to platinum drugs. In A2780/T, this collateral sensitivity, confirmed in vivo, was associated with an increased formation of DNA interstrand crosslinks. Our finding that resistance to trabectedin is associated with the loss of NER function, with a consequent increased sensitivity to platinum drugs, provides the rational for sequential use of these drugs in patients who have acquired resistance to trabectedin.


How 'preventable' are lower extremity amputations? A qualitative study of patient perceptions of precipitating factors.
Clinicians commonly believe that lower extremity amputations are potentially preventable with coordinated care and motivated patient self-management. We used in-depth interviews with recent amputees to assess how patients viewed their initial amputation risk and causes. We interviewed 22 patients at a rehabilitation hospital 2-6 weeks after an incident amputation. We focused on patients' representations of amputation cause and methods of coping with prior foot and leg symptoms. Patients reported unexpected onset and rapid progression of ulceration, infection, progressive vascular disease, foot trauma and complications of comorbid illness as precipitating events. Fateful delays of care were common. Many had long histories of painful prior treatments. A fatalistic approach to self-management, difficulties with access and communication with providers and poor understanding of medical conditions were common themes. Few patients seemed aware of the role of smoking as an amputation risk factor. Most patients felt out of control and had a poor understanding of the events leading to their initial amputations. Prevention of subsequent amputations will require rehabilitation programs to address low health literacy and psychosocial obstacles to self-management.


Probing lectin and sperm with carbohydrate-modified quantum dots.
We report the encapsulation of quantum dots with biologically important beta-N-acetylglucosamine (GlcNAc) in different ratios, together with studies of their specific/sensitive multivalent interactions with lectins and sperm by fluorimetry, transmission electron microscopy, dynamic light scattering microscopy, confocal imaging techniques, and flow cytometry. These GlcNAc-encapsulated quantum dots (QDGLNs) specifically bind to wheat germ agglutinin, and cause fluorescence quenching and aggregation. Further studies of QDGLNs and the mannose-encapsulated QDs (QDMANs) with sperm revealed site-specific interactions, in which QDGLNs bind to the head of the sperm, while QDMANs spread over the whole sperm body.


Response to total sleep deprivation and clomipramine in endogenous depression.
In 44 endogenously depressed patients, response to total sleep deprivation (TSD) was investigated as a function of several biographical and clinical variables. All patients were subjected to a schedule of sleep-TSD-sleep-TSD. Antidepressant drug treatment (clomipramine) was started on the day before the first TSD. Sex, age, educational status, number of previous hospitalizations and duration of the current depressive episode were not related to the response to either the first or the second TSD. Likewise, no significant differences were found in the responses of unipolar and bipolar patients. In contrast, diurnal variation appeared to be positively correlated with response to TSD. Depressives with psychotic features reacted more favourably than non-psychotic depressives.


A rare case of lymphangioma in the gluteal region: surgical treatment combined with sclerotherapy and laser therapy.
Lymphangioma, a rare benign malformation of lymphatic channels, is among the surgically treatable diseases of the lymphatic vessels. However, damage to surrounding structures together with incomplete resection due to adjacent organ infiltration and a high recurrence rate have encouraged the search for alternative treatments. This study aimed to identify the best therapeutic management for this difficult-to-treat disease. This report describes a case of congenital lymphangioma in the gluteal region in a young woman. First, sclerotherapy of the lymphangioma was performed and then surgical excision of residual lesions. Finally, as a third therapeutic step, the patient also was subjected to a cycle of laser therapy with the aim of further improving the appearance of the gluteal region. Pulsed dye laser was used to remove cutaneous dyschromias, and an erbium:yttrium-aluminum-garnet laser was used to remove surface irregularities and obtain better skin smoothness. The outcome assessments included standardized photography, the physician's global assessment, the patient's satisfaction scores, and magnetic resonance imaging of the gluteal region. All the lesions of lymphangioma were removed. After the last laser treatment, the skin of the entire treated region was eutrophic and uniform in color, and it appeared to be smooth and soft when palpated. The patient was satisfied with the clinical and aesthetic results achieved. The combination of sclerotherapy with surgery can be a good solution for the treatment of lymphangioma. The authors also propose laser therapy as an additional therapeutic approach that may follow surgery or sclerotherapy with the aim of improving the skin trophism and the appearance of the affected region.


The Escherichia coli SeqA protein binds specifically and co-operatively to two sites in hemimethylated and fully methylated oriC.
The Escherichia coli SeqA protein has been found to affect initiation of replication negatively, both in vivo and in vitro. The mechanism of inhibition is, however, not known. SeqA has been suggested to affect the formation and activity of the initiation complex at oriC, either by binding to DNA or by interacting with the DnaA protein. We have investigated the binding of SeqA to oriC by electron microscopy and found that SeqA binds specifically to two sites in oriC, one on each side of the DnaA binding site R1. Specific binding was found for fully and hemimethylated but not unmethylated oriC in good agreement with earlier mobility shift studies. The affinity of SeqA for hemi-methylated oriC was higher than for fully methylated oriC. The binding was in both cases strongly cooperative. We suggest that SeqA binds to two nucleation sites in oriC, and by the aid of protein-protein interaction spreads to adjacent regions in the same oriC as well as recruiting additional oriC molecules and/or complexes into larger aggregates.


Progressive changes in pancreatic vasculature accompanying copper deficiency-induced glandular atrophy.
Pancreatic vasculature was studied in rats treated with a dietary copper-deficient regimen to assess and characterize changes in the exocrine angioarchitecture of the gland. The deficient state is known to induce progressive acinar degeneration, atrophy, and subsequent replacement with noninflammatory lipomatosis. This study was carried out since little information exists regarding changes in the vasculature that accompany acute glandular necrosis. Corrosion casts produced from Mercox injected deficient rats were studied using scanning electron microscopy and compared to injected preparations studied by light microscopy. Results show that with initial atrophy of degenerative acini (6-8 wk), pancreatic lobules decreased in size and the volume of the vascular bed reduced. From wk 8 onward, the accumulation of fat cells expanded the configuration of lobules to more normal dimensions. Although vascular interconnectivity within lobules remained reduced, its basic angioarchitecture remained intact and served to vascularize fat cells in lieu of acini. No acute angiopathic changes indicative of vascular disorganization were found. These observations support the hypothesis that the vasculature of the atrophied pancreas, although modified in regions of the gland most severely targeted by acinar necrosis, remains intact and its basic structural features preserved. Preliminary evidence also supports the observation that preservation of the basic elements of lobular angioarchitecture may form the basis for subsequent regeneration of acinar tissue in the reversed deficient state.


