Effects of Oxygen Supplementation on Injectable and Inhalant Anesthesia in C57BL/6 Mice.
Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundly hypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects of oxygen supplementation on physiologic parameters and depth of anesthesia in male and female C57BL/6 mice. Anesthesia was performed via common injectable anesthetic protocols and with isoflurane. Mice anesthetized with injectable anesthesia received one of 3 drug protocols. Low-dose ketamine/xylazine (100/8 mg/kg) was chosen to provide immobilization of mice, suitable for imaging procedures. Medium-dose ketamine/xylazine/acepromazine (100/10/1 mg/kg) was chosen as a dose that has been recommended for surgical procedures. High-dose ketamine/xylazine/acepromazine (150/12/3 mg/kg) was chosen after pilot studies to provide a long duration of a deep plane of anesthesia. We also tested the effects of oxygen supplementation on the minimum alveolar concentration (MAC) of isoflurane in mice. Mice breathed supplemental 100% oxygen, room air, or medical air with 21% oxygen. Anesthetized mice that did not receive supplemental oxygen all became hypoxic, while hypoxia was prevented in mice that received oxygen. Oxygen supplementation did not affect the MAC of isoflurane. At the high injectable dose, all mice not receiving oxygen supplementation died while all mice receiving oxygen supplementation survived. At low and medium doses, supplemental oxygen reduced the duration of the surgical plane of anesthesia (low dose with oxygen: 22 ± 14 min; low dose without supplementation: 29 ± 18 min; medium dose with oxygen: 43 ± 18 min; medium dose without supplementation: 61 ± 27 min). These results suggest that mice anesthetized with injectable and inhalant anesthesia without supplemental oxygen are routinely hypoxic. This hypoxia prolongs the duration of anesthesia with injectable drug protocols and affects survival at high doses of injectable anesthetics. Because of variable responses to injectable anesthetics in mice, oxygen supplementation is recommended for all anesthetized mice.


Optimized Biomimetic Minerals Maintain Activity of mRNA Complexes after Long Term Storage.
mRNA therapeutics can be readily designed, manufactured, and brought to scale, as demonstrated by widespread global vaccination against COVID-19. However, mRNA therapies require cold chain shipment and storage from manufacturing to administration, which may limit them to affluent communities. This problem could be addressed by mimicking the known ability of mineralized fossils to durably stabilize nucleic acids under extreme conditions. We synthesized and screened 40 calcium-phosphate minerals for their ability to store and maintain the activity of lyophilized mRNA complexes. The optimal mineral formulation incorporated mRNA complexes with high efficiency (77%), and increased mRNA transfection efficiency by 5.6-fold. Lyophilized mRNA complexes stored with the optimized mineral formulation for 6 months at 25°C were 3.2-fold more active than those stored with state-of-the-art excipients, but without a mineral. mRNA complexes stored with minerals at room temperature did not decline in transfection efficacy from 3 days to 6 months of storage, indicating that minerals can durably maintain activity of therapeutic mRNA complexes without cold chain storage. STATEMENT OF SIGNIFICANCE: Therapeutic mRNA, such as mRNA COVID-19 vaccines, require extensive cold chain storage that limits their general application. This work screened a library of minerals to maintain the activity of mRNA complexes with freeze-drying. The optimized mineral was able to maintain mRNA activity up to 6 months of storage at room temperature outperforming current methods of freeze-drying therapeutic mRNA complexes.


Multilevel prenatal socioeconomic determinants of Mexican American children's weight: Mediation by breastfeeding.
Objective: Mexican American (MA) children are more likely to grow up in poverty than their non-Hispanic/Latinx white peers and are at an elevated risk for early onset obesity. The current study evaluated the effects of prenatal family- and neighborhood-level disadvantage on children's weight and weight gain from 12 months through 4.5 years of age. Maternal breastfeeding duration was evaluated as a potential mechanism underlying the relation between multilevel disadvantage and weight. Methods: Data was collected from 322 low-income, MA mother-child dyads. Women reported the degree of family socioeconomic disadvantage and breastfeeding status. Neighborhood disadvantage was evaluated with census-level metrics. Children's weight and height were measured at laboratory visits. Results: Greater prenatal neighborhood disadvantage predicted higher child Body Mass Index (BMI) at 12 months, over and above family-level disadvantage; this effect remained stable through 4.5 years. Breastfeeding duration partially mediated the effect of neighborhood disadvantage on child BMI. Breastfeeding duration predicted child BMI at all timepoints. Conclusions: Maternal prenatal residence in a neighborhood with high concentrated disadvantage may place low-income, MA children at increased risk of elevated weight status during the first few years of life. Breastfeeding duration emerged as potentially modifiable pathway through which the prenatal neighborhood impacts children's early life weight. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Can postoperative dexamethasone nanoparticle eye drops replace mitomycin C in trabeculectomy?
Compare (a) nonmitomycin C (MMC) trabeculectomy and 1.5% dexamethasone nanoparticle (DexNP) eye drops postoperatively with (b) trabeculectomy with MMC and Maxidex® eye drops postoperatively. Randomized prospective single masked clinical trial with 20 patients with primary open-angle glaucoma undergoing primary trabeculectomy. The study group consisted of 10 patients without MMC intraoperatively and postoperative DexNP eye drops, and the control group consisted of 10 patients treated with MMC intraoperatively and postoperative Maxidex® . The drops were tapered out over 8 weeks. The main outcome measures were as follows: rates of complete success, that is intraocular pressure (IOP) within target pressures at different time-points without IOP-lowering medication, or reoperation. Secondary outcome measures included the following: relative success rate (with IOP-lowering medications), number of glaucoma medications and reoperations. Patients were followed for 36 months. Both groups showed similar postoperative course and IOP reduction. Intraocular pressures (IOPs) in the DexNP group and in the control group were 25.6 and 24.4 mmHg, respectively, at baseline. Intraocular pressures (IOPs) were reduced to 13.2 and 14.5 mmHg at 12 months, 11.7 and 12.6 mmHg at 24 months and 11.7 and 12.1 mmHg at 36 months, respectively. There were no statistically significant differences between the groups in absolute (p = 0.36) or relative (p = 1.0) success rates, number of medications (p = 0.71) or reoperations (p = 1.0) between the groups at any time-point. DexNP eye drops are effective postoperative treatment following trabeculectomy. The potent anti-inflammatory and antifibrotic effect of DexNP may offer an alternative to mitomycin C in glaucoma surgery.


Absence of two membrane proteins containing extracellular thiol groups in Rhnull human erythrocytes.
Rhnull human erythrocytes lack all the antigens of the Rhesus blood-group system and are associated with mild chronic haemolytic anaemia. These erythrocytes have an abnormal shape and increased osmotic fragility. Labelling studies with the impermeant maleimide N-maleoylmethionine [35S]sulphone show that Rhnull erythrocytes lack two extracellular thiol-group-containing membrane components of apparent mol.wts. 32 000 and 34 000. Immunoprecipitation with mouse monoclonal antibody R6A (which reacts with all normal erythrocytes, but fails to react with Rhnull erythrocytes) specifically precipitates the 34 000-mol.wt. component from normal erythrocytes. Similar studies with human anti-Rh(D) serum shows that this antibody reacts with the 32 000-mol.wt. component. The results suggest that the R6A-binding polypeptide and the Rh(D) polypeptide may be involved in the maintenance of the shape and viability of the human erythrocyte.


Does performance at medical school predict success at the Intercollegiate Membership of the Royal College of Surgeons (MRCS) examination? A retrospective cohort study.
Identifying predictors of success in postgraduate examinations can help guide the career choices of medical students and may aid early identification of trainees requiring extra support to progress in specialty training. We assessed whether performance on the educational performance measurement (EPM) and situational judgement test (SJT) used for selection into foundation training predicted success at the Membership of the Royal College of Surgeons (MRCS) examination. This was a longitudinal, cohort study using data from the UK Medical Education Database (https://www.ukmed.ac.uk). UK medical graduates who had attempted Part A (n=2585) and Part B (n=755) of the MRCS between 2014 and 2017 were included. χ2 and independent t-tests were used to examine the relationship between medical school performance and sociodemographic factors with first-attempt success at MRCS Part A and B. Multivariate logistic regression was employed to identify independent predictors of MRCS performance. The odds of passing MRCS increased by 55% for Part A (OR 1.55 (95% CI 1.48 to 1.61)) and 23% for Part B (1.23 (1.14 to 1.32)) for every additional EPM decile point gained. For every point awarded for additional degrees in the EPM, candidates were 20% more likely to pass MRCS Part A (1.20 (1.13 to 1.29)) and 17% more likely to pass Part B (1.17 (1.04 to 1.33)). For every point awarded for publications in the EPM, candidates were 14% more likely to pass MRCS Part A (1.14 (1.01 to 1.28)). SJT score was not a statistically significant independent predictor of MRCS success. This study has demonstrated the EPM's independent predictive power and found that medical school performance deciles are the most significant measure of predicting later success in the MRCS. These findings can be used by medical schools, training boards and workforce planners to inform evidence-based and contemporary selection and assessment strategies.


Quality of life in adult survivors of pediatric kidney transplantation.
There are few studies assessing long-term adult outcome and health-related quality of life (HRQOL) in former pediatric high-risk kidney transplant (TX) recipients. Twenty-one patients were assessed at mean age of 21.1 years. Mean age at first TX was 2.4 years. Brain arterial border zone infarcts had been documented in 54% of the children. HRQOL was assessed with the general 15-dimensional (15D) instrument generating an index on a 0 and 1 scale (1 for best). The results were compared with the corresponding childhood 17-dimensional instrument and an adult control group from the general population. Psychosocial adjustment was assessed with the ASEBA Adult Self Report (ASR) and compared with the childhood Child Behavior Checklist assessments. Half of the patients (52%) had a secondary level general or vocational education. The educational outcome was evenly distributed (compulsory vs. secondary) regardless of previous childhood brain ischemia. The ASR Total Problems score was in the normal range for all patients. Four patients had scores in the pathological range for Externalizing or Internalizing Problems. There was a correlation between the childhood Child Behavior Checklist problem scores and the adult ASR scores for Internalizing and Total Problems but not for Externalizing Problems. Their mean 15D HRQOL index was 0.94 and lower than for the control group (0.97, P=0.04). There was a strong correlation between the childhood 17-dimensional and the adult 15D HRQOL index (r=0.63, P=0.003). The long-term outcome is fair in former high-risk pediatric TX patients with neurological comorbidity. Childhood psychosocial adjustment and HRQOL may predict the outcome in adults.


