Comparison of perioperative spirometric data following spinal or general anaesthesia in normal-weight and overweight gynaecological patients.
There is limited data comparing the impact of spinal anaesthesia (SA) and general anaesthesia (GA) on perioperative lung function. Here we assessed the differences of these two anaesthetic techniques on perioperative lung volumes in normal-weight (BMI < 25) and overweight (BMI 25-30) patients using spirometry. We prospectively studied 84 consenting patients having operations in the vaginal region receiving either GA (n = 41) or SA (n = 43). Both groups (GA and SA) were further divided into two subgroups each (normal-weight vs. overweight). We measured vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), midexpiratory (MEF25-75) and peak expiratory flow rates (PEFR) at the preoperative assessment (baseline), after premedication, after effective SA, and 20 min, 1 h, 2 h and 3 h after the operation (last measurement after patient mobilization). Premedication was associated with a small but significant decrease in lung volumes in direct correlation with BMI (-5%). Spinal anaesthesia resulted in a significant reduction in lung volumes in overweight as opposed to normal-weight patients. Postoperatively, lung volumes were significantly more reduced following GA than SA as indicated by differences in mean VC (SD) of -12 (6)% vs. -6 (5)% 20 min after the end of the operation in the normal-weight and -18 (5)% vs. -10 (5)% in the overweight patients. There was a significant impact of BMI on postoperative respiratory function, which was significantly more important in the GA group than in the SA group, and recovery of lung volumes was more rapid in the normal-weight patients than in the overweight patients, particularly in the SA group. In gynaecological patients undergoing vaginal surgery, the impact of anaesthesia on postoperative lung function as assessed by spirometry was significantly less after SA than GA, particularly in overweight patients.


Thermal Adaptation Alters Response to Thermal Stress and Expression of Virulent Genes (eae, stx1, stx2, and hlyA) in Pathogenic Escherichia coli Isolated from Pork.
Escherichia coli encounter variety of environmental and processing stresses during their growth, survival, and infection. Herein, the thermotolerance behavior and transcription of virulent genes responsible for the pathogenicity in isolated strains of pathogenic E. coli were evaluated. Among 176 E. coli isolates, 4 isolates (2.27%) were confirmed to be pathogenic E. coli, out of which 2 isolates were positive for EHEC and 2 were positive for EPEC based on their virulence factors. Thermotolerance was induced under thermal adaptation at higher temperature, regardless of the pathotypes. Cells grown and adapted at 42 °C, exhibited highest transcription of genes associated with adhesion (eae), hemolysis (hlyA), and shiga toxin production (stx1). However, expression of these genes was downregulated in cells adapted at lower temperature of 4 °C and 25 °C compared to control. Further, transcription of stx2 was upregulated by 70% and 17% at 4 °C and 25 °C, respectively, while the transcription level was reduced by 44% relative to control at 42 °C. The findings indicate that expression of virulent genes in pathogenic E. coli at elevated temperature do not be depend on thermotolerance of the strain harboring these genes.


The influence of a glucose containing drink on the behavior of children in school.
The influence of a glucose containing drink on the behavior of children in school was examined in a double-blind placebo controlled cross-over trial. A child maybe particularly susceptible to the provision of blood glucose, as in childhood the brain uses relatively more glucose than when adult. After drinking a glucose containing drink, children aged 9-11 years were found to have better memories and spent more time on task when working in class, although the ability to sustain attention was not influenced.


Invasive candidiasis presenting bronchiectatic cavity as chest radiological findings: A case report.
Invasive candidiasis is rare but is associated with high mortality in immunocompromised or critically ill patients. Here, we present a case of a 55-year-old man with untreated diabetes who was diagnosed with coronavirus disease 2019 and subsequently developed invasive candidiasis. The patient presented with fever, tachycardia, and tachypnea. Chest computed tomography revealed multiple consolidations mainly distributed around the bronchovascular bundles with bronchiectatic cavity formation, which initially raised suspicion for invasive pulmonary aspergillosis. However, subsequent testing confirmed Candida albicans infection; hence, we changed the antifungal agents effective for invasive candidiasis. This improved the patient's respiratory status, and he was then successfully weaned from mechanical ventilation. This case report highlights the importance of considering invasive candidiasis in the differential diagnosis of patients with bronchiectatic cavities on chest computed tomography, particularly in immunocompromised or critically ill patients with risk factors for invasive candidiasis.


Structure-function studies on Acanthamoeba myosins IA, IB, and II.
Myosins IA and IB are globular proteins with only a single, short (for myosins) heavy chain (140,000 and 125,000 daltons for IA and IB, respectively) and are unable to form bipolar filaments. The amino acid sequence of IB heavy chain shows 55% similarity to muscle myosins in the N-terminal 670 residues, which contain the active sites, and a unique 500-residue C-terminus highly enriched in proline, glycine, and alanine. The C-terminal region contains a second actin-binding site which allows myosins IA and IB to cross-link actin filaments and support contractile activity. Myosins IA and IB are regulated solely by phosphorylation of one serine on the heavy chain positioned between the catalytic site and the actin-binding site that activates ATPase. Myosin II is a more conventional myosin in composition (two heavy chains and two pairs of light chains), heavy chain sequence (globular head 45% identical to muscle myosins and a coiled-coil helical tail), and structure (bipolar filaments). The tail of myosin II is much shorter than that of other conventional myosins, and it contains a 25 amino acid sequence in which helical structure is predicted to be weak or absent. The position of this sequence corresponds to the position of a bend in the monomer. Myosin II heavy chains also have a 29-residue nonhelical tailpiece which contains three regulatory, phosphorylatable serines. Phosphorylation at the tip of the tail regulates ATPase activity in the globular head apparently through an effect on filament structure.


Th17/Treg imbalance mediates hepatic intolerance to exogenous lipopolysaccharide and exacerbates liver injury in triptolide induced excessive immune response.
Triptolide (TP) is a major active ingredient and toxic component of Tripterygium wilfordii Hook F (TWHF), which exhibits multiple activities and remarkable hepatotoxicity, the latter of which limits its clinical application due to the risk of liver injury. Previous research has revealed the hepatotoxicity of TP resulting in liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, existing research has not elucidated the potential immune mechanism such as Th17/Treg imbalance in TP-induced hepatic excessive immune response to exogenous LPS. To investigate the role of Th17/Treg imbalance in TP-induced hepatic excessive immune response to exogenous LPS. Mice were administered with TP, LPS, neutralization antibody and small molecule inhibitor respectively. Serum transaminase level was measured to determine the severity of liver injury. Frequencies of liver Th17 and Treg cells were analyzed by flow cytometry. Serum cytokine levels were performed by ELSIA, and mRNA levels of liver cytokine were performed by qPCR. The status of neutrophil infiltration was performed by myeloperoxidase (MPO) IHC measurement. Morphological observation of liver was performed by hematoxylin and eosin (H&E) staining. Mice given a single intragastric dose of TP (500 μg/kg) developed lethal fulminant hepatitis following intraperitoneal injection of LPS (0.1 mg/kg), characterized by low survival rate, severe liver injury, high levels of inflammation and neutrophil infiltration. Hepatic Th17/Treg imbalance emerged together with liver injury in these mice. Neutralization of IL-17A attenuated the liver injury and ameliorated the neutrophil infiltration. The TP-induced alteration of hepatic Th17/Treg balance was closely related to the outcome of immune-mediated acute liver injury triggered by LPS. Pretreatment with the STAT3 inhibitor AG490 effectively restored Th17/Treg balance, significantly reducing the production of IL-17A and finally attenuating the degree of liver injury. Hepatic Th17/Treg imbalance not only exacerbates TP- and LPS-induced liver injury, but also serves as an indispensable part in the mechanisms of TP-induced hepatic intolerance to exogenous endotoxin.


Magnetic resonance arthrography.
For decades, fluoroscopic arthrography was the only method available to image a joint with contrast enhancement. Advances in CT led to the natural development of CT arthrography. Development of MRI and its capability for multiplanar imaging led to direct magnetic resonance arthrography (MRA). This technique has been performed since 1987 and has surpassed CT arthrography in popularity in the United States. Indirect MRA developed subsequently to offer a less invasive alternative. This article presents an overview of direct MRA and addresses joint-specific issues regarding direct MRA. An overview of indirect MRA also is provided.