Effect of nanoparticles on color stability and mechanical and biological properties of maxillofacial silicone elastomer: A systematic review.
The aim of this systematic review was to evaluate the effect of addition of various nanoparticles into maxillofacial silicone elastomer on color stability and mechanical and biological properties of the silicone elastomer. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines(PRISMA). The electronic database search in MEDLINE/PubMed was based on population (silicone elastomer), intervention (nanoparticles), comparison (unreinforced silicone elastomer with nanoparticle-reinforced silicone elastomer), outcome (color stability and mechanical, physical, and biological properties), i.e., PICO framework. The key words used are ("maxillofacial silicone" OR "silicone elastomer" OR "facial silicone") AND ("nanoparticles" OR "Nano-oxides") AND ("colour stability" OR "Hardness," "tensile strength" OR "tear strength" OR "antifungal activity"). The database search resulted in 2099 studies, of which 2066 articles were excluded as they were irrelevant, duplicates, and data were not available. The remaining 33 full-text articles were assessed for eligibility, out of which 2 articles were in Chinese language, 3 articles were thesis documents, and 8 were review articles. A total of 12 articles were excluded and the remaining 20 articles were included. One article was yielded by hand search of references of included studies. A total of 21 studies were included in the present systematic review. With the available evidence in the literature, it can be concluded that addition of nanoparticles at various concentrations may improve the physical and mechanical properties and color stability of the prosthesis made from the silicone elastomers.


Accumulation of floating microplastics behind the Three Gorges Dam.
We investigated the occurrence and distribution of microplastics in surface water from the Three Gorges Reservoir. Nine samples were collected via trawl sampling with a 112 μmmesh net. The abundances of microplastics were from 3407.7 × 10(3) to 13,617.5 × 10(3) items per square kilometer in the main stream of the Yangtze River and from 192.5 × 10(3) to 11,889.7 × 10(3) items per square kilometer in the estuarine areas of four tributaries. The abundance of microplastics in the main stream of the Yangtze River generally increased as moving closer to the Three Gorges Dam. The microplastics are made exclusively of polyethylene (PE), polypropylene (PP), and polystyrene (PS). Together with microplastics, high abundance of coal/fly ash was also observed in the surface water samples. Comparing with previously reported data, microplastics in the TGR were approximately one to three orders of magnitudes greater, suggesting reservoirs as potential hot spot for microplastic pollution.


A projection method to extract biological membrane models from 3D material models.
This paper presents a projection method for deriving membrane models from the corresponding three-dimensional material models. As a particular example the anisotropic Holzapfel-Gasser-Ogden model is considered. The projection procedure is based on the kinematical and constitutive assumptions of a general membrane theory, considering the membrane to be a general two-dimensional manifold. By assuming zero transverse stress, the Lagrange multiplier associated with the incompressibility constraint can be eliminated from the formulation. The resulting nonlinear model is discretized and linearized within the finite element method. Several numerical examples are shown, considering quadratic Lagrange and NURBS finite elements. These show that the proposed model is in very good agreement with analytical solutions and with full 3D finite element computations.


Dermoscopic findings of umbilical granuloma.
Dermoscopic findings in umbilical granuloma are vascular polymorphism comprised of linear irregular and arborizing vessels with structureless areas distributed over a milky-red background. The increase of angiogenesis and neovascularization is represented by the linear irregular and arborizing vessels. Structureless areas over an irregularly milky-red background are originated by the proliferation of vascular endothelial cells and fibroblasts, with capillary and granulation tissue formation.


Impact of settings and culture on nurses' knowledge of and attitudes and perceptions towards people with dementia: An integrative literature review.
Well-trained nurses are required to support dementia patients; however, the quality of the provided dementia nursing care can be impacted by nurses' knowledge, attitudes and perceptions towards people with dementia. To obtain an overview of the current nursing practice towards people with dementia around the world. An integrated literature review was conducted based on Whittemore and Knafl's method. A total of 72 articles met the inclusion criteria. Three main themes were identified: (1) nurses' knowledge, attitudes and perceptions towards dementia; (2) nursing experience of caring for people with dementia in acute and community care settings; and (3) dementia nursing care across health regions. Nurses play the role of facilitators in the efficient delivery of quality care for dementia patients. A variety of attitudes and perceptions towards people with dementia were found to be triggered by the severity of dementia, religion, ethnicity and gender. Healthcare organisations and educational settings need to coordinate and function together to improve nurses' knowledge and encourage positive attitudes towards people with dementia.


The relationship between retrieval success and task performance during the recognition of meaningless shapes: an event-related near-infrared spectroscopy study.
Retrieval success of episodic memory has been studied intensively through the investigation of old/new effects. Recognized stimuli used in event-related functional magnetic resonance imaging studies on old/new effects have been words and visual materials which can evoke semantic associations. To elucidate the neural basis of retrieval success uninfluenced by semantic processing, we investigated the correlation between old/new effects and task performance during the recognition of meaningless shapes, by using event-related near-infrared spectroscopy. Forty-two right-handed subjects made recognition judgments about old (studied) or new (unstudied) meaningless shapes. The old/new effects of the shapes were positively correlated with task performance in the bilateral inferior lateral parietal cortex (ILP), but predominantly in the left ILP. This finding indicated that the ILP was directly associated with retrieval success and its lateralization was consistently left-sided irrespective of the type of stimulus.


Cerebellopontine angle lipoma.
Lipomas rarely occur intracranially. Moreover, the cerebellopontine angle is one of the more unusual sites of such hamartomas. Of the 11 reported cases, all but three caused symptoms related to compression of the cranial nerves in the cerebellopontine angle. Only three separate cases have been studied by computed tomography, and in one the fat density was not recognized. This report deals with the clinical presentations, surgical management, and radiologic assessment of these lesions.


Symptoms of prolonged grief, post-traumatic stress, and depression after loss in a Dutch community sample: A latent class analysis.
Mental health problems following loss can manifest as heterogeneous symptomatology that may include symptoms of Prolonged Grief Disorder (PGD), Post-Traumatic Stress Disorder (PTSD), and Major Depressive Disorder (MDD). However, the co-occurrence of symptoms of these three disorders is still only partially explored. The aims of this study were to identify subgroups (i.e., classes) in a Dutch sample of bereaved individuals, based on severity and/or co-occurrence of symptoms and to identify predictors for these subgroups, taking into account all three disorders. Using data from 496 participants who filled in questionnaires assessing PGD, PTSD and MDD, we conducted latent class analyses to identify different symptom classes. Predictors of these classes were identified using one-way ANOVA, Chi Square tests and multinomial regression analysis. We found three different classes: a resilient class, a PGD class and a combined PGD/PTSD class. Violent cause of death, loss of a child, and loss of a partner were associated with membership of the combined PGD/PTSD class. This study increases our understanding of the predictability of symptomology outcome following bereavement. This is a first step towards designing assessment and intervention methods, specifically directed towards subgroups of individuals sharing characteristic symptomatology.