Body mass index and old-age survival: a comparative study between the Union Army Records and the NHANES-I Epidemiological Follow-Up Sample.
On the basis of a historical review of the BMI trend among white male Americans since the late 19th century, this paper investigates the association between BMI measured at age 50-59 years and survival in the subsequent 18 years of follow-up through a comparative study between the Union Army Records (n = 1,238) and the 1971-1975 National Health and Nutritional Examination Survey Epidemiological Follow-up Sample (n = 861). A descriptive analysis of the trend in BMI suggests that the age-adjusted average BMI among adult white males has increased from 22.8 in the late 19th century to 28.0 in the year of 2000. The corresponding increase in the age-adjusted percentage of obesity is from 2.5% to 28.2%. Given the significant increase in BMI, it becomes important to evaluate how the BMI-mortality association has changed since the 19th century, and what implications these changes might have to mortality in the future. The results from the Cox proportional hazard analysis indicate that as the average BMI at population level increases, the optimal BMI in terms of survival increases, rather than stable. With the whole American population moving into a higher BMI regime, the optimal BMI in terms of old-age survival for white male Americans has experienced a substantial upward shift, from 20.6-23.6 in the late 19th century to 22.7-27.3 in the early 1970s. Mortality differentials across BMI quintiles have become more salient since the late 19th century. There is still good potential for old-age mortality to further decline. However, to what extent this potential can be developed will partially depend on the future trend in the prevalence of obesity.


Transcapillary osmotic flows in the in vitro perfused heart.
Hearts were removed from rabbits anesthetized with pentobarbitol sodium, heparinized, and then perfused through the aorta with Ringer solution. Addition of sucrose to the perfusate caused an osmotic transcapillary flow (Jv). Measurements of Jv with two independent methods, one using the rate of organ weight change and the other the variation of effluent concentration of an impermeant dye (Blue dextran), agreed very closely, giving an initial Jv per unit concentration and wet heart weight of 0.306 (microliters/s) (mmol/l).g (corrected for viscosity, 25 degrees C). Because dye dilution was free of vascular volume interference, its agreement with weight measurements suggests that vascular volume changes were relatively small. Measurements using 51Cr-labeled erythrocytes supported the above conclusion. The effect of temperature and concentration on Jv was ascribed to viscosity changes. Organ condition remained stable for several hours, based on maximum ventricular pressure (107 +/- 6.4 cmH2O) and dP/dt (1,145 +/- 98 cmH2O/s) values close to those in blood-perfused rabbit hearts. Repeat weight response to osmotic testing showed approximately 5% variation during an experiment.


Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens.
Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens. Antigen specificity of purified mc IgG from a large patient cohort (n = 244) was determined using a multiplex infectious-antigen array (MIAA), which screens for reactivity to purified antigens or lysates from 9 pathogens. Purified mc IgG from 23.4% of patients (57 of 244) specifically recognized 1 pathogen in the MIAA. EBV was the most frequent target (15.6%), with 36 of 38 mc IgGs recognizing EBV nuclear antigen-1 (EBNA-1). MM patients with EBNA-1-specific mc IgG (14.0%) showed substantially greater bone marrow plasma cell infiltration and higher β2-microglobulin and inflammation/infection-linked cytokine levels compared with other smoldering myeloma/MM patients. Five other pathogens were the targets of mc IgG: herpes virus simplex-1 (2.9%), varicella zoster virus (1.6%), cytomegalovirus (0.8%), hepatitis C virus (1.2%), and H. pylori (1.2%). We conclude that a dysregulated immune response to infection may underlie disease onset and/or progression of MGUS and MM for subsets of patients.


Further Progress Toward Automating Functional Analysis Interpretation.
It is considered best practice to conduct a functional analysis and visually inspect data collected to determine the function of problem behavior, which then informs the intervention approaches applied. Visual inspection has been described as a "subjective" process that may be affected by factors unrelated to the data. Structured decision-making guidelines have been established to address some of these shortcomings. The current paper is a follow-up to earlier work describing positive outcomes related to the viability of a decision support system based on structured criteria from Roane et al. Here, we demonstrate important improvements in a computer script's interpretation of functional analysis data, including improvement in agreement between the updated computer script version and experienced human raters (89%) compared to our original agreement outcomes (81%). This paper further supports the use of decision support systems for functional analysis interpretation.


Effect of L-arginine therapy on the glomerular injury of preeclampsia: a randomized controlled trial.
To assess the benefit of l-arginine, the precursor to nitric oxide, on blood pressure and recovery of the glomerular lesion in preeclampsia. Forty-five women with preeclampsia were randomized to receive either l-arginine or placebo until day 10 postpartum. Primary outcome measures including mean arterial pressure, glomerular filtration rate, and proteinuria were assessed on the third and 10th days postpartum by inulin clearance and albumin-to-creatinine ratio. Nitric oxide, cyclic guanosine 3'5' monophosphate, endothelin-1, and asymmetric-dimethyl-arginine and arginine levels were assayed before delivery and on the third and 10th days postpartum. Healthy gravid women provided control values. Assuming a standard deviation of 10 mm Hg, the study was powered to detect a 10-mm Hg difference in mean arterial pressure (alpha .05, beta .20) between the study groups. No significant differences existed between the groups with preeclampsia before randomization. Compared with the gravid control group, women with preeclampsia exhibited significantly increased serum levels of endothelin-1, cyclic guanosine 3'5' monophosphate, and asymmetric-dimethyl-arginine before delivery. Despite a significant increase in postpartum serum arginine levels due to treatment, no differences were found in the corresponding levels of nitric oxide, endothelin-1, cyclic guanosine 3'5' monophosphate, or asymmetric-dimethyl-arginine between the two groups with preeclampsia. Further, there were no significant differences in any of the primary outcome measures with both groups demonstrating similar levels in glomerular filtration rate and equivalent improvements in both blood pressure and proteinuria. Blood pressure and kidney function improve markedly in preeclampsia by the 10th day postpartum. Supplementation with l-arginine does not hasten this recovery. I.


Effects of dietary protein and lysine levels on plasma amino acids, nitrogen retention and egg production in laying hens.
The effects of dietary protein and graded dietary lysine levels on plasma free amino acids (PFAA), nitrogen retention and egg production in laying hens were studied. There were no significant differences in the PFAA pattern and nitrogen retention between hens fed 15% and 12% dietary protein whereas the hen-day egg production was greater with hens fed the 15% protein diet. Supplementing the 12% protein diet with a nonessential amino acid mixture at the 2% level improved egg production to the level of hens fed the 15% protein diet. When hens were fed a diet containing varying amounts of lysine, plasma lysine remained at relatively low levels until dietary lysine was increased to a level where egg production and nitrogen retention were maximized but therefore increased rapidly. When dietary lysine was increased, plasma concentrations of essential amino acids except methionine and lysine, half cystine and tyrosine tended to decrease. The plasma taurine concentration decreased when dietary lysine increased from 0.35% to 0.55%. Thereafter, it was the same as at 0.55% lysine. The dietary lysine requirement of laying hens determined by plasma free lysine, nitrogen retention and egg production were 677, 664 and 687 mg/hen/day, respectively. The PFAA technique appeared to be useful in evaluating the dietary requirement of laying hens for lysine and perhaps other amino acids.


Pericardial Graft vs. Host Disease in a Patient with β-Thalassemia Major.
Bone marrow transplantation (BMT) in young children improves results in β-thalassemia major. Graft versus host disease (GVHD) is an important complication of peripheral blood stem cell transplantation. GVHD affects heart with a behavior resembling an autoimmune disease, including pericardial effusion. We describe a 22-year-old β-thalassemia major patient who underwent bone marrow transplantation with an HLA-identical sibling donor. The patient didn't have any serious problem until 15 months after transplantation. He presented with chest discomfort and progressive dyspnea. Early echocardiogram showed mild pericardial effusion. Four days later, the effusion had increased, impending to cardiac temponade requiring pericardectomy. Immunospressive drugs and pericardectomy resulted in significant improvement in ventricular filling. Cardiac cGVHD, an un-common complication of HSCT may be presented as pericardial effusion. Although early initiation of steroids is very important, heart monitoring is necessary to diagnose cardiac temponade.


The Influence of Maturity Status on Drop Jump Kinetics in Male Youth.
Kumar, NTA, Radnor, JM, Oliver, JL, Lloyd, RS, CSCSD, Pedley, JS, Wong, MA, and Dobbs, IJ. The influence of maturity status on drop jump kinetics in male youth. J Strength Cond Res 38(1): 38-46, 2024-The aim of this study was to examine the effects of maturity status on drop jump (DJ) kinetics in young male athletes (categorized as early-pre-peak height velocity [PHV] [<-2.51 years], late-pre-PHV [-1.99 to -1.00 years], circa-PHV [-0.50 to 0.50 years], and post-PHV [>1.00 years]). All athletes performed a DJ from a 30-cm box onto force plates with performance variables (jump height, ground contact time, and reactive strength index) and absolute and relative kinetic variables during the braking and propulsive phases assessed. Subjects were categorized into GOOD (no impact-peak and spring-like), MODERATE (impact-peak and spring-like), or POOR (impact-peak and not spring-like) stretch-shortening cycle (SSC) function. The post-PHV group exhibited significantly greater values for most absolute kinetic variables compared with early-pre-PHV, late-pre-PHV, and circa-PHV (p < 0.05). The differences observed between consecutive maturity groups were similar in magnitude for most absolute variables (Cohen's d = 0.53-1.70). Post-PHV male athletes outperform their less mature counterparts during a DJ, and this may be attributed to the growth and maturity-related structural and motor control strategy changes that occur in children. Stretch-shortening cycle function in boys seems to improve with maturity status reflected by a greater number of post-PHV participants displaying GOOD SSC function (65.8%) and a greater number of early-pre-PHV participants displaying POOR SSC function (54.4%). However, a number of mature boys displayed POOR SSC function (17.8%), suggesting that the development of SSC function is not exclusively related to maturation.