The Effect of Ovariectomy and Orchiectomy on Orthodontic Tooth Movement and Root Resorption in Wistar Rats.
Root resorption (RR) after orthodontic tooth movement (OTM) is known as a multifactorial complication of orthodontic treatments. Hormonal deficiencies and their effect on bone turnover are reported to have influences on the rate of tooth movement and root resorption. This study was designed to evaluate the effect of female and male steroid sex hormones on tooth movement and root resorption. Orthodontic appliances were placed on the right maxillary first molars of 10 ovariectomized female and 10 orchiectomized male Wistar rats as experimental groups and 10 female and 10 male healthy Wistar rats as control groups. NiTi closed-coil springs (9mm, Medium, 011"×.030", Ortho Technology(®); Tampa, Florida) were placed between the right incisors and the first right maxillary molars to induce tipping movement in the first molars with the application of a 60g force. After 21 days, the rats were sacrificed and tooth movement was measured by using a digital caliper (Guanglu, China). Orthodontic induced root resorption (OIRR) was assessed by histomorphometric analysis after hematoxylin and eosin staining of sections of the mesial root. The rate of tooth movement was significantly higher in all female rats, with the root resorption being lower in the experimental group. The rate of tooth movement in experimental male rats was significantly higher than the control group (p= 0.001) and the rate of root resorption was significantly lower in the experimental group (p= 0.001). It seems that alterations in plasma levels of estrogen, progesterone, and testosterone hormones can influence the rate of OTM and RR. The acceleration in tooth movement increased OTM and decreased RR.


Usefulness of serum Mac-2 binding protein glycosylation isomer in patients undergoing hepatectomy: A case controlled study.
To evaluate the clinical significance of Mac-2 binding protein glycosylation isomer (M2BPGi), we investigated the relationship between M2BPGi and clinicopathological and surgical parameters and posthepatectomy complications. We examined M2BPGi in 115 patients with hepatic malignancies undergoing hepatectomy. Significance as an independent prognostic marker was determined with multivariate logistic regression analysis. The mean serum M2BPGi level was 1.14 ± 1.03 C.O.I. (range 0.2-5.79). M2BPGi in the chronic viral hepatitis group (1.42 ± 1.25) was significantly higher than that in the other disease groups (p < 0.05). The M2BPGi level correlated negatively with platelet count, LHL15 and GSA-Rmax (r = -0.36, -0.69 and -0.56, respectively; p < 0.01) but correlated positively with serum hyaluronate level (fibrotic marker), ICGR15 and HH15 (r = 0.52, 0.63 and 0.57, respectively; p < 0.01). In 53 patients examined for histological hepatic fibrosis, the M2BPGi level was highest for hepatic fibrosis stage 4, indicating cirrhosis (2.15 ± 1.56), and was significantly higher than that for stages 0-2 (p < 0.05). M2BPGi level did not correlate significantly with any surgical parameters. The preoperative level correlated significantly only with increased alanine aminotransferase level (r = -0.21, p < 0.05) and was significantly higher in patients with (1.35 ± 0.78) than without (1.11 ± 1.07) hepatectomy-related complications (p < 0.05). Area under the ROC curve analysis for prediction of hepatic fibrosis score 4 showed a cut-off value of 0.78 for M2BPGi to have high sensitivity (90%) and specificity (58%). For postoperative hepatectomy-related complications, only the M2BPGi level (at a cut-off value 0.90) tended to show significance (p = 0.06). The non-invasively measured serum level of M2BPGi reflected impaired liver function or cirrhosis and hepatectomy-related complications after surgery, making it potentially useful as a complementary parameter accompanying other liver function parameters.


Modified triple chemotherapy in the management of high-risk metastatic gestational trophoblastic tumors.
Modified triple chemotherapy (MAC III: methotrexate with citrovorum factor, actinomycin D, and cyclophosphamide) was administered as primary treatment to 14 patients with high-risk metastatic gestational trophoblastic tumors (GTT). Ten (71.4%) patients attained complete remission with 1 to 4 courses of MAC III (mean = 2.7 courses). Three of the remaining patients subsequently achieved remission with the modified Bagshawe regimen or vinblastine, bleomycin, and cis-platinum. Following 38 courses of MAC III, moderate hepatotoxicity (SGOT greater than or equal to 150 U) developed after 1 (2.6%) course. Marked thrombocytopenia (platelets less than 50,000/mm3) and marked granulocytopenia (granulocytes less than 500/mm3) developed after 7 (18.4%) and 19 (50%) of the courses, respectively. Platelet transfusions were administered after 4 (10.5%) courses of MAC III and no patient required granulocyte transfusions. MAC III is an effective alternative treatment for patients with high-risk metastatic GTT.


Size fractionated speciation of nitrate and sulfate aerosols in a sub-tropical industrial environment.
Size fractionated chemical speciation of acidic aerosols were performed for ammonium sulfate, other sulfates, ammonium nitrate and other nitrates in a sub-tropical industrial area, Bina, India during December 2003 to November 2004. Analysis of variance (ANOVA) revealed highly significant temporal variations (p > .001) in the concentrations of nitrate and sulfate aerosols in all the three size fractions (fine, mid-size and coarse). Winter demonstrated utmost concentrations of ammonium sulfate, which ranged from 3.2 to 26.4 microg m(-3) in fine particles and 0.20-0.34 microg m(-3) in coarse particles. Ammonium sulfate was chiefly in fine mode (43.77% of total particulate sulfate) as compared to coarse particles (28.60% of total particulate sulfate). The major fraction Ammonium sulfate existed in different forms in atmospheric aerosols, for example NH4Fe(SO4)2, (NH4)2SO4, (NH4)3H(SO4)2 in fine particles, and (NH4)4(NO3)SO4+ in coarse particles. Other sulfate concentrations were also higher during winter ranging from 1.89 to 14.3 microg m(-3) in fine particles and 0.12-0.65microg m(-3) in coarse particles. Ammonium nitrate constituted the major fraction of total particulate nitrate all through the year and was principally in fine particles (the highest concentration in January i.e. 14.2 microg m(-3)). Other nitrates were mainly distributed in the fine particles (highest concentration in January i.e. 11.2 microg m(-3)) All the sulfate and nitrate species were mainly distributed in fine mode and have significant impact on human health.


Megavoltage therapy of glioblastoma multiforme.
Supervolt radiation therapy produced no improved survival rates in the treatment of glioblastoma multiforme as compared to orthovolt therapy. Survival times of more than one year or two years must still be considered a rarity. The application of computer techniques to the calculation of dose distributions greatly enhances the optimization of treatment planning. Tumour doses of 5,000 to 7,000 rad are considered necessary, and are dangerously close to the dose levels tolerated by brain tissue. Improvements could conceivably be expected from a) combinations of chemotherapy and radiation therapy, b) intra-arterial application of radiating substances with tumour affinity, c) neutron therapy. Whether or not such measures will in the future produce improved therapeutic results remains to be seen.


Cortical motor activation patterns following hand transplantation and replantation.
We studied cortical activation patterns by functional MRI in a patient who received bilateral hand transplantation after amputation 6 years ago and in a patient who had received unilateral hand replantation within 2 hours after amputation. In the early postoperative period, the patient who had had the hand transplantation revealed strong activation of a higher motor area, only weak activation of the primary sensorimotor motor cortex and no activation of the primary somatosensory cortex. At 1-year follow-up, a small increase in primary sensorimotor motor cortex activation was observed. Activation of the primary somatosensory cortex was only seen at the 2 year follow-up. By contrast, after hand replantation, the activation pattern was similar to that of the uninjured hand within 6 weeks. This included activation of the primary sensorimotor motor cortex, higher motor areas and primary somatosensory cortex. Transplantation after long-standing amputation results in cortical reorganization occurring over a 2-year period. In contrast, hand replantation within a few hours preserves a normal activation pattern.


