A comparative study of the interaction of two structurally analogous ruthenium complexes with human telomeric G-quadruplex DNA.
Two new polypyridine ligands and their corresponding ruthenium(II) complexes have been prepared and characterized. The interactions of both complexes with human telomere quadruplex DNA (both the antiparallel basket and the mixed-hybrid G-quadruplex) have been studied by circular dichroism (CD), CD melting, UV-visible (UV-Vis), fluorescent intercalator displacement (FID) assays and molecular docking studies. The results show that both complexes can stabilize G-quadruplexes DNA and two complexes show different binding affinity for different G-quadruplexes DNA. The 1:1 stoichiometry was confirmed in the buffered solutions by the UV-Vis spectrophotometer using Job's plot method and molecular docking studies. We have also investigated the interaction between the complexes and duplex DNA to gain some insight into the selectivity of the complexes for G-quadruplex structures. FID studies have shown that the complexes have a modest selectivity for G-quadruplex versus duplex DNA.


Is HER2 ultra-low breast cancer different from HER2 null or HER2 low breast cancer? A study of 1363 patients.
This study aims to analyze whether there are any differences in clinicopathological features and prognosis between HER2 ultra-low, HER2-null, and HER2-low expression in Chinese breast cancer (BC) patients. The clinicopathological data of 1363 HER2-negative BC patients were retrospectively collected (from January 2018 to December 2019). HER2 status was further classified into HER2-null, HER2 ultra-low, and HER2-low. HER2-null expression is defined as infiltrating cancer cells completely free of staining. HER2 ultra-low expression is defined as ≤10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining. HER2-low expression is defined as HER2 immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization (ISH) assay. Of 1363 patients, there were 86 (6.3%) HER2-null patients, 395 (29.0%) HER2 ultra-low patients, and 882 (64.7%) HER2-low patients. HER2 ultra-low patients were different from HER2-low patients in terms of N stage, hormone receptor (HR) status, Ki-67 expression, and type of surgery. There were also significant differences in histologic type and postoperative endocrine therapy between HER2 ultra-low and HER2-null patients. HR+ (81.0%) tumors was more common than HR- (19.0%) in HER2 ultra-low patients. In addition, there was a significant difference in HR status between HER2 ultra-low and HER2-low patients (P = 0.001). The survival analysis showed that HER2 status had no effect on disease-free survival (DFS) in HER2-negative patients (all P > 0.05). However, regardless of HER2 status, HR+ patients had better DFS than HR- patients (P = 0.003). Cox multivariate analysis revealed that age (HR [95% CI] = 0.950 [0.928, 0.972], P < 0.001), HR status (HR [95% CI] = 3.342 [1.658, 6.736], P = 0.001), and postoperative endocrine therapy (HR [95% CI] = 0.048 [0.048, 0.023], P < 0.001) were important influencing factors of DFS in HER2-negative BC patients. HER2 ultra-low BC patients demonstrated distinct clinicopathological features from HER2-null and HER2-low tumors; while, HER2 status (null, ultra-low, or low) had no prognostic value in these HER2-negative BC population. Consistent with the published literature, HR status was an independent prognostic factor for DFS in HER2-negative BC patients.


Pregnancy as a tissue expander in the correction of a scar deformity.
Tissue expansion is an established method for the correction of scars and tissue defects. During pregnancy the abdominal skin becomes gradually stretched over the growing uterus, providing a "natural" tissue expander. We present a case of a woman with posttraumatic scarring of the lower abdomen and thigh where tissue expansion during pregnancy was successfully used for scar correction.


Automated methods in microbiology: I. Bacterial detection systems.
The rapid and efficient screening of blood and urine specimens for the presence of bacteria is now possible. Bioluminescent, colorimetric, and nephelometric bacterial detection systems are described in this paper. In addition, enzyme immunoassay for bacterial antigens is discussed.


Disparities in general education inclusion for students of color with disabilities: Understanding when and why.
Research on disproportionality in special education has largely overlooked how students of color with disabilities are less likely to spend time in general education classrooms than White peers with disabilities. Although disparities in general education inclusion for students of color with disabilities raise larger concerns about educational inequality within schools, when these gaps begin to emerge and what factors may explain them remain less understood due to methodological challenges. In leveraging individual-level administrative data from a large school district over a 10-year period, this longitudinal study found general education inclusion declines for all students as they age. However, Black students with disabilities experienced the least inclusion, whereas Asian American and Pacific Islander (AAPI) students with disabilities were included in the general education classroom more than Latinx and White peers with disabilities; this disparity was largely associated with academic test score differences and disability type.


Association of leptin with orthostatic blood pressure changes in Parkinson's disease.
Leptin is involved in the regulation of blood pressure; however, no studies have evaluated the role of leptin in blood pressure changes during orthostatic stress in PD patients. The aim of this study was to determine whether plasma leptin levels influence orthostatic blood pressure changes in PD patients. We enrolled 55 patients and 25 age-matched healthy controls in this study. Associations between head-up tilt test measurements and leptin levels were evaluated. Systolic blood pressure changes during the head-up tilt tests were strongly correlated with leptin levels at baseline and at a 60-degree head-up tilt in PD patients, but not in control subjects. Multiple regression analysis also demonstrated that leptin levels were associated with orthostatic blood pressure changes. These observations suggest that low leptin levels may be associated with orthostatic hypotension during the head-up tilt test in patients with PD. © 2016 International Parkinson and Movement Disorder Society.


Inverse free reduced universum twin support vector machine for imbalanced data classification.
Imbalanced datasets are prominent in real-world problems. In such problems, the data samples in one class are significantly higher than in the other classes, even though the other classes might be more important. The standard classification algorithms may classify all the data into the majority class, and this is a significant drawback of most standard learning algorithms, so imbalanced datasets need to be handled carefully. One of the traditional algorithms, twin support vector machines (TSVM), performed well on balanced data classification but poorly on imbalanced datasets classification. In order to improve the TSVM algorithm's classification ability for imbalanced datasets, recently, driven by the universum twin support vector machine (UTSVM), a reduced universum twin support vector machine for class imbalance learning (RUTSVM) was proposed. The dual problem and finding classifiers involve matrix inverse computation, which is one of RUTSVM's key drawbacks. In this paper, we improve the RUTSVM and propose an improved reduced universum twin support vector machine for class imbalance learning (IRUTSVM). We offer alternative Lagrangian functions to tackle the primal problems of RUTSVM in the suggested IRUTSVM approach by inserting one of the terms in the objective function into the constraints. As a result, we obtain new dual formulation for each optimization problem so that we need not compute inverse matrices neither in the training process nor in finding the classifiers. Moreover, the smaller size of the rectangular kernel matrices is used to reduce the computational time. Extensive testing is carried out on a variety of synthetic and real-world imbalanced datasets, and the findings show that the IRUTSVM algorithm outperforms the TSVM, UTSVM, and RUTSVM algorithms in terms of generalization performance.


Provision of Air Conditioning and Heat-Related Mortality in Texas Prisons.
There is a large body of epidemiologic evidence that heat is associated with increased risk of mortality. One of the most effective strategies to mitigate the effects of heat is through air conditioning (AC); Texas regulates the internal temperature of jails to stay between 65 and 85 °F degrees, but these same standards do not apply to state and private prisons. To analyze whether heat during warm months is associated with an increased risk of mortality in Texas prisons without AC. This case-crossover study included individuals who died in Texas prisons between 2001 and 2019. The association of heat in warm months with mortality in Texas prisons with and without AC was estimated. Data analysis was conducted from January to April 2022. Increasing daily heat index above 85 °F and extreme heat days (days above the 90th percentile heat index for the prison location). Daily mortality in Texas prisons. There were 2083 and 1381 deaths in prisons without and with AC, respectively, during warm months from 2001 to 2019. Most of the deceased were male (3339 of 3464 [96%]) and the median (IQR) age at death was 54 (45-62) years. A 1-degree increase above 85 °F heat index and an extreme heat day were associated with a 0.7% (95% CI, 0.1%-1.3%) and a 15.1% (95% CI, 1.3%-30.8%) increase in the risk of mortality in prisons without AC, respectively. Approximately 13% of mortality or 271 deaths may be attributable to extreme heat during warm months between 2001 to 2019 in Texas prison facilities without AC. In prisons with AC, a negative percentage change in mortality risk was observed, although the 95% CI crossed zero (percentage change in mortality risk: -0.6%; 95% CI, -1.6% to 0.5%). The estimates in prisons without AC were statistically different than the estimates in prisons with AC (P = .05). This study found an average of 14 deaths per year between 2001 to 2019 were associated with heat in Texas prisons without AC vs no deaths associated with heat in prisons with AC. Adopting an AC policy in Texas prisons may be important for protecting the health of one of our most vulnerable populations.


Dynamic signatures of microplastic distribution across the water column of Yangtze River Estuary: Complicated implication of tidal effects.
Riverine microplastic (MP) discharge into the ocean contributes greatly to global MP contamination, yet our understanding of this process remains primitive. To deepen our interpretation of the dynamic MP variation throughout the estuarine water columns, we sampled at Xuliujing, the saltwater intrusion node of the Yangtze River Estuary, over the course of ebb and flood tides in four seasons (July and October 2017, January and May 2018 respectively). We observed that the collision of downstream and upstream currents contributed to the high MP concentration and that the mean MP abundance fluctuated with the tide. A model of microplastics residual net flux (MPRF-MODEL), taking the seasonal abundance and vertical distribution of MP along with current velocity into consideration, was developed to predict the net flux of MP throughout the full water columns. 2154 ± 359.7 t/year of MP was estimated to flow into the East China Sea via the River in 2017-2018. Our study suggests that riverine MP flux can be overestimated due to reciprocating current carried MP from the estuary. Using the tidal and seasonal variation in MP distribution, we calculated the tide impact factor index (TIFI) for the Yangtze River Estuary to be between 38.11% and 58.05%. In summary, this study provides a baseline of MP flux research in the Yangtze River for similar tidal-controlled rivers and a contextual understanding of how to appropriately sample and accurately estimate in a dynamic estuary system. The redistribution of microplastics may be impacted by complex tide processes. Although not observed in this study, it may merit investigation.


Pearls and pitfalls of respiratory testing in a patient with amyotrophic lateral sclerosis and COPD.
Interpretation of pulmonary function testing in patients with amyotrophic lateral sclerosis must account for coexisting lung diseases, when making patient care decisions. https://bit.ly/3Co2yR0.