[Radiodiagnostics of brain tumors before and after operation].
The radiation diagnosis made before and after operation was analyzed in 231 case histories of patients with brain tumors treated in hospitals of St.Petersburg in 2009. Most typical errors of administration and interpretation of radiation diagnostic methods were established. MRI was not performed in 54% of cases, in 32% operative intervention was performed without SCT findings. Contrast enhancement was used but in 68% of observations, angiographic methods--in 8%. Not a single radiation examination was performed in 61% of patients, in 33% SCT was made, in 6%--MRI, only in a third of patients contrast enhancement was used. In 52% of cases control radiation examination was not prescribed in dynamics. The estimation of the data obtained helped to obtain more exact criteria of using radiation methods in patients with tumors of the brain before and after operation.


Open reduction through a medial approach in developmental dislocation of the hip: a follow-up study to skeletal maturity.
Forty-four developmentally dislocated hips occurring in 30 patients with an average age at initial surgery of 10.7 (range 2-19) months underwent medial open reduction by Ferguson's approach. All patients were skeletally mature at most recent evaluation. Mean follow-up was 19.8 (range 13-27.5) years. No redislocation or sub-luxation occurred. Additional surgery was required in 11 hips (25%). Avascular necrosis was detected in nine hips (20%). The acetabular index was decreased and the center-edge angle was increased during follow-up. Excellent or good outcome (Severin group 1 or 2) was observed in 79% of the hips at skeletal maturity. At the most recent evaluation, all but two patients had the highest score on the Iowa Hip Rating. The authors conclude that open reduction through the medial approach is effective in developmental dislocation of the hip. Follow-up until skeletal maturity is necessary for an accurate assessment of treatment.


Spanish version of the Northwick Park Neck Pain Questionnaire: reliability and validity.
To validate a Spanish version of the Northwick Park Neck Pain Questionnaire (NPQ) and to prove its usefulness in clinical practice. We studied 58 patients with non-inflammatory neck pain of more than 4 months duration. A blind back translation of the NPQ was made, and the resulting back-translation version was then compared with the original. The NPQ comprises 9 questions with 5 statements of increasing difficulty. Patients completed the questionnaire 3 times: on their initial assessment; 8-10 days later (test-retest); and after physiotherapy treatment 3 months later. Neck pain was assessed by a visual analogue scale (VAS). Fifty-three patients completed the questionnaire (90%). There was a good intra-class correlation between the test-retest NPQ (r = 0.63), indicating good agreement. For each of the 9 sections, agreement ranged from r = 0.43 to r = 0.85, p < 0.05 in all cases. Correlation with the VAS was also good, between r = 0.51 (test) and r = 0.74 (retest) (p < 0.05 in all cases). Pain measured by the VAS increased according to the NPQ score, grouped by percentages (p = 0.003). The mean scores for each section increased with that of the intensity of pain, in most sections showing good internal consistency. Pain and the NPQ score improved after treatment (56.1 +/- 20.2 to 29.9 +/- 20.1, p = 0.0001 and 45.9% +/- 12.7% to 28.9% +/- 15.3%, p = 0.0001 respectively), as did all the other items except for driving (p < 0.05). The Spanish version of the NPQ is a feasible, reliable and valid instrument to measure pain in Spanish-speaking patients with chronic neck pain.


Hostility modifies the association between TV viewing and cardiometabolic risk.
It was hypothesized that television viewing is predictive of cardiometabolic risk. Moreover, people with hostile personality type may be more susceptible to TV-induced negative emotions and harmful health habits which increase occurrence of cardiometabolic risk. The prospective association of TV viewing on cardiometabolic risk was examined along with whether hostile personality trait was a modifier. A total of 3,269 Black and White participants in the coronary artery risk development in young adults (CARDIA) study were assessed from age 23 to age 35. A cross-lagged panel model at exam years 5, 10, 15, and 20, covering 15 years, was used to test whether hours of daily TV viewing predicted cardiometabolic risk, controlling confounding variables. Multiple group analysis of additional cross-lagged panel models stratified by high and low levels of hostility was used to evaluate whether the association was modified by the hostile personality trait. The cross-lagged association of TV viewing at years 5 and 15 on clustered cardiometabolic risk score at years 10 and 20 was significant (B = 0.058 and 0.051), but not at 10 to 15 years. This association was significant for those with high hostility (B = 0.068 for exam years 5 to 10 and 0.057 for exam years 15 to 20) but not low hostility. These findings indicate that TV viewing is positively associated with cardiometabolic risk. Further, they indicate that hostility might be a modifier for the association between TV viewing and cardiometabolic risk.


Effects of sodium artesunate, a new antimalarial drug, on renal function.
Sodium artesunate is currently used in malaria treatment. Adverse effects of this drug have not been described, probably because they cannot be differentiated from malaria-related effects. The effects on renal function of an acute infusion of sodium artesunate (12 mg/kg body weight) were studied in the rat with clearance techniques. We also evaluate the effect of sodium artesunate on chloride lumen-bath flux (Cl Jlb) in the isolated thick ascending limb of the loop of Henle (TALH) microperfused in vitro. Acute infusion of artesunate to the rat decreased inulin clearance, despite an increase in renal blood flow. These effects were associated with an increase in urinary excretion of sodium, chloride, potassium, and nitric oxide metabolites (NO(2)/NO(3)). In water-loaded animals, artesunate increased sodium and water distal delivery and decreased free water clearance (C(H(2)O)) factored for sodium and water delivery. Following hypertonic NaCl infusion, artesunate decreased free water excretion (Tc(H(2)O)) corrected by clearance of osmolarity (C(Osm)). In vitro, artesunate 10(-6) and 10(-3) mol/L added to bath solution decreased chloride lumen-bath flux in isolated rabbit TALH in a dose-dependent manner, with the threshold effect at 10(-4) mol/L. This effect was completely blocked by N(G)-nitroL-arginine-metilester (L-NAME) 5 mmol/L. Artesunate 10(-4) mol/L added to the perfusion solution did not change Cl Jlb. These findings suggest that artesunate decreases glomerular filtration rate and increases renal blood flow and urinary excretion of Na, Cl, and K. These effects were due, at least in part, to the inhibition of Cl transport across cortical and medullary TALH, and were mediated by local production of nitric oxide, since it is associated with an increase in NO(2)/NO(3) urinary excretion and it is blocked by L-NAME in vitro.


Recovery of protein structure from contact maps.
Prediction of a protein's structure from its amino acid sequence is a key issue in molecular biology. While dynamics, performed in the space of two-dimensional contact maps, eases the necessary conformational search, it may also lead to maps that do not correspond to any real three-dimensional structure. To remedy this, an efficient procedure is needed to reconstruct three-dimensional conformations from their contact maps. We present an efficient algorithm to recover the three-dimensional structure of a protein from its contact map representation. We show that when a physically realizable map is used as target, our method generates a structure whose contact map is essentially similar to the target. furthermore, the reconstructed and original structures are similar up to the resolution of the contact map representation. Next, we use nonphysical target maps, obtained by corrupting a physical one; in this case, our method essentially recovers the underlying physical map and structure. Hence, our algorithm will help to fold proteins, using dynamics in the space of contact maps. Finally, we investigate the manner in which the quality of the recovered structure degrades when the number of contacts is reduced. The procedure is capable of assigning quickly and reliably a three-dimensional structure to a given contact map. It is well suited for use in parallel with dynamics in contact map space to project a contact map onto its closest physically allowed structural counterpart.


Genetic Variants and Protective Immunity against SARS-CoV-2.
The novel coronavirus-19 (SARS-CoV-2), has infected numerous individuals worldwide, resulting in millions of fatalities. The pandemic spread with high mortality rates in multiple waves, leaving others with moderate to severe symptoms. Co-morbidity variables, including hypertension, diabetes, and immunosuppression, have exacerbated the severity of COVID-19. In addition, numerous efforts have been made to comprehend the pathogenic and host variables that contribute to COVID-19 susceptibility and pathogenesis. One of these endeavours is understanding the host genetic factors predisposing an individual to COVID-19. Genome-Wide Association Studies (GWAS) have demonstrated the host predisposition factors in different populations. These factors are involved in the appropriate immune response, their imbalance influences susceptibility or resistance to viral infection. This review investigated the host genetic components implicated at the various stages of viral pathogenesis, including viral entry, pathophysiological alterations, and immunological responses. In addition, the recent and most updated genetic variations associated with multiple host factors affecting COVID-19 pathogenesis are described in the study.


Coupled Air Quality and Boundary-Layer Meteorology in Western U.S. Basins during Winter: Design and Rationale for a Comprehensive Study.
Wintertime episodes of high aerosol concentrations occur frequently in urban and agricultural basins and valleys worldwide. These episodes often arise following development of persistent cold-air pools (PCAPs) that limit mixing and modify chemistry. While field campaigns targeting either basin meteorology or wintertime pollution chemistry have been conducted, coupling between interconnected chemical and meteorological processes remains an insufficiently studied research area. Gaps in understanding the coupled chemical-meteorological interactions that drive high pollution events make identification of the most effective air-basin specific emission control strategies challenging. To address this, a September 2019 workshop occurred with the goal of planning a future research campaign to investigate air quality in Western U.S. basins. Approximately 120 people participated, representing 50 institutions and 5 countries. Workshop participants outlined the rationale and design for a comprehensive wintertime study that would couple atmospheric chemistry and boundary-layer and complex-terrain meteorology within western U.S. basins. Participants concluded the study should focus on two regions with contrasting aerosol chemistry: three populated valleys within Utah (Salt Lake, Utah, and Cache Valleys) and the San Joaquin Valley in California. This paper describes the scientific rationale for a campaign that will acquire chemical and meteorological datasets using airborne platforms with extensive range, coupled to surface-based measurements focusing on sampling within the near-surface boundary layer, and transport and mixing processes within this layer, with high vertical resolution at a number of representative sites. No prior wintertime basin-focused campaign has provided the breadth of observations necessary to characterize the meteorological-chemical linkages outlined here, nor to validate complex processes within coupled atmosphere-chemistry models.