Kampanols: novel Ras farnesyl-protein transferase inhibitors from Stachybotrys kampalensis.
Farnesyl-protein transferase (FPTase) is a critical enzyme that participates in the post-translational modification of the Ras protein. Inhibitors of this enzyme have the potential of being novel anticancer agents for tumors in which the ras oncogene is found mutated and contributes to cell transformation. Continued screening of natural product extracts led to the isolation of kampanols, which are novel and specific inhibitors of FPTase. The most active kampanols exhibited IC50 values between 7 to 13 microM against human recombinant FPTase. The isolation, structure determination, and biological activity of these compounds are described.


The impact of nurse education on the caring behaviours of nursing students.
This study aimed to ascertain whether nursing students' perceptions of caring behaviours as part of nursing practice change over a three-year, pre-registration, undergraduate nursing course. Students are expected to have a predisposition to care with nurse education nurturing and developing this into professional caring behaviour. However, there is some evidence that this process inures rather than develops these behaviours. This was a quantitative, single cross section survey of two nursing student cohorts from one Higher Education Institution (HEI) in Wales, United Kingdom (UK). There were two sample groups; sample group A were 80 first year students and sample group B were 94 third year students. Students completed a questionnaire incorporating the caring behaviors inventory (CBI) [Wolf, Z.R., Colahan, M., Costello, A., Warwick, F., Ambrose, M.S., Giardino, E.R., 1994. Dimensions of nurse caring. Journal of Nursing Scholarship 26 (2), 107-111]. The key finding was a statistically significant difference in the means in caring behaviours between first years and third years with third years scoring lower than first years. This was exaggerated for those under 26 and increased further for those under 26 with no previous experience of caring. Caring is a core nursing value and a desirable attribute in nursing students, but the educational process seemed to reduce their caring behaviours.


Helper-dependent adenoviral vectors for liver-directed gene therapy of primary hyperoxaluria type 1.
Primary hyperoxaluria type 1 (PH1) is an inborn error of liver metabolism due to deficiency of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT), which catalyzes conversion of glyoxylate into glycine. AGT deficiency results in overproduction of oxalate that ultimately leads to end-stage renal disease and death. Organ transplantation as either preemptive liver transplantation or combined liver/kidney transplantation is the only available therapy to prevent disease progression. Gene therapy is an attractive option to provide an alternative treatment for PH1. Toward this goal, we investigated helper-dependent adenoviral (HDAd) vectors for liver-directed gene therapy of PH1. Compared with saline controls, AGT-deficient mice injected with an HDAd encoding the AGT under the control of a liver-specific promoter showed a significant reduction of hyperoxaluria and less increase of urinary oxalate following challenge with ethylene glycol, a precursor of glyoxylate. These studies may thus pave the way to clinical application of HDAd for PH1 gene therapy.


Raising the Legal Age of Tobacco Sales: Policy Support and Trust in Government, 2014-2015, U.S.
The National Academy of Medicine has called for an increase in the minimum age of tobacco product sales. It is not clear what age increase would garner the greatest public support, or whether trust in the U.S. government predicts policy support. The data for these analyses are from a nationally representative telephone sample of U.S. adults (N=4,880) conducted from September 2014 to May 2015. The authors assessed whether support varied by the proposed minimum age of tobacco sales using a survey experiment (i.e., random assignment to the 19-, 20-, or 21-year age minimum condition) and, in cross-sectional analyses, whether smoking status, individual demographics, state-level politics, and general trust in the government predicted policy support. Analyses were conducted from May to December 2015. Odds of support for raising the minimum sales age to 21 years trended higher than support for raising to age 20 or 19 years (AOR=1.22, 95% CI=0.97, 1.53, p=0.09). There was majority support for raising the age of sales for cigarettes in all regions of the U.S. (66.3%, 95% CI=64.0, 68.6). Race, age, and trust in government were significant predictors of support. Raising the age of tobacco sales is broadly supported by the public. An age 21 years tobacco sales policy trends toward garnering more support than a policy at age 19 or 20 years. Trust in government may be an important consideration in understanding policy support beyond demographics.


Prediction of near-term risk of developing breast cancer using computerized features from bilateral mammograms.
Asymmetry of bilateral mammographic tissue density and patterns is a potentially strong indicator of having or developing breast abnormalities or early cancers. The purpose of this study is to design and test the global asymmetry features from bilateral mammograms to predict the near-term risk of women developing detectable high risk breast lesions or cancer in the next sequential screening mammography examination. The image dataset includes mammograms acquired from 90 women who underwent routine screening examinations, all interpreted as negative and not recalled by the radiologists during the original screening procedures. A computerized breast cancer risk analysis scheme using four image processing modules, including image preprocessing, suspicious region segmentation, image feature extraction, and classification was designed to detect and compute image feature asymmetry between the left and right breasts imaged on the mammograms. The highest computed area under curve (AUC) is 0.754±0.024 when applying the new computerized aided diagnosis (CAD) scheme to our testing dataset. The positive predictive value and the negative predictive value were 0.58 and 0.80, respectively.


Biological cellulose saccharification using a coculture of Clostridium thermocellum and Thermobrachium celere strain A9.
An anaerobic thermophilic bacterial strain, A9 (NITE P-03545), that secretes β-glucosidase was newly isolated from wastewater sediments by screening using esculin. The 16S rRNA gene sequence of strain A9 had 100% identity with that of Thermobrachium celere type strain JW/YL-NZ35. The complete genome sequence of strain A9 showed 98.4% average nucleotide identity with strain JW/YL-NZ35. However, strain A9 had different physiological properties from strain JW/YL-NZ35, which cannot secrete β-glucosidases or grow on cellobiose as the sole carbon source. The key β-glucosidase gene (TcBG1) of strain A9, which belongs to glycoside hydrolase family 1, was characterized. Recombinant β-glucosidase (rTcBG1) hydrolyzed cellooligosaccharides to glucose effectively. Furthermore, rTcBG1 showed high thermostability (at 60°C for 2 days) and high glucose tolerance (IC50 = 0.75 M glucose), suggesting that rTcBG1 could be used for biological cellulose saccharification in cocultures with Clostridium thermocellum. High cellulose degradation was observed when strain A9 was cocultured with C. thermocellum in a medium containing 50 g/l crystalline cellulose, and glucose accumulation in the culture supernatant reached 35.2 g/l. In contrast, neither a monoculture of C. thermocellum nor coculture of C. thermocellum with strain JW/YL-NZ35 realized efficient cellulose degradation or high glucose accumulation. These results show that the β-glucosidase secreted by strain A9 degrades cellulose effectively in combination with C. thermocellum cellulosomes and has the potential to be used in a new biological cellulose saccharification process that does not require supplementation with β-glucosidases. KEY POINTS: • Strain A9 can secrete a thermostable β-glucosidase that has high glucose tolerance • A coculture of strain A9 and C. thermocellum showed high cellulose degradation • Strain A9 achieves biological saccharification without addition of β-glucosidase.


Prospective audit of diabetes care and outcomes in a group of geriatric French care homes.
In geriatric institutions, diabetes prevalence varies from 10 to 20%. However, little is known about patterns of care and their outcomes. To assess both, an 18-month prospective audit was conducted in 240-bed nursing and 80-bed residential care homes. In diabetic subjects, items of care were compared to the corresponding French guideline end-points. Dependency in activities for daily living (ADL) was evaluated at inclusion and at the end of the survey for survivors. Diabetic residents were compared to others for age, sex, mortality and one-year change of iso-resource group ranging (IRG), a need-of-care scale. The 73 diabetic patients among 494 residents (14.8%) were not different from the others for age and sex (respectively age: 76.0 y +/- 7.9 compared to 78.2 y +/- 9.4; M/F sex ratio: 0.59 compared to 0.31). Oral hypoglycemic agents were prescribed in 29 (39.7%) and insulin in 26 (35.6%). Control of diabetes with HbA(1C) was in keeping with guidelines in 23.3%, HbA(1C) was never performed in 26%, and > 8% in 20.5%. Rates of items of guidelines that were never addressed ranged from 2 to 80%. During the stay, ADL dependency worsened in diabetic patients, but their one-year change in GIR range was not different from that in the others. Mortality was 30.1% compared to 37.1% in the others (NS). This mortality rate and the evolution of functional dependency were not influenced by the quality of diabetes control. In these disabled elderly patients, diabetes management needs to be improved. However, mortality and the evolution of functional dependency were similar in diabetic people than in others. Interventional studies for controlling with reference to geriatric evaluation, i.e. function, nutrition and mental health, are needed in order to establish specific guidelines based on benefit-burden analysis.