Mast cell modulates tumorigenesis caused by repeated bowel inflammation condition in azoxymethane/dextran sodium sulfate-induced colon cancer mouse model.
Mast cells infiltrate the inflammatory microenvironment and regulate the production of many pro-inflammatory cytokines and mediators of inflammatory cell production to promote tumor development and growth in intestinal lesions. Currently, there are insufficient studies of the mediators and signaling pathways regulated by mast cells that influence the pathogenesis of colon cancer in inflamed colon tissue. This study aimed to confirm the role of mast cells in the incidence and growth of colitis-associated colon cancer (CAC) and to identify inflammation-mediated factors and signaling pathways related to tumor development. CAC was induced by the administration of azoxymethane (AOM) and dextran sodium sulfate (DSS) in mast cell-deficient (WBB6F1/J-W/WV) and mast cell-sufficient control (WBB6F1_+/+) mice. The results confirmed that mast cell-deficient mice exhibited less tumor formation than normal mice under the same conditions, and down-regulated expression of pro-inflammatory cytokines and mediators. Mast cells play an important role in tumor formation by regulating pro-inflammatory cytokines and inflammatory mediators in CAC, indicating that they can act as new targets for the prevention and treatment of CAC.


Risk factors of acute coagulation dysfunction after aneurysmal subarachnoid hemorrhage.
Although coagulopathy have been proved to be a contributor to a poor outcome of aneurysmal subarachnoid hemorrhage (aSAH), the risk factors for triggering coagulation abnormalities have not been studied after aneurysm clipping. We investigated risk factors of coagulopathy and analyzed the relationship between acute coagulopathy and outcome after aneurysm clipping. The clinical data of 137 patients with ruptured CA admitted to our institution was collected and retrospectively reviewed. Patient demographic data (age, sex), smoking, alcohol use, hypertension, diabetes, Hunt-Hess grade, Fisher grade, operation time, intraoperative total infusion volume, intraoperative blood loss, intraoperative transfusion, intraoperative hemostatic drug treatment, calcium reduction (preoperative free calcium concentration-postoperative free calcium concentration) were recorded. Coagulation was assessed within 24 h. Postoperative hemorrhage and infarction, deep venous thrombosis (DVT), and mortality were analyzed. Coagulopathy was detected in a total of 51 cases (group I), while not in 86 cases (group II). Univariable analysis demonstrated that age, smoking, alcohol use, intraoperative total infusion volume, intraoperative blood loss, intraoperative transfusion, and calcium reduction (≥ 1.2 mg/dl) were related to coagulopathy. Non-conditional logistic regression analysis showed that age [OR, 1.037 (95% CI, 1.001-1.074); p = 0.045] and calcium reduction (≥ 1.2 mg/dl) [OR, 5.509 (95% CI, 1.900-15.971); p = 0.002] were considered as the risk factors for coagulopathy. Hunt-Hess grade [OR, 2.641 (95% CI, 1.079-6.331); p = 0.033] and operation time [OR, 0.107 (95% CI, 1.012-0.928); p = 0.043] were considered as the risk factors for hypocoagulopathy. There were 6 cases (11.7%) with cerebral infarction in group I, while 6 cases (6.98%) in group II (χ 2 = 0.918, p = 0.338). There were 4 cases (7.84%) with rebleeding in group I, while 5 cases (5.81%) in group II (χ 2 = 0.215, p = 0.643). The mortality was 9.80% (5/51) in group I, while 1.16% (1/86) in group II (χ 2 = 5.708, p = 0.017). DVT was not detected in all cases. In conclusion, age (≥ 65 years) and calcium reduction (≥ 1.2 mg/dl) were considered as the risk factors for coagulopathy and have been proved to be associated with higher mortality after aneurysm clipping.


Case control analysis of repeat expansion size in ataxia.
Spinocerebellar ataxias (SCAs) are a group of clinically and genetically heterogeneous neurological diseases. The expansion of unstable microsatellite repeats has been identified as the underlying pathogenic cause of 10 subtypes of autosomal dominant SCAs. The aetiology of sporadic SCA is unknown. The aim of this study was to investigate the effect of large normal repeats in patients presenting with sporadic or familial ataxia compared to a control population. The size of the expansion was determined using a fluorescent PCR approach in 10 common SCA genes: SCA-1 (ATXN1), SCA-2 (ATXN2), SCA-3 (ATXN3), SCA-6 (CACNA1A), SCA-7 (ATXN7), SCA-8 (ATXN8OS), SCA-10 (ATXN10), SCA-12 (PPP2R2B), SCA-17 (TBP) and DRPLA (ATN1), in 165 ataxia patients and 307 controls of Welsh origin. There was no difference between cases and controls in the distribution of the large normal alleles, or in the distribution of the combined CAG repeats. The normal allele distribution in the Welsh population was largely similar to that of other Caucasian populations. Our study failed to demonstrate an effect of large normal repeats on the susceptibility to develop ataxia.


Intraoperative Fluid Restriction in Pancreatic Surgery: A Double Blinded Randomised Controlled Trial.
Perioperative fluid restriction in a variety of operations has shown improvement of: complications, recovery of gastrointestinal function and length of stay (LOS). We investigated effects of crystalloid fluid restriction in pancreatic surgery. Our hypothesis: enhanced recovery of gastrointestinal function. In this double-blinded randomized trial, patients scheduled to undergo pancreatoduodenectomy (PD) were randomized: standard (S:10ml/kg/hr) or restricted (R:5ml/kg/hr) fluid protocols. gastric emptying scintigraphically assessed on postoperative day 7. In 66 randomized patients, complications and 6-year survival were analyzed. 54 patients were analyzed in intention to treat: 24 S-group and 30 R-group. 32 patients actually underwent a PD and 16 patients had a palliative gastrojejunostomy bypass operation in the full protocol analysis. The median gastric emptying time (T½) was 104 minutes (S-group, 95% confidence interval: 74-369) versus 159 minutes (R-group, 95% confidence interval: 61-204) (P = 0.893, NS). Delayed gastric emptying occurred in 10 patients in the S-group and in 13 patients in the R-group (45% and 50%, P = 0.779, NS). The primary outcome parameter, gastric emptying time, did not show a statistically significant difference between groups. A fluid regimen of 10ml/kg/hr or 5ml/kg/hr during pancreatic surgery did not lead to statistically significant differences in gastric emptying. A larger study would be needed to draw definite conclusions about fluid restriction in pancreatic surgery. ISRCTN62621488.


MRI Findings of Disc Degeneration are More Prevalent in Adults with Low Back Pain than in Asymptomatic Controls: A Systematic Review and Meta-Analysis.
Imaging features of spine degeneration are common in symptomatic and asymptomatic individuals. We compared the prevalence of MR imaging features of lumbar spine degeneration in adults 50 years of age and younger with and without self-reported low back pain. We performed a meta-analysis of studies reporting the prevalence of degenerative lumbar spine MR imaging findings in asymptomatic and symptomatic adults 50 years of age or younger. Symptomatic individuals had axial low back pain with or without radicular symptoms. Two reviewers evaluated each article for the following outcomes: disc bulge, disc degeneration, disc extrusion, disc protrusion, annular fissures, Modic 1 changes, any Modic changes, central canal stenosis, spondylolisthesis, and spondylolysis. The meta-analysis was performed by using a random-effects model. An initial search yielded 280 unique studies. Fourteen (5.0%) met the inclusion criteria (3097 individuals; 1193, 38.6%, asymptomatic; 1904, 61.4%, symptomatic). Imaging findings with a higher prevalence in symptomatic individuals 50 years of age or younger included disc bulge (OR, 7.54; 95% CI, 1.28-44.56; P = .03), spondylolysis (OR, 5.06; 95% CI, 1.65-15.53; P < .01), disc extrusion (OR, 4.38; 95% CI, 1.98-9.68; P < .01), Modic 1 changes (OR, 4.01; 95% CI, 1.10-14.55; P = .04), disc protrusion (OR, 2.65; 95% CI, 1.52-4.62; P < .01), and disc degeneration (OR, 2.24; 95% CI, 1.21-4.15, P = .01). Imaging findings not associated with low back pain included any Modic change (OR, 1.62; 95% CI, 0.48-5.41, P = .43), central canal stenosis (OR, 20.58; 95% CI, 0.05-798.77; P = .32), high-intensity zone (OR = 2.10; 95% CI, 0.73-6.02; P = .17), annular fissures (OR = 1.79; 95% CI, 0.97-3.31; P = .06), and spondylolisthesis (OR = 1.59; 95% CI, 0.78-3.24; P = .20). Meta-analysis demonstrates that MR imaging evidence of disc bulge, degeneration, extrusion, protrusion, Modic 1 changes, and spondylolysis are more prevalent in adults 50 years of age or younger with back pain compared with asymptomatic individuals.


Submerged arc furnace process superior to the Waelz process in reducing PCDD/F emission during thermal treatment of electric arc furnace dust.
Besides the Waelz process, the submerged arc furnace (SAF) process has also been extensively used to retain metals from ashes and scraps in the metallurgical industry. However, very little is known about the formation and depletion of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from this thermal process. In this study, an electric arc furnace (EAF) dust treatment plant adopting the SAF process was investigated and compared to the plant adopting the Waelz process. The predominant contributor of PCDD/F I-TEQ input was the EAF dusts, accounting for 98.4% of the total. The PCDD/F contents in the generated fly ashes of the SAF were extremely low, as almost all the organic compounds for PCDD/F formation were decomposed by the high operating temperatures (1500-1700 °C) of the SAF. Therefore, the PCDD/F emission factor of the SAF process (46.9 μg I-TEQ/tonne-EAF dust) was significantly lower than that of the Waelz process (840-1120 μg I-TEQ/tonne-EAF dust). Its PCDD/F output/input ratios (0.23 and 0.50 based on mass and toxicity) were also lower than those of the Waelz process plant (0.62 and 1.19). Therefore, the SAF process is superior to the Waelz process in reducing the potential of PCDD/F formation.


Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women.
Current guidelines for cardiovascular risk detection are controversial with regard to the clinical utility of different lipid measures, non-high-density lipoprotein cholesterol (non-HDL-C), lipid ratios, apolipoproteins, and C-reactive protein (CRP). To directly compare the clinical utility of total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL-C, non-HDL-C, apolipoproteins A-I and B(100), high-sensitivity CRP, and the ratios of total cholesterol to HDL-C, LDL-C to HDL-C, apolipoprotein B(100) to apolipoprotein A-I, and apolipoprotein B(100) to HDL-C as predictors of future cardiovascular events in women. Prospective cohort study of 15,632 initially healthy US women aged 45 years or older (interquartile range, 48-59 years) who were enrolled between November 1992 and July 1995. All participants were followed up over a 10-year period for the occurrence of future cardiovascular events. Hazard ratios (HRs) and 95% confidence intervals (CIs) for first-ever major cardiovascular events (N = 464) according to baseline levels of each biomarker. After adjustment for age, smoking status, blood pressure, diabetes, and body mass index, the HRs for future cardiovascular events for those in the extreme quintiles were 1.62 (95% CI, 1.17-2.25) for LDL-C, 1.75 (95% CI, 1.30-2.38) for apolipoprotein A-I, 2.08 (95% CI, 1.45-2.97) for total cholesterol, 2.32 (95% CI, 1.64-3.33) for HDL-C, 2.50 (95% CI, 1.68-3.72) for apolipoprotein B(100), 2.51 (95% CI, 1.69-3.72) for non-HDL-C, and 2.98 (95% CI, 1.90-4.67) for high-sensitivity CRP (P<.001 for trend across all quintiles). The HRs for the lipid ratios were 3.01 (95% CI, 2.01-4.50) for apolipoprotein B(100) to apolipoprotein A-I, 3.18 (95% CI, 2.12-4.75) for LDL-C to HDL-C, 3.56 (95% CI, 2.31-5.47) for apolipoprotein B(100) to HDL-C, and 3.81 (95% CI, 2.47-5.86) for the total cholesterol to HDL-C (P<.001 for trend across all quintiles). The correlation coefficients between high-sensitivity CRP and the lipid parameters ranged from -0.33 to 0.15, and the clinical cut points for CRP of less than 1, 1 to 3, and higher than 3 mg/L provided prognostic information on risk across increasing levels of each lipid measure and lipid ratio. Non-HDL-C and the ratio of total cholesterol to HDL-C were as good as or better than apolipoprotein fractions in the prediction of future cardiovascular events. After adjustment for age, blood pressure, smoking, diabetes, and obesity, high-sensitivity CRP added prognostic information beyond that conveyed by all lipid measures.


Alzheimer type II astrocytes in the brains of pigs with salt poisoning (water deprivation/intoxication).
The finding of Alzheimer type II astrocytes, in addition to the pathognomonic combination of laminar cerebrocortical necrosis and eosinophil infiltration, in the brains of pigs is reported for the first time in cases of indirect salt poisoning following water deprivation.


Associated factors for higher lead and cadmium blood levels, and reference values derived from general population of São Paulo, Brazil.
Human activities are associated with emissions of various metals into the environment, among which the heavy metals lead and cadmium stand out, as they pose a risk to human life even at low concentrations. Thus, accurate knowledge of the levels of these metals exhibited by the overall population, including children, is important. The aim of this study was to estimate the concentrations of lead and cadmium in the blood of adults, adolescents and children residing in the city of São Paulo, assess factors associated with higher lead and cadmium blood levels, and to establish reference values for this population. The study sample consisted of 669 adults over 20 years old, 264 adolescents aged 12 to 19 years old and 391 children under 11 years old from both genders. The samples were collected at the end of 2007 and during 2008 in different city zones. Higher blood lead concentration was significantly associated with gender, smoking, offal intake, area of residence and age. The blood cadmium concentration was significantly associated with gender, smoking, consumption of distilled beverages and age. The reference values of lead and cadmium established for adults above 20 years old were 33 μg/L and 0.6 μg/L, respectively, for adolescents (12 to 19 years old) were 31 μg/L and 0.6 μg/L, respectively and for children under 11 years old were 29 μg/L and 0.2 μg/L, respectively. The results of this study indicate that the exposure levels of the investigated population to lead and cadmium are low.


Endoscopic cochlear implant procedure.
The objective was to asses the feasibility of the endoscopic technique for cochlear implant (CI) positioning avoiding mastoidectomy and to discuss the benefits and drawbacks of the technique. The study design is a surgical procedure description and prospective case series report. From December 2011 to October 2012, six patients underwent endoscopic CI. All cases were selected based on CT and MRI studies. All surgical steps were analyzed; intra-and post-operative complications were noted. The length of time for each surgical procedure was recorded. The surgical procedure was described step by step focusing on the anatomy of the round window (RW) niche, analyzing the critical point during the dissection. The timing of the surgical procedures was 120 ± 21 (mean ± SD) min. In 1/6 patients, intra-operative injury of the chorda tympani occurred. In all cases, an endoscopic identification was performed and the anatomical details of the RW niche were noted. In 6/6 cases, a RW niche magnification was performed endoscopically. 5/6 cases showed a normal conformation of the RW. In 1/6 patients, obliteration of the RW niche was found. In 4/6 patients, an endoscopic cochleostomy through the RW was performed. In 1/6 patients, a difficult insertion of the array was observed. The current follow-up is 7.3 months (SD ± 3.7). No post-operative short- or long-term complications were noted in this series. Endoscopic CI is a safe and viable technique with a low rate of complications and with good outcomes.


The clinical benefit of sequential therapy with androgen receptor axis-targeted agents alone in patients with castration-resistant prostate cancer: A propensity score-matched comparison study.
The optimal sequential therapy for castration-resistant prostate cancer (CRPC) remains unknown. In recent years, some doubts have emerged regarding the clinical benefit of sequential therapy with androgen receptor axis-targeted agents (ART) such as abiraterone (ABI) or enzalutamide (ENZ) for patients with CRPC. We compared the effect of ART-to-ART (AA) sequential therapy after castration resistance with that of docetaxel (DTX)-combined sequential therapy (ART to DTX or DTX to ART) in patients with CRPC. We retrospectively identified and analyzed the data of 315 patients with CRPC treated in our seven affiliated institutions between 2009 and 2019. All patients received either DTX or ART (ABI or ENZ) as the first- or second-line therapy after castration resistance. We compared the overall survival (OS) and the second progression-free survival (PFS2), calculated from the initiation of first-line therapy after castration resistance, between the AA sequence group and the DTX-combined sequence group. PFS2 was defined as the period from the start of first-line treatment after castration resistance to progression on second-line treatment. To minimize selection bias from possible confounders, we performed propensity score matching using one-to-one nearest neighbor matching without replacement. Overall, 106 and 209 patients were administered the AA sequential therapy and DTX-combined sequential therapy, respectively. The clinicopathological variables of patients were well balanced after propensity score matching, and there were no significant differences between the two groups. In the propensity score-matched cohort, OS was not significantly different between the two groups (median, 37.9 vs. 45.4 months; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.68-1.79; p = .701), while PFS2 was significantly shorter in the AA group than in the DTX-combined group (median, 12.9 vs. 21.6 months; HR, 1.70; 95% CI, 1.16-2.48; p = .007). Certain patients with CRPC can benefit from ART-to-ART sequential therapy in a daily clinical setting.


The Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylase and is required for synaptic transmission but not synaptic development.
The neurotransmitter GABA has been proposed to play a role during nervous system development. We show that the Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylase (GAD), the GABA biosynthetic enzyme. unc-25 is expressed specifically in GABAergic neurons. Null mutations in unc-25 eliminate the UNC-25 protein or alter amino acids conserved in all known GADs, result in a complete lack of GABA, and cause defects in all GABA-mediated behaviors. In unc-25 mutants the GABAergic neurons have normal axonal trajectories and synaptic connectivity, and the size and shape of synaptic vesicles are normal. The number of synaptic vesicles at GABAergic neuromuscular junctions is slightly increased. Cholinergic ventral nerve cord neurons, which innervate the same muscles as GABAergic ventral cord neurons, have normal morphology, connectivity, and synaptic vesicles. We conclude that GAD activity and GABA are not necessary for the development or maintenance of neuromuscular junctions in C. elegans.


Augmentation of sensitivity of FBG strain sensor for biomedical operation: publisher's note.
This publisher's note reports a correction to Appl. Opt.57, 6906 (2018)APOPAI0003-693510.1364/AO.57.006906.


Bilateral lung transplantation in asymmetric thorax: case reports.
Suppurative lung diseases, such as cystic fibrosis and bronchiectasis, when diffuse and associated with important functional loss, can be treated with bilateral lung transplantation with good results. These diseases are frequently associated with previous lung resections presenting an asymmetric thorax, thus making lung extraction difficult and generating disproportion between the graft and the pleural cavity. To treat this condition, pneumonectomy and single lung transplantation is a feasible option; however, there are associated comorbidities and an invariable need for extracorporeal circulation. Described herein are 2 patients with an asymmetric thorax, treated with bilateral transplantation and lung volume reduction with lobectomy.


Direct immunochemical sensing: basic chemical principles and fundamental limitations.
Models describing the binding of antigens to surface immobilised antibodies have been developed. These models are applied to the assessment of the likely analytical utility of direct immunochemical sensors employing immobilised antibody layers. Fundamental limitations to the device response arising from the equilibrium and kinetic characteristics of the binding reaction and from mass transport constraints imply that measurement over the micromolar to nanomolar concentration range may be practical.


Discovery of enzymes to biotransform ginsenoside Rd into ginsenosides F2 and CK using metagenomics and genomic mining.
Ginsenosides are the main active components of ginseng, including many types and different contents. Among them, minor ginsenosides have better biological functions and pharmacological activities than those of the major ginsenosides. However, minor ginsenosides cannot be obtained in large quantities, but by means of enzymatic transformation technology, some major ginsenosides can be de-glycosylated at a specific position to generate minor ginsenosides. In this study, we report two glycosidase genes associated with the conversion of ginsenoside Rd to ginsenosides F2 or CK. SWMU-CK-1 was identified among the total genes extracted from the feces of plum deer by local Blast screening for putative ginsenoside conversion function, which could cause the conversion of ginsenoside Rd → F2 → CK. The other gene was found in the Bifidobacterium breve 689b SGAir 0764 chromosome genome, which might have the same function as the β-glucosidase gene testified by the gene matching, named SWMU-F2-2, and can achieve the Rd → F2 transformation. This study reports two genes that enable achieving the biotransformation of rare ginsenosides, while it provides a new insight and a promising approach to explore new genes and develop new functions of existing genes.