Polymorphism at the TNF-alpha gene interacts with Mediterranean diet to influence triglyceride metabolism and inflammation status in metabolic syndrome patients: From the CORDIOPREV clinical trial.
To examine whether the consumption of a Mediterranean diet (MedDiet), compared with a low-fat diet, interacts with two single nucleotide polymorphisms at the tumor necrosis factor alpha gene (rs1800629, rs1799964) in order to improve triglycerides (TG), glycemic control, and inflammation markers. Genotyping, biochemical measurements, dietary intervention, and oral fat load test meal were determined in 507 metabolic syndrome (MetS) patients selected from all the subjects included in CORDIOPREV clinical trial (n = 1002). At baseline, G/G subjects (n = 408) at the rs1800629 polymorphism, showed higher fasting and postprandial TG (p = 0.003 and p = 0.025, respectively), and high sensitivity C-reactive protein (hsCRP) (p = 0.003) plasma concentrations than carriers of the minor A-allele (G/A + A/A) (n = 99). After 12 months of MedDiet, baseline differences between genotypes disappeared. The decrease in TG and hsCRP was statistically significant in G/G subjects (n = 203) compared with carriers of the minor A-allele (p = 0.005 and p = 0.034, respectively) (n = 48). No other gene-diet interactions were observed in either diet. These results suggest that the rs1800629 at the tumor necrosis factor alpha gene interacts with MedDiet to influence TG metabolism and inflammation status in MetS subjects. Understanding the role of gene-diet interactions may be the best strategy for personalized treatment of MetS.


Auditory steady-state response audiometry in profound SNHL: the impact of abnormal middle ear function.
Auditory steady-state response (ASSR) audiometry is a commercially available tool that is used to predict behavioral auditory threshold levels. Its particular value stems from the technology's ability to measure frequency-specific responses in the background electroencephalogram to auditory stimuli presented across a broad range of frequencies and sound pressure levels. It is clearly of benefit when used to assess threshold levels in infants and children with severe-to-profound hearing impairment (i.e., cochlear implant candidates). Although numerous authors have provided evidence of the usefulness of ASSR testing, their reports have concerned patients whose middle ear impedance measures were normal. We report the cases of 2 patients who, following improvement of abnormal middle ear impedance values, experienced a marked improvement in measurable thresholds by ASSR testing.


Pharmacokinetics and tissue distribution of deferoxamine-based nanochelator in rats.
Aim: To characterize the pharmacokinetics of deferoxamine-conjugated nanoparticles (DFO-NPs), a novel nanochelator for removing excess iron. Materials & methods: The pharmacokinetics of DFO-NPs were evaluated in Sprague-Dawley rats at three doses (3.3, 10 and 30 μmol/kg) after intravenous and subcutaneous administration. Results: DFO-NPs exhibited a biphasic concentration-time profile after intravenous administration with a short terminal half-life (2.0-3.2 h), dose-dependent clearance (0.111-0.179 l/h/kg), minimal tissue distribution and exclusive renal excretion with a possible saturable reabsorption mechanism. DFO-NPs after subcutaneous administration exhibited absorption-rate-limited kinetics with a prolonged half-life (5.7-10.1 h) and favorable bioavailability (47-107%). Conclusion: DFO-NPs exhibit nonlinear pharmacokinetics with increasing dose, and subcutaneous administration substantially improves drug exposure, thereby making it a clinically viable administration route for iron chelation.


Concern, pressure and lack of knowledge affect choice of not wanting to know high-risk status.
The 'right not to know' one's genetic status has been increasingly more recognised in ethical and legal instruments. Yet empirical research is limited, leaving discussion on a theoretical level. There are also divergent ideas as to what extent it should be respected. In this study, we explored the clinical preconditions for disclosure of increased risk of getting diabetes in children. We included questions in the clinical 5-year questionnaire of a predictive screening for the risk of type 1 diabetes (T1DM), asking the respondents (n=7206) whether they wished to be informed of their children's potential risk status. The group of 2% of the respondents who did not want to know about risk status proved to be significantly associated to concern with natural history data (OR 4.03), lack of knowledge (OR 3.17), pressure to participate (OR 2.99) and the child's disease development (OR 2.18). We discuss whether parents'/participants' 'no' to high-risk information may call for a more nuanced response such as information and support, rather than simply respect their wish not to know. We furthermore argue that it is ethically questionable whether the parents' expressed wish not to know should prima facie override the potential benefits for their child. We conclude that this constitutes sufficient reason not to promote a default solution where people's expressed wishes not to know are taken at face value.


Treatment of intractable discogenic low back pain. A systematic review of spinal fusion and intradiscal electrothermal therapy (IDET).
A growing number of patients suffer from severe low back pain of discogenic origin that is not responsive to conservative medical management. These patients must consider the option of surgical spinal fusion or minimally-invasive intradiscal electrothermal therapy (IDET). To conduct a systematic review of clinical outcomes in patients undergoing spinal fusion or the intradiscal electrothermal therapy (IDET) procedure for intractable discogenic low back pain. Systematic literature review. English-language journal articles published from January 1995 to December 2005 were identified through computerized searches of the PubMed database and bibliographies of identified articles and review papers. Articles were selected if disc degeneration or disruption was the primary indication for spinal fusion or the IDET procedure and if follow-up outcome data included evaluations of back pain severity, condition-specific functional impairment and/or health-related quality of life. The literature reviewed encompassed 33 spinal fusion articles: 10 randomized controlled trials, 1 nonrandomized controlled trial, 9 before-after trials, and 13 case series. There were 18 IDET articles: 2 randomized controlled trial, 2 nonrandomized controlled trials, 11 before- after trials, and 3 case series. Data were extracted and summarized on patient characteristics, surgical methods, and clinical outcomes. Overall, there were similar median percentage improvements realized after spinal fusion and the IDET procedure, respectively, for 2 of the 3 outcomes evaluated: pain severity (50%, 51%), back function (42%, 14%) and quality of life (46%, 43%). There was an identifiable randomized controlled trials trend of both treatments reporting a smaller magnitude of improvement in all 3 primary outcomes (pain severity, back function, quality of life) compared to other types of trials. Perioperative complications were commonly associated with spinal fusion (median: 14%, range: 2% to 54%, n = 31 study groups) whereas adverse events were rarely experienced with the IDET procedure (median: 0%, range: 0% to 16%, n = 14 studies). Randomized controlled trials of spinal fusion, in particular, had important methodological limitations. The majority of patients reported improvement in symptoms following both spinal fusion and the IDET procedure. The IDET procedure appears to offer sufficiently similar symptom amelioration to spinal fusion without the attendant complications.


Colonic diverticular bleeding and predictors of the length of hospitalization: An observational study.
A significant percentage of patients with colonic diverticular bleeding (CDB) experience bleeding that is severe enough to necessitate prolonged hospitalization. Prolonged hospitalization causes deterioration in patients' quality of life, as well as difficulties with cost-effective utilization of medical resources, and is a financial burden to the society. Therefore, we investigated the factors associated with the length of hospitalization for the optimal management of patients hospitalized with CDB. This study included patients who were hospitalized for the treatment of CDB and underwent colonoscopy between July 2008 and February 2016. Logistic regression analysis was performed to investigate the association between the length of hospitalization and the patients' baseline characteristics, in-hospital procedures performed, and the clinical outcomes. The study included 223 patients. Diabetes mellitus (odds ratio [OR] 3.4, P = 0.014) and blood transfusion (OR 3.1, P = 0.0006) were identified as risk factors for prolonged hospitalization (≥ 8 days). Urgent colonoscopy (OR 0.41, P = 0.0072) predicted a shorter length of hospitalization (≤ 7 days). The study also indicated that endoscopic treatment showed a stronger association with urgent colonoscopy (OR 7.8, P < 0.0001) than with elective colonoscopy and that urgent colonoscopy was not associated with an increased rate of adverse events or re-bleeding. Compared with elective colonoscopy, urgent colonoscopy shortens the length of hospitalization in patients with CDB. Moreover, it is not associated with an increased rate of adverse events. Urgent colonoscopy may be impracticable in a few cases; however, if possible, aggressive urgent colonoscopy should be considered for the efficient management of the patient's hospital stay.


Effects of scopolamine and ketamine on reconsolidation of morphine conditioned place preference in rats.
Persistent memory associated with addictive drugs contributes to the relapse of drug abuse. The current study was conducted to examine the effects of scopolamine and ketamine on reconsolidation of morphine-induced conditioned place preference (CPP). In experiment 1, after morphine CPP was acquired, rats were injected with ketamine (60 mg/kg, intraperitoneally) and scopolamine (2 mg/kg, intraperitoneally), respectively, after reexposure to an earlier morphine-paired context or in their home cages. The CPP was reassessed 24 and 48 h after reexposure. An additional group of rats received saline following reexposure to the earlier morphine-paired context. In experiment 2, two groups of rats were only given saline during the CPP training and subsequent administration of ketamine or scopolamine during the reexposure. In experiment 1, rats failed to exhibit morphine CPP when ketamine and scopolamine were administered only after reexposure to a morphine-paired context. CPP was not abolished by ketamine or scopolamine administration in the animals' home cages. Also, the animals receiving only saline injections showed strong morphine CPP 24 h after a short exposure to the morphine-paired context. In experiment 2, ketamine or scopolamine treatment alone did not induce CPP or aversion. Administration of scopolamine and ketamine, after reexposure to a drug-paired context, resulted in the disruption of morphine CPP, suggesting the potential effects of scopolamine and ketamine in disrupting memory associated with environmental cues and addictive drugs.


Mandibular advancement devices in 630 men and women with obstructive sleep apnea and snoring: tolerability and predictors of treatment success.
To evaluate the tolerability and to find predictors of treatment success for an individually adjusted, one-piece mandibular advancement device in patients with snoring and obstructive sleep apnea. Prospective study. Departments of Respiratory Medicine and Orthodontics, Umeå University. Six hundred nineteen of 630 patients (98%), who consecutively received treatment for sleep apnea and snoring from February 1989 to August 2000, were followed up. They had a mean apnea-hypopnea index of 16 (range, 0.0 to 76) and a mean body mass index of 28 (range, 19 to 42). Interviews, questionnaires, and overnight sleep apnea recordings. Patients with an apnea-hypopnea index of >or=10 in the supine and/or lateral position were considered to have obstructive sleep apnea. A lateral apnea-hypopnea index of < 10, together with a supine apnea-hypopnea index of >or= 10, defined supine-dependent sleep apneas. One hundred forty-eight of the 619 patients (24%) discontinued treatment. Female gender predicted treatment success, defined as an apnea-hypopnea index of < 10 in both the supine and lateral positions, with an odds ratio of 2.4 (p = 0.01). In the women, the odds ratios for treatment success were 12 for mild sleep apnea (p = 0.04), and 0.1 for complaints of nasal obstruction (p = 0.03). In the men, the odds ratios for treatment success were 6.0 for supine-dependent sleep apneas (p < 0.001), 2.5 for mild sleep apnea (p = 0.04), 1.3 for each millimeter of mandibular advancement (p = 0.03), and 0.8 for each kilogram of weight increase (p = 0.001). The mandibular advancement device is recommended for women with sleep apnea, for men with supine-dependent sleep apneas defined by a lateral apnea-hypopnea index of < 10, and for snorers without sleep apnea. Men who increase in weight during treatment reduce their chance of treatment success and are advised to be followed up with a new sleep apnea recording with the device.


Macronutrient intakes and serum oestrogen, and interaction with polymorphisms in CYP19A1 and HSD17B1 genes: a cross-sectional study in postmenopausal Japanese women.
Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47-69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2-Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1·15 (95 % CI 1·04, 1·28) and 1·15 (95 % CI 1·04, 1·26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0·90 (95 % CI 0·82, 0·99), 0·89 (95 % CI 0·81, 0·98) and 0·91 (95 % CI 0·83, 1·00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.


Interleukin-1-induced nuclear factor-kappaB-IkappaBalpha autoregulatory feedback loop in hepatocytes. A role for protein kinase calpha in post-transcriptional regulation of ikappabalpha resynthesis.
The IkappaB inhibitors regulate the activity of the potent transcription factor nuclear factor-kappaB (NF-kappaB). Following signal-induced IkappaB proteolysis, NF-kappaB translocates into the nucleus to activate transcription of target genes, including IkappaBalpha itself, initiating the "NF-kappaB-IkappaBalpha autoregulatory feedback loop." Upon IkappaBalpha resynthesis, NF-kappaB is subsequently inactivated and redistributed back into the cytoplasm. We have previously reported a robust NF-kappaB-IkappaBalpha autoregulatory feedback loop in HepG2 hepatocytes. Sixty minutes after tumor necrosis factor (TNF-alpha) stimulation, IkappaBalpha is resynthesized to approximately 2-fold greater level than in control cells and completely inhibits NF-kappaB binding. Here we investigate the mechanism for IkappaBalpha resynthesis comparing the effect of stimulation of TNF-alpha with that of interleukin-1 (IL-1alpha). Although either TNF-alpha or IL-1alpha stimulation of protein kinase C (PKC)-down-regulated cells equivalently induces NF-kappaB translocation, the kinetics of IkappaBalpha resynthesis is slowed. Moreover, pretreatment with selective calcium-dependent PKC inhibitors selectively slowed the kinetics of the IL-1alpha-induced overshoot without affecting that produced by TNF-alpha. Down-regulation of PKCalpha by antisense phosphorothioate oligonucleotides and expression vectors selectively blocked the IL-1alpha-induced IkappaBalpha overshoot. In the absence of PKCalpha, although IL-1alpha induced similar amounts of IkappaBalpha transcription and changes in steady-state mRNA, a greater component of IkappaBalpha mRNA was retained in the nucleus. These data indicate a selective role for PKCalpha in IL-1alpha-induced IkappaBalpha resynthesis, which is mediated, at least in part, by post-transcriptional control of mRNA export.


Predation by an omnivorous fish and food availability alter zooplankton functional diversity: a microcosm approach.
Studies considering the functional traits of organisms, populations, and communities functional indices increase the understanding of many factors on ecosystem functioning. Here, we analyze the predation effect (by fish) on zooplankton functional diversity and the effects of biomass and density of periphytic algae on zooplankton feeding type trait and body size. We expect that intense predation by fish on zooplankton leads to higher values of zooplankton functional diversity and that food resource will be positively related to the abundance of zooplankton trait and body size. For that, microcosms were established (T1- fish-absence, and T2- fish-presence, both with periphytic algae as food). We observed that fish presence decreased zooplankton functional diversity through modifications in the availability of nutrients and algae, through the middle-out effect. We also observed that body size had a negative relationship with the food resource, reaffirming that high food availability in subtropical lakes is linked to small-bodied zooplankton. The raptorial copepods covariate positively with the periphytic algae, which was an alternative food resource and, in this case, the main form of carbon input into the system. In this study, omnivorous fish reduced zooplankton functional traits, which can alter the energy stock and energy flow in aquatic ecosystems.


Vaccine strategies against schistosomiasis: from concepts to clinical trials.
Schistosomiasis, the second major parasitic disease in the world after malaria, affects 200 million people. Vaccine strategies represent an essential component of the control of this chronic debilitating disease where the deposition of millions of eggs in the tissues is the main cause of pathology. Research developed in our laboratory over the last 20 years has led to the identification of novel effector mechanisms, pointing for the first time to the protective role of Th2 responses and of IgE antibodies now supported by seven studies in human populations. The identification and molecular cloning of a target antigen, a glutathione S-transferase (GST), has made it possible to demonstrate its vaccine potential in several animal species (rodents, cattle, primates) and to establish consistently the capacity of vaccination to reduce female worm fecundity and egg viability through the production of neutralizing antibodies (IgA and IgG). Following promising preclinical studies, clinical trials (phase I and II) have been undertaken using Schistosoma haematobium GST, Sh28GST. High titers of neutralizing antibodies were produced (IgG3 and IgA) together with Th2 cytokines, consistently with the concepts developed from experimental models. With these results we are on the way towards a feasible approach of vaccine development against a major human parasitic disease.


The value of combined pulsed-Doppler and high-resolution real-time sonography of the extracranial carotid system.
Duplex carotid sonography (DCS) (high-resolution real-time with combined pulsed Doppler) was performed in 374 symptomatic patients. Biplane angiographic correlation was available in 172 extracranial carotid systems. Degree of stenosis was estimated by the Doppler spectrum and by real-time appearances and categorized as: normal; less than 10% diameter reduction; 10-49% diameter reduction; 50-99% diameter reduction; or occlusion. The overall accuracy of sonography was 88%. Normal arteries were identified with a specificity of 96% and a positive predictive value of 97%. Hemodynamically, significant lesions were differentiated from less severe disease with an accuracy of 95%, a positive predictive value of 87%, and a negative predictive value of 100%. Occlusions were identified with a sensitivity of 80% and a positive value of 91%. Duplex sonography is an accurate, noninvasive method of evaluating the extracranial carotid system.


Sleep and sleepiness 1 and 9 months after cataract surgery.
This study was undertaken to analyze sleep development in a group of patients during the first 9 months after cataract extraction. Men and women (n=407) undergoing cataract surgery at the Department of Ophthalmology, Sundsvall Hospital during two periods in 2000-2002 were asked to complete a questionnaire on the state and change of sleep and sleepiness 1 and 9 months after the operation. The response rate was 90.8%. The mean ages of the participating men and women were 74.5 and 75.6 years, respectively. One week after cataract extraction the visual acuity in the treated eye was 0.67 (+/-0.31) in men and 0.69 (+/-0.28) in women (NS), and showed an inverse relationship to age in both men (P<0.01) and women (P<0.0001). One month after cataract extraction 28.3% of the men and 37.5% of the women experienced poor sleep, and after 9 months the figures were 15.8 and 31.4%, respectively. Frequent awakenings and difficulty in falling asleep after nocturnal awakenings improved correspondingly. Being well rested in the morning increased and daytime sleepiness decreased. The results indicate that in elderly persons with cataract sleep is improved 1 month after cataract extraction and further improvement during the first 9 months may be experienced.


Accelerating the speed of innovative anti-tumor drugs to first-in-human trials incorporating key de-risk strategies.
Pharmaceutical companies have recently focused on accelerating the timeline for initiating first-in-human (FIH) trials to allow quick assessment of biologic drugs. For example, a stable cell pool can be used to produce materials for the toxicology (Tox) study, reducing time to the clinic by 4-5 months. During the coronavirus disease 2019 (COVID-19) pandemic, the anti-COVID drugs timeline from DNA transfection to the clinical stage was decreased to 6 months using a stable pool to generate a clinical drug substrate (DS) with limited stability, virus clearance, and Tox study package. However, a lean chemistry, manufacturing, and controls (CMC) package raises safety and comparability risks and may leave extra work in the late-stage development and commercialization phase. In addition, whether these accelerated COVID-19 drug development strategies can be applied to non-COVID projects and established as a standard practice in biologics development is uncertain. Here, we present a case study of a novel anti-tumor drug in which application of "fast-to-FIH" approaches in combination with BeiGene's de-risk strategy achieved successful delivery of a complete CMC package within 10 months. A comprehensive comparability study demonstrated that the DS generated from a stable pool and a single-cell-derived master cell bank were highly comparable with regards to process performance, product quality, and potency. This accomplishment can be a blueprint for non-COVID drug programs that approach the pace of drug development during the pandemic, with no adverse impact on the safety, quality, and late-stage development of biologics.


Anaerobic oxidation of long-chain n-alkanes by the hyperthermophilic sulfate-reducing archaeon, Archaeoglobus fulgidus.
The thermophilic sulfate-reducing archaeon Archaeoglobus fulgidus strain VC-16 (DSM 4304), which is known to oxidize fatty acids and n-alkenes, was shown to oxidize saturated hydrocarbons (n-alkanes in the range C10-C21) with thiosulfate or sulfate as a terminal electron acceptor. The amount of n-hexadecane degradation observed was in stoichiometric agreement with the theoretically expected amount of thiosulfate reduction. One of the pathways used by anaerobic microorganisms to activate alkanes is addition to fumarate that involves alkylsuccinate synthase as a key enzyme. A search for genes encoding homologous enzymes in A. fulgidus identified the pflD gene (locus-tag AF1449) that was previously annotated as a pyruvate formate lyase. A phylogenetic analysis revealed that this gene is of bacterial origin and was likely acquired by A. fulgidus from a bacterial donor through a horizontal gene transfer. Based on three-dimensional modeling of the corresponding protein and molecular dynamic simulations, we hypothesize an alkylsuccinate synthase activity for this gene product. The pflD gene expression was upregulated during the growth of A. fulgidus on an n-alkane (C16) compared with growth on a fatty acid. Our results suggest that anaerobic alkane degradation in A. fulgidus may involve the gene pflD in alkane activation through addition to fumarate. These findings highlight the possible importance of hydrocarbon oxidation at high temperatures by A. fulgidus in hydrothermal vents and the deep biosphere.