Cognition in relation to independency in older, comorbid stroke patients in a stroke unit.
The objective of this study was to ascertain if cognition helps to predict functional outcome in older comorbid stroke patients with severe loss of independence. This is a cross-sectional study. The subjects of this study are patients who have suffered a stroke and who rehabilitated in the nursing homes' rehabilitation units and patients (n = 160) (mean age: 77; SD: 9.5) with a mean Barthel Index of 11.02. Demographic, illness-related, functional and cognitive data were selected at baseline. Functional abilities were tested using the Barthel Index. Cognitive functions were assessed using a wide variety of neuropsychological tests. Patients faced cognitive impairments especially in executive functioning and memory. Stepwise linear regression analysis shows that executive functioning (p = 0.050) and memory (p = 0.000; confidence interval -1.255, -0.403) are significantly associated with functional outcome. From a clinical point of view, we suggest combining physical and cognitive training from the very early phase of recovery.


Genetic recoding to dissect the roles of site-specific protein O-GlcNAcylation.
Modification of specific Ser and Thr residues of nucleocytoplasmic proteins with O-GlcNAc, catalyzed by O-GlcNAc transferase (OGT), is an abundant posttranslational event essential for proper animal development and is dysregulated in various diseases. Due to the rapid concurrent removal by the single O-GlcNAcase (OGA), precise functional dissection of site-specific O-GlcNAc modification in vivo is currently not possible without affecting the entire O-GlcNAc proteome. Exploiting the fortuitous promiscuity of OGT, we show that S-GlcNAc is a hydrolytically stable and accurate structural mimic of O-GlcNAc that can be encoded in mammalian systems with CRISPR-Cas9 in an otherwise unperturbed O-GlcNAcome. Using this approach, we target an elusive Ser 405 O-GlcNAc site on OGA, showing that this site-specific modification affects OGA stability.


Clinical manifestations of Fabry disease in children: data from the Fabry Outcome Survey.
Fabry disease is a rare X-linked disorder caused by deficient activity of the enzyme alpha-galactosidase A. This produces progressive lysosomal accumulation of globotriaosylceramide throughout the body, leading to organ failure and premature death. Here, we present the clinical manifestations of Fabry disease in children enrolled in FOS--the Fabry Outcome Survey--a European database of the natural history of Fabry disease and the effects of enzyme replacement therapy with agalsidase alfa (Replagal). Currently, there are 545 patients in FOS, from 11 European countries. We analysed the baseline demographic and clinical characteristics of 82 of these patients (40 boys, 42 girls) who were below 18 y of age. The median age at evaluation (defined as the median age at entry into FOS) was 12.5 and 13.2 y for boys and girls, respectively. The most frequent early clinical manifestations of Fabry disease were neurological (acroparaesthesiae, altered temperature sensitivity) and gastrointestinal symptoms (altered bowel habits and abdominal pain), which were documented in about 80% and 60% of patients, respectively, at the time of evaluation and subsequent entry into FOS. Tinnitus, vertigo, fatigue and angiokeratoma were present in over 40% of patients. Symptoms were noted in early childhood and occurred with similar frequency in boys and girls, although the onset of symptoms was 2-5 y later in girls than in boys. There was an approximately 3-y delay from onset of symptoms to diagnosis, and patients were frequently misdiagnosed. Although the life-threatening complications of Fabry disease, such as stroke and renal and heart failure, are not seen in children, the present analysis shows that other symptoms are common and may have an impact on quality of life.


Stakeholders' Perspectives towards the Use of the Comprehensive Health Assessment Program (CHAP) for Adults with Intellectual Disabilities in Manitoba.
No standardized tool is used in Canada for comprehensive health assessments of adults with intellectual disabilities. This study was conducted to determine the feasibility of implementing the Comprehensive Health Assessment Program (CHAP) in Manitoba, Canada. This was a qualitative study using a purposive sample of physicians, nurse practitioners, support workers and families. Data were collected through individual interviews and focus groups and were analysed using content analysis. Use of the CHAP was perceived as beneficial for persons with intellectual disabilities. Improved continuity of care was of the reported benefits. Six barriers for the future implementation of the CHAP were identified including the time required to complete the CHAP, and the perceived lack of physicians' willingness to do comprehensive assessments. The future implementation of the CHAP was strongly supported. For its successful implementation, training of healthcare professionals and support staff and change in regulations and policies were recommended.


When is the dyspnea worth it? Understanding functional performance in people with alpha-1 antitrypsin deficiency.
OBJECTIVE AND SIGNIFICANCE: To examine functional performance in people with emphysema because of alpha-1 antitrypsin (AAT) deficiency. A severe deficiency of AAT affects 1:3,500 to 1:1,670 Americans who can develop debilitating emphysema in the third to fifth decades of life. Exploratory. People with a severe deficiency of AAT. SAMPLE AND DEMOGRAPHICS: Thirty-three patients (21 men) with a mean age of 47 (SD = 7) years. Data were collected 1993-1996. Activities patients identified as important on the dyspnea subscale of the Chronic Respiratory Disease Questionnaire were categorized and interpreted within the context of an integrity framework (i.e., effectiveness--or connectedness-related). Patients identified over 25 activities. Effectiveness activities, such as bathing, were mentioned most frequently (78%). Connectedness activities, such as playing with children, were mentioned less often (22%) but were ranked more important. Two patients reviewed and supported the content validity of the framework. Results offer insight into the activities patients with genetic emphysema choose to perform and the factors that influence the decision that "the dyspnea is worth it." Identifying the activities people with AAT deficiency choose to perform and understanding why these activities are meaningful can guide interventions to help patients maintain a sense of integrity.


Cloning and expression of a smooth muscle caldesmon.
Caldesmon is a smooth muscle and nonmuscle regulatory protein that interacts with actin, myosin, tropomyosin, and calmodulin. Two overlapping clones, isolated from a chicken oviduct cDNA plasmid library and a chicken gizzard cDNA lambda NM1149 library, were used to generate a 4108-base pair sequence coding for one caldesmon. Expression of the coding sequence confirms this is one of the large smooth muscle caldesmons. The deduced protein molecular weight is 86.974, significantly less than the molecular weights estimated by sodium dodecyl sulfate gel electrophoresis. The protein has a high content of Gly, Lys, Arg, and Ala; there are two cysteine residues, one at either end of the molecule. Comparison with the Protein Identification Resource database demonstrates a similarity with a tropomyosin binding domain of troponin T, but none with any calmodulin or actin binding proteins. The center of the protein has an 8-fold repeat of a 13 amino acid sequence whose general motif is -Glu3-(Lys/Arg)2-Ala2-Glu2-(Lys/Arg)1-X-(Lys/Arg)1-Ala1-, where X is Glu, Gln, or Ala. Comparison with peptide sequences from a chymotryptic fragment that binds actin and calmodulin places this domain on the C terminus of caldesmon adjacent to the troponin T similarity. A tentative map of the major binding domains is proposed on the basis of available data.


St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis.
Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.


Evaluation of a Precision Biotic on the Growth Performance, Welfare Indicators, Ammonia Output, and Litter Quality of Broiler Chickens.
A dietary glycan-based precision biotic (Glycan PB) was evaluated on the performance, welfare indicators, and litter characteristics of broiler chickens. In Trial 1, the main effects of Glycan PB dose (0, 250 and 500 g/metric ton (MT)) and xylanase supplementation (0 or 100 g/MT) were tested, as was their interaction. In Trial 2, pens located inside a commercial house were used to test the effect of Glycan PB supplementation (500 g/MT) versus a control diet. In Trial 1, Glycan PB supplementation at 250 and 500 g/MT improved feed conversion ratio (FCR) by 7 and 11 points when compared to diets without Glycan PB (p < 0.001). At 35 d, Glycan PB reduced the pH and ammonia concentration in diets with xylanase. In Trial 1, the supplementation with 500 g of Glycan PB/MT of feed reduced litter scores (p < 0.05). In both trials, 500 g of Glycan PB/MT of feed increased the proportions of birds without footpad lesions (Trial 1: 72.2% vs. 82.7%; p < 0.001; Trial 2: 14 to 27.3% (p = 0.05) or gait defects (Trial 1: 96.1% vs. 98.4%; p < 0.001) and decreased the proportion of birds with footpad lesions (Trial 2: 86% vs. 72.7%; p = 0.05).