A single-center observational study assessing the predictive factors associated with the prognosis of acromegaly.
The aim of this study was to clarify the prognostic values of various preoperative factors, including the surgeon's ability as well as the patient's age, gender, tumor size, cavernous sinus invasion, compression of the optic chiasm, hypopituitarism, immunohistochemical (IHC) staining pattern of the adenoma, and insulin-like growth factor-1 (IGF-1) level, in acromegalic patients who had undergone pituitary surgery. This single-center, retrospective study assessed the medical records of 108 patients who had undergone pituitary surgery with the same neurosurgical team. The mean total follow-up period after surgery was 44.8 (min: 24, max: 59) months. Remission was reported in 67 (62.0%) patients, and 57 (52.8%) patients did not experience recurrence. Initial tumor volume, IGF-1 level, and optic chiasm compression, but not patients' age, gender, cavernous sinus invasion, and IHC staining patterns of the adenoma, were prognostic of either remission or recurrence. An IGF-1 level of 860 ng/mLwas found to be a convenient cut-off point for determining remission. The experience of the surgical team suggests that the initial tumor volume, IGF-1 level, and optic chiasm compression have high prognostic values in relation to pituitary surgery for patients with acromegaly.


Diagnosis and management of core-binding factor leukemias.
The core-binding factor (CBF) leukemias are the subtype of acute myelogenous leukemia (AML) associated with the highest response to therapy and longest remission duration. Although CBF leukemias have two distinctly different morphologic and clinical presentations (i.e., AML M2 and AML M4eo), their molecular pathophysiology is linked by their abnormalities in different subunits of CBF, a transcription factor important in several pathways in hematopoietic cells. This article summarizes the recent biologic and clinical advances made in the treatment of these diseases.


Lead exposure in an Italian population: Food content, dietary intake and risk assessment.
Lead is a highly toxic heavy metal released into the environment after natural and anthropogenic activities. Excluding populations in occupations where there is possible lead contamination, food is the major source of human exposure. In this study, we determined lead contamination in food and beverages consumed in a Northern Italy community and performed a health risk assessment. We collected a total of 908 food samples and measured lead levels using inductively coupled plasma mass spectrometry. Using a validated food frequency questionnaire, we assessed the dietary habits and estimated daily lead dietary intakes in a sample of 719 adult individuals. We performed risk assessment using a benchmark dose and margin of exposure approach, based on exposure levels for both adverse effect of systolic blood pressure and chronic kidney disease. Foods with the highest lead levels include non-chocolate confectionery (48.7 µg/kg), leafy (39.0 µg/kg) and other vegetables (42.2 µg/kg), and crustaceans and molluscs (39.0 µg/kg). The estimated mean lead intake was 0.155 µg/kg bw-day in all subjects, with little lower intakes in men (0.151 µg/kg bw-day) compared to women (0.157 µg/kg bw-day). Top food contributors were vegetables, cereals, and beverages, particularly wine. In relation to risk assessment, the estimated dietary intake was lower than levels associated with cardiovascular risk and nephrotoxicity. Our study provides an updated assessment of lead food contamination and dietary exposure in a Northern Italian community. The margin of exposure risk assessment approach suggests that risk of detrimental effects due to dietary lead intake is low in the investigated population. Nonetheless, these exposure levels for adverse effects are not reference health standards, and no safety threshold value can be established for lead. As a consequence, other and more subtle adverse effects may still occur in vulnerable and occupationally exposed individuals, particularly in relation to the nervous system.


SYSTEMATIC LITERATURE REVIEW ON MODELS AND PRACTICES OF EARLY CHILDHOOD INTERVENTION IN BRAZIL.
To identify which Early Childhood Intervention practices and models are described in the Brazilian literature. A systematic integrative review of the literature indexed in databases from Virtual Health Library, Bielefeld Academic Search Engine, Education Resources Information Center and Portal of Periodicals of the Coordination of Improvement of Higher Education Personnel was carried out, considering the period between 2005 and 2015. The following articles were analyzed: those published in English or Portuguese, fully available online, with the terms "Early Intervention", "Early Stimulation" or "Essential Stimulation" in the title, abstract or keywords; studies that enrolled children aged from 0 to 6 years, their caregivers or professionals in Early Intervention services; manuscripts published in journals classified as ≥ B2 (WebQualis; Qualis 2014) in the fields of Education or Physical Education; and studies that described Early Intervention practices. Early Intervention seems to be developed exclusively related to the health sector, with prevalence of practices aimed at stimulating skills through the use of clinical approaches, whose focus is centered on the child and structured in the model of rehabilitative care. The adoption of Early Intervention practices and models are far from those recommended and recognized by the international literature as good practices. In this sense, the need of continuous education of professionals involved in this area is shown, as well the need for investments in research on this subject.


Variation in work tasks in relation to pinch grip strength among middle-aged female dentists.
We aimed to investigate the relationship of task variation during dental work history with pinch grip strength among dentists. We measured pinch grip strength among 295 female Finnish dentists aged 45-63 years. Variation in dental work tasks during work history was empirically defined by cluster analysis. Three clusters of task variation emerged: low (most work time in restoration treatment/endodontics), moderate (about 50% in the former and 50% in prosthodontics/periodontics/surgery), and high (variable tasks including administrative duties). Hand radiographs were examined for the presence of OA in the wrist and each joint of the 1-3rd fingers. Information on hand-loading leisure-time activities, and joint pain was obtained by questionnaire. Glove size was used as a proxy for hand size. BMI (kg/m2) was based on measured weight and self-reported height. Dentists with low variation of work task history had an increased risk of low pinch grip strength in the right hand (OR 2.3, 95% CI 1.2-4.3), but not in the left (1.13, 0.62-2.08), compared to dentists with high task variation, independent of age, hand size, hand-loading leisure-time activities, BMI and symptomatic hand OA. The dentists with the most hand-loading tasks were at an increased risk of low pinch grip strength, independent of e.g. symptomatic hand OA. It is advisable among dentists to perform as diverse work tasks as possible to reduce the risk of decreased pinch grip strength.


Cytosolic Ca(2+) and Ca(2+)-activated Cl(-) current dynamics: insights from two functionally distinct mouse exocrine cells.
The dynamics of Ca(2+) release and Ca(2+)-activated Cl(-) currents in two related, but functionally distinct exocrine cells, were studied to gain insight into how the molecular specialization of Ca(2+) signalling machinery are utilized to produce different physiological endpoints: in this case, fluid or exocytotic secretion. Digital imaging and patch-clamp methods were used to monitor the temporal and spatial properties of changes in cytosolic Ca(2+) concentration ([Ca(2+)](c)) and Cl(-) currents following the controlled photolytic release of caged-InsP(3) or caged-Ca(2+). In parotid and pancreatic acinar cells, changes in [Ca(2+)](c) and activation of a Ca(2+)-activated Cl(-) current occurred with close temporal coincidence. In parotid, a rapid global Ca(2+) signal was invariably induced, even with low-level photolytic release of threshold amounts of InsP(3). In pancreas, threshold stimulation generated an apically delimited [Ca(2+)](c) signal, while a stronger stimulus induced a global [Ca(2+)](c) signal which exhibited characteristics of a propagating wave. InsP(3) was more effective in parotid, where [Ca(2+)](c) signals initiated with shorter latency and exhibited a faster time-to-peak than in pancreas. The increased potency of InsP(3) in parotid probably results from a four-fold higher number of InsP(3) receptors as measured by radiolabelled InsP(3) binding and western blot analysis. The Ca(2+) sensitivity of the Cl(-) channels in parotid and pancreas was determined from the [Ca(2+)]-current relationship measured during a dynamic 'Ca(2+) ramp' produced by the continuous, low-level photolysis of caged-Ca(2+). In addition to a greater number of InsP(3) receptors, the Cl(-) current density of parotid acinar cells was more than four-fold greater than that of pancreatic cells. Whereas activation of the current was tightly coupled to increases in Ca(2+) in both cell types, local Ca(2+) clearance was found to contribute substantially to the deactivation of the current in parotid. These data reveal specializations of common modules of Ca(2+)-release machinery and subsequent effector activation that are specifically suited to the distinct functional roles of these two related cell types.


Prevalence of Hospital-Associated Disability in Older Adults: A Meta-analysis.
Hospital-associated disability (HAD), defined as loss of independence in activities of daily living (ADL) following acute hospitalization, is observed among older adults. The study objective is to determine overall prevalence of HAD among older adults hospitalized in acute care, and to assess the impact of study initiation year in moderation of prevalence. Meta-analysis of data collected from randomized trials, quasi-experimental, and prospective cohort studies. English-language searches to identify included studies were completed February 2018 and updated May 2018 of electronic databases and reference lists of studies and reviews. Included studies were human subjects investigations that measured ADL ≥2 time points before or during and after hospitalization and reported prevalence of ADL decline among older adults. Acute care hospital units. Adults aged ≥65 years hospitalized in medical-surgical acute care; total sample size across all included studies was 7375. Independence in ADL was assessed using the Katz Index of Independence in Activities of Daily Living and Barthel Index of Independence in Activities of Daily Living. Random effects meta-analysis across included studies identified combined prevalence of HAD as 30% (95% CI 24%, 33%; P < .001). The effect of study initiation year on the prevalence rate was minimal. A large amount of heterogeneity was observed between studies, which may be due in part to nonstandardized measurement of ADL impairment or other methodological differences. Hospitalization in acute care poses a significant risk to functional independence of older adults, and this risk is unchanged despite shorter lengths of stay. The evidence supports the continued need for hospital-based programs that provide assessment of functional ability and identification of at-risk older adults in order to better treat and prevent HAD.


Visible chemiluminescence from rat brain homogenates undergoing autoxidation. II. Kinetics of the luminescence decay.
The visible luminescence emitted in the autoxidation of brain homogenates is only partially quenched when antioxidants are added at concentrations such that further oxidation is prevented. From the time course of the emission after antioxidant addition, it can be estimated that nearly 50% of the light arises from an intermediate that decays with a first order kinetics and with a lifetime of ca. 40 s at 32 degrees C. The remaining light arises from the decomposition of one or several intermediates, and show a kinetics that is independent of the incubation time. From the data obtained it is concluded that bimolecular free radical processes, such as the recombination of peroxy radicals, do not significantly contribute to the observed luminescence.