SAIL study of stroke, systemic embolism and bleeding outcomes with warfarin anticoagulation in non-valvular atrial fibrillation (S4-BOW-AF).
In patients with non-valvular atrial fibrillation (NVAF) prescribed warfarin, the association between guideline defined international normalised ratio (INR) control and adverse outcomes in unknown. We aimed to (i) determine stroke and systemic embolism (SSE) and bleeding events in NVAF patients prescribed warfarin; and (ii) estimate the increased risk of these adverse events associated with poor INR control in this population. Individual-level population-scale linked patient data were used to investigate the association between INR control and both SSE and bleeding events using (i) the National Institute for Health and Care Excellence (NICE) criteria of poor INR control [time in therapeutic range (TTR) <65%, two INRs <1.5 or two INRs >5 in a 6-month period or any INR >8]. A total of 35 891 patients were included for SSE and 35 035 for bleeding outcome analyses. Mean CHA2DS2-VASc score was 3.5 (SD = 1.7), and the mean follow up was 4.3 years for both analyses. Mean TTR was 71.9%, with 34% of time spent in poor INR control according to NICE criteria.SSE and bleeding event rates (per 100 patient years) were 1.01 (95%CI 0.95-1.08) and 3.4 (95%CI 3.3-3.5), respectively, during adequate INR control, rising to 1.82 (95%CI 1.70-1.94) and 4.8 (95% CI 4.6-5.0) during poor INR control.Poor INR control was independently associated with increased risk of both SSE [HR = 1.69 (95%CI = 1.54-1.86), P < 0.001] and bleeding [HR = 1.40 (95%CI 1.33-1.48), P < 0.001] in Cox-multivariable models. Guideline-defined poor INR control is associated with significantly higher SSE and bleeding event rates, independent of recognised risk factors for stroke or bleeding.


Influences of Dietary Supplementation with Maca (Lepidium meyenii) on Performance, Parameters of Growth Curve and Carcass Characteristics in Japanese Quail.
Maca plant contains rich nutrients and in addition, it has various bioactive substances (N-benzyl-palmitamide, benzyl isothiocyanate, glucosinolates and phenolics). It is used to improve reproductive properties and has antioxidant effects for both humans and animals. The aim of this study was to determine the effects of adding maca plant powder to the ration at different levels on growth, slaughter carcass, partial egg production and some reproductive characteristics in Japanese quail (Coturnix coturnix japonica). The experimental groups were formed by adding 0% (control), 0.05% and 0.1% maca powder to the diet, and a total of 300 birds were used. Growth (weekly body weights, parameters of Gompertz growth function), feed efficiency and carcass characteristics of quails in the 42-day fattening trial were determined. Reproductive characteristics were measured up to 22 weeks of age. Addition of maca powder to the diet increased the feed consumption (p < 0.05) but did not affect body weights at 35 and 42 days of age, β0 and β1 parameters or point of inflection weight of the Gompertz model, carcass traits, partial egg production or fertility. It may be advisable to add 0.1% maca powder to the diets of breeders. Besides, maca powder reduced embryonic deaths and improved chick quality (both p < 0.05). It is thought that different results for reproductive traits can be obtained if maca powder is used for a longer period in the diets of breeder quail flocks.


Artificial sweat enhances dermal transfer of chlorpyrifos from treated nylon carpet fibers.
The dermal transfer and absorption of 14C-ring-chlorpyrifos from nylon carpet fibers was measured in skin penetration-evaporation cells with excised pig skin. Prior to application, synthetic sweat was applied to skin in half of the cells. Radioactivity was measured in receptor fluid, dermis, epidermis, tape stripping samples, and vapor trap samples during a 24-h period. The sum of radiolabel recovered from the dermis and receptor fluid represented the absorbed dose. There was no significant difference (p > 0.05) in percutaneous absorption between cells that received the synthetic sweat application and "dry" cells (1.3 +/- 0.3% of applied dose). There was significantly more (p < 0.05) radiolabel recovered from tape stripping (5.4 +/- 2.1 vs. 2.8 +/- 0.6%) and in the epidermis (4.5 +/- 0.8 vs. 3.1 +/- 0.3%) from cells that received the synthetic sweat application, which indicated synthetic sweat facilitated transfer of chlorpyrifos from a treated substrate to the skin surface. The measured value for percutaneous absorption of chlorpyrifos agreed with the value predicted from an empirical model previously developed for nitro compound-containing soil.


[Preventive training of parents].
General conditions, the theoretical frame, the contents and purposes of our preventive training of parents are discussed. The attention is drawn to the fact that our preventive training of parents is--at the time being--examined in a pilot study with regard to acceptability and understanding. First results let suppose that our preventive training supports the parents in their educational behavior. An extensive study with two control groups and an accompanying study basing on psycho-pedagogical and social-medical criteria are planned.


Effects of gallopamil, diltiazem and nifedipine on the loss of K+ from ischaemic pig hearts.
K+ release into the extracellular space was investigated during repeated 6-min coronary occlusions before and after the intravenous administration of cardiovascular active doses of gallopamil (0.02; 0.05 mg/kg), diltiazem (1.0; 2.0 mg/kg) or nifedipine (0.01; 0.05 mg/kg) to anaesthetized pigs. [K+]e was measured epicardially using silver valinomycin electrodes calibrated in vivo. During control occlusions [K+]e- rose steeply in all groups, from a pre-ischaemic baseline value of about 3.5 mmol/l reaching a plateau value within the ischaemic period. This response was reproducible in an untreated control group. Gallopamil reduced the ischaemic K+ efflux dose dependently and significantly 10 min after injection; the higher dose also did 60 min after injection. Diltiazem had less effect on K+ efflux 10 min after administration and an effect was no longer detectable after 60 min. Nifedipine did not significantly inhibit the ischaemic K+ loss. Besides these differences in the direct protection of the ischaemic myocardium, the Ca2+ antagonists also had the following effects on the haemodynamic profile. Diltiazem and gallopamil significantly prolonged PQ intervals whereas nifedipine caused a shortening accompanied by a significant increase in heart rate. Blood pressure and LV dP/dtmax were significantly reduced by all compounds, but to a different degree. Diltiazem reduced blood pressure to a greater extent than did nifedipine and gallopamil. LV dP/dtmax was comparably reduced by gallopamil and diltiazem, while nifedipine had less effect. Thus, gallopamil exerted pronounced protective effects on the ischaemic pig heart.


Scaling of dimensions of small intestines in non-ruminant eutherian mammals and its significance for absorptive mechanisms.
The mucosal surface area of small intestines in non-ruminant eutherian mammals increases approximately in proportion to the 0.6 power of body mass, whereas resting metabolic rate (RMR) increases approximately with the 0.74 power of body mass; the mass exponent for field metabolic rates (FMR) may exceed 0.8. These relationships imply that the average rate of absorption of metabolic substrates, expressed per unit area of mucosal surface, is greater in large animals than in small. In the present paper I collate data from the literature relating mucosal surface area, fluid absorption and glucose transport rates to body size. Glucose-stimulated fluid absorption per unit area of mucosal surface increases with body size, whereas transcellular, carrier-mediated glucose transport per unit area decreases with body size. In perfused jejunal segments of normal human subjects the rates of fluid absorption per unit area of mucosa are five to ten times greater than in laboratory rats. The absorbed fluid contains glucose in amounts that may greatly exceed the maximum transport capacity of the apical glucose transporter. It follows that the paracellular component of glucose absorption increases with body size. Scaling of intestinal dimensions and transport therefore provides new information about the relative contributions of transcellular and paracellular pathways to absorption of nutrients.