Vitamin A eyedrops for superior limbic keratoconjunctivitis.
We treated 12 patients with superior limbic keratoconjunctivitis with topical vitamin A (retinol palmitate) eyedrops. After a follow-up period of at least three months, this therapy was found to be effective, to a varying extent, in ten patients (83%). Superior limbic keratoconjunctivitis lesions did not recur in these patients as long as topical application was continued.


Mechanisms of hedgehog, calcium and retinoic acid signalling pathway inhibitors: Plausible modes of action along the MLL-EZH2-p53 axis in cellular growth control.
Understanding the molecular mechanism(s) of small compounds in cellular growth control are essential for using those against the disease(s). Oral cancers exhibit a very high mortality rate due to higher metastatic potential. Aberrant EGFR, RAR, HH signalling, enhanced [Ca2+] and oxidative stress are some of the important characteristics of oral cancer. So, we target these for our study. Herein, we tested the effect of fendiline hydrochloride (FH) as an LTCC Ca2+-channel inhibitor, erismodegib (a SMO inhibitor of HH-signalling) and all-trans retinoic acid (RA) inducer of RAR signalling that causes cellular differentiation. OCT4 activating compound (OAC1) counters differentiation and induces stemness properties. Cytosine β-D arabinofuranoside (Cyto-BDA), a DNA replication inhibitor was used to reduce high proliferative capacity. Treatment of FaDu cells with OAC1, Cyto-BDA and FH increase G0/G1 population by 3%, 20% and 7% respectively, and lead to reduction of cyclin D1, CDK4/6 levels. Erismodegib arrests the cells in S-phase with reduced cyclin-E1&A1 levels, whereas RA-treatment causes G2/M phase arrest with reduced cyclin-B1. There was a decrease in the expression of EGFR and mesenchymal markers, Snail/Slug/Vim/Zeb/Twist, and increased E-cadherin expression in all the drug treatments, indicating a reduction in proliferative signal and EMT. Enhanced MLL2 (Mll4) and reduced EZH2 expression associated overexpression of p53 and p21 were traced out. We conclude that these drugs impact expression of epigenetic modifiers by modulating signalling pathways and the epigenetic modifiers then controls the expression of cell cycle control genes, including p53 and p21.


Seasonal variation of territory size with the Little Owl (Athene noctua).
In a population of Little Owls (Athene noctua) at the Lower Rhine (FRG), the factors were studied that influence the size and shape of territories of this non-migrating, all-year territorial owl species. These studies were carried out between September 1984 and June 1987. The birds were individually marked with transmitter packages so that their locomotional movements could be monitored. Using a standard protable stimulus (a dummy with an attached loudspeaker) the territorial boundaries of 19 male Little Owls were surveilled during the different seasons of the year. Male Little Owls defended their territories in all seasons, but distinct seasonal changes of intraspecific aggressiveness and territory size were observed. The seasonal variations of territory size followed a common pattern in all studied Little Owls, in spite of individual differences in the size of the defended areas. The largest territories were defended in March/April during the courtship season [Formula: see text]. In May/June all male Little Owls reduced the size of their territories [Formula: see text]. This corresponds to the breeding and nestling period. The yearly minimum of territory size [Formula: see text] was reached in the summer months July and August when the fledglings were still fed in the parental territory. When the first-year birds started to disperse in autumn (September/October), the size of the defended areas of the adult tenants again increased [Formula: see text]. In winter (November to February), a further increase in territory size was observed for periods of warm weather [Formula: see text]. Male Little Owls, however, were less aggressive during winter than in the following courtship season. On cold winter days with a ground cover of snow territorial aggressiveness ceased. Pastures and meadows offered a continuous food supply almost throughout the year. In some seasons they were overproportionally represented in the territories of Little Owls compared to the general surroundings. In reaction to changing accessibility of food, the hunting ranges within the home ranges were shifted much faster than the boundaries of the defended territories. The significance of various factors contributing to the variability of territory size in Little Owls are discussed (e.g. availability of food, seasonal and individual differences in aggressiveness, experience in the occupied area, population density).


The endochondral bone protein CHM1 sustains an undifferentiated, invasive phenotype, promoting lung metastasis in Ewing sarcoma.
Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by EWS-ETS translocations and early metastasis to lung and bone. In this study, we investigated the role of the BRICHOS chaperone domain-containing endochondral bone protein chondromodulin I (CHM1) in ES pathogenesis. CHM1 is significantly overexpressed in ES, and chromosome immunoprecipitation (ChIP) data demonstrate CHM1 to be directly bound by an EWS-ETS translocation, EWS-FLI1. Using RNA interference, we observed that CHM1 promoted chondrogenic differentiation capacity of ES cells but decreased the expression of osteolytic genes such as HIF1A, IL6, JAG1, and VEGF. This was in line with the induction of the number of tartrate-resistant acid phosphatase (TRAP+ )-stained osteoclasts in an orthotopic model of local tumor growth after CHM1 knockdown, indicating that CHM1-mediated inhibition of osteomimicry might play a role in homing, colonization, and invasion into bone tissues. We further demonstrate that CHM1 enhanced the invasive potential of ES cells in vitro. This invasiveness was in part mediated via CHM1-regulated matrix metallopeptidase 9 expression and correlated with the observation that, in an xenograft mouse model, CHM1 was essential for the establishment of lung metastases. This finding is in line with the observed increase in CHM1 expression in patient specimens with ES lung metastases. Our results suggest that CHM1 seems to have pleiotropic functions in ES, which need to be further investigated, but appears to be essential for the invasive and metastatic capacities of ES.


Use of breast MRI surveillance in women at high risk for breast cancer: a single-institutional experience.
The study aim is to investigate indications for breast magnetic resonance imaging (MRI) screening for high-risk women and to determine outcomes, correlation with routine imaging, and adherence to current guidelines for use. We identified 200 patients undergoing 275 breast MRIs for high-risk surveillance from 2005 to 2008. Data collected included patient characteristics, need for additional imaging and/or biopsy, correlation with routine imaging, and outcomes. Gail scores were calculated for patients without hereditary breast cancer syndromes or previous chest radiation. Descriptive statistics were utilized for data summary. Two hundred patients underwent 275 breast MRIs for high-risk surveillance (mean age 45 years, range 18-76 years). Indications included BRCA mutation (n =21), history of chest radiation (n = 10), and perceived high risk (n =169). The mean Gail score for the latter group was 25% (range 10-46%); 32 (16%) patients had Gail score <20%. Of 275 MRIs, 49 (18%) required additional imaging and 21 (8%) prompted biopsy. Of 21 biopsies, 4 were malignant; 2 were also visible on routine imaging performed concurrently with breast MRI. The false-positive rate for breast MRI screening in our cohort of high-risk patients was 23%. The rate of cancer detection in high-risk patients undergoing breast MRI at our institution is similar to that of large, multicenter trials. Sixteen percent of patients undergoing breast MRI did not meet high-risk criteria. Because the need for additional imaging and biopsy remains high, further investigation is necessary to determine if this strategy is cost effective.