Activation of mu- and delta-opioid receptors causes presynaptic inhibition of glutamatergic excitation in neocortical neurons.
The mechanism underlying the depressant effect of opioids on neuronal activity within the neocortex is still not clear. Three modes of action have been suggested: (1) inhibition by activation of postsynaptic potassium channels, (2) interaction with postsynaptic glutamate receptors, and (3) presynaptic inhibition of glutamate release. To address this issue, the authors investigated the effects of mu- and delta-receptor agonists on excitatory postsynaptic currents (EPSCs) and on membrane properties of neocortical neurons. Intracellular recordings were performed in rat brain slices. Stimulus-evoked EPSCs mediated by different glutamate receptor subtypes were pharmacologically isolated, and opioids were applied by addition to the bathing medium. Possible postsynaptic interactions between glutamate and opioid receptors were investigated using microiontophoretic application of glutamate on neurons functionally isolated from presynaptic input. delta-Receptor activation by d-Ala2-d-Leu5-enkephalin (DADLE) reduced the amplitudes of EPSCs by maximum 60% in a naltrindole-reversible manner (EC50: 6-15 nm). In 30-40% of the neurons investigated, higher concentrations (0.1-1 micrometer) of DADLE activated small outward currents. The mu-receptor selective agonist d-Ala2-N-MePhe5-Gly5-ol-enkephalin (0.1-1 micrometer) depressed the amplitudes of EPSCs by maximum 30% without changes in postsynaptic membrane properties. In the absence of synaptic transmission, inward currents induced by microiontophoretic application of glutamate were not affected by DADLE. Activation of mu- and delta-opioid receptors depresses glutamatergic excitatory transmission evoked in neocortical neurons by presynaptic inhibition. A weak activation of a postsynaptic potassium conductance becomes evident only at high agonist concentrations. There is no evidence for a postsynaptic interaction between glutamate and opioid receptors.


Chemical regulation of body feather microbiota in a wild bird.
The microbiota has a broad range of impacts on host physiology and behaviour, pointing out the need to improve our comprehension of the drivers of host-microbiota composition. Of particular interest is whether the microbiota is acquired passively, or whether and to what extent hosts themselves shape the acquisition and maintenance of their microbiota. In birds, the uropygial gland produces oily secretions used to coat feathers that have been suggested to act as an antimicrobial defence mechanism regulating body feather microbiota. However, our comprehension of this process is still limited. In this study, we for the first time coupled high-throughput sequencing of the microbiota of both body feathers and the direct environment (i.e., the nest) in great tits with chemical analyses of the composition of uropygial gland secretions to examine whether host chemicals have either specific effects on some bacteria or nonspecific broad-spectrum effects on the body feather microbiota. Using a network approach investigating the patterns of co-occurrence or co-exclusions between chemicals and bacteria within the body feather microbiota, we found no evidence for specific promicrobial or antimicrobial effects of uropygial gland chemicals. However, we found that one group of chemicals was negatively correlated to bacterial richness on body feathers, and a higher production of these chemicals was associated with a poorer body feather bacterial richness compared to the nest microbiota. Our study provides evidence that chemicals produced by the host might function as a nonspecific broad-spectrum antimicrobial defence mechanism limiting colonization and/or maintenance of bacteria on body feathers, providing new insight about the drivers of the host's microbiota composition in wild organisms.


Use of non-invasive serum glycan markers to distinguish non-alcoholic steatohepatitis from simple steatosis.
Serum glycans have been reported to be promising diagnostic markers for many inflammatory diseases and cancers. The aims of this study were to investigate whole glycan expression in patients with non-alcoholic fatty liver diseases and to evaluate the potential use of glycan profiles as new clinical biomarkers to distinguish non-alcoholic steatohepatitis (NASH) from simple steatosis (SS). We collected sera from 42 histologically proven NASH and 15 SS patients prior to treatment. Serum glycan profiles were measured by comprehensive, quantitative, high-throughput glycome analysis, and diagnostic values of serum glycans for NASH prediction were examined. Among the 41 serum glycans examined, the expression levels of 8 glycans in NASH were significantly higher than those of SS. Out of these eight glycans, three glycans (m/z 1955, 2032, and 2584) showed high areas under the receiver operating characteristic curve (0.833, 0.863, and 0.866, respectively) for distinguishing NASH from SS. In multivariate analyses with clinical parameters and serum glycans, these three glycans were significant predictive factors for distinguishing NASH from SS. The odds ratio of m/z 1955, 2032, and 2584 were 48.5, 6.46, and 11.8, respectively. These glycans also correlated significantly with lobular inflammation, ballooning, and fibrosis, but not with steatosis. We clearly demonstrated whole-serum glycan profiles in NASH patients, and the feasibility of serum glycans (m/z 1955, 2032, and 2584) as new noninvasive biomarkers for distinguishing NASH from SS.


lncRNA KCNQ1OT1 enhances the chemoresistance of oxaliplatin in colon cancer by targeting the miR-34a/ATG4B pathway.
The chemoresistance of colon cancer to oxaliplatin (L-OHP) indicates poor prognosis. Long non-coding RNA (lncRNA) KCNQ1OT1 (KCNQ1 opposite strand/antisense transcript 1) has been shown to participate in the tumorigenesis of several types of cancers. However, little is known about the role of KCNQ1OT1 in the chemoresistance and prognosis of colon cancer. Quantitative-PCR and Western blot were used to measure the expression profiles of KCNQ1OT1, miR-34a, and Atg4B in colon cancer tissues and cells. Cell viability assay and flow cytometry were used to examine their effects on cell proliferation and death. Cleavage of LC3 and GFP-LC3 plasmid transfection were used to detect autophagic activity. Double luciferase reporter assay was used to verify the interactions between miRNA and lncRNA or mRNA. Xenograft tumor model was used to verify the effects of KCNQ1OT1 in vivo. In this study, it is shown that the expression level of KCNQ1OT1 was increased in tumor, which indicated poor prognosis in colon cancer patients. Using colon cancer cell lines HCT116 and SW480, it was demonstrated that knockdown of KCNQ1OT1 decreased the cell viability and increased the apoptosis rates upon L-OHP treatment. Further studies indicated that Atg4B upregulation was partially responsible for KCNQ1OT1-induced protective autophagy and chemoresistance. Moreover, miR-34a functioned as a bridge between KCNQ1OT1 and Atg4B, which could be sponged by KCNQ1OT1, while it could also bind to the 3'-UTR of Atg4B and downregulate its expressions. Finally, we show that the KCNQ1OT1/miR-34a/Atg4B axis regulated the chemoresistance of colon cancer cells in vitro and in vivo. lncRNA KCNQ1OT1 promoted the chemoresistance of colon cancer by sponging miR-34a, thus upregulating the expressions of Atg4B and enhancing protective autophagy. KCNQ1OT1 might become a promising target for colon cancer therapeutics.


Extending the Phenotypic Spectrum of Huntington Disease: Hypothermia.
Huntington disease (HD) is an autosomal dominant progressive neurodegenerative disorder associated with expanded CAG repeat size in the huntingtin gene and usually presenting with movement disorder, psychiatric symptoms, and cognitive decline. Sleep problems, weight loss, and cachexia are also common. Here, we report a patient presenting with hypothermia in late-stage HD. Although thermoregulatory defects were documented in animal models, this is the first report describing HD with hypothermia in humans.


Effects of risperidone on auditory information processing in neuroleptic-naive patients with schizophrenia spectrum disorders.
Early effects of risperidone (2.5 +/- 1 mg/day) on auditory information processing were investigated in 9 neuroleptic naive patients with schizophrenia spectrum disorders and 9 healthy controls by using event-related potentials (ERPs). ERPs were elicited during active auditory "oddball" paradigm and were recorded before and after two weeks of treatment. Baseline P3 latencies were significantly delayed in patient group. Risperidone treatment did not change P3 amplitudes and latencies. However, P2 amplitudes were reduced in parallel with the clinical improvement measured by Positive and Negative Syndrome Scale (PANSS). Although risperidone did not change neural bases of active attention after two weeks of treatment, the reduction of P2 amplitude suggests that risperidone may affect auditory information processing in patients with schizophrenia spectrum disorders who never have been exposed to antipsychotic treatment.


What is narrative therapy and what is it not?: the usefulness of Q methodology to explore accounts of White and Epston's (1990) approach to narrative therapy.
OBJECTIVE. 'What is narrative therapy and how do you do it?' is a question that is repeatedly asked of narrative therapy, with little consistent response. This study aimed to explore and distil out the 'common themes' of practitioner definitions of White and Epston's approach to narrative therapy. DESIGN. This was an Internet-based study involving current UK practitioners of this type of narrative therapy using a unique combination of a Delphi Panel and Q methodology. METHOD. A group of experienced practitioners were recruited into the Delphi Poll and were asked two questions about what narrative therapy is and is not, and what techniques are and are not employed. These data combined with other information formed the statements of a Q-sort that was then administered to a wider range of narrative practitioners. FINDINGS. The Delphi Panel agreed on a number of key points relating to the theory, politics and practice of narrative therapy. The Q-sort produced eight distinct accounts of narrative therapy and a number of dimensions along which these different positions could be distinguished. These included narrative therapy as a political stance and integration with other approaches. CONCLUSIONS. For any therapeutic model to demonstrate its efficacy and attract proponents, an accepted definition of its components and practice should preferably be established. This study has provided some data for the UK application of White and Epston's narrative therapy, which may then assist in forming a firmer base for further research and practice.