Evidence that the catalytic mechanism of heme a synthase involves the formation of a carbocation stabilized by a conserved glutamate.
In eukaryotes and many aerobic prokaryotes, the final step of aerobic respiration is catalyzed by an aa3-type cytochrome c oxidase, which requires a modified heme cofactor, heme a. The conversion of heme b, the prototypical cellular heme, to heme o and ultimately to heme a requires two modifications, the latter of which is conversion of a methyl group to an aldehyde, catalyzed by heme a synthase (HAS). The N- and C-terminal halves of HAS share homology, and each half contains a heme-binding site. Previous reports indicate that the C-terminal site is occupied by a heme b cofactor. The N-terminal site may function as the substrate (heme o) binding site, although this has not been confirmed experimentally. Here, we assess the role of conserved residues from the N- and C-terminal heme-binding sites in HAS from prokaryotic (Shewanella oneidensis) and eukaryotic (Saccharomyces cerevisiae) species - SoHAS/CtaA and ScHAS/Cox15, respectively. A glutamate within the N-terminal site is found to be critical for activity in both types of HAS, consistent with the hypothesis that a carbocation forms transiently during catalysis. In contrast, the residue occupying the analogous C-terminal position is dispensable for enzyme activity. In SoHAS, the C-terminal heme ligands are critical for stability, while in ScHAS, substitutions in either heme-binding site have little effect on global structure. In both species, in vivo accumulation of heme o requires the presence of an inactive HAS variant, highlighting a potential regulatory role for HAS in heme o biosynthesis.


NADH in situ laser fluorimetry: effect of pentobarbital on continuously monitored myocardial redox state.
NADH laser fluorimetry was applied to in situ monitoring of pentobarbital overload effect on myocardial redox state in rats. Experiments were carried out on open-chest rats anesthetized with pentobarbital. Use of very thin optical probes allowed measurements of NADH fluorescence directly within the myocardial wall. Quantitative analysis of fluorescent and backscattered light signals was made possible on-line. In 8 animals, a slow IV infusion of 6% pentobarbital (2 mg.min-1 for 10 min) induced an average twofold increase in NADH fluorescence, with constant return to baseline level prior to injection after a maximum period of 50 min. Thus, pentobarbital overload strongly affects the myocardial energetic state, and this effect was precisely evaluated with NADH fluorescence monitoring. In situ-monitored myocardial redox state variations during pentobarbital infusion can constitute a reference for similar studies on pharmacological agents aimed at protecting tissues against ischemic biochemical damages.


A Mathematical Model for Simulation of Vasoplegic Shock and Vasopressor Therapy.
To develop a high-fidelity mathematical model intended to replicate the cardiovascular (CV) responses of a critically ill patient to vasoplegic shock-induced hypotension and vasopressor therapy. The mathematical model consists of a lumped-parameter CV physiology model with baroreflex modulation feedback and a phenomenological dynamic dose-response model of a vasopressor. The adequacy of the proposed mathematical model was investigated using an experimental dataset acquired from 10 pigs receiving phenylephrine (PHP) therapy after vasoplegic shock induced via sodium nitroprusside (SNP). Upon calibration, the mathematical model could (i) faithfully replicate the effects of PHP on dynamic changes in blood pressure (BP), cardiac output (CO), and systemic vascular resistance (SVR) (root-mean-squared errors between measured and calibrated mathematical responses: mean arterial BP 2.5+/-1.0 mmHg, CO 0.2+/-0.1 lpm, SVR 2.4+/-1.5 mmHg/lpm; r value: mean arterial BP 0.96+/-0.01, CO 0.65+/-0.45, TPR 0.92+/-0.10) and (ii) predict physiologically plausible behaviors of unmeasured internal CV variables as well as secondary baroreflex modulation effects. This mathematical model is perhaps the first of its kind that can comprehensively replicate both primary (i.e., direct) and secondary (i.e., baroreflex modulation) effects of a vasopressor drug on an array of CV variables, rendering it ideally suited to pre-clinical virtual evaluation of the safety and efficacy of closed-loop control algorithms for autonomous vasopressor administration once it is extensively validated. This mathematical model architecture incorporating both direct and baroreflex modulation effects may generalize to serve as part of an effective platform for high-fidelity in silico simulation of CV responses to vasopressors during vasoplegic shock.


Effectiveness of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in predicting the incidence of nausea and vomiting after total knee arthroplasty in patients with hemophilia A.
To investigate the ability of preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to predict postoperative nausea and vomiting (PONV) after total knee arthroplasty (TKA). The clinical data of 108 male patients with hemophilia A who underwent TKA an our institution were collected and analyzed. Confounding factors were adjusted by propensity score matching. The best cutoffs of the NLR and PLR were determined by the area under the receiver operating characteristic curve (ROC). The predictive ability of these indexes was assessed by measuring the sensitivity, specificity, and positive and negative likelihood ratios. There were significant differences in the use of antiemetics (p = 0.036) and the incidence of nausea (p < 0.001) and vomiting (p = 0.006) between the two groups (NLR <2 and ≥2). An increase in preoperative NLR was an independent risk factor for PONV in patients with hemophilia A (p < 0.05). ROC analysis showed that NLR significantly predicted the occurrence of PONV (cutoff value: 2.20, ROC: 0.711, p < 0.001). In turn, the PLR did not strongly predict PONV. The NLR is an independent risk factor for PONV in patients with hemophilia A and can significantly predict this event. Thus, follow-up monitoring is essential for these patients.


Mixed mesenchymal sarcoma of the broad ligament: case report.
A 55-year-old patient who presented with a pelvic mass was found to have a mixed mesenchymal sarcoma of the broad ligament. The histogenesis and diagnostic criteria of this rare tumour are discussed.


Twisted Gastric Tube after Laparoscopic Sleeve Gastrectomy-An Unusual but Effective Surgical Approach to Achieve Full Recovery.
Sleeve gastrectomy is at present the most practiced bariatric intervention for patients suffering from severe obesity. Although rare, post-operative complications such as leakages and strictures may represent a challenging issue for bariatric surgeons and cause impaired quality of life for patients. Gastric twist is even more rare. This complication is a functional obstruction rather than a stricture of the gastric remnant most likely due to technical mistakes at index surgery. If endoscopy usually allows diagnosis and constitutes the first-line treatment for this condition, surgery is mandatory when endoscopy is not successful. The conversion of the sleeve to a Roux-en-Y gastric bypass is the usually chosen intervention but a wide range of reconstruction has been proposed. In this report, we discuss the surgical technique we employed to achieve a full resolution of a gastric twist.


[Role of serum factors in regulating interferon production].
A relationship between the level of interferon production, intensity of lipid peroxidation, the activity of proteolytic enzymes, and the age of the blood serum donor was established on a model of peritoneal exudate cells from mice of different ages. Trypsin was found to inhibit interferon production levels in the same way as did the serum of newborn mice. Introduction of protease inhibitor increased interferon production considerably. Unlike that of mature animals, the blood serum of newborn mice had prooxidant properties.


Coordination-driven structure reconstruction in polymer of intrinsic microporosity membranes for efficient propylene/propane separation.
Polymers of intrinsic microporosity (PIMs), integrating unique microporous structure and solution-processability, are one class of the most promising membrane materials for energy-efficient gas separations. However, the micropores generated from inefficient chain packing often exhibit wide pore size distribution, making it very challenging to achieve efficient olefin/paraffin separations. Here, we propose a coordination-driven reconstruction (CDR) strategy, where metal ions are incorporated into amidoxime-functionalized PIM-1 (AO-PIM) to in situ generate coordination crosslinking networks. By varying the type and content of metal ions, the resulting crosslinking structures can be optimized, and the molecular sieving capability of PIM membranes can be dramatically enhanced. Particularly, the introduction of alkali or alkaline earth metals renders more precise micropores contributing to superior C3H6/C3H8 separation performance. K+ incorporated AO-PIM membranes exhibit a high ideal C3H6/C3H8 selectivity of 50, surpassing almost all the reported polymer membranes. Moreover, the coordination crosslinking structure significantly improves the membrane stability under higher pressure as well as the plasticization resistant performance. We envision that this straightforward and generic CDR strategy could potentially unlock the potentials of PIMs for olefin/paraffin separations and many other challenging gas separations.


The impact of Diglossia-Effect on Reading Acquisition Among Arabic-Speaking Children: A Longitudinal Study.
Arabic is a diglossic language, where two language varieties are used: spoken Arabic (SpA) and standard Arabic (StA). The words may be "identical" (maintaining the same phonological expression in the SpA and StA) or "unique" to StA). This study examined the effect of diglossia on reading according to the lexical distance between the SpA and StA forms and whether this influence changes with age. The participants were 137 first-graders that were followed to the second grade. The findings indicated a significant effect of grade level with higher performance in the second grade. A significant association was obtained between the lexical distance and reading accuracy and rate with better performance for identical than unique items across grade levels. No significant interaction between lexical distance and grade level was found. The results indicate the contribution of reading unique and identical forms in the first grade to reading in the second grade. The advantage in reading identical among unique words is discussed in light of the lexical quality hypothesis and dual-route model. The implications of these results were discussed in the context of diglossia, especially the need for StA oral language enrichment at the preschool level.


Absence of prognostic significance, peritoneal dissemination and treatment advantage in endometrial cancer patients with positive peritoneal cytology.
Peritoneal cytology has been shown to be one of the prognostic factors in endometrial cancer. A series of 134 patients was seen between January 1977 and March 1985 with clinical Stage I (or treated as a clinical Stage I) endometrial adenocarcinoma at the University of Rochester Cancer Center. The majority of patients underwent extrafascial hysterectomy with the majority of washings obtained at the time of surgery. Fourteen percent (19/134) of the patients were found to have positive cytology. Eleven patients with positive cytology (11/19) were treated with local-regional pelvic treatment; the other eight patients received whole abdominal therapy. The recurrence rates were less with the local treatment than with the whole abdominal treatment groups (9.1% vs. 25%) in those patients having positive cytology. There was no statistical difference in recurrence rates between the pathologic Stage I patients with positive cytology (10%) versus those patients having negative cytology (5%), nor was there statistical difference in survival between pathologic Stage I positive or negative cytology patients. It is suggestive from this non-randomized study that positive cytology in endometrial cancer is not an independent prognostic factor and that whole abdominal irradiation did not influence outcome.