Incidence, risk factors and outcomes of acute kidney injury in surgical intensive care unit octogenarians at the Jordan University Hospital.
Acute kidney damage (AKI) is among the most severe consequences observed in surgical intensive care units (SICUs). We aim to observe the incidence, risk factors, and outcomes of acute kidney injury in SICU octogenarians. A cross-sectional retrospective study was conducted at the SICU of Jordan University Hospital (JUH), a tertiary teaching hospital in a developing country, between January 2018 and December 2019. Patients who were 80 years or older at the time of data collection were included. The definition of AKI was based on Kidney Disease Improving Global Outcomes (KDIGO) criteria. Demographic, clinical, and laboratory data were reviewed. A total number of 168 patients were included. The mean age was 84.0 ± 3.8 years, and 54.8% of the participants were women. Of those, 115 (68.5%) had surgery before or during ICU stay, and 28.7% of the patients' surgeries were an emergency surgery. Also, 47.8% of surgeries were considered by anesthesia to be high-risk surgeries. A total of 55 patients (32.7%) developed AKI during their SICU stay. The factors that were significantly associated with AKI in the ICU patients included use of beta blocker [AOR: 3.7; 95% CI: 1.2-11.8; p = 0.025], and inotropes [AOR:4.0; 95% CI: 1.2-13.3; p = 0.03]. The factors that were significantly associated with mortality in the ICU included using mechanical ventilation [AOR:18.7; 95% CI: 2.4-141.9; p = 0.005] and inotropes use [AOR: 12.3; 95% CI: 1.2-120.7; p = 0.031]. The incidence of AKI during SICU stay in this study was 32.7% and it was significantly associated with the use of beta blockers, mechanical ventilation, and inotropes. The mortality rate among octogenarians who developed AKI during SICU stay was 36.4%. Further studies are needed globally to assess the incidence of AKI in octogenarian surgical patients and identify risk factors to provide preventative measurements and strategies.


More than just caffeine: psychopharmacology of methylxanthine interactions with plant-derived phytochemicals.
In general, preparations of coffee, teas, and cocoa containing high levels of polyphenols, L-theanine and other bioactive compounds selectively enhance mood and cognition effects of caffeine. This review summarizes the bioactive components of commonly consumed natural caffeine sources (e.g. guayusa, mate and camellia teas, coffee and cocoa) and analyzes the psychopharmacology of constituent phytochemicals: methylxanthines, polyphenols, and L-theanine. Acute and chronic synergistic effects of these compounds on mood and cognition are compared and discussed. Specific sets of constituent compounds such as polyphenols, theobromine and L-theanine appear to enhance mood and cognition effects of caffeine and alleviate negative psychophysiological effects of caffeine. However, more research is needed to identify optimal combinations and ratios of caffeine and phytochemicals for enhancement of cognitive performance.


Absence of 60-Hz, 0.1-mT magnetic field-induced changes in oncogene transcription rates or levels in CEM-CM3 cells.
Our objective was to assess the reproducibility of the 60-Hz magnetic field-induced, time-dependent transcription changes of c-fos, c-jun and c-myc oncogenes in CEM-CM3 cells reported by Phillips et al. (Biochim. Biophys. Acta, 1132 (1992) 140-144). Cells were exposed to a 60-Hz magnetic field (MF) at 0.1 mT (rms), generated by a pair of Helmholtz coils energized in a reinforcing (MF) mode, or to a null magnetic field when the coils were energized in a bucking (sham) mode. After MF or sham exposure for 15, 30, 60 or 120 min, nuclei and cytoplasmic RNA were extracted. Transcription rates were measured by a nuclear run-on assay, and values were normalized against either their zero-time exposure values, or against those of the c-G3PDH (housekeeping) gene at the same time points. There was no significant difference, at P=0.05, detected between MF and either sham-exposed or control cells at any time point. Transcript levels of the oncogenes were measured by Northern analysis and normalized as above. No significant difference (P=0.05) in transcript levels between MF and either sham-exposed or control cells was detected.


The hypothalamus: cross-roads of endocrine and behavioural regulation in grooming and aggression.
Anatomical and functional studies show that the hypothalamus is at the junction of mechanisms involved in the exploratory appraisal phase of behaviour and mechanisms involved in the execution of specific consummatory acts. However, the hypothalamus is also a crucial link in endocrine regulation. In natural settings it has been shown that behavioural challenges produce large and fast increases in circulating hormones such as testosterone, prolactin, corticotropin and corticosterone. The behavioural function and neural mechanisms of such fast neuroendocrine changes are not well understood. We suggest that behaviourally specific hypothalamic mechanisms, at the cross-roads of behavioural and endocrine regulation, play a role in such neuroendocrine changes. Mild stimulation of the hypothalamic aggressive area, produces stress levels of circulating prolactin, corticotropin, and corticosterone. Surprisingly luteinizing hormone does not change. This increase in stress hormones is due to the stimulation itself, and not caused by the stress of fighting. Similar increases in corticosterone are observed during electrical stimulation of the hypothalamic self-grooming area. The corticosterone response during self-grooming-evoking stimulation is negatively correlated with the amount of self-grooming observed, suggesting that circulating corticosterone exerts a negative feedback control on grooming. Earlier literature, and preliminary data form our laboratory, show that circulating corticosterone exerts a fast positive feedback control over brain mechanisms involved in aggressive behaviour. Such findings suggest that the hormonal responses caused by the activity of behaviourally specific areas of the hypothalamus may be part of a regulation mechanism involved in facilitating or inhibiting the very behavioural responses that can be evoked from those areas. We suggest that studying such mechanisms may provide a new approach to behavioural dysfunctions associated with endocrine disorders and stress.


Carbon/nutrient balance as a predictor of plant defense in Alaskan balsam poplar: Potential importance of metabolite turnover.
The carbon/nutrient balance hypothesis fails to correctly predict effects of fertilization and shading on concentrations of defensive metabolites in Alaskan balsam poplar (Populus balsamifera). Of six metabolites analyzed, only one responded in the predicted fashion to fertilization and one to shading. These results and those of other similar studies suggest that while the carbon/nutrient balance hypothesis may correctly predict the effects of fertilization and shading on the concentrations of metabolic "end products", it fails for many metabolites because of the dynamics associated with their production and turnover. In metabolites that turn over, static concentration is a poor predictor of defensive investment.


The interaction of 2-hydroquinone-5,10,15,20-tetra(p-hydroxyphenyl)porphyrin with surfactants: solubilization and J-aggregates.
J-aggregates of 2-hydroquinone-5,10,15,20-tetra(p-hydroxyphenyl)porphyrin (HQTHPP) induced by N-lauroyl sarcosine (SKL) in aqueous neutral solutions have been studied by optical absorption, fluorescence, and resonance light-scattering spectroscopies. As SKL concentration increases, the spectra evolve to reveal the presence of four independent species with relative concentration. The most important species is J-aggregates. The J-aggregates have two strong exciton bands corresponding to the B-band and Q-bands of HQTHPP monomers, and are found to be stable when the surfactant concentration is below 8.0 mmol/L. But above 8.0 mmol/L, the J-aggregates dissolve gradually into another species: porphyrin monomers. The total fluorescence of HQTHPP is quenched due to the aggregate formation. A strong and sharply peaked resonance light-scattering signal (>1800 counts/s, centered at 490 nm) is observed just slightly to the red of the J-aggregate absorption maximum. In the case of cetyltrimethyl-ammonium bromide, increasing surfactant concentrations have only shown to favor solubilization of porphyrin monomers. Evidently, the nature of polar headgroups of surfactants influences the tendency of THPP to aggregate.


Generation of a NIS-EGFP-Fluc triple-reporter human embryonic stem cell line by PiggyBac transposon system.
One major challenge in stem cell therapy is to longitudinally track cell fate after cells transplantation. Molecular Imaging approaches enabling noninvasive long-term monitoring the transplanted cells are imperative for assessment of the safety and efficiency. Here, we used PiggyBac technology to insert triple reporter genes: NIS, EGFP and Firefly luciferase into a human embryonic stem cell line (hESCs, H9) and obtained a reporter hESCs line (NIS-EGFP-Fluc H9). The triple-reporters allows the transplanted NIS-EGFP-Fluc H9 cells and their derivates to be fluorescence, bioluminescence and even PET/SPECT imaged. This triple-reporter hESCs line provides a valuable imaging platform for cell-based therapeutics clinical translation.