Serum levels of the interferon-gamma-inducible alpha chemokine CXCL10 in patients with active Graves' disease, and modulation by methimazole therapy and thyroidectomy.
The interferon-gamma-inducible chemokine CXCL10 is highly expressed in infiltrating inflammatory cells, and in thyrocytes in patients with Graves' disease. The aim of this study was to measure serum levels of CXCL10 in relation to thyroid function and treatment. Serum levels of CXCL10 were measured in 22 patients with Graves' disease when hyperthyroid, when euthyroid under methimazole therapy, and 3 days after near-total thyroidectomy. They were compared with levels in three groups of age- and sex-matched controls: 44 subjects with no thyroid disorder, 44 patients with euthyroid autoimmune thyroiditis and 20 with toxic nodular goitre. Basal serum levels of CXCL10 in patients with Graves' disease were higher than levels in patients with toxic nodular goitre or no thyroid disorder, and similar to levels in patients with autoimmune thyroiditis (mean(s.d.) 167(121), 100(24), 78(46) and 142(107) pg/ml respectively; P < 0.010). Among patients with Graves' disease, serum levels of CXCL10 were significantly higher in those aged over 50 years (P = 0.010), with a hypoechoic pattern at thyroid ultrasonography (P < 0.001) or with hypervascularity (P = 0.001). CXCL10 levels in patients with Graves' disease decreased significantly when euthyroidism was achieved by methimazole therapy (P < 0.010), and a further decrease was observed after thyroidectomy (P < 0.010). Serum levels of CXCL10 are higher in newly diagnosed hyperthyroid patients with Graves' disease than in those with toxic nodular goitre, and decrease when euthyroidism is achieved with antithyroid therapy. This high level may be related to the active inflammatory phase of Graves' disease. A further reduction of CXCL10 levels after thyroidectomy indicates that it is produced mainly in the thyroid in patients with autoimmune thyroid disease.


An assessor-blinded, randomized comparative trial of transcutaneous auricular vagus nerve stimulation (taVNS) combined with cranial electroacupuncture vs. citalopram for depression with chronic pain.
Depression accompanying chronic pain (CP) is one of the most common comorbid psychiatric disorders. This study aimed to investigate the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) combined with electroacupuncture at Baihui (GV20) and Yintang (GV29) acupoints compared with citalopram. Sixty patients with depression and pain comorbidity were enrolled in a prospective 8-week, single-blind, randomized controlled trial. Participants were randomly assigned to receive either taVNS combined with electroacupuncture treatment (taVNS: 8 weeks, 3 sessions per week; electroacupuncture: 8 weeks, twice per day, no drugs) or citalopram treatment (8 weeks, 40 mg/day). The primary outcome was Montgomery-Åsberg Depression Rating Scale (MADRS). The secondary endpoints were evaluated using the McGill Pain Questionnaire (SF-MPQ), self-reported 36-Item Short Form Survey (SF-36), Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Scale (HAMA). Both the taVNS combined with electroacupuncture and citalopram groups had significant reductions in depressive and pain symptoms, as indicated by the decrease in MARDS and SF-MPQ scores. Regarding the analgesic effect, the pain intensity score of the SF-MPQ showed a larger reduction with citalopram than with taVNS combined with electroacupuncture at 6 weeks (P = 0.036). The reduction in the BP score of the SF-36 was higher at week 4 (P = 0.000), with no significant difference observed at week 8 (P = 0.1110). This result indicated that the pain intensity can be improved rapidly with citalopram compared with taVNS combined with electroacupuncture. Similarly, the comparison of PSQI scores at 4, 6, and 8 weeks indicates that there was no significant difference between groups, except in the use of sleeping medications. At week 6, higher medication use was found in the citalopram group than in the taVNS combined with electroacupuncture group (P = 0.049). In summary, compared with citalopram, taVNS combined with electroacupuncture produces similar positive effects on depressive and pain symptoms in patients with depression and chronic pain, which last for at least 8 weeks.


Antisocial and human capital pathways to socioeconomic exclusion: A 42-year prospective study.
Nordic welfare states have been very successful at reducing poverty and inequality among their citizens. However, the presence of a strong social safety net in these countries has not solved the problem of socioeconomic exclusion, manifesting in such outcomes as chronic unemployment and welfare dependency. In an effort to understand this phenomenon, the current study builds on the assumption that psychological risk factors emerge as important determinants of socioeconomic disadvantage in an environment where ascribed characteristics have less impact on educational and occupational attainment. Using data from Finland, this research examined a life course model linking childhood differences in cognitive skills and antisocial propensity to midlife socioeconomic exclusion. The Jyväskylä Longitudinal Study of Personality and Social Development (n = 369) follows individuals from age 8 (b. 1959) through age 50. Evidence from a structural equation model found support for key theoretical predictions: (a) human capital and antisocial pathways contributed independently to socioeconomic exclusion; (b) the effect of childhood psychological factors on midlife socioeconomic exclusion was mediated by adolescent and adult life course outcomes; and (c) the human capital and antisocial domains intersected such that antisocial children struggled in school as adolescents, which contributed to their persistence in crime and deviance in adulthood-a behavioral pattern that directly increased the risk of socioeconomic exclusion in midlife. In short, the findings suggest that early emerging differences in cognitive ability and antisociality set in motion a process of negative life outcomes with enduring consequences for socioeconomic well-being. The results are discussed from the perspective of sociohistorical context and public policy. (PsycINFO Database Record


Severe tinnitus in a patient with acquired deafness for over 50 years: a case report.
There have been many reports on the treatment effect of cochlear implantation and hearing aids in the treatment of tinnitus in patients with severe hearing loss. However, as far as we are aware, there are no reports of investigation of treatment approaches for the tinnitus of deaf patients whose communication is solely carried out in sign language due to a long duration of deafness. We experienced a case of severe tinnitus with bilateral deafness for more than 50 years. The patient is a 69-year-old woman who communicates with her family solely in sign language. Family stress triggered the onset of tinnitus, accompanied by sleep disorder and palpitations. At the initial visit, she suffered from severe tinnitus (THI 94) as well as strong tendencies toward depression and anxiety. Because neither the patient nor her family was willing to use cochlear implantation, the administration of an antidepressant and a sleep-inducing agent was started, which resulted in improvement of the psychological conditions. Tinnitus distress, synchronized with the heartbeat, was relieved by the addition of autogenic training. At four and half years after the initial visit, the THI score had dropped to 0, and the subjective tinnitus and palpitation had almost disappeared, with only a low dose of antidepressant necessary. A deaf patient with severe tinnitus was successfully treated with drug and psychotherapy.


Transmission on an active electrical response between fibroblasts (L cells) in cell culture.
An active electrical response, the hyperpolarizing activation or H.A. response, is characteristic of L cells (a continuous line of fibroblasts) and is transmitted in a decremental manner between contiguous cells. Direct electrical coupling between pairs of L cells occurs occasionally, but transmission of the active electrical response is not dependent on such electrical connections. Some L cells are sensitive to acetylcholine but the transmitted response is not dependent on a cholinergic mechanism. 5-Iodosalicylate blocks the active electrical response. The response can be elicited readily by mechanical stimuli, and thus can serve both as a mechanical and chemical receptor mechanism and as a means of communication between cells.


Cloning and characterization of the gene for beta-tubulin from a benomyl-resistant mutant of Neurospora crassa and its use as a dominant selectable marker.
We cloned the beta-tubulin gene of Neurospora crassa from a benomyl-resistant strain and determined its nucleotide sequence. The gene encodes a 447-residue protein which shows strong homology to other beta-tubulins. The coding region is interrupted by six introns, five of which are within the region coding for the first 54 amino acids of the protein. Intron position comparisons between the N. crassa gene and other fungal beta-tubulin genes reveal considerable positional conservation. The mutation responsible for benomyl resistance was determined; it caused a phenylalanine-to-tyrosine change at position 167. Codon usage in the beta-tubulin gene is biased, as has been observed for other abundantly expressed N. crassa genes such as am and the H3 and H4 histone genes. This bias results in pyrimidines in the third positions of 96% of the codons in codon families in which there is a choice between purines and pyrimidines in this position. Bias is also evident by the absence of 19 of the 61 sense codons. We demonstrated that benomyl resistance is due to the cloned beta-tubulin gene of strain Bml511(r)a and that this gene can be used as a dominant selectable marker in N. crassa transformation.


Rituximab treatment for fibrillary glomerulonephritis.
Approximately 50% of patients with fibrillary glomerulonephritis (GN) progress to end-stage renal disease (ESRD) within 2 years of diagnosis, and no standard therapy exists. The data on rituximab therapy for fibrillary GN are limited and have inconsistent outcomes. Here, we report the largest case series to date using rituximab for fibrillary GN. Retrospective chart reviews were conducted on 12 patients with fibrillary GN who were treated with rituximab (1 g i.v. × 2 doses or 375 mg/m(2) × 4 doses) at the Center for Glomerular Diseases at Columbia University Medical Center. Non-progression of disease was defined as stable/improved serum creatinine (SCr) with a minimum of 1 year of follow-up. The median SCr was 2.1 (range 0.7-2.7) mg/dL, median estimated glomerular filtration rate (eGFR) 39 (range 21-98) mL/min/1.73 m(2) and median proteinuria 4497 (range 210-7542) mg/day at the time of rituximab initiation. Four patients had received immunosuppression before rituximab, and nine received immunosuppression after rituximab, with four receiving a second rituximab course. Four of 12 patients were non-progressors, 3 of 12 had progressive renal dysfunction without reaching ESRD, and 5 patients reached ESRD. The median follow-up for patients who did not reach ESRD was 38 (range 14-76) months after rituximab treatment. Non-progressors had lower SCr values, higher eGFRs and shorter median duration from diagnosis to treatment than progressors. No serious adverse events were noted. Rituximab therapy was associated with non-progression of renal disease in 4 of 12 patients. At the time of treatment, these non-progressors had better renal function and shorter time from diagnosis to treatment than progressors.