Adjunctive effects to non-surgical periodontal therapy of systemic metronidazole and amoxycillin alone and combined. A placebo controlled study.
Several studies have reported adjunctive benefits to scaling and root planing (SRP) of systemic amoxycillin and metronidazole in the treatment of periodontal diseases. To date no comparisons have been made of these antimicrobials alone or in combination. The aim of this study was to compare the adjunctive benefits to SRP of amoxycillin and metronidazole alone and combined. 66 subjects <46 years of age with advanced chronic periodontal disease participated in this randomised, double blind, 4 parallel treatment group designed study. All subjects received quadrant SRP and then were prescribed amoxycillin capsules (250 mg) and metronidazole tablets (200 mg) (AM) or lactate capsules and metronidazole (PM) or amoxycillin and calcium lactate tablets (AP) or lactate and calcium lactate (PP). All medication was 3 of each per day for 7 days. Subgingival plaque samples were obtained and probing depth (PD), loss of attachment (LOA), bleeding on probing (BOP), suppuration (SUPP) and plaque (DEP) were recorded pre-treatment, 1, 3 and 6 months post-treatment. Final group sizes were: AM=15, PM=16, AP=16 and PP=15. PD improved in all groups. Treatment effects were highly significantly different and always greatest in the AM and least in the PP groups. Benefits of PM and AP over PP were also noted. LOA improved in all groups and showed the same highly significant treatment differences, again favouring AM. BOP improved in all groups, particularly in AM compared to the other groups. SUPP improved in all groups and was virtually eradicated in AM with differences among treatments highly significant. DEP changed little in any group and there were no significant differences among groups. Microbiological data showed significant differences in favour of AM compared to PP and PM for total aerobes and anaerobes at 1 month. P. intermedia counts were always lower in active groups compared to PP and reached significance for AM and AP at 1 month and AM and PM at 3 months. The significant differences among treatment groups and the overall trend in the data, in line with other studies, support the considerable adjunctive benefits to SRP of amoxycillin and metronidazole combined in the treatment of advanced chronic periodontal disease.


Detection and quantification of Kaposi's sarcoma-associated herpesvirus to predict AIDS-associated Kaposi's sarcoma.
To identify immunologic and virologic predictors of AIDS-associated Kaposi's sarcoma (KS). Nested case-control analysis of KS risk in a cohort of 132 HIV-infected homosexual men in New York and Washington, DC, USA. For each KS case, we selected two HIV-infected controls, matched for CD4 cell count and Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8; KSHV) serostatus (enzyme immunoassay for antibody to KSHV protein K8.1). Cell-associated KSHV and Epstein-Barr virus (EBV) viral loads were measured with quantitative real-time PCR assays on samples collected 1 year (median) before KS diagnosis. Thirty-one men developed AIDS-associated KS (incidence 3.1 per 100 person years). Among HIV-infected men, KS incidence was higher among those with K8.1 seropositivity (5.0 versus 1.4 per 100 person years; P = 0.004), low CD4 cell count [hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.24-1.79 per 100 x 10(6) cells/l decline), or high HIV RNA level (HR, 3.96; 95% CI, 2.19-7.16 per log(10)). In the case-control analysis, nine of 70 evaluated subjects had KSHV viremia, generally low level (median viral load 180 copies per 1 x 10(6) cells). KSHV viremia was associated with increased KS risk (unadjusted odds ratio, 9.1; 95% CI, 1.7-48; odds ratio, 11.7; 95% CI, 1.8-76 after adjustment for K8.1 serostatus, CD4 cell count, and HIV RNA). Among K8.1-seropositive subjects, KS incidence was tenfold higher in those with KSHV viremia (30.3 per 100 person years versus 3.4 per 100 person years in those without viremia). Also, EBV viral loads were higher in cases than in controls (P = 0.07). Among individuals with HIV-KSHV coinfection, KSHV viremia identifies a subgroup with extremely high risk for developing KS.


The del(2)(q32.2q33) deletion syndrome defined by clinical and molecular characterization of four patients.
We report four patients with an interstitial deletion of chromosome 2q32-->2q33. They presented similar clinical findings including pre- and postnatal growth retardation, distinct facial dysmorphism, thin and sparse hair and fair built, micrognathia, cleft or high palate, relative macroglossia, dacrocystitis, persisting feeding difficulties, inguinal hernia and broad based gait. All were severely mentally retarded. Three patients had a specific behavioral phenotype with hyperactivity and motor restlessness, chaotic behavior, happy-personality but with periods of aggression and anxiety, sleeping problems and self-mutilation. (head-banging). Array CGH and fluorescence in situ hybridization (FISH) allowed us to delineate the deletion size and showed that the four patients share a 8.1 Mb minimal deleted region. Reviewing additional nine case reports of patients with similar deletions showed striking phenotypic similarities which enabled the delineation of the 2q32.2q33 syndrome. Deletion of 2q32 has been also associated with the wrinkly skin syndrome (WWS) and isolated cleft palate. Although the patients presented here shared many aspects of WWS, they did not had the wrinkly skin. All patients had a cleft or high palate, most likely as a result of hemizygosity for SATB2. A potential commonly deleted interval of the three patients with behavioral problems, excluding the deletion in the patient without behavioral problems, is at most 0.5 Mb in size harboring only two genes.


Improving self-directed learning ability of medical students using the blended teaching method: a quasi-experimental study.
Self-directed learning (SDL) is one of the most important abilities for medical students in terms of their future clinical medical practice. During the blended teaching process, teachers can design a variety of learning activities to cultivate students' SDL abilities. This study aimed to assess the differences between the SDL abilities of medical students using blended and traditional didactic teaching. This study included 239 medical students from eight administrative classes. The students were divided into two groups: (1) the experimental group (EG), which included 119 students from four administrative classes, and (2) the control group (CG), which included 120 students from the remaining four classes. From February to July 2022, blended teaching methods were applied to the EG group, and SDL abilities were assessed in comparison to the CG group receiving traditional didactic teaching methods. At the end of the semester, significant differences (p < 0.05) were observed between EG and CG in all six SDL ability factors. Furthermore, when k-means cluster analysis was used to analyze the learning behavior of students in the EG after classifying them as comprehensive, interactive, and passive types, significant differences were observed in all six Self-directed learning factors of students with the comprehensive type, whereas significant differences were observed in four factors (setting learning goals and plans, self-monitoring and regulation, information processing, and communication and cooperation) of students with the interactive type. For students with passive type, only one factor of SDL (information processing) showed significant improvement. There were on differences between comprehensive, interactive, and passive types of CG. The blended teaching approach is better than the conventional didactic teaching for cultivating clinical medical students' SDL abilities.


Growth rate of myelin figures of egg-yolk phosphatidylcholine.
The growth length of myelin figures was measured in detail using a video tape recording system of optical microscopy. In the beginning stage of growth, the growth process was not adapted to the diffusion-limited process of lipid molecules, which has been recently proposed. Another interpretation for the growth mechanism was proposed, where the growth results from swelling. The initial growth rate measured was in good agreement with the estimated value in consideration with the water flux in the first approximation of the lipid concentration gradient.


Structure-Function Relationship Studies In Vitro Reveal Distinct and Specific Effects of Long-Chain Metabolites of Vitamin E.
Cytochrome-dependent metabolism of vitamin E initially forms the long-chain metabolites (LCM) 13'-hydroxychromanols (13'-OH) and 13'-carboxychromanols (13'-COOH), which occur in human blood. Little is known about their biological functions. A structure-activity relationship study using α- and δ-tocopherol (TOH), their LCM (α-13'-OH, δ-13'-OH, α-13'-COOH, and δ-13'-COOH) and representatives of their substructures (α-carboxyethylhydroxychromanol and pristanic acid) is performed to unravel critical structural elements of the LCM for biological activity. Prominent effects are mediated by α- and δ-LCM, as scavenger receptor cluster of differentiation 36 (CD36) expression is induced in human THP-1 macrophages and lipopolysaccharide-stimulated inducible nitric oxide synthase (iNos) expression is inhibited in murine RAW264.7 macrophages, while the other molecules are less or not effective. The LCM effects depend on the presence of the chromanol ring system and on the modification of the side-chain but not on the substitution pattern of the chromanol ring. Therefore, it can be concluded that for mediation of effects by LCM the entire molecule is needed and that the effects are specific. We propose the LCM of the micronutrient vitamin E as a new class of regulatory metabolites, but further studies are needed to corroborate this hypothesis.


Assess and address: Screening and management of depression in patients with chronic heart failure.
About one in three patients with heart failure (HF) have depression. Comorbid HF and depression are associated with poor outcomes and increased health care burden. Clinical guidelines recommend routine depression screening in patients with HF. Depression screening was not being systematically implemented in an outpatient cardiology clinic. To create a sustainable process for a cardiology clinic to screen adults with chronic HF for depression, identify patients who have an elevated depression screening score and initiate an evidence-based treatment algorithm for patients with depressive symptoms. A nurse practitioner (NP)-led process improvement project administered the Patient Health Questionnaire (PHQ-9) tool to patients with HF. The score was reviewed by the NP and, if elevated, addressed with assessment and plan. Compliance was measured by the percentage of patients screened. Clinical impact was measured by percentage of patients with an elevated score with a documented treatment plan. Postimplementation results for four Plan-Do-Study-Act cycles were 38%, 68%, 72%, and 66%, respectively, with a total 63% of patients screened during the entire project. Twenty unique patients (13.2%) had elevated PHQ-9 scores; all had a documented treatment plan. We demonstrated how a screening protocol and an accompanying treatment algorithm can be successfully implemented in an outpatient cardiology clinic. Elements of success included a standardized screening protocol, a clinical support algorithm for treatment/referral, an optimized electronic medical record, and a follow-up system for patients with significant depressive symptoms. Stakeholder engagement throughout the project informed iterative changes and provided direction for sustainability.


The psychobiology of stress, depression, adjustment disorders and resilience.
This paper focuses on the psychobiology of stress, depression, adjustment disorders (ADs), and resilience. Since the ADs fall under the rubric in DSM-5 of Trauma and Stressor-Related Disorders, essentials of the psychobiology of stress-response syndromes will be reviewed. A narrative review of the psychobiology of stress-response syndromes is undertaken, and the implications for our understanding of ADs are discussed. Advances in our understanding of the psychobiology of stress-response syndromes provide an important foundation for understanding ADs, and for conceptualizing their diagnosis, as well as issues of resilience. Future investigations of the psychobiology of trauma- and stressor-related disorders may shed additional light on ADs, and ultimately improve their treatment.


Mechanism of Akt regulation of the expression of collagens and MMPs in conjunctivochalasis.
Akt is a central node of many signaling pathways, which plays important roles in cell survival, proliferation, migration, metabolism and collagen synthesis. Conjunctivochalasis (CCH) is one of the most common age-related ocular superficial diseases related to abnormalities in conjunctival extracellular matrix. Here, we studied the role of Akt regulating collagens and MMPs in the pathogenesis of CCH. Primary conjunctival fibroblasts were obtained from CCH patients (n = 13) and age-matched normal controls (n = 10). The levels of Akt, collagen type I, collagen type III, MMP1, and MMP3 were determined by Western blot, qRT-PCR, immunohistochemistry, and immunofluorescence staining. Normal control conjunctival fibroblasts were treated with Akt inhibitor A6730, and CCH fibroblasts were transfected with Akt overexpression vector. The expression of Akt in CCH was significantly lower than that in normal control of conjunctival tissues and cultured fibroblasts. Blocking Akt signaling with Akt inhibitor could inhibit the expression of collagen type I and collagen type III and upregulate the expression of MMP1 and MMP3. Meanwhile, compared with CCH fibroblasts transfected with control mimics, the protein and mRNA expression of collagen type I and collagen type III were increased significantly in Akt overexpression group, while the results of MMP1 and MMP3 in transfected fibroblasts were opposite. Taken together, Akt upregulated the expression of collagen type I and collagen type III and downregulated the expression of MMP1 and MMP3. Akt signaling pathway could provide a direct negative contribution to CCH and might be an attractive target for CCH therapy.


Management of complications of Dupuytren contracture.
This evidence-based article discusses the current management options of Dupuytren disease and strategies to avoid and manage any potential complications. Treatment options include fasciectomy, needle fasciotomy/aponeurotomy, and collagenase injection. Complications include digital nerve and artery injury, flexor tendon injury, skin fissures and wound healing complications, hematoma, infection, flare reaction/complex regional pain syndrome, and recurrence. Complication rates, prevention, and management differ with each treatment modality. A detailed understanding of each of these options allows hand surgeons to select the most appropriate treatment for each patient.


Severe outcomes of COVID-19 among patients with multiple sclerosis under anti-CD-20 therapies: A systematic review and meta-analysis.
COVID-19 may spread through various ways ranging from asymptomatic to severe forms, until respiratory failure, critical conditions and death occurs. There is a particular concern for patients affected by multiple sclerosis, especially for those under disease-modifying treatments. Some studies have found an association between anti-CD20 therapies (especially rituximab) and severe COVID-19. However, results were not always clear and thus a systematic review was helpful. A systematic literature search was performed independently by two authors on the main search tools considering as key inclusion criterion the presence of data on patients under ocrelizumab or rituximab positive to COVID-19. The quality of the included studies was evaluated based on a modified version of the Dutch Cochrane center critical review checklist proposed by MOOSE and in case of missing data an email was sent to the corresponding authors asking for missing information. After excluding case-reports, a random effects meta-analysis of proportions was conducted using the continuity correction and the I2statistic was calculated to measure heterogeneity. 29 articles were included in the analysis and the median quality of the articles reached 4/5 after having integrated the additional details provided by the authors. The articles included 5173 patients, of whom 770 (14.8%) and 455 (8.8%) were, respectively, under ocrelizumab and rituximab. Pooled estimates of hospitalization, pneumonia and intensive care unit admission were 18.1%, 14.8% and 3.3%, respectively, while pooled estimate for death was 1.8% overall and 1.6% and 4.5%, respectively, for patients under ocrelizumab and rituximab. Patients treated with rituximab seem to be at higher risk of severe COVID-19 outcomes compared to patients under other treatments.


Exercise-induced distal atrioventricular block.
Three patients with 1:1 atrioventricular (AV) conduction at rest developed fixed 2:1 or 3:1 AV block during treadmill exercise testing. Electrophysiologic study documented block distal to the AV node in all three patients, and suggested that the exercise-induced block occurred because of increased atrial rate and abnormal refractoriness of the His-Purkinje conduction system. The findings in these three patients suggest that high grade AV block appearing during exercise reflects conduction disease of the His-Purkinje system rather than of the AV node, even in the absence of bundle branch block. Patients with this diagnosis should be considered for permanent cardiac pacing.


Hypovirus molecular biology: from Koch's postulates to host self-recognition genes that restrict virus transmission.
The idea that viruses can be used to control fungal diseases has been a driving force in mycovirus research since the earliest days. Viruses in the family Hypoviridae associated with reduced virulence (hypovirulence) of the chestnut blight fungus, Cryphonectria parasitica, have held a prominent place in this research. This has been due in part to the severity of the chestnut blight epidemics in North America and Europe and early reports of hypovirulence-mediated mitigation of disease in European forests and successful application for control of chestnut blight in chestnut orchards. A more recent contributing factor has been the development of a hypovirus/C. parasitica experimental system that has overcome many of the challenges associated with mycovirus research, stemming primarily from the exclusive intracellular lifestyle shared by all mycoviruses. This chapter will focus on hypovirus molecular biology with an emphasis on the development of the hypovirus/C. parasitica experimental system and its contributions to fundamental and practical advances in mycovirology and the broader understanding of virus-host interactions and fungal pathogenesis.


Patient Perceptions of Participating in the RSNA Image Share Project: a Preliminary Study.
The purpose of this study was to gauge patient perceptions of the RSNA Image Share Project (ISP), a pilot program that provides patients access to their imaging studies online via secure Personal Health Record (PHR) accounts. Two separate Institutional Review Board exempted surveys were distributed to patients depending on whether they decided to enroll or opt out of enrollment in the ISP. For patients that enrolled, a survey gauged baseline computer usage, perceptions of online access to images through the ISP, effect of patient access to images on patient-physician relationships, and interest in alternative use of images. The other survey documented the age and reasons for declining participation for those that opted out of enrolling in the ISP. Out of 564 patients, 470 enrolled in the ISP (83 % participation rate) and 456 of these 470 individuals completed the survey for a survey participation rate of 97 %. Patients who enrolled overwhelmingly perceived access to online images as beneficial and felt it bolstered their patient-physician relationship. Out of 564 patients, 94 declined enrollment in the ISP and all 94 individuals completed the survey for a survey participation rate of 100 %. Patients who declined to participate in the ISP cited unreliable access to Internet and existing availability of non-web-based intra-network images to their physicians. Patients who participated in the ISP found having a measure of control over their images to be beneficial and felt that patient-physician relationships could be negatively affected by challenges related to image accessibility.


Changes in metabolic syndrome of Korean children and adolescents in the period 1998 to 2001.
The aim of this study was to compare the prevalence and pattern of metabolic syndrome in children and adolescents in the interval between the Korean National Health and Nutrition Examination Surveys (KNHANES) in 1998 and 2001. Two nationwide surveys (KNHANES) were conducted in Korea in 1998 and 2001. A stratified multistage probability sampling design was used to ensure representation of the entire Korean population. The National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III)-derived definition was used for the definition of metabolic syndrome. A total of 1763 (mean age+/-SD of 14.6+/-2.8 yr) and 1245 (14.1+/-2.8 yr) Korean children and adolescents in the age range 10-19 yr participated in the studies of 1998 and 2001, respectively. The prevalence of metabolic syndrome in male children and adolescents increased significantly from 5.7% in 1998 to 9.0% in 2001. However, there was no increase in females (5.1% in 1998 and 4.9% in 2001). Of the 5 components of metabolic syndrome, low HDL-cholesterolemia showed the highest increase in males and females during the 3 yr. Hypertriglyceridemia increased next in both genders. In contrast, the proportion of female subjects meeting the fasting glucose criterion decreased over the same period. As dyslipidemia was the principal contributor to the increase in metabolic syndrome in Korean male children and adolescents during the 3 yr, a strategy of dietary pattern change and the encouragement of physical activity should be introduced to these groups at a national level.


Environmental exposure to combustion-derived air pollution is associated with reduced functional capacity in apparently healthy individuals.
Prior toxicological exposure reports demonstrated the decremental effect of several air pollutants on the metabolic equivalents achieved during exercise testing (METs). There are no prior large scale epidemiological reports about the effect of environmental air pollution exposure on those parameters. We analyzed a cohort of apparently healthy individuals attending a screening survey program held between 2003 and 2009. Participants were included if residing within an 11 km radius from the nearest air pollution monitoring station. Linear regression models were fitted for the metabolic equivalents and adjusted to short- and long-term air pollutant exposure (particulate matter under 10 micron, sulfur dioxide, nitrogen dioxide, carbon monoxide and ozone). The models were adjusted for possible confounders that affect air pollution and stress testing measurements. The study population comprised 6,612 individuals (4,201 males and 2,411 females). We found a statistically significant short- and long-term negative correlation between air pollutants, mainly CO and NO2 and between the metabolic equivalents achieved. A similar short-term effect was found for SO2. We conclude that exposure to combustion-derived air pollutants has a short- and long-term decremental effect on cardiorespiratory fitness as measured by exercise stress testing. Our epidemiological data support previous toxicological reports.


Cystinosis as a cause of noncirrhotic portal hypertension.
Cystinosis is a rare autosomal recessive storage disorder, characterized by the abnormal accumulation of cystine in cellular lysosomes. This accumulation, which can occur in any organ system, leads to crystallization of trapped cystine and ultimately cellular death. Hepatic manifestations of Cystinosis although rare, have been described in the literature. However, to our knowledge, only one other case of non-cirrhotic portal hypertension secondary to cystine accumulation in Kupffer cells has been reported. In this case and ours, portal hypertension was found in the absence of bridging fibrosis. Furthermore, in our case, for the majority of the patient's course, hepatic synthetic function remained normal. Cysteamine is therapeutic in this disorder, and can lead to significant removal of cystine, and thus to reversibility of disease, however, it requires high doses and must be taken regularly. Porto-systemic shunting in combination with aggressive medical therapy could potentially benefit patients who develop non-cirrhotic portal hypertension in this clinical setting.


Clinical experience with newer electronic radial-type endoscopic color Doppler ultrasonography in the diagnosis of esophageal varices.
Endoscopic color Doppler ultrasonography (ECDUS) is a method for obtaining color images of flow in blood vessels. In this study, we report the utility of a newer electronic radial ECDUS for evaluating cases with esophageal varices. Nineteen patients with esophageal varices were selected. The ECDUS was performed using a Pentax EG-3670URK (forward-view) with a distal tip diameter of 12 mm. A Hitachi EUB 7500, which provides a 360° view, was used for display. The newer electronic radial ECDUS more clearly delineates images of vessels in patients with esophageal varices. We found two chief advantages over the old probe, i.e., it is easier to manipulate in the distal esophagus than the old probe and it produces 360° images instead of 60° or 270° images. Forward-view optics and an extended 360° viewing angle enabled clear color flow images to be obtained from all cases of esophageal varices examined.