Biogenic synthesis of iron oxide nanoparticles via Skimmia laureola and their antibacterial efficacy against bacterial wilt pathogen Ralstonia solanacearum.
Plant diseases are threat to global food security. The excessive use of agrochemicals is the leading cause of pesticides resistance and toxicity to beneficial life forms. The quest for innocuous and alternate antimicrobial agent is crucial in order to overcome the pathogen resistance and the birth of nanotech offers pledge to combat pathogenic organisms. In this study, a facile benign biogenic approach was adopted for the synthesis of biocompatible iron oxide nanoparticles (Fe2O3-NPs) via Skimmia laureola leaf extract and the synthesized nanoparticles were evaluated for their antibacterial efficacy against bacterial wilt pathogen Ralstonia solanacearum in vitro and in planta. Physico-chemical characterization of the synthesized nanoparticles was performed through UV-Visible spectroscopy, Fourier Transform Infrared Spectroscopy, X-Ray Diffraction, Energy Dispersive X-ray Spectroscopy and Scanning Electron Microscopy. The results revealed polydisperse nanoparticles in the size range of 56 nm to 350 nm. The culture media containing 6 mg/mL of Fe2O3-NPs dramatically inhibited the bacterial growth in vitro. Scanning electron microscopy revealed degenerative characteristics including degraded, shriveled and concentrated cell walls. Diseases severity was effectively reduced with 6% w/v of Fe2O3-NPs treated root zone in planta. Plant shoots, root length and fresh biomass were enhanced with Fe2O3-NPs treatments. The results indicated that the biosynthesized Fe2O3-NPs have the potential to control agriculturally important phytopathogen Ralstonia solanacearum in vitro and in planta.


Managing homozygous familial hypercholesterolaemia from cradle to grave.
To describe the phenotypic and genotypic features and management of clinically homozygous familial hypercholesterolaemia (FH). An analysis of current knowledge based on personal experience and published evidence. Atherosclerotic involvement of the aortic root is common in homozygous FH and can cause death before age 5. Receptor negative patients are at greatest risk, irrespective of whether they have identical mutations (homozygous) or dissimilar mutations (compound heterozygous). Lipoprotein apheresis combined with high dose statin and ezetimibe slows but does not arrest progression of atherosclerosis. Adjunctive use of novel compounds such as lomitapide and evolocumab should facilitate achieving the latter objective by enhancing the reduction in LDL cholesterol.


Increased cell apoptosis in bone marrow trephine biopsies and immunomagnetically isolated myeloid progenitor cells in patients with chronic idiopathic neutropenia.
The frequency of apoptotic cells in bone marrow trephine biopsies and cytospins of immunomagnetically isolated myeloid progenitor cells was determined in 39 patients with chronic idiopathic neutropenia (CIN) and 12 hematologically normal individuals using the in situ end-labeling (ISEL) apoptosis detection method. We found that 66.7% of the patients but none of the normal controls displayed apoptotic cells equal to or higher than 5% of the total mononuclear cells in bone marrow biopsies (p<0.01). In the double stain, we also found that the proportion of apoptotic CD15(+) myeloid precursor cells did not differ significantly between patients and control subjects, while the proportion of apoptotic CD34(+) hemopoietic cells could not be estimated with accuracy because of the presence of CD34(+) endothelial cells. Significantly increased apoptosis was noted in cytospins of immunomagnetically isolated patient CD34(+) and CD34(+)/CD33(+) cells but not CD34(-)/CD33(+) cells, compared to the controls ( p<0.001, p<0.02 and p>0.05, respectively). These findings confirm and extend our previous observations in flow-cytometric studies of apoptosis in CIN, indicating that increased apoptosis in CIN bone marrow concerns mainly the CD34(+) and CD34(+)/CD33(+) progenitor cell compartments. We conclude that the accelerated apoptosis in these compartments may account for the impaired neutrophil production in CIN patients.


Nitrogen addition effect overrides warming effect on dissolved CO2 and phytoplankton structure in shallow lakes.
Shallow lakes are numerous in all climate zones, but our knowledge about their dissolved carbon dioxide (CO2) response to future climate change and nutrient enrichment is rather limited. Here we performed a mesocosm experiment with four treatments to investigate how warming and nitrogen addition will impact the partial pressure of CO2 (pCO2) and phytoplankton community individually and combined. We found that warming alone had no significant effect on pCO2, while nitrogen addition increased pCO2 significantly. The combined effects of nitrogen addition and warming on pCO2 level were prevalent, indicating that eutrophic shallow lakes would be double-jeopardized in the future climate. Warming and nitrogen addition together also showed to have changed the phytoplankton community structure, suggesting a potential shifting of biological system in shallow lakes under changing climate. These findings highlight the importance of reducing nitrogen pollution to shallow lake systems for sustainable development goal.


Mandibular fracture fixation and reconstruction using the lower-border threaded rod: an eleven-year follow-up study.
Twenty-five cases in which a lower border threaded rod was used for fracture fixation and mandibular reconstruction were reviewed. These cases were performed during the last 11 years and have been followed for periods of up to five years and ten months. The fixation technique, originally reported in 1978, is well tolerated and provides excellent mechanical stability when enhanced security of fixation is indicated. Three unusual cases are reported in detail.


A molecular ensemble in the rER for procollagen maturation.
Extracellular matrix (ECM) proteins create structural frameworks in tissues such as bone, skin, tendon and cartilage etc. These connective tissues play important roles in the development and homeostasis of organs. Collagen is the most abundant ECM protein and represents one third of all proteins in humans. The biosynthesis of ECM proteins occurs in the rough endoplasmic reticulum (rER). This review describes the current understanding of the biosynthesis and folding of procollagens, which are the precursor molecules of collagens, in the rER. Multiple folding enzymes and molecular chaperones are required for procollagen to establish specific posttranslational modifications, and facilitate folding and transport to the cell surface. Thus, this molecular ensemble in the rER contributes to ECM maturation and to the development and homeostasis of tissues. Mutations in this ensemble are likely candidates for connective tissue disorders. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum.


Trade-off in healthy tissue sparing of FLASH and fractionation in stereotactic proton therapy of lung lesions with transmission beams.
Besides a dose-rate threshold of 40-100 Gy/s, the FLASH effect may require a dose > 3.5-7 Gy. Even in hypofractioned treatments, with all beams delivered in each fraction (ABEF), most healthy tissue is irradiated to a lower fraction dose. This can be circumvented by single-beam-per-fraction (SBPF) delivery, with a loss of healthy tissue sparing by fractionation. We investigated the trade-off between FLASH and loss of fractionation in SBPF stereotactic proton therapy of lung cancer and determined break-even FLASH-enhancement ratios (FERs). Treatment plans for 12 patients were generated. GTV delineations were available and a 5 mm GTV-PTV margin was applied. Equiangular arrangements of 3, 5, 7, and 9 244 MeV proton transmission beams were used. To facilitate SBPF, the number of fractions was equal to the number of beams. Iso-effective fractionation schedules with a single field uniform dose prescription were used: D95%,PTV = 100%Dpres per beam. All plans were evaluated in terms of dose to lung and conformity of dose to target of FLASH-enhanced biologically equivalent dose (EQD2). Compared to ABEF, SBPF resulted in a median increase of EQD2mean to healthy lung of 56%, 58%, 55% and 54% in plans with 3, 5, 7 and 9 fractions respectively and of 236%, 78%, 50% and 41% in V100% EQD2, quantifying conformity. This can be compensated for by FERs of at least 1.28, 1.32, 1.30 and 1.23 respectively for EQD2mean and 1.29, 1.18, 1.28 and 1.15 for V100%,EQD2. A FLASH effect outweighing the loss of fractionation in SBPF may be achieved in stereotactic lung treatments. The trade-off with fractionation depends on the conditions under which the FLASH effect occurs. Better understanding of the underlying biology and the impact of delivery conditions is needed.


Tinbergen's "four questions" provides a formal framework for a more complete understanding of prosocial biases in favour of attractive people.
We adopt Tinbergen's (1963) "four questions" approach to strengthen the criticism by Maestripieri et al. of the non-evolutionary accounts of favouritism toward attractive individuals, by showing which levels of explanation are lacking in these accounts. We also use this approach to propose ways in which the evolutionary account may be extended and strengthened.