A Glimpse of Membrane Transport through Structures-Advances in the Structural Biology of the GLUT Glucose Transporters.
The cellular uptake of glucose is an essential physiological process, and movement of glucose across biological membranes requires specialized transporters. The major facilitator superfamily glucose transporters GLUTs, encoded by the SLC2A genes, have been a paradigm for functional, mechanistic, and structural understanding of solute transport in the past century. This review starts with a glimpse into the structural biology of membrane proteins and particularly membrane transport proteins, enumerating the landmark structures in the past 25years. The recent breakthrough in the structural elucidation of GLUTs is then elaborated following a brief overview of the research history of these archetypal transporters, their functional specificity, and physiological and pathophysiological significances. Structures of GLUT1, GLUT3, and GLUT5 in distinct transport and/or ligand-binding states reveal detailed mechanisms of the alternating access transport cycle and substrate recognition, and thus illuminate a path by which structure-based drug design may be applied to help discover novel therapeutics against several debilitating human diseases associated with GLUT malfunction and/or misregulation.


Individualized Nursing Interventions in Patients with Comorbid Chronic Obstructive Pulmonary Disease and Chronic Heart Failure.
Individuals with chronic obstructive pulmonary disease (COPD) are more likely to develop heart failure (HF) compared with the general population, and the presence of HF may contribute to reduced quality of life (QoL), increased hospitalizations and worse survival rates in patients with COPD. Our study examined the exercise capacity, QoL, mental health, family burden and rehospitalization rate of patients with comorbid COPD and chronic heart failure (CHF) after individualized inpatient and outpatient nursing care. A total of 100 patients with comorbid COPD and CHF admitted to Affiliated Hospital of Jiangnan University January 2021 to July 2022 were enrolled in our study and then randomly assigned to one of two groups of 50 patients: patients receiving traditional nursing care and patients receiving individualized nursing care. Exercise capacity, mental health, QoL and family burden were assessed by means of the 6-minute walk test (6MWT), Zung's Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), the short-form health survey (SF-36) and the Perceived Family Burden Scale (PFBS). The patients receiving individualized nursing care had notable differences regarding distance walked in the 6MWT, the scores in all domains of both the physical and mental composites, SAS and SDS scores and PFBS scores of patients at on admission (T0), at discharge (T1) and at 2 months after discharge (T2) (P < .05). The patients receiving individualized nursing care walked longer distances on the 6MWT, more scores reflecting improved QoL and reduced SAS and SDS scores at both T1 and T2 compared with patients receiving traditional nursing care (P < .05). The patients receiving individualized nursing care exhibited decreased PFBS scores at T2 compared with patients receiving traditional nursing care (P < .05). None of the patients receiving individualized nursing care were rehospitalized, but 2 patients receiving traditional nursing care were rehospitalized due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and acute HF, respectively. Our study demonstrates that individualized inpatient and outpatient nursing care can enhance exercise capacity and improve QoL and mental health in patients with comorbid COPD and CHF.


Elastase inhibitors of sputum sol phase: variability, relationship to neutrophil elastase inhibition, and effect of corticosteroid treatment.
The concentrations of three known elastase inhibitors (alpha 1 proteinase inhibitor, antileucoprotease, and alpha 2 macroglobulin) have been determined in the sputum of six patients with obstructive bronchitis over five consecutive days. Antileucoprotease was the major inhibitor measured and potentially could provide more than 80% of the elastase inhibition, whereas the contribution of alpha 2 macroglobulin was less than 0.2%. Comparison with the inhibitory capacity of the secretions active against human neutrophil elastase showed that the inhibitors could account for only about half of the inhibition measured. This suggests the presence of a substantial amount of unrecognised inhibitor. Corticosteroid treatment in 10 patients reduced the mean alpha 1 proteinase inhibitor concentration (p less than 0.025) from 18.6 micrograms/ml (SD 22.5) to 9.8 (6.6). Antileucoprotease, however, increased (p less than 0.05) from 20.5 micrograms/ml (24.3) to 39.3 (23.4). These changes were associated with an increase in elastase inhibition (p less than 0.025) from 180 (160) micrograms elastase/ml secretion to 310 (130), suggesting a beneficial effect of steroid treatment on the antielastases in lung secretions.


[Primary diagnosis in acute adnexitis].
Though acute salpingitis is the most frequent gynecological illness of a young woman, it occurs nevertheless less frequently than it is diagnosed. The reason for this is to be found above all in the fact, that the criteria of the findings are judged too superficially. If simple anamnestic, clinical or biochemical parameters such as the characteristics and duration of the pain, the findings of gynecological examination, BSR and considerations about differential diagnosis were rated more precisely, considerably fewer cases would have to be assigned to laparoscopy and the elucidation of the indistinct abdominal pains could be started more efficiently.


Detection of human papillomavirus genotypes, herpes simplex, varicella zoster and cytomegalovirus in breast cancer patients.
The role of viruses as a cause of breast cancer (BC) has been significantly investigated in recent years. Human papillomavirus (HPV) has been detected in invasive breast carcinomas, while most studies have only focused on the detection of viral DNA, we aimed to examine the prevalence and genotypes of HPV among Iranian BC patients. We also examined the presence of herpes simplex-1 (HSV-1), herpes simplex-2 (HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV) in these samples. We collected and analyzed 70 Formalin-Fixed Paraffin-Embedded (FFPE) blocks including 59 BC samples, and 11 benign breast lesions as control from Iranian patients using nested PCR. Real-time PCR utilized as a confirming test to nested PCR findings. Genotyping of HPV positive samples was performed, the samples were also subjected to a multiplex PCR to detect HSV-1, HSV-2, VZV, and CMV in BC. Papillomavirus DNA was present in 7 of 59 BC samples (11.8%); while none was detected in control samples. The most prevalent type was HPV18, followed by HPV 6. All HPV positive patients had high tumor grades (II/ III) with a histologic diagnosis of ductal carcinoma. The patient age range was 33 to 73 years with a median of 51 years. Most of HPV positive patients had low levels of education. HPV16 was not detected. Also, 5 of 59 BC specimens (8.47%), were positive for HSV-1. But none of the samples were positive for HSV-2, VZV, and CMV. Our results suggest a carcinogenesis role for High-risk HPV (HPV18) in breast tumors. Our findings of HSV-1 and low-risk HPV (HPV6) in BCs may propose a cancer-causing role for them. Further large-scale studies are warranted to assess the significance of our findings.


Psychometric properties of tools for initial screening for oropharyngeal dysphagia in older people: a scoping review protocol.
The objective of this scoping review is to identify and map the psychometric properties of screening tools designed to identify oropharyngeal dysphagia in older people. Oropharyngeal dysphagia is a geriatric syndrome associated with reduced quality of life, malnutrition, dehydration, medical administration problems, and poor health care outcomes. It requires a multidimensional approach to treatment. The syndrome is present in approximately 60% of institutionalized, frail older patients and in 47% of frail older patients who are hospitalized. This review will consider studies of screening tools for oropharyngeal dysphagia used in people older than 65 years who do not have stroke, Parkinson disease, sclerosis, or head and neck cancer. Patients who depend on respiratory support or feeding tubes will be excluded. All health care settings will be included. The JBI methodology for scoping reviews will be followed. The Cochrane Library, CINAHL, MEDLINE, Embase, and Epistemonikos will be searched for relevant studies. Sources of unpublished studies and gray literature, including Google Scholar, will be searched. Articles published in English, Danish, Swedish, and Norwegian will be included. Two independent reviewers will screen titles and abstracts against the inclusion criteria. The full text of included studies will be read and relevant citations included. Disagreements between the reviewers will be resolved through discussion or with a third reviewer. The proposed data extraction form will be modified as necessary during the process. Data will be presented in diagrammatic form, and a narrative summary that aligns with the objective will be included.


Coxofemoral joint laxity from distraction radiography and its contemporaneous and prospective correlation with laxity, subjective score, and evidence of degenerative joint disease from conventional hip-extended radiography in dogs.
A 3-year prospective study of large-breed dogs (4 months to 3 years of age) was conducted to evaluate the influence of radiographic positioning and age on coxofemoral joint (hip) laxity, subjective hip score, and development of degenerative joint disease (DJD). The dogs (n = 142) were breeder- or client-owned and represented 14 breeds. With dogs under heavy sedation, hips were radiographed in the standard hip-extended position and in the new compression/distraction position at 4, 6, 12, 24, and 36 months of age. The standard hip-extended radiographic view was evaluated by 3 methods: subjective evaluation by a board-certified veterinary radiologist (WHR), according to the standard 7-point Orthopedic Foundation for Animals (OFA) scoring scheme (OFA/WHR); joint laxity quantitation, using the Norberg angle (NA) method; and subjective scoring by a veterinary orthopedic surgeon for radiographic evidence of DJD. The hips in the distraction radiographic view were evaluated for passive hip laxity, as measured by use of a unitless distraction index (DI). Results of the study indicated that at a specific age (4, 6, 12, 24, or 36 months), all methods of hip evaluation correlated with each other at a moderate level (P < 0.05). The strength of contemporaneous correlation tended to increase with age of evaluation. Longitudinally, the between-method correlations were usually significant (P < 0.05), but not at a sufficiently high level to permit reliable between-method prediction. Prospective intraclass (within-method) statistical analysis of the various hip-scoring methods indicated that DI was superior to NA and OFA/WHR in comparability of score over time. The intraclass correlation coefficient ranged from 0.55 to 0.91 for DI in contrast to 0.40 to 0.78 for NA, and 0.06 to 0.39 for OFA/WHR over the age intervals of the study. For reference, the highest Kappa of 0.39 for the subjective OFA/WHR scoring reflected a maximal level of agreement between time intervals, only slightly better than chance. The associated large error questions the predictive use of the 7-point, subjective hip-scoring scheme, particularly prior to the age of 2 years.


Self-awareness after traumatic brain injury: a comparison of measures and their relationship to executive functions.
Poor awareness of deficit is common after brain injury. Recent literature has examined various tools for measurement of this phenomenon; the most widely used being self-other rating scales. Although self-other scale measures have face validity, their criterion-related validity has not been adequately demonstrated, and there is little information as to whether and how they relate to other neuropsychological measures. The present study compared measurement of awareness by the Dysexecutive (DEX) Questionnaire self-other rating scale with the Self-Awareness of Deficits Interview (SADI), a semistructured interview measure. Evaluation of awareness by these measures was compared to tests of executive functioning and IQ. Results indicated significant, albeit marginal relationships between the two measures, and better correlation of the SADI with measures of frontal lobe functioning. The SADI also predicted injury severity.