AF cell derived exosomes regulate endothelial cell migration and inflammation: Implications for vascularization in intervertebral disc degeneration.
The intervertebral disc is the largest avascular organ of the body. Vascularization of the disc has been typically regarded as a pathological feature of intervertebral disc degeneration (IDD). However, the underlying mechanism of vascularization in IDD is still unclear. The current study aimed to investigate the role of AF cell derived exosome (AF-exo) in the interaction with human umbilical vein endothelial cells (HUVECs) and its potential role in the regulation of vascularization in IDD. Human AF tissues were obtained from patients with IDD and idiopathic scoliosis. The AF-exo were isolated and identified by transmission electron microscopy (TEM), nanoparticle trafficking analysis (NTA) and Western blotting. Then, the AF-exo were used for HUVECs cultures. The migration of HUVECs was observed in 2D and 3D cultures. The inflammatory phenotype of HUVECs was examined by Real-time PCR and enzyme-linked immunosorbent assay (ELISA). Additionally, apoptosis of HUVECs were analyzed by flow cytometry. Here, we for the first time found that AF cells could secrete AF-exo and that the AF-exo could be phagocytosed by HUVECs. Additionally, we found that degenerated AF-exo exerted pro-vascularization effect on HUVECs by promoting cell migration (in 2D and 3D cultures) and inflammatory factor expression including IL-6, TNF-α, MMP-3, MMP-13 and VEGF, whereas the application of non-degenerated AF-exo demonstrated inverse effects. These results showed that AF-exo is an essential regulator mediating intercellular communication between AF cells and HUVECs, suggesting its important role in vascularization in the intervertebral disc.


Outcomes of off-pump versus on-pump coronary artery bypass grafting: Impact of preoperative risk.
It is unknown whether purported benefits of off-pump coronary artery bypass grafting are patient-specific within the Society of Thoracic Surgeons National Cardiac Database or dependent on center volume or operating surgeon. The Society of Thoracic Surgeons National Cardiac Database was queried for all patients undergoing nonemergency, isolated coronary artery bypass between January 1, 2005, and December 31, 2010, who had Predicted Risk of Mortality scores and participant/surgeon identifiers. Of these 876,081 patients ("all sites"), 210,469 underwent surgery at participant sites that had performed more than 300 off-pump and 300 on-pump coronary artery bypass operations during the 6-year study period ("high-volume sites"). Operative mortality, stroke, acute renal failure, mortality or morbidity, and prolonged postoperative length of stay were analyzed with conditional logistic models for all sites and for high-volume sites, stratified by participant center and surgeon, and adjusted for 30 variables that comprise the Society of Thoracic Surgeons coronary artery bypass grafting risk models. Off-pump coronary artery bypass was associated with a significant reduction in risk of death, stroke, acute renal failure, mortality or morbidity, and postoperative length of stay compared with on-pump coronary artery bypass after adjustment for 30 patient risk factors in the overall sample. This held true within high-volume centers. In the overall sample, there was a significant (P < .05) interaction between off-pump coronary artery bypass and Predicted Risk of Mortality for death, stroke, acute renal failure, and mortality or morbidity. Off-pump coronary artery bypass was associated with reduced adverse events compared with on-pump coronary artery bypass after adjustment for 30 patient risk factors and center and surgeon identity. Patients with higher Predicted Risk of Mortality scores had the largest apparent benefit.


Priming of human neutrophils by peroxynitrite: potential role in enhancement of the local inflammatory response.
Peroxynitrite is a potent oxidant generated from the reaction of nitric oxide (NO) and superoxide anion (O2-), both of which can be produced in inflammatory tissues. In these studies, we analyzed what direct effect peroxynitrite had on neutrophil (PMN) function. We found that peroxynitrite was an effective priming agent for PMNs, as demonstrated by enhanced O2- production on subsequent activation with low doses of PMA or N-formyl-methionine-leucine-phenylalanine (fMLF), changes in the expression of PMN surface markers (L-selectin, Mac-1, flavocytochrome b, and fMLF receptor), and increased intracellular calcium levels. Analysis of the mechanism of PMN priming by peroxynitrite demonstrated that peroxynitrite resulted in minimal oxidation of protein sulfhydryl groups and subsequent protein cross-linking. In contrast, treatment of PMNs with peroxynitrite resulted in significant nitration of tyrosine residues on neutrophil proteins. In addition, inhibition of tyrosine nitration with a pyrrolopyrimidine antioxidant blocked the majority of peroxynitrite-induced priming effects, further suggesting that PMN priming was mediated primarily by nitration of tyrosine residues on PMN proteins. The ability of peroxynitrite to serve as an effective priming agent for PMNs at sites of inflammation may play a key role in modulating the host-defense process.


Cystic nephroma: an ultrastructural and biochemical study.
A case of a multilocular renal cyst (cystic nephroma) in an 18-month-girl is presented. The light and electron microscopy studies failed to demonstrate nephroblastomatous elements. Analysis of cystic fluid constituents showed levels resembling serum. Measurable levels of prostaglandins E and F also were found. The possible relationship of a cystic nephroma to a nephroblastoma is discussed.


Additive effect of frailty with distinct multimorbidity patterns on mortality amongst middle-aged and older adults in Taiwan: A 16-year population-based study.
This study aimed to explore the association between multimorbidity patterns with/without frailty and future mortality among Taiwanese middle-aged and older adults through a population-based cohort study design. Data were collected from the Taiwan Longitudinal Study on Aging. The data were obtained from Wave 3, with the multimorbidity patterns in the years of 1996 being analyzed through latent class analysis. Frailty was defined using the modified Fried criteria. The association between each disease group with/without frailty and mortality was examined using logistic regression, with the reference group as the Relatively healthy group without frailty. Survival analysis was performed using Cox regression, and the follow-up period of mortality was from 1 January 1996 to 31 December 2012. A total of 4748 middle-aged and older adults with an average age of 66.3 years (SD: 9.07 years) were included. Four disease patterns were identified in 1996, namely the Cardiometabolic (21.0%), Arthritis-cataract (11.9%), Relatively healthy (61.6%), and Multimorbidity (5.5%) groups. After adjusting for all covariates, the Relatively healthy group with frailty showed the highest risk for mortality (odds ratio: 3.66, 95% confidence interval [95% CI]: 2.24-5.95), followed by the Cardiometabolic group with frailty (odds ratio: 3.58, 95% CI: 1.96-6.54), Multimorbidity group with frailty (odds ratio: 2.28, 95% CI: 1.17-4.44), Multimorbidity group without frailty (odds ratio: 1.44, 95% CI: 1.01-2.04), and the Cardiometabolic group without frailty (odds ratio: 1.24, 95% CI: 1.04-1.49). Frailty plays an important role in mortality among middle-aged and older adults with distinct multimorbidity patterns. Middle-aged and older adults with a relatively healthy multimorbidity pattern or a cardiometabolic multimorbidity pattern with frailty encountered dismal outcomes. Geriatr Gerontol Int 2023; 23: 684-691.


Clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.
Clinical impact of imatinib was evaluated in 20 patients (median age, 37 years; range, 15-67 years) with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), who were administered with induction chemotherapy of daunorubicin, vincristine, prednisolone, and L-asparaginase, along with imatinib 600 mg/day during remission induction and 400 mg/day during consolidation courses. One patient died on day 14 from septic shock, while the remaining 19 achieved complete remission (CR). In total, 15 patients underwent allogeneic hematopoietic cell transplantation (HCT) during first CR. After median follow-up period of 799 days, six patients experienced recurrence; two with early recurrence within 100 days, one with leptomeningeal recurrence at 11 month, and three with post-HCT recurrence. Eight patients died. Median CR duration (821 days) and median patient survival (894 days) in the study were significantly longer by 2.9- and 2.3-fold, respectively, when compared to those of 18 historical patients treated with same regimen of combination chemotherapy without imatinib. Toxicities of the combined treatment were manageable and included grade 4 myelosuppression (n = 20) and reversible > or = grade 3 hyperbilirubinemia (n = 4). Beneficial clinical effects were observed when imatinib was added to combination chemotherapy in patients with newly diagnosed Ph+ ALL. Further studies with larger number of patients are necessary.


Mesophilic anaerobic co-digestion of poultry dropping and Carica papaya peels: Modelling and process parameter optimization study.
The study evaluated anaerobic co-digestion of poultry dropping and pawpaw peels and the optimization of important process parameters. The physic-chemical analyses of the substrates were done using standard methods after application of mechanical, thermal and chemical pre-treatments methods. Gas chromatography analysis revealed the gas composition to be within the range of 66-68% methane and 18-23% carbon dioxide. The study equally revealed that combination of the different pre-treatment methods enhanced enormous biogas yield from the digestion. Optimization of the generated biogas data were carried out using the Response Surface Methodology and the Artificial Neural Networks. The coefficient of determination (R(2)) for RSM (0.9181) was lower compare to that of ANN (0.9828). This shows that ANN model gives higher accuracy than RSM model for the current. Further usage of Carica papaya peels for biogas generation is advocated.


pH dependence of proton translocation by Escherichia coli.
Proton translocation in spheroplasts from Escherichia coli has been studied in two mutants, one of which expresses cytochrome o and the other cytochrome d as the terminal oxidase. Using the O2 pulse method, the H+/e- ratio of proton translocation associated with cytochrome o was confirmed to be near 2 at neutral pH, but was found to decrease considerably when the medium pH was raised above 8. At high pH there was an increase in H+/OH- permeability of the cell membrane, but this was not sufficient to explain the decline in proton ejection. The pH effect was confined to cytochrome o-linked activity. It was not present when cytochrome d generated the electrochemical proton gradient. This makes it improbable that the Na+/H+ antiporter is responsible. The most likely explanation for our finding is that there is a "slip" in the proton-pumping mechanism of cytochrome o at high pH.


Monitoring long-term spatial and temporal trends of the infaunal community characteristics along the shallow waters of the Mediterranean coast of Israel.
Sandy sediment and its infauna were annually sampled along the shallow waters of the Israeli coast during the 2005-2016 period, as a part of the Israeli National Environmental Program framework, aiming to detect anthropogenic interference in that province by monitoring changes in the species composition, abundance, and diversity of the infaunal communities and in accompanied abiotic parameters: the levels of total organic carbon and a series of heavy metals and the site-specific grain size distribution. The > 250-μm fraction of the fauna was segregated from the sampled sediment and was identified to species or higher taxonomic level. Three spatial biotopes were determined based on their unique faunal composition, Haifa Bay, Haifa harbor, and the southern coast. Species homogeneity among samples of each biotope was evaluated. Temporal and spatial changes of the species composition, abundance, and diversity were calculated for each biotope, mostly revealing random annual fluctuations. Only two minor temporal trends were observed: two spatially identical and temporally different faunal communities in the southern coast biotope, distinguishing the 2005-2007 and 2008-2016 periods, and a slight increase in the number of species across time in the two Haifa Bay provinces. Total organic carbon was highly correlated to the faunal composition with the highest organic carbon levels in the Haifa harbor biotope. The biotopes' mutually occurring abundant species were sufficient to determine biotope borders and the contribution of intermittently sampled rare species, including the zoogeographically Indo-Pacific originated ones was feeble, important only to identify species migration and faunistics. Practically, three sampling sites along the Israeli shallow soft substrate, corresponding to the defined spatial biotopes, are sufficient to monitor the effect of environmental changes. Seasonal sampling twice a year is recommended as well as more accurate species identification using molecular taxonomy.


Lack of Knowledge, the main Stumbling Block of Fertility Preservation Promotion in China.
The aim of this study is to evaluate fertility preservation (FP) popularization in China among female cancer patients in terms of awareness of fertility, knowledge about FP, and attitudes toward FP. A questionnaire-based survey was conducted among female cancer patients in Tongji Hospital in China from March 2019 to July 2019. The 29 fertility-related issues, which were presented in either five-point Likert scales or "yes or no", in this questionnaire consisted of demographic characteristic and disease-related situation, awareness of fertility, knowledge about FP, and attitudes toward FP. Participants were required to finish the questionnaire, and data were gathered and analyzed by SPSS. Forty-five valid questionnaires without missing data remained in the final analysis. The survey discovered that a regional imbalanced limitation in knowledge of infertility risk and FP in young cancer patients acted as a major obstacle in FP promotion nationwide and FP decision-making in patients. Compared with rural patients, patients from urban areas were more eager to give birth and more likely to have a better understanding of FP with a more positive attitude. Moreover, most of the participants (62.2%) had a low level of understanding of FP, although they remained positive toward it. "Cancer treatment as the priority", "Cancer relapse caused by FP", and "Health of the next generation" were the top three factors affecting decisions on FP. The findings revealed a general FP actuality in China and specifically offered some intervention targets in the near future to improve FP service and networks, benefiting more female patients of childbearing age who are at risk of infertility.


Illuminating the allosteric modulation of the calcium-sensing receptor.
Many membrane receptors are regulated by nutrients. However, how these nutrients control a single receptor remains unknown, even in the case of the well-studied calcium-sensing receptor CaSR, which is regulated by multiple factors, including ions and amino acids. Here, we developed an innovative cell-free Förster resonance energy transfer (FRET)-based conformational CaSR biosensor to clarify the main conformational changes associated with activation. By allowing a perfect control of ambient nutrients, this assay revealed that Ca2+ alone fully stabilizes the active conformation, while amino acids behave as pure positive allosteric modulators. Based on the identification of Ca2+ activation sites, we propose a molecular basis for how these different ligands cooperate to control CaSR activation. Our results provide important information on CaSR function and improve our understanding of the effects of genetic mutations responsible for human diseases. They also provide insights into how a receptor can integrate signals from various nutrients to better adapt to the cell response.


Role of Otoacoustic Emission Test in Neonatal Screening at Tertiary Center.
To study the role of Otoacoustic emission test in neonatal screening at tertiary center. The study was conducted in the ENT department of LN medical college and JK hospital Bhopal (M.P) as a territory center between 2015 and 2017 were 1250 newborns were screened with Otoacoustic emission test with portable Interacoustics OAE DK-5610 assens an routine screening investigation. In our study a multistep screening with OAE was done, 1250 newborns (659 boys and 591 girls) were assessed. In our study we have found that OAE has 66.7% sensitivity and 98.8% specificity in diagnosis of neonatal hearing impairment. Its positive and negative predictive value was 33.3% and 99.7% respectively. It is essential to examine the generalized development of newborns by identifying hearing loss at birth and providing a screening test for assessment of them. 1250 newborns were assessed we compared the results of OAE (screening test) with the results of ABR (diagnostic test) and found sensitivity of OAE to be 66.7% and its specificity 98.8%. We conclude from these results that OAE is a good screening test for hearing loss of neonates, but the results must be confirmed with BERA test.


Prediction of gene expression levels and the role of cis-acting elements in age-related cataract by applying a promoter-based modeling approach.
Cataract is a dynamical process of lens opacity formation involving many inter- and intracellular regulations, as well as metabolic genes and transcription factors. Using a series of microarray-derived mRNA profiles for human cataractogenesis (Hawse et al. Mol. Vision 2003, 9, 515-537), we develop a promoter-based system-theoretic modeling to demonstrate model-driven prediction of gene expression levels and to identify the role of critical cis-acting elements. In this study, 14 key mRNA expression data from the structural and pathological molecules of age-related cataract samples are used. The first seven genes consist of structural molecules, and the second half of genes are composed of heat shock proteins, filensin, and glutathione peroxidase 3. The presented result demonstrates that mRNA expression levels of structural proteins such as crystallins can be successfully predicted from 5' flanking regulatory DNA sequences. In addition, predicted gene expression levels of heat shock protein, beta-tubulin, and alphaA-crystallin accurately estimate the stimulatory or inhibitory role of distributed cis-acting elements, i.e., c-Myc, GATA-1, GR, NE-E, and Pit-1. Although it is difficult to predict the overall gene expression levels in cataract samples, the present study shows the potential use of promoter-based modeling and prediction of the gene expression levels for age-related cataract.


[Identification and differentiation of nonfermentative gram-negative bacteria in the clinical laboratory (author's transl)].
Identification of nonfermentative gram negative rods encountered in medical bacteriology exhibit some difficulties in the clinical laboratory. However, we believe that, if identification procedures are applied systematicaly and step by step more than 90% of nonfermentative gram negative bacteria can be identified within 72 hours.


Bone mineral density and walking ability of elderly patients with hip fracture: a strategy for prevention of hip fracture.
The main risk factors for proximal femoral fracture include the hazard of falling and osteoporosis. The change in walking ability of patients before injury was evaluated over the last 10 years in a rapidly advancing aging society in Tokyo, Japan. The bone quality of patients was clarified in order to develop a strategy for prevention of hip fractures. The subjects were 157 women with proximal femoral fractures treated between 1989 and 1993 (group A) and 216 women treated between 1999 and 2003 (group B). Bone mineral density (BMD) of the radius of the patients showed slightly lower values than those of the elderly general population, but no statistically significant difference was observed in each age group except for the 75-79-year-old age group (p<0.05). Many patients had problems in walking, and 27% of patients in group A and 44% in group B could not walk outdoors or go shopping alone before the injury, and their bone mineral density was reduced. For the prevention of hip fractures, it is important to improve the physical function to avoid falls, which directly cause hip fracture. Patients who have difficulty performing effective physical exercise because of reduced walking ability require medication for osteoporosis.


Renal excretory responses of taurine-depleted rats to hypotonic and hypertonic saline infusion.
Male Wistar-Kyoto rats were given either tap water (control) or 3% beta-alanine (taurine-depleted) for three weeks. To prepare for the kidney function studies, the animals were then implanted with femoral vessels and bladder catheters. Two days after surgery, each rat was given an intravenous infusion of saline at the rate of 50 microliter/min and urine samples were collected at specific time intervals. An isotonic saline solution (0.9% NaCl) was infused for determination of baseline parameters and was followed by the infusion of a hypotonic saline solution (0.45% NaCl). Two days later, the infusion protocol was repeated in the same animals; however, a hypertonic saline solution (1.8% NaCl) was substituted for the hypotonic saline solution. Renal excretion of fluid and sodium increased in the control, but not taurine-depleted, rats during the hypotonic saline infusion. Interestingly, diuretic and natriuretic responses were similar between the groups during hypertonic saline infusion. The results suggest that taurine-depletion in rats affects renal excretory responses to a hypotonic, but not a hypertonic, saline solution.


An enzymatic method for determination of azide and cyanide in aqueous phase.
A halohydrin dehalogenase (HHDH-PL) from Parvibaculum lavamentivorans DS-1 was characterized and applied to determine azide and cyanide in the water. In this methodology, HHDH-PL catalysed azide and cyanide to react with butylene oxide and form corresponding β-substituted alcohols 1-azidobutan-2-ol (ABO) and 3-hydroxypentanenitrile (HPN) that could be quantitatively detected by gas chromatograph. The detection calibration curves for azide (R(2)=0.997) and cyanide (R(2)=0.995) were linear and the lower limits of detection for azide and cyanide were 0.1 and 0.3mM, respectively. Several other nucleophiles were identified having no effect on the analysis of azide and cyanide, excepting nitrite which influenced the detection of cyanide. This was the first report of a biological method to determine the inorganic azide and cyanide by converting them to the measurable organics.


Urinary Tumor DNA MRD Analysis to Identify Responders to Neoadjuvant Immunotherapy in Muscle-invasive Bladder Cancer.
Bladder preservation is a viable option for some patients with muscle-invasive bladder cancer (MIBC), but an effective noninvasive biomarker test to accurately identify promising candidates is lacking. Here we present the clinical application of a novel tissue-agnostic, urine-based minimal residual disease (MRD) assay in the neoadjuvant setting for personalized disease surveillance and actionable target identification to facilitate bladder-sparing treatment approaches. The urinary tumor DNA (utDNA) analysis was evaluated in an investigator-initiated phase I trial RJBLC-I2N003 in which 20 patients diagnosed with resectable MIBC were treated presurgically with the PD-1 inhibitor toripalimab followed by radical cystectomy (RC). We showed that neoadjuvant toripalimab therapy was feasible, safe, and induced a 40% rate (8/20) of pathologic complete response. Longitudinal utDNA profiling outperformed radiographic assessment and conventional biomarkers to predict the pathologic outcome of immune checkpoint blockade. In addition to detecting 3 exceptional responders with molecular MRD-negative status, we identified 7 other individuals characterized for utDNA response and 4 harboring FGFR3 mutants, all of whom (60%, 12/20) could have postponed or avoided RC. These findings demonstrate the safety and efficacy of neoadjuvant toripalimab, and suggest the immense potential of noninvasive utDNA MRD testing to guide tailored decision-making with regard to bladder preservation and change the current treatment paradigm for patients with MIBC.


A novel recombinant 6Aβ15-THc-C chimeric vaccine (rCV02) mitigates Alzheimer's disease-like pathology, cognitive decline and synaptic loss in aged 3 × Tg-AD mice.
Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-β (Aβ) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6Aβ15-THc-C immunogen was formulated with alum adjuvant as a novel Aβ B-cell epitope candidate vaccine (rCV02) for AD. We examined its efficacy in preventing the cognitive deficit and synaptic impairment in 3 × Tg-AD mice. Using a toxin-derived carrier protein, the rCV02 vaccine elicited robust Aβ-specific antibodies that markedly reduced AD-like pathology and improved behavioral performance in 3 × Tg-AD mice. Along with the behavioral improvement in aged 3 × Tg-AD mice, rCV02 significantly decreased calpain activation concurrent with reduced soluble Aβ or oligomeric forms of Aβ, probably by preventing dynamin 1 and PSD-95 degradation. Our data support the hypothesis that reducing Aβ levels in rCV02-immunized AD mice increases the levels of presynaptic dynamin 1 and postsynaptic PSD-95 allowing functional recovery of cognition. In conclusion, this novel and highly immunogenic rCV02 shows promise as a new candidate prophylactic vaccine for AD and may be useful for generating rapid and strong Aβ-specific antibodies in AD patients with pre-existing memory Th cells generated after immunization with conventional tetanus toxoid vaccine.


Determination of daily variations of brain 5-hydroxytryptamine and dopamine turnovers and of the clearance of their acidic metabolites in conscious rats by repeated sampling of cerebrospinal fluid.
Central 5-hydroxytryptamine (5-HT) and dopamine (DA) turnovers were estimated simultaneously in conscious freely moving rats kept on a 12-h dark/12-h light cycle by sampling cisternal CSF of each animal before and after giving probenecid and determining the accumulation of the acidic metabolites of the two amines. The turnovers of both transmitters and the clearances of their acid metabolites from the brain were shown to be significantly greater during the dark (red light) period than during the white light period.


Cardioembolic Stroke Due to Cardiac Sarcoidosis Diagnosed by Pathological Evaluation of the Retrieved Thrombus.
A 70-year-old woman undergoing glucocorticoid therapy for cardiac sarcoidosis was brought to our hospital with the sudden onset of right hemiplegia and aphasia. Brain magnetic resonance imaging showed a high diffusion-weighted imaging signal in the left frontotemporal lobe and disruption of blood flow in the M1 segment of the left middle cerebral artery. Hence, she underwent thrombolysis and mechanical thrombectomy, resulting in marked improvement in her neurological symptoms. A pathologic evaluation of the thrombus suggested its cardiogenicity, and the absence of any obvious abnormality other than a left ventricular aneurysm indicated stroke due to a cardioembolic etiology secondary to cardiac sarcoidosis.


Loss of Drs2p does not abolish transfer of fluorescence-labeled phospholipids across the plasma membrane of Saccharomyces cerevisiae.
The yeast DRS2 gene, which is required for growth at 23 degreesC or below, encodes a member of a P-type ATPase subgroup reported to transport aminophospholipids between the leaflets of the plasma membrane. Here, we evaluated the potential role of Drs2p in phospholipid transport. When examined by fluorescence microscopy, a drs2 null mutant showed no defect in the uptake or distribution of fluorescent-labeled 1-palmitoyl-2[6-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl (NBD))aminocaproyl]phosphatidylserine) or 1-myristoyl-2[6-NBD-aminocaproyl]phosphatidylethanolamine. Quantification of the amount of cell-associated NBD fluorescence using flow cytometry indicated a significant decrease in the absence of Drs2p, but this decrease was not restricted to the aminophospholipids (phosphatidylserine and phosphatidylethanolamine) and was dependent on culture conditions. Furthermore, the absence of Drs2p had no effect on the amount of endogenous PE exposed to the outer leaflet of the plasma membrane as detected by labeling with trinitrobenzene sulfonic acid. The steady state pool of Drs2p, which was shown to reside predominantly in the plasma membrane, increased upon shift to low temperature or exposure to various divalent cations (Mn2+, Co2+, Ni2+, and Zn2+ but not Ca2+ or Mg2+), conditions that also inhibited the growth of a drs2 null mutant. The data presented here call into question the identification of Drs2p as the exclusive or major aminophospholipid translocase in yeast plasma membranes (Tang, X., Halleck, M. S., Schlegel, R. A., and Williamson, P. (1996) Science 272, 1495-1497).


Acute appendicitis in a patient with situs viscerum inversus totalis: Role of laparoscopic approach. A case report and brief literature review.
Abdominal pain due to acute appendicitis in one of the most causes of access to Emergency Room requiring surgical consult and treatment. The occurrence of anatomical anomalies should be considered especially when clinical and imaging features are misleading. In these cases laparoscopic surgery can be a safe tool in order to confirm uncertain diagnosis. We report a case of acute appendicitis in a 23-year-old Caucasian men with situs viscerum inversus detected on radiological investigation. Laparoscopic approach was used to confirm the diagnosis and to perform appendectomy. Trocars placement was tailored for this peculiar case. One third of patient with acute appendicitis complains abdominal pain in an unexpected location due to various anatomical position of appendix. Left-sided acute appendicitis is a cause of misdiagnosis and it can occur in association with anatomical anomalies such as situs viscerum inversus and midgut malrotation. Laparoscopic surgery may represent a valuable approach in terms of differential diagnosis and treatment in these patients. Left-sided acute appendicitis should always be considered in young male patients with left lower quadrant pain. Laparoscopic approach is useful and safe procedure both for diagnosis and treatment of these unclear clinical pictures.


Evidence of a greater activity of LH/HCH binding inhibitor present in aqueous extracts from old compared to young porcine corpus luteum.
As porcine corpus luteum tissue ages there is an increase in amount of LH/hCG vinding inhibitor. This inhibitor is absent in non-luteal ovarian tissue, heart and lung.


Certification of visinin-like protein-1 (VILIP-1) certified reference material by amino acid-based and sulfur-based liquid chromatography isotope dilution mass spectrometry.
As an emerging neurodegenerative disease, Alzheimer's disease (AD) has become a leading cause of dementia in older adults. Visinin-like protein-1 (VILIP-1) is an increasingly used biomarker for AD besides the widely accepted Aβ1-40, Aβ1-42, and tau. However, significant variations exist in the commercial immuno-based assays for VILIP-1 quantification, underlining the necessity to establish a traceability chain. Certified reference materials (CRMs) located at the top of the traceability chain are traceability sources for relevant matrix standard materials. In this work, VILIP-1 solution CRM with a certified value and uncertainty of 39.82±1.52 μg·g-1 was developed and certified using amino acid-based isotope dilution mass spectrometry (AA-ID-MS) and sulfur-based isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). Certified values from both strategies showed great consistency, with traceability to SI units. Moreover, the candidate VILIP-1 CRM shows excellent homogeneity and can be stable for at least 7 days at -20°C and 12 months at -70°C. The VILIP-1 CRM developed can be used in value assignment to secondary calibrators and clinical matrix CRMs, showing prospects in early diagnosis and disease monitoring for AD.


The sigmaS subunit of RNA polymerase as a signal integrator and network master regulator in the general stress response in Escherichia coli.
The sigmaS (RpoS) subunit of RNA polymerase in Escherichia coli is a key master regulator which allows this bacterial model organism and important pathogen to adapt to and survive environmentally rough times. While hardly present in rapidly growing cells, sigmaS strongly accumulates in response to many different stress conditions, partly replaces the vegetative sigma subunit in RNA polymerase and thereby reprograms this enzyme to transcribe sigmaS-dependent genes (up to 10% of the E. coli genes). In this review, we summarize the extremely complex regulation of sigmaS itself and multiple signal input at the level of this master regulator, we describe the way in which sigmaS specifically recognizes "stress" promoters despite their similarity to vegetative promoters, and, while being far from comprehensive, we give a short overview of the far-reaching physiological impact of sigmaS. With sigmaS being a central and multiple signal integrator and master regulator of hundreds of genes organized in regulatory cascades and sub-networks or regulatory modules, this system also represents a key model system for analyzing complex cellular information processing and a starting point for understanding the complete regulatory network of an entire cell.


Incidence of venous thromboembolism in nursing home residents.
Venous thromboembolism (VTE) is common in the elderly, but its epidemiology in nursing home residents remains unclear. This study estimated rates of VTE recorded on nursing home admission and incidence during residence. Retrospective analysis of AnalytiCare long term care (LTC) database for the period January 2007 to June 2009. 181 nursing homes in 19 US states. Eligible residents had 1 or more admission Minimum Data Set (MDS) 2.0 assessment(s) over the study period. All VTE cases were extracted if MDS indicated deep vein thrombosis or pulmonary embolism. The number of admissions and days at risk were estimated from a random sample (n = 1350) of all residents. The earliest admission was identified as the admission index date. VTE cases were classified as either "On Admission" (VTE coded on admission index date) or "During Residence" (coded afterward). Residents were followed from admission index date until censoring. A total of 2144 VTE admission cases (3.7% of all admissions) were identified. A further 757 cases of VTE occurring during residence were identified, yielding an incidence of 3.68 cases of VTE per 100 person-years of postadmission residence. VTE admission rates were highest for residents younger than 50 years (4.8%, confidence interval [CI]: 3.9%-5.9%) and 50 to 64 years (5.1%, CI: 4.6%-5.7%) but similar for those aged 65 to 74 (3.6%, CI: 3.3%-4.0%), 75 to 84 (3.6%, CI: 3.3%-3.9%), and 85 years or older (3.1%, CI: 2.9%-3.4%). The incidence of VTE during residence was similar among these age strata. Approximately 1 in 25 nursing home admissions had a VTE diagnosis. VTE incidence during residence was higher than reported in earlier nursing home studies. These incidence rates merit further investigation because diagnostic improvements may be driving greater recognition of VTE in LTC.


[The anaesthetist-patient relationship (author's transl)].
The busy atmosphere and routine of a hospital is apt to induce apprehension in a patient about to have a surgical operation. To calm and reassure him and relieve his anxiety is an important part of the anaesthetist's work.


Remotely Successful: Telehealth Interventions in K-12 Schools During a Global Pandemic.
The K-12 school setting is often considered an ideal environment to provide social emotional programming for children and youths. However, the COVID-19 pandemic caused most K-12 schools to close their physical doors and shift to telehealth approaches to fulfill students' academic and non-academic needs. For the first time, school social workers (SSWs), often responsible for the social emotional well-being of students, were required to provide social emotional services virtually. Subsequently, this research study explored SSWs' experiences implementing social emotional telehealth services in K-12 public schools during the spring semester of 2020. Twenty SSWs from nine school districts across three states participated in key informant interviews related to their experiences navigating their professional role during distance learning. Data were analyzed using a constant comparative approach. The findings highlight the barriers SSWs encountered when providing social emotional telehealth interventions, including poor attendance resulting in ineffective group interventions, technology-specific barriers, and concerns for students' privacy. Opportunities and potential solutions to strengthen telehealth in schools are discussed.


Modulation of Caenorhabditis elegans transcription factor activity by HIM-8 and the related Zinc-Finger ZIM proteins.
The previously reported negative regulatory activity of HIM-8 on the Sox protein EGL-13 is shared by the HIM-8-related ZIM proteins. Furthermore, mutation of HIM-8 can modulate the effects of substitution mutations in the DNA-binding domains of at least four other transcription factors, suggesting broad regulatory activity by HIM-8.


A botanical from the antiproliferative Cameroonian spice, Imperata cylindrica is safe at lower doses, as demonstrated by oral acute and sub-chronic toxicity screenings.
The cytotoxicity of the root's methanol extract of Imperata cylindrica (ICR). was previously reported in a panel of human cancer cell lines, including multi-drug resistant phenotypes. The aim of this study was to assess the acute and sub-chronic oral toxicity of methanol root extract of Imperata cylindrica. The acute toxicity was carried out according to the experimental protocol of OECD. The plant extract was administered orally to female rats at a single dose of 5000 mg/kg for 14 days and the animals were observed for any behavioral changes or mortality. For sub-chronic toxicity study, ICR was orally administered daily to male and female rats at different doses (250, 500 and 1000 mg/kg per b.w.) for 30 days. During these treatment days the animals were observed for any appearance of toxicity symptoms; following the treatment period, animals were sacrificed for hematological, biochemical and histopathology analysis. From the results of the acute oral toxicity assay, ICR was found to be non-toxic at the dose of 5000 mg/kg b.w. During the period of sub-chronic toxicity test, observation of signs, behavior and health status of the animals showed no abnormality in the groups of animals treated with ICR as compared to the controls. Significant variation of the relative body weights of heart and kidney were observed at dose a 1000 mg/kg b.w. Significant decrease of aspartate aminotransferase, creatinine level, low density lipoprotein concentration, triglyceride and total cholesterol were observed. In males, we noticed a significant decrease of the level of granulocytes with an increase of lymphocytes and mean corpuscular hemoglobin concentration levels. Histological examinations performed on kidney and liver showed a normal kidney architecture and liver also presented a normal hepatic architecture with slight degeneration at a dose 1000 mg/kg b.w. ICR is safe for acute oral administration; however, for long-term oral administration, safety measures should be taken. Thus, oral sub-chronic exposure of ICR at lower doses are recommended while higher doses around 1000 mg/kg b.w. should be discouraged.


The inorganic dust pneumoconioses.
Collectively, the pneumoconioses represent a spectrum of pulmonary diseases initiated by inorganic dust exposure. Although multiple humoral and cellular immune alterations have been demonstrated in these interstitial and commonly fibrotic lung diseases, the exact role of immune changes in disease pathogenesis presently is undefined. Insight into disease mechanisms may have to await the careful characterization of suitable animal models, along with analysis of local, human bronchopulmonary immune responses through the vehicle of bronchoalveolar lavage.


Neonatal echocardiography.
Echocardiography is a technique within neonatal care increasingly used in acute management of patients because of its potential to guide care and hemodynamic management. However, its use continues to provoke controversy, as it was originally within the purview of pediatric cardiologists trained to identify structural as well as functional heart disease. This article examines some of the echocardiographic techniques available to the neonatologist, their applications, and the concerns surrounding their use on neonatal units.