Inactivation of deoxynivalenol-contaminated cereal grains with sodium metabisulfite: a review of procedures and toxicological aspects.
Both hydrothermal treatment and wet preservation of mainly deoxynivalenol (DON)-containing, Fusarium toxin (FUS)-contaminated cereal grains with sodium metabisulfite (Na2S2O5 [SBS]) were successfully demonstrated to reduce the DON contamination through formation of the sulfonated derivative of DON, termed as DON sulfonate (DONS). The wet preservation is particularly interesting from a practical viewpoint as it can be easily performed at the farm level where the cereal grains are harvested and utilized in pig feeding. This review compiles the literature with regard to the chemical characterization and the detection of DONS, technical procedures and their efficacies, toxicological aspects and toxic effects of DON, DONS and SBS, and detection of DONS, DON and further metabolites in physiological specimens of pigs.


Nonparaxial TE and TM vector beams with well-defined orbital angular momentum.
A new formalism is developed for diffraction-free vector beams in free space. The solutions of Maxwell's equations are separated into two polarization modes, TE and TM. We discuss the validity of the method by applying it to a particular solution, the vectorial Bessel beam of order m.


Bee wax and honey-a primer for OMFS.
Beeswax is the natural secretion from the wax gland of the genus Apis mellifera and Apis cerana whereas honey is a by-product of flower nectar and the upper aero-digestive tract of the honey bee. The introduction of beeswax and honey to clinical use dates back to the fourteenth century but subsequently it was restricted to the cosmetic and food industry. With the emerging trend of using natural resources as cure for many diseases, beeswax and honey have regained its popularity in medical field. The presented manuscript describes the production, composition, and attempts to highlight the uses of beeswax, honey, and advances especially in oral and maxillofacial surgery.


Effects of orchidectomy on adaptation of arcuate neuropeptide Y, proopiomelanocortin, and cocaine- and amphetamine-related transcript gene profiles to recurring insulin-induced hypoglycemia in the male rat.
Our studies show that recurring insulin-induced hypoglycemia (RIIH) diminishes neuronal activation in several key components of the central metabolic regulatory circuitry, including the hypothalamic arcuate nucleus (ARH), and that orchidectomy (ORDX) modifies this impact of RIIH on Fos protein expression in this and other select neural structures. The testicular hormone, testosterone, regulates the expression of ARH neuropeptide genes of characterized metabolic relevance, including neuropeptide Y (NPY) and proopiomelanocortin (POMC). We investigated the hypothesis that acute hypoglycemia-associated patterns of ARH NPY, POMC, and cocaine and amphetamine-related transcript (CART) gene transcription, and potential RIIH-associated adaptive modifications in these expression profiles are regulated by testes-dependent mechanisms. ARH tissue was micropunched from serial frozen brains sections obtained from sham-operated (SHAM) or bilaterally ORDX male rats after sc injection of one or four doses of neutral protamine Hagedorn insulin, over as many days, or vehicle alone, and analyzed by quantitative real-time RT-PCR. In SHAM rats, acute hypoglycemia increased ARH NPY mRNA; precedent hypoglycemia elevated baseline gene expression in this group, but suppressed transcription during RIIH. In ORDX rats, ARH NPY mRNA was decreased during acute hypoglycemia and after multiple exposures; however, gene expression was not further suppressed by RIIH. ARH POMC gene transcription was not modified by acute or recurring hypoglycemia in the SHAM group. ORDX caused a reduction in both basal and acute hypoglycemic patterns of POMC transcription, relative to the SHAM controls, but enhanced baseline and RIIH-associated patterns of gene expression. ARH CART transcripts were not altered by acute or recurring hypoglycemia in SHAM rats, whereas ORDX animals exhibited elevated CART gene expression during RIIH. These data show that acute and recurring hypoglycemia exert opposite effects on ARH NPY gene expression in testes-intact male rats, and that these transcriptional responses are abolished by ORDX. Hypoglycemia had no impact on POMC nor CART mRNA profiles in the SHAM group, but both genes were upregulated during RIIH in ORDX rats. Collectively, these results demonstrate that in the male rat, testes-dependent mechanisms underlie patterns of acclimated or unvarying reactivity to RIIH of the specific ARH metabolic neuropeptide genes evaluated here.


Fractal analysis of muscle activity patterns during locomotion: pitfalls and how to avoid them.
Time-dependent physiological data sets are often difficult to interpret objectively. Biosignals such as electromyogram, electroencephalogram, or single-neuron recordings can be interpreted using various linear and nonlinear methods. Each analysis technique aims at the explanation of different data features that might be visible or not to the naked eye. Here, we used linear decomposition based on machine learning to extract motor primitives (the time-dependent coefficients of muscle synergies) from the hindlimb electromyographic activity of mice during normal and mechanically perturbed locomotion. We set out to investigate the effects of calculation parameters and data quality on two nonlinear metrics derived from fractal analysis: the Higuchi's fractal dimension (HFD) and the Hurst exponent (H). Both HFD and H proved to be exceptionally sensitive to changes in motor primitives induced by external perturbations to locomotion. We discuss the potential pitfalls that might arise from fractal analysis by using examples based on surrogate data. We conclude giving some simple, data-driven suggestions to reduce the chance of misinterpretations when metrics such as HFD and H are applied to any biological signal containing elements of periodicity.NEW & NOTEWORTHY Despite the lack of consensus on how to perform fractal analysis of physiological time series, many studies rely on this technique. Here, we shed light on the potential pitfalls of using the Higuchi's fractal dimension and the Hurst exponent. We expose and suggest how to solve the drawbacks of such methods when applied to data from normal and perturbed locomotion by combining in vivo recordings and computational approaches.


Drosophila melanogaster heterochromatin protein HP1b plays important roles in transcriptional activation and development.
The condensed heterochromatic domains are known to be associated with transcriptional repression and cell differentiation. Here, we investigate the function of heterochromatin protein HP1b, a member of the HP1 family in Drosophila melanogaster, in transcription and development. Both knockdown and overexpression of HP1b resulted in partial lethality, indicating that HP1b is essential for the normal development. In contrast to the positive role of HP1a in heterochromatin formation, overexpression of HP1b decondensed the pericentromeric heterochromatin and reduced the association of HP1a and H3K9me2 with it, both known markers of pericentric heterochromatin. Interestingly, the structure of the heterochromatic fourth chromosome appeared not to be affected. Further experiments showed that the presence of HP1a partially rescued the lethality caused by HP1b overexpression in males, and it fully rescued the lethality in females. Consistent with this observation, the defective transcription of heterochromatic genes was also partially restored in the presence of HP1a. Overall, this study argues that HP1b counteracts HP1a function both in heterochromatin formation and in the transcriptional regulation of euchromatic genes.


The association between low skeletal muscle mass and low skeletal muscle radiodensity with functional impairment, systemic inflammation, and reduced survival in patients with incurable cancer.
Factors associated with the concomitant occurrence of low muscle mass and low muscle radiodensity are unclear. This study investigated whether different skeletal muscle phenotypes are associated with functional impairment, serum inflammatory markers, and survival in patients with incurable cancer. Three hundred and twenty-six patients (median age, 60 years; 67.5% female) who had abdominal or pelvic computed tomography (CT) scans up to 30 days before the initial assessment were enrolled in the study. CT images were used for the assessment of skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD). Optimal stratification analysis was used to derive cohort-specific cutoff points to define SMI and SMD groups with a higher risk for mortality (SMI, males <45.0 cm2 /m2 and females <44.0 cm2 /m2 ; SMD, males <34 Hounsfield units [HU] and females <30 HU). Based on these cutoffs, participants were classified into four phenotypes: low-risk SMI + low-risk SMD, high-risk SMI + low-risk SMD, low-risk SMI + high-risk SMD, and high-risk SMI + high-risk SMD. Phenotypes with high-risk SMI or high-risk SMD, especially when combined, were associated with low handgrip strength, poor performance status, higher C-reactive protein, and lower serum albumin levels. The phenotypes with high-risk SMD, regardless of low-risk SMI (hazard ratio [HR], 1.74; 95% CI, 1.05-2.88) or high-risk SMI (HR, 1.99; 95% CI, 1.29-3.05) were associated with higher 90 days' mortality risk. In patients with incurable cancer, phenotype groups with high-risk SMI and high-risk SMD, particularly when combined, were associated with worse functional impairment and inflammation. Moreover, high-risk SMD was associated with increased mortality risk.