Primary hemostasis during women's life cycle measured by Thrombostat 4000.
The Thrombostat 4000 was used to investigate primary hemostasis in women during different stages of their life cycle. Nonpregnant females were studied during their proliferative and luteal phases; pregnant women were investigated during their 28-35th weeks of gestation and some women between the ages of 70-84. Data were compared to those obtained from male volunteers injected with 40 mg estrogen. No significant differences between proliferative and luteal phases were found, but BT2 was prolonged in the elderly women. In the pregnant women extremely short BT2 values were measured. Shortening of BT2 was also seen in the males injected with estrogen.


Intake of household salt in a Danish population.
To quantify the intake of household salt and its contribution to the total salt intake in a Danish population. Eighty-seven healthy individuals (37 men and 50 women), aged 20-55 years, recruited from the area of Copenhagen, completed the study. Total salt intake was estimated from the mean urinary excretion of sodium in four 24-h collections. Household salt, added to the food by the volunteers, was assessed using a lithium-marker technique. Total salt intake was 10.6+/-3.3 g day(-1) (mean+/-s.d.) in men and 7.1+/-2.3 g day(-1) in women. Median intake of household salt was 1.0 g day(-1) in men and 0.5 g day(-1) in women, corresponding to 10.2 and 8.7% of total salt intake in men and women, respectively. A significant difference between sexes was found regarding total salt intake (P<0.0001), but no difference was found if total salt intake was measured per energy intake. No significant difference was found between sexes regarding intake of household salt, and neither the educational level nor the age was associated to either total salt intake or intake of household salt. These findings support the assertion that the total salt intake in the Danish population is above the recommended intake and that the salt intake cannot be sufficiently lowered simply by lowering the use of household salt. Focus needs to be addressed to salt added during the processing or manufacture of foods, as this is the greatest source of salt intake at least in this group of healthy volunteers.


Fluidity-dependence of membrane adhesiveness can be explained by thermotropic shifts in surface potential.
It is demonstrated that the transition of both dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) from the gel to liquid-crystalline phase is paralleled by a pronounced increase in the negative surface potential of liposomes composed of either lipid. The Derjaguin-Landau-Verwey-Overbeek (DLVO) theory is applied to show that this phenomenon can serve as a simple explanation of diverse adhesive properties of solid and fluid lipid bilayers.


Unravelling the complexity of attention-deficit hyperactivity disorder: a behavioural genomic approach.
International research has established that there is a strong genetically inherited contribution to attention-deficit hyperactivity disorder (ADHD) and the genetic mechanisms involved are being sought with considerable success. It is now established that certain alleles of the genes coding for the dopamine D4 receptor and the dopamine transporter occur more frequently in children with ADHD than in healthy controls, and we are finding other DNA changes associated with ADHD. A major challenge for the field now is to clarify how genetic susceptibility is translated into disorder by integrating the fields of quantitative and molecular genetics, neuropsychology and environmental risks.


Rhabdoid and papillary meningioma with leptomeningeal dissemination.
Rhabdoid meningioma is a rare variant of meningioma classified as grade III under the new World Health Organization (WHO) classification of brain tumors. Although this tumor is known for its aggressive behavior, dissemination into cerebral spinal fluid (CSF) is extremely rare. We report here a case of rhabdoid meningioma in a young man, operated on twice previously, who presented with multiple CSF areas of seeding in the brain and spinal cord. The imaging findings for this tumor, including diffusion and perfusion MR sequences, are highlighted. This particular histological subtype of meningioma has a poor prognosis and must be treated aggressively.


Efficacy and Tolerability of Cosmetic Serums Enriched with Five Forms of Hyaluronic Acid as Part of Biweekly Diamond Tip Microdermabrasion Treatments for Facial Skin Dryness and Age-Associated Features.
There is growing interest in combining topical treatments with aesthetic procedures to combat signs of aging skin. This study aimed to assess the efficacy and tolerability of a novel cosmetic serum containing 5 different forms of HA (HA5 DG) when used via a proprietary diamond-tip microdermabrasion procedure (DG) to treat skin dryness, fine lines/wrinkles, rough texture, and dullness. In this open-label, single-center study, participants received HA5 DG as part of a biweekly DG procedure on the face and neck for 12 weeks. Study participants also applied another take-home HA5 serum to the face twice daily at home, along with a basic skincare regimen. The efficacy of the combined treatment was measured by clinical quantification of multiple skin appearance features, analysis of bioinstrumental measurements, and digital photography. This study enrolled 27 participants, with an average age of 42.7 years and Fitzpatrick skin phototypes I-III (59.3%), IV (18.5%), and V-VI (22.2%), and 23 participants completed the study. The combined treatment had effects in fine lines/wrinkles, skin dryness, smoothness, radiance, firmness, and hydration 15 minutes post-DG. Furthermore, the significant improvements observed in dryness, fine lines/wrinkles, skin smoothness, and radiance were still visible 3 days after and maintained at week 12. Additionally, smoothing of coarse lines/wrinkles, improvement of skin tone evenness, hyperpigmentation, photodamage, and transepidermal water loss were observed at week 12. The treatment had a favorable tolerability profile and was perceived as efficacious and highly satisfactory. This novel combined treatment delivered immediate and prolonged skin hydration and high participant satisfaction, proving it can be an excellent approach for skin rejuvenation.


Common clinical features as predictors of bacterial diarrhea in infants.
Identification of infants with bacterial diarrhea during the first year of life is important to limit potentially serious complications, but indications for stool leukocyte examination and culture are not well defined. The ability of three clinical features--temperature, history of blood in the stool, and stool frequency--to predict the presence of bacterial gastroenteritis was analyzed. Over a 1-year period, 108 (10.4%) bacterial pathogens were isolated from 1,035 infants aged less than 1 year with diarrhea. Bacterial culture was positive in 14.9% of cases from May to October, compared with 6.2% of cases from November to April. A history of blood in the stool was the best individual predictor with sensitivity of 39%, specificity of 88%, and a positive predictive value of 30%. Temperature greater than 39 degrees C had sensitivity of 34% and specificity of 85%; greater than or equal to 10 stools in 24 hours had sensitivity of 28% and specificity of 85%. Using combinations of factors, we identified (1) a group of patients at high risk for bacterial diarrhea (infants with two of the three factors studied); (2) a low-risk group (those with temperature less than or equal to 38 degrees C, less than 10 stools in 24 hours, and the absence of blood in the stool); and (3) a group at intermediate risk for bacterial diarrhea (all other patients). We recommend routine stool cultures for infants with a high-risk combination. Additional clinical and laboratory features, such as stool leukocytes, should be studied among patients in the intermediate-risk group.


Activation of second-messenger pathways reactivates latent herpes simplex virus in neuronal cultures.
Herpes simplex virus type 1 (HSV-1) establishes latent infections in neurons of sympathetic and sensory ganglia in humans, and reactivation of latent virus results in recurrent disease. Previously, we reported establishment of latent HSV-1 infections in neuronal cultures derived from rats, monkeys, and humans; reactivation occurs following nerve growth factor (NGF) deprivation. The processes controlling HSV latency are not understood. Using the in vitro neuronal latency system, we have shown that latent HSV-1 reactivated in response to stimulation of at least two second-messenger pathways. Stimulation of cAMP-dependent pathways by several mechanisms or activation of protein kinase C by phorbol myristate acetate (PMA) resulted in reactivation of latent HSV-1. The reactivation kinetics following treatment with activators of protein kinase A and C were accelerated compared with those following NGF deprivation. 2-Aminopurine, which inhibits NGF-stimulated protein kinases and other classes of protein kinases, but does not effect protein kinase A or C, blocked reactivation produced by NGF deprivation or treatment with a cAMP analog, but not reactivation by PMA treatment. These results demonstrate that latent HSV-1 reactivates in neurons in vitro in response to activation of second-messenger pathways.


Preferences and utilities for health states after treatment for oropharyngeal cancer: transoral robotic surgery versus definitive (chemo)radiotherapy.
Treatment of oropharyngeal cancer with transoral robotic surgery (TORS) or definitive (chemo)radiotherapy impacts quality of life. Utility scores are needed for quality of life and economic comparisons. Fifty healthy subjects and 9 experts reviewed scenarios describing treatment (TORS alone or with adjuvant radiotherapy or chemoradiotherapy [CRT], definitive radiotherapy, and CRT), complications, remission, and recurrences. Utilities were assessed using visual analog scale (VAS) and standard gamble (SG) techniques. Treatments were compared using paired comparisons and demographic variability was assessed. TORS had higher SG utilities than radiotherapy (p = .001) and CRT (p < .001) and was preferred in paired comparisons (p < .001 for both) for healthy subjects. Utilities did not vary by demographic group and correlated between experts and subjects (VAS r = 0.95; p < .001; SG r = 0.97; p < .001). TORS has higher utility scores than CRT. Utilities can be used for cost-utility analyses.


Critical review of major sources of human exposure to N-nitrosamines.
More than 24 N-nitrosamine compounds contribute to the total N-nitrosamine (TNA) burden monitored routinely to assess human exposure to this important group of known and suspected human carcinogens. A literature review (n = 122) identified multiple sources of human exposure to TNAs, including waters (40 ± 10.5 ng/L; average ± standard deviation), food and beverages (6.7 ± 0.8 ng/g), tobacco (16,100 ± 3650 ng/g) and personal care products (1500 ± 750 ng/g). Due to source control interventions, levels of TNAs in beer have dropped by about 96% between 1980 and 1990, whereas N-nitrosamine levels in other known sources have shown little to no change. Maximum daily TNA exposure in the U.S. in units of ng/d is estimated at 25,000 ± 4,950, driven by consumption of tobacco products (22,000 ± 4350), food (1900 ± 380), alcohol (1000 ± 200), and drinking water (120 ± 24). Behavioral choices of individuals in non-occupational settings were calculated to result in a spectrum of exposure values ranging from a lower bound of 1900 ± 380 ng/d to a higher bound of 25,000 ± 4950 ng/d, indicating opportunities for a possible 12-fold reduction in TNA exposure to 8% of the above maximum through deliberate choices in diet and lifestyle.


Use of a polysulfone membrane support for immunochemical analysis of a glycolipid from Mycobacterium leprae.
Polysulfone membranes have been used as a solid support for chromatography and immunoblotting of phenolic glycolipid I from Mycobacterium leprae. These membranes have an advantage over other supports such as nitrocellulose and silica gel in that very little non-specific background binding of antibodies occurs and assays can readily be carried out with IgM antibodies from human sera. An example of use of the polysulfone chromatography system for detection of phenolic glycolipid I in sera from leprosy patients is described.