Exercise-induced myocardial dysfunction in patients with coronary artery disease with and without angina.
Left ventricular dysfunction during exercise is considered a relatively sensitive marker of ischemia in patients with coronary artery disease. The purpose of this study was to determine whether exercise-induced myocardial dysfunction was more severe in patients with angina than in patients with ischemia without angina. Seventy-seven patients with angiographically documented coronary artery disease and an abnormal left ventricular response to exercise were studied by means of gated blood pool imaging. The arteriographic and functional parameters of 24 patients with angina during exercise testing imaging. The arteriographic and functional parameters of 24 patients with angina during exercise testing were compared with those of 53 patients who were pain free at the time of the test. Both groups were similar with regard to rate of multivessel disease (50% vs 51%, p = NS) and prior myocardial infarction (46% vs 51%, p = NS), as well as age, sex, and history of angina. Mean global ejection fraction remained unchanged (but abnormal) in both groups of patients during exercise. Furthermore, evidence of new regional asynergy during exercise assessed by a five-point scoring system was found to be equally abnormal in the two groups. Results of this study suggest that the severity of exercise-induced global and regional left ventricular dysfunction is independent of the presence of absence of angina during exercise testing.


Impact of zinc and arginine on antioxidant status of weanling piglets raised under commercial conditions.
The effects of dietary zinc and L-arginine supplements on the weight gain, feed efficiency, antioxidant capacity and oxidative status of weanling piglets raised under commercial conditions were examined. A total of 288 piglets aged 21 d were fed for 15 d a diet supplemented or not with 2,500 mg/kg of zinc (provided as zinc oxide) and 1% L-arginine·HCl. The 4 treatments were distributed in a randomized complete block design with 6 initial body weight categories (12 animals per pen). Access to feed and water was ad libitum. Data were analyzed as a 2 × 2 factorial experiment using the SAS MIXED procedure, with zinc and arginine as the main independent variables. Blood collection day (d 8 and 15, samples were collected from the same 2 piglets in each pen before the morning feeding) was included as a third factor. The zinc supplement increased the average daily gain (ADG) from d 0 to 7, d 8 to 15 and d 0 to 15 (0.289 vs. 0.217 kg/d), average daily feed intake (ADFI) from d 8 to 15 and d 0 to 15 (0.338 vs. 0.279 kg/d) and the gain to feed (G:F) ratio from d 0 to 7 and d 0 to 15 (0.86 vs. 0.77) (P < 0.001). Both supplements significantly decreased the malondialdehyde concentration (zinc: 4.37 vs. 3.91 μmol/L, P = 0.005; arginine: 4.38 vs. 3.89 μmol/L, P = 0.002). Total antioxidant capacity and reduced glutathione (GSH) increased from d 8 to 15 (0.953 vs. 1.391 μmol/L, 2.22 vs. 3.37 μmol/L, P < 0.05) regardless of dietary treatment. Total and oxidized GSH concentrations on d 8 were higher in response to the combined supplements (zinc × arginine interaction, P < 0.05). Piglets fed either Zn-supplemented diet had a lower haptoglobin serum concentration (509 vs. 1,417 mg/L; P < 0.001). In conclusion, the zinc supplement improved piglet growth performance (ADG and ADFI) and oxidative status (based on malondialdehyde concentration). The arginine supplement had a limited effect on growth performance and oxidative status under these conditions.


The Usefulness of Platelet Distribution Width and Platelet Distribution Width to Lymphocyte Ratio in Predicting Severity and Outcomes in Patients with Snakebite.
Tissue damage, inflammatory response, and hematologic abnormalities may occur in snakebite envenomation. This study aimed to evaluate the predictive ability of platelet distribution width (PDW) and platelet distribution width to lymphocyte ratio (PDWLR) in the severity and outcome of envenomation in patients with snakebites in the emergency department (ED). All adult patients admitted to the ED after a snakebite were retrospectively evaluated. Patients were classified according to the severity of envenomation. The relationship between the PDW and PDWLR and envenomation severity and patient outcomes was analyzed. Multivariate logistic regression analysis was performed to determine the predictors of severe envenomation. Results were presented as 95% CIs with odds ratios. Statistical significance was accepted at P<0.05. Envenomation was classified as none/minimal in 42 patients and moderate/severe in 29. PDW and PDWLR were significantly higher in the moderate/severe group (P=0.016 and P<0.001, respectively). Cut-off values of 16.5 for PDW and 6.15 for PDWLR were related to more severe envenomation (area under the curve 0.67, 95% CI 0.55-0.78 and area under the curve 0.85, 95% CI: 0.74-0.92, respectively). Blood product replacement, thrombocytopenia, hematologic abnormality, advanced local findings, compartment syndrome/fasciotomy, antivenom dosing, and moderate/severe envenomation were associated with PDWLR >6.15 (P<0.05). In multivariate analysis, PDWLR (odds ratio 1.19 [95% CI 1-1.4]; P=0.04) was an independent predictor of severe envenomation. Higher PDW and PDWLR were associated with severe envenomation in patients with snakebites in the ED. PDWLR may be used as a predictor of severe envenomation and adverse outcomes.


The association between urate-lowering therapies and treatment-related adverse events, liver damage, and major adverse cardiovascular events (MACE): A network meta-analysis of randomized trials.
Hyperuricemia is a common disease that may lead to gout, renal damage, and cardiovascular events. Oral medication is the main treatment for hyperuricemia patients when lifestyle intervention fails. An evaluation of the safety of various urate-lowering therapies (ULTs) is integral to clinical decision-making. We constructed a network meta-analysis (NMA) to evaluate the safety of oral ULTs. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched up to April 1, 2021, for randomized controlled trials that examined the safety of ULTs. The language restriction was English. The three outcomes used to assess the safety of uric acid lowering medications were treatment-related adverse events, liver damage, and major adverse cardiovascular events (MACE). Thirty-two trials enrolling 23,868 individuals were included in the study. In terms of treatment-related adverse events, there were no statistically significant differences between five uric acid lowering medications and placebo: allopurinol (risk ratio (RR): 1.08; 95% credible interval (CrI): 0.91, 1.29), febuxostat (RR: 1.05; 95% CrI: 0.89, 1.25), lesinurad (RR: 1.19; 95% CrI: 0.85, 1.67), lesinurad combined with xanthine oxidase inhibitor (XOI, RR: 1.05; 95% CrI: 0.83, 1.32), and topiroxostat (RR: 1.01; 95% CrI: 0.83, 1.23). Topiroxostat likely increases risk of liver damage (RR: 2.65; 95%CI: 1.24, 5.70; NNH: 33.40) as compared with placebo. With regard to MACE, there were no statistically significant differences between three uric acid lowering medications and placebo: allopurinol (RR: 0.63; 95% CrI: 0.36, 1.34), febuxostat (RR: 0.69; 95% CrI: 0.38, 1.66), and lesinurad combined with XOI (RR: 0.56; 95% CrI: 0.23, 1.85). The rankings of different interventions were depicted by cumulative ranking curve (SUCRA). Through NMA, we provide some evidence for the safety of ULTs. We found no statistically significant differences in their effects on treatment-related adverse events and MACE. However, topiroxostat likely increases the risk of liver damage.


Disease progression and defects in primary hemostasis as major cause of bleeding in multiple myeloma.
In patients with multiple myeloma (MM), unexpected bleeding complications remain a major issue. Since routine coagulation parameters are often inconspicuous, diagnosis and treatment of the underlying coagulation disorders are challenging. In our single-center observational study, we analyzed 164 patients with MM for coagulation disorders and bleeding complications. Prolonged closure times (CTs), measured by PFA-100, were the most common, abnormal coagulation test, found in 66% of bleeding patients vs 5% in non-bleeding, followed by qualitative defects of von Willebrand factor (VWF:CB/VWF:Ag ratios), found in 34% vs 1% in the non-bleeding group. Increased serum free light chains (SFLC) and SFLC ratios were significantly associated with prolonged CTs and acquired von Willebrand syndrome (AVWS). Prolonged CTs and AVWS were associated with disease progression, determined by dynamics of SFLC ratios (P < .001), serum creatinine level (P = .013), Beta-2 microglobulin (P = .03), LDH (P = .016), and bone marrow infiltration (P < .001). Of note, response to myeloma therapy was frequently correlated with normalization of coagulation parameters. Bleeding complications in MM are predominantly caused by defects in primary hemostasis and associated with disease progression. In a peri-interventional workup, determination of CTs and VWF:CB/VWF:Ag ratios are of significant importance to assess bleeding risk.


The fragility of statistical findings in distal biceps tendon repairs: a systematic review of randomized controlled trials.
The purpose of this present study was to perform a fragility analysis to assess the robustness of randomized controlled trials (RCTs) evaluating the distal biceps tendon repairs. We hypothesize that the dichotomous outcomes will be statistically fragile, and higher fragility will exist among statistically significant outcomes comparable to other orthopedic specialties. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), randomized controlled trials from 4 orthopedic journals indexed on PubMed from 2000 to 2022 reporting dichotomous measures relating to distal biceps tendon repairs were included. The fragility index (FI) of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The fragility quotient (FQ) was calculated by dividing each fragility index by study sample size. The interquartile range (IQR) was also calculated for the FI and FQ. Of the 1038 articles screened, 7 RCTs containing 24 dichotomous outcomes were included for analysis. The fragility index and fragility quotient of all outcomes was 6.5 (IQR 4-9) and 0.077 (IQR 0.031-0.123), respectively. However, statistically significant outcomes had a fragility index and fragility quotient of 2 (IQR 2-7) and 0.036 (IQR 0.025-0.091), respectively. The average number of patients lost to follow-up was 2.7 patients, with 28.6% of the included studies reporting loss to follow-up (LTF) greater than or equal to 6.5. The literature surrounding distal biceps tendon repair may not be as stable as previously thought and presents a similar fragility index to other orthopedic subspecialties. We therefore recommend triple reporting the P value, fragility index, and fragility quotient to aid in the interpretation of clinical findings reported in biceps tendon repair literature.


Factors Influencing Medication Adherence Among Adults Living with Diabetes and Comorbidities: a Qualitative Systematic Review.
Medication adherence plays an important role in improving health outcomes related to diabetes and comorbidity. The potential factors influencing medication adherence and how they contribute to health behaviors have not been synthesized to date. This review synthesized qualitative studies that identified factors influencing medication adherence among adults living with diabetes and comorbidity. Twenty-eight findings were extracted and synthesized into four themes: perceived support, lack of knowledge, medication issues, and the importance of routine. The findings highlight the factors that support medication adherence and areas that can be targeted to support and promote medication adherence. The findings also support the potential role of healthcare providers in supporting people living with diabetes and comorbidity to adhere to and maintain medication regimes. Several factors were identified that are amenable to intervention within the clinical practice setting and have the potential to enhance medication adherence and improve health outcomes for people living with diabetes and comorbidities. The development of acceptable and effective interventions could have a positive effect on medication adherence and health outcomes.


Cortisol secretion and Alzheimer's disease progression.
Mild hypercortisolemia is a frequent concomitant of Alzheimer's disease (AD). In an effort to ascertain the relationship between serum cortisol concentration (CORT) and disease progression, aging, and survival, we followed 9 persons with AD, ages from 56 to 84 years, from an original cohort of 19 enrollees with serial cognitive testing and CORT determinations. The cognitive instrument was a modification of the Alzheimer's Disease Assessment Scale-Cognitive (mADAS-COG). Serum cortisol determinations were performed at noon, and an Afternoon Cortisol Test (ACT) was used to obtain an estimate of average CORT. Baseline 12:00 hours CORT but not ACT correlated significantly with the change in mADAS-COG (r = .90, p < .01). ACT levels increased as the mADAS-COG increased over time (p = .037), by 0.156 +/- 0.06 microgram/dL for each one-point increase (indicating greater impairment) in cognitive test score. ACT levels did not increase significantly simply with aging. For the entire cohort of 19 subjects, neither baseline ACT nor 12:00 hours CORT was significantly related to survival. Hypercortisolemia in AD appears related to the clinical progression of the disease, but not to aging or length of survival.


Inhomogeneous mechanotransduction defines the spatial pattern of apoptosis-induced compensatory proliferation.
The number of cells in tissues is controlled by cell division and cell death, and its misregulation could lead to pathological conditions such as cancer. To maintain the cell numbers, a cell-elimination process called apoptosis also stimulates the proliferation of neighboring cells. This mechanism, apoptosis-induced compensatory proliferation, was originally described more than 40 years ago. Although only a limited number of the neighboring cells need to divide to compensate for the apoptotic cell loss, the mechanisms that select cells to divide have remained elusive. Here, we found that spatial inhomogeneity in Yes-associated protein (YAP)-mediated mechanotransduction in neighboring tissues determines the inhomogeneity of compensatory proliferation in Madin-Darby canine kidney (MDCK) cells. Such inhomogeneity arises from the non-uniform distribution of nuclear size and the non-uniform pattern of mechanical force applied to neighboring cells. Our findings from a mechanical perspective provide additional insight into how tissues precisely maintain homeostasis.


Psoriasis decreases the anti-oxidation and anti-inflammation properties of high-density lipoprotein.
Psoriasis is a chronic inflammatory skin disease, which has been linked to dyslipidemia with potential functional impairment of lipoproteins. This cross-sectional study was designed to characterize the biological activities of plasma lipoproteins in 25 patients with psoriasis and 25 age- and sex-matched healthy controls. In the present study, we found that plasma levels of high-density lipoprotein (HDL) cholesterol were decreased in the psoriasis group compared to healthy controls. The malondialdehyde (MDA) content in plasma, in HDL3 and in low-density lipoprotein (LDL) were increased. However, the activity of plasma paraoxonase-1 (PON-1) decreased in psoriasis and negatively correlated with the psoriasis area and severity index (PASI). Moreover, plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were increased in psoriasis and positively correlated with the PASI. High-sensitivity C-reactive protein (hs-CRP) was increased in psoriasis, but did not reach significance when correlated with PASI. In vitro tests displayed that the functionalities of HDL3 isolated from psoriatic patients significantly decreased, which were assessed in four independent ways, namely (1) protection against LDL oxidation, (2) inhibition of tumor necrosis factor-α (TNF-α) induced monocyte adherence to endothelial cells, (3) prevention of oxidized low density lipoprotein (ox-LDL) induced monocyte migration, and (4) protection of endothelial cells from TNF-α induced apoptosis. Further, pro-oxidative and pro-inflammatory properties of LDL isolated from psoriatic patients were increased. In conclusion, the biological activities of psoriatic lipoproteins are impaired in both HDL and LDL which may provide a link between psoriasis and cardiovas- cular disease.


Timing Matters: Circadian Effects on Energy Homeostasis and Alzheimer's Disease.
Metabolic syndrome and Alzheimer's disease (AD) are two major health issues in modern society causing an extraordinary financial burden for the global healthcare systems. A tight link between the pathologies of obesity and type 2 diabetes (T2D), and more recently between T2D and AD, has been discovered. Furthermore, in recent years it has become apparent that the circadian clock has an important function in controlling metabolism. This review integrates the role of the circadian clock in the development of these metabolic derangements and vice versa. Common features such as central insulin resistance, altered glycogen synthase kinase 3β (GSK3β) signalling, and central inflammation are discussed, and therapeutic interventions targeting those mechanisms are mentioned briefly.


Tumor necrosis factor in lung cancer: Complex roles in biology and resistance to treatment.
Tumor necrosis factor (TNF) and its receptors are widely expressed in non-small cell lung cancer (NSCLC). TNF has an established role in inflammation and also plays a key role in inflammation-induced cancer. TNF can induce cell death in cancer cells and has been used as a treatment in certain types of cancer. However, TNF is likely to play an oncogenic role in multiple types of cancer, including NSCLC. TNF is a key activator of the transcription factor NF-κB. NF-κB, in turn, is a key effector of TNF in inflammation-induced cancer. Data from The Cancer Genome Atlas database suggest that TNF could be a biomarker in NSCLC and indicate a complex role for TNF and its receptors in NSCLC. Recent studies have reported that TNF is rapidly upregulated in NSCLC in response to targeted treatment with epidermal growth factor receptor (EGFR) inhibition, and this upregulation leads to NF-κB activation. The TNF upregulation and consequent NF-κB activation play a key role in mediating both primary and secondary resistance to EGFR inhibition in NSCLC, and a combined inhibition of EGFR and TNF can overcome therapeutic resistance in experimental models. TNF may mediate the toxic side effects of immunotherapy and may also modulate resistance to immune checkpoint inhibitors. Drugs inhibiting TNF are widely used for the treatment of various inflammatory and rheumatologic diseases and could be quite useful in combination with targeted therapy of NSCLC and other cancers.


Study of the "molten globule" intermediate state in protein folding by a hydrophobic fluorescent probe.
Binding of the hydrophobic fluorescent probe, 1-anilino-naphthalene-8-sulfonate (ANS), to synthetic polypeptides and proteins with a different structural organization has been studied. It has been shown that ANS has a much stronger affinity to the protein "molten globule" state, with a pronounced secondary structure and compactness, but without a tightly packed tertiary structure as compared with its affinity to the native and coil-like proteins, or to coil-like, alpha-helical, or beta-structural hydrophilic homopolypeptides. The possibility of using ANS for the study of equilibrium and kinetic molten globule intermediates is demonstrated, with carbonic anhydrase, beta-lactamase, and alpha-lactalbumin as examples.


Single and joint impact of type 2 diabetes and of congestive heart failure on albuminuria.
Albuminuria is a characteristic feature of diabetic nephropathy, and urine albumin excretion is also increased in patients with congestive heart failure (CHF). However, no data are available on the single and joint associations of type 2 diabetes mellitus (T2DM) and CHF with albuminuria. This issue was addressed in the present study. We investigated 4 groups of patients: 180 patients with CHF, of whom 83 had T2DM (CHF+/T2DM+) and 97 did not have diabetes (CHF+/T2DM-) and 223 controls without CHF, of whom 39 had T2DM (CHF-/T2DM+) and 184 did not have diabetes (CHF-/T2DM-). The albumin-creatinine ratio (ACR) was 9.2 [5.7-16.9] mg/g in CHF-/T2DM- patients. Compared to this group it was higher in CHF-/T2DM+ patients (16.1 [7.7-27.8] mg/g; p = 0.004), in CHF+/T2DM- patients (22.0 [9.0-76.8] mg/g; p < 0.001) and in CHF+/T2DM+ patients (66.2 [16.0-177.0] mg/g; p < 0.001), in whom in turn it was higher than in CHF-/T2DM+ (p < 0.001) or in CHF+/T2DM- (p = 0.001) patients. The ACR did not differ significantly between CHF-/T2DM+ and CHF+/T2DM- patients (p = 0.188). In multivariate analysis of covariance, CHF and T2DM proved to be independent predictors of ACR after multivariate adjustment (F = 5.68; p = 0.018 and F = 4.79; p = 0.029, respectively). We conclude that T2DM and CHF are mutually independent determinants of albuminuria.


Nasobiliary guided laparoscopic cholecystectomy following endoscopic retrograde cholangiopancreatography, randomized controlled trial.
Endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC) is the most common management of gallstones combined with common bile duct (CBD) stones. This study aims to evaluate the impact of routine insertion of nasobiliary catheter during ERCP in cases of difficult LC. From total 110 patients who underwent ERCP followed by LC in the period from April 2019 to April 2020, nasobiliary (NB) catheter was inserted during ERCP in 55 patients after CBD clearance (NB group). In the other 55 patients, only CBD clearance was done (Control group). In the NB group, dynamic trans-nasobiliary intraoperative cholangiography (TN-IOC) was done during dissection of Calot's triangle. At the end of the procedure, trans-nasobiliay methylene blue (MB) test was done to detect any missed biliary injury. The primary outcome to be analyzed was the incidence and severity of bile duct injury (BDI), secondary outcomes were the operative time, conversion to open surgery, and hospital stay. Of the 110 patients, 57 patients (51.8%) were males and 53 (48.2%) were females. Median age was 55 years. One case of biliary leak was reported in the NB group (1.8%), while 2 cases (3.6%) were reported in the Control group. The average operative time in the NB group was 115 min versus 128 min in the Control group (P value < 0.001). No cases were converted to open cholecystectomy in the NB group (0%) with 5 cases (9.1%) converted to open in the Control group. The average postoperative hospital stay was 2 ± 0.1 days in the NB group versus 3.6 ± 5.3 days in the Control group (P value = 0.037). Routine insertion of nasobiliary tube during ERCP, in patients with combined gallbladder and CBD stones, is a simple, safe and dynamic method for IOC. This maneuver does not statistically decrease the incidence of BDI but can diagnose, minimize and treat BDI with shorter operative time and hospital stay.


Survival of individuals with cerebral palsy in Victoria, Australia: A longitudinal cohort study spanning four decades.
To provide an updated description of the rates, trends, and predictors of mortality of individuals with cerebral palsy (CP), born in the Australian state of Victoria between 1970 and 2012. Data were extracted for 4807 individuals (2091 females; 2716 males). The probability of survival to 30th June 2017 was calculated using the Kaplan-Meier method. Mortality rates were calculated per 1000 person-years using age strata and compared with population mortality rates to produce mortality ratios. Cox proportional hazards regression was used to calculate hazard ratios for selected demographic and clinical characteristics and to estimate the effect of birth epoch on 15-year survival. There were 666 recorded deaths. Compared to the general population, mortality was higher for all persons with CP and highest for children aged 1 to 15 years (45-62 times). We observed 35% improvement in the probability of survival to 15 years for births in the 2000s relative to the 1970s (hazard ratio 0.65, 95% confidence interval [CI] 0.49, 0.86), but only 4% improvement for the subgroup with complex CP (hazard ratio 0.96, 95% CI 0.69, 1.33). The observed improvements in survival for those born in the 2000s is likely related predominantly to a proportional reduction in complex CP within the cohort. Length of survival improved for Australians with cerebral palsy (CP) born this millennium. Improved survival was mainly because of a proportional reduction in complex CP. A small improvement in length of survival was seen for children with complex CP.


Migraine headaches.
Once the definitive diagnosis of migraine has been formulated, the physician has many options available for abortive and prophylactic therapy. Nonpharmacologic modalities, including behavioral modification methods such as biofeedback training, may also be considered. Migraine does not necessarily have to disrupt the lives of those afflicted. The patient with mixed headache presents a more difficult diagnostic and therapeutic problem. These patients can also be helped when the disorder is identified, and inpatient therapy for these patients may be required.


Fast and specific: insights into the acquisition and generalization of motor acuity.
Motor acuity is considered to be the outcome of prolonged practice and to involve morphological changes in the motor cortex. We have previously designed a curved pointing task, the arc pointing task (APT), to study motor acuity acquisition, defined as a change in the speed-accuracy tradeoff function (SAF) of the task. Here, we studied the generalization of motor acuity between hands and between tasks (drawing the arc in the opposite direction and with the untrained hand) and the effect of training duration on motor acuity. We report that training-induced motor acuity improvement did not generalize across hands and across tasks performed with the same hand, suggesting a task-specific representation of motor acuity. To our surprise, the largest gains in motor acuity, measured both by changes in SAF and by improvement in multiple kinematic variables, were seen following a short exposure to the task. Our results suggest that motor acuity training-induced improvement is task specific and that motor acuity starts to improve following a very short practice.NEW & NOTEWORTHY We report that training induced motor acuity improvement does not generalize from one hand to another or between movements that are performed with the same effector. Furthermore, significant improvements in acuity were found following a very short exposure to the task (∼20 trials). Therefore, our results suggest that the nervous system has the capacity to rapidly improve motor acuity.


Cysticercosis cellulosae. An unusual cause of a labial swelling.
A case of cysticercosis cellulosae presenting as an isolated swelling of the labial mucosa, clinically diagnosed as a mucocele, is described. The important implications of such a diagnosis are discussed along with a resumé of the natural history of Taenia solium, the pork tapeworm.


Assessment of shared decision making in pediatrics: Developing German scales for patients aged 7-18 years, parents and parent-proxy reports (CollaboRATEpediatric).
To develop parsimonious German scales (CollaboRATEpediatric) to assess shared decision making (SDM) with patients aged 7-18 years, parents and parents on behalf of their children (parent-proxy reports), and to establish comprehensibility and preliminary face validity. Based on an existing SDM scale for adults (CollaboRATE) we developed CollaboRATEpediatric in a two-step approach: (1) team-based translation of the English CollaboRATE scale into German and adaptation for pediatric patients, parents and parent-proxy reports, followed by (2) iterative revisions of the CollaboRATEpediatric scales based on cognitive interviews with patients and parents until comprehensibility and preliminary face validity were established. Taking into account seven problem areas identified in four rounds of cognitive interviews (e.g., item complexity) we developed CollaboRATEpediatric scales for patients, parents and parent-proxy reports. By iteratively revising items we were able to resolve all problem areas and achieved full comprehensibility and intended interpretation of all items. The scales enable the parsimonious assessment of SDM with pediatric patients and parents as well as comparisons between the two groups. Future empirical work will establish the psychometric performance of CollaboRATEpediatric. CollaboRATEpediatric can be used in quality improvement initiatives to foster the comprehensive implementation of SDM in pediatrics.


Use of a skin adhesive (octyl-2-cyanoacrylate) and the optimum reinforcing combination for suturing wounds.
The adhesion strength of a skin adhesive, octyl-2-cyanoacrylate (Dermabond), was measured under various conditions using porcine skin. The combined use of a skin adhesive and a skin closure tape (n = 5) was significantly stronger than a single application of skin adhesive (n = 5) (p < 0.01). We have tentatively named the wound closure in which a skin adhesive and reinforcement material were combined the Reinforcing Combination Method. To obtain optimum conditions, further studies were done for sequence of application, type of reinforcement material, a number of layers, and width of the suture. The optimum condition for the reinforcement combination was established by applying one layer of skin adhesive over a skin closure tape, over one layer of skin adhesive, with a suture width of 4 cm. This reinforcement combination might be useful in clinical practice.


Model of ultrafast intersystem crossing in photoexcited transition-metal organic compounds.
The mechanism behind fast intersystem crossing in transition-metal complexes is shown to be a result of the dephasing of the photoexcited state to the phonon continuum of a different state with a significantly different transition metal-ligand distance. The coupling is a result of the spin-orbit interaction causing a change in the local moment. A recurrence to the initial state is prevented by the damping of the phonon oscillation. The decay time is faster than the oscillation frequency of the transition metal-ligand stretch mode, in agreement with experiment. For energies above the region where the strongest coupling occurs, a slower "leakage-type" decay is observed. If the photoexcited state is lower in energy than the state it couples to, then there is no decay.


Correction to: Assessment of the efficacy of firocoxib (Previcox®) and grapiprant (Galliprant®) in an induced model of acute arthritis in dogs.
The original article [1] contains two mistaken instances of the molecule 'fipronil' in the results. These should instead have stated 'firocoxib'.


Baicalein inhibits RLS3-induced ferroptosis in melanocytes.
We explored the effect of baicalein on the ferroptosis of melanocytes in vitiligo. Melanocytes were treated with single RSL3 or combined RSL3 with FAC for 24 h and the effect of baicalein on RSL3 toxicity was further evaluated. Cell viability was examined by CCK8 assay. The mitochondrial membrane potential and the level of iron ion were measured by assay kit. Intracellular and lipid ROS production was detected by flow cytometry. The results indicated that RSL3 induced cell death, mitochondrial dysfunction, ROS production, and iron ion accumulation in melanocytes, which was aggravated by the addition of FAC. The damage induced by RSL3 was significantly relieved by baicalein treatment. Besides, baicalein up-regulated GPX4 and reduced TFR1 level in melanocytes treated with RSL3+FAC. Baicalein protected melanocytes against ferroptosis through up-regulating GPX4. Ferroptosis might be pervasive in the occurrence and development of vitiligo, and could be proposed as the potential therapeutic target.


Factors associated with 5-min APGAR score, death and survival in neonatal intensive care: a case-control study.
The 5-minute APGAR score is clinically used as a screening tool to assess how the newborn has reacted to previous care, remaining relevant for predicting neonatal survival. This study aimed to analyze the determinants of the 5th minute APGAR score, and the factors associated with the death and survival of newborns with low APGAR scores hospitalized in the neonatal intensive care unit (NICU) at a referral public hospital in North Brazil. This was a hospital-based retrospective case-control study with 277 medical records. Newborns who presented with a 1-minute APGAR score < 7 followed by a 5-minute APGAR score < 7 were considered cases, while a score ≥ 7 was categorized as controls. Univariate and multivariable logistic regression analyses were used to establish the determinant factors of the low APGAR score and death outcome in this group. Survival curves were obtained using the Kaplan-Meier estimator, and then univariate and multivariate Cox regression was performed. After adjusted analysis, the factor associated with low APGAR scores was vaginal delivery (OR = 3.25, 95%CI = 1.60-6.62, p = 0.001). Birth injury (OR = 0.39, 95%CI = 0.19-0.83, p = 0.014) was associated with upper APGAR scores. No significant independent associations were observed between the variables analyzed and death in the low APGAR score group. The Kaplan-Meier curve showed that individuals who presented Cesarean delivery had a shorter survival time in the ICU. In this setting, a 5-minute Apgar score < 7 was associated with the occurrence of vaginal delivery and birth injury with a 5-minute Apgar score ≥ 7. Survival in ICU was lower in newborns that were delivered via cesarean section.


Post-tonsillectomy bleeding rate decreases with limitation in maximum post-operative ibuprofen dosage: A quality improvement study.
The objective of this study is to investigate the effect of a reduction in the prescribed post-operative ibuprofen dosage on frequency of post-tonsillectomy bleeding. A quality improvement study was conducted at a single tertiary care pediatric hospital with patients weighing >40 kg undergoing tonsillectomy. The intervention was limiting the post-operative ibuprofen dosage to a maximum of 400 mg per dose. Data was collected on all patients returning to the hospital with bleeding after tonsillectomy. The primary outcome was the rate of post-tonsillectomy bleeding. Statistical analysis was conducted using nonparametric comparisons and a run chart. A total of 199 tonsillectomy patients >40 kg were included in the study. There were 119 (59.8 %) females and 80 (40.2 %) males total. The pre-intervention group had a total of 56 patients while the post-intervention group had a total of 143 patients. There was no statistical difference in age, weight, or sex between the pre- and post-intervention groups (p > .05). The post-tonsillectomy hemorrhage rate was 11/56 (19.6 %) before the intervention, and 11/143 (7.7 %) after the intervention (p = .016). Children who experienced a bleeding event were significantly older (mean 15.9 years, 95 % CI 14.5-17.3) than those who did not (13.5 years, 95 % CI 12.9-14.1; p = .011). The run chart revealed that the intervention resulted in a nonrandom decrease in rate of post-tonsillectomy bleeding. Post-tonsillectomy bleeding rate decreased with a ceiling post-operative ibuprofen dose of 400 mg/dose in this quality improvement study. Further research is warranted.


Enantioselective determination of cetirizine in human plasma by normal-phase liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.
A highly sensitive and enantioselective method has been developed and validated for the determination of levocetirizine [(R)-cetirizine] in human plasma by normal-phase liquid chromatography coupled to tandem mass spectrometry with an atmospheric pressure chemical ionization (APCI) interface in the positive ion mode. Enantioselective separation was achieved on a CHIRALPAK AD-H column using an isocratic mobile phase consisting of a mixture of n-hexane, ethyl alcohol, diethylamine, and acetic acid (60:40:0.1:0.1, v/v/v/v). Levocetirizine-D(8) was used as an internal standard (IS). Levocetirizine and the IS were detected by multiple-reaction monitoring (MRM). Mass transitions of analyte and IS were m/z 389.2→201.1 and 397.2→201.1, respectively. Under optimized analytical conditions, a baseline separation of two enantiomers and IS was obtained in less than 11 min. Samples were prepared by a simple two-step extraction by protein precipitation using acetonitrile followed by liquid-liquid extraction with a n-hexane-dichloromethane mixture (50:50, v/v). The standard curve for levocetirizine was linear (r(2)>0.995) in the concentration range 0.5-300 ng/mL. Recovery was between 97.0 and 102.2% at low, medium, and high concentration. The limit of quantification (LOQ) was 0.5 ng/mL. Other method validation parameters, such as precision, accuracy, and stability, were very satisfactory. Finally, the proposed method was successfully applied to the study of enantioselective oral pharmacokinetics of levocetirizine in healthy Korean volunteers.


Effect of delta-lysin on the phase transitions of lipid assemblies.
X-ray small-angle diffraction, differential scanning calorimetry (DSC), and temperature scanning densitometry (TSD) were used to study the effect of delta-lysin on the phase transitions of lipid assemblies from 1,2-0-dixehadecyl-sn-glycero-3-phosphocholine (DHPC). The experiments were carried out in excess of water in a temperature range of 0-55 degrees C, and at low peptide concentrations between 10(-4) and 10(-2) moles peptide per mole phospholipid. The incorporation of delta-lysin into lipid assemblies alters the lipid structure without significant changes on the temperatures of phase transition from gel to liquid crystalline phase. The temperature of the main transition was nearly unaffected. A reduction in the transition volume of the lipids with increasing concentrations of delta-lysin was observed. The minor changes in these parameters were interpreted as long-range structural changes caused by the peptide incorporation. The results are discussed in terms of the concept of cooperative phase transition of entire clusters occurring within a membrane implying that relative stable domains of gel phase, and liquid crystalline phase co-exist.


Various sodium salts, potassium salts, a calcium salt and an ammonium salt induced ornithine decarboxylase and stimulated DNA synthesis in rat stomach mucosa.
Studies were made on the possible tumor-promoting activities of various salts of food additives in the glandular stomach mucosa of F344 male rats after their administration by gastric intubation. Up to 100-fold increases in ornithine decarboxylase (ODC) activity in the pyloric mucosa of the stomach with maxima after 8 h were observed after administration of sodium acetate at doses of 3.68-13.6 mmol/kg body weight, sodium L-ascorbate at doses of 8.55-17.1 mmol/kg body weight, Na2CO3 at doses of 4.73-14.2 mmol/kg body weight, sodium L-glutamate at doses of 12.8-17.1 mmol/kg body weight, sodium sorbate at doses of 8.92-17.1 mmol/kg body weight and (NH4)2SO4 at doses of 7.56-20.1 mmol/kg body weight. Increases of up to 100-fold in ODC activity with maxima after 16 h were also observed after intubation of KCl at doses of 10.1-22.0 mmol/kg body weight, K2SO3 at doses of 2.84-8.45 mmol/kg body weight, K2S2O5 at doses of 2.25-6.75 mmol/kg body weight and CaCl2 at doses of 2.0-4.08 mmol/kg body weight. Sodium acetate at a dose of 11.0 mmol/kg body weight, KCl at a dose of 20.1 mmol/kg body weight, K2S2O5 at a dose of 5.40 mmol/kg body weight and CaCl2 at a dose of 3.4 mmol/kg body weight induced up to 10-fold increase in DNA synthesis in the pyloric mucosa of the stomach with maxima after 16-24 h. These results suggest that these salts of food additives may, like NaCl, have tumor-promoting activities in the pyloric mucosa of rat stomach.


Circulating biomarkers are associated with disease severity of chronic hand eczema and atopic dermatitis.
Although chronic hand eczema (CHE) is a highly prevalent and disabling skin disease, it is currently unknown if CHE is associated with systemic inflammation. To characterize the plasma inflammatory signature of CHE. Using Proximity Extension Assay technology, we assessed 266 inflammatory and cardiovascular disease risk proteins in the plasma of 40 healthy controls, 57 patients with atopic dermatitis (AD) with active lesions, 11 with CHE and a history of AD (CHEPREVIOUS_AD), and 40 with CHE and no history of AD (CHENO_AD). Filaggrin gene mutation status was also assessed. Protein expression was compared between groups and according to disease severity. Correlation analyses for biomarkers, and clinical- and self-reported variables, were performed. Very severe CHENO_AD was associated with systemic inflammation when compared with controls. Levels of T helper (Th)2- and Th1-, general inflammation and eosinophil activation markers increased with severity of CHENO_AD, primarily being significantly increased in very severe disease. Significant, positive correlations were found between markers from these pathways and severity of CHENO_AD. Moderate-to-severe but not mild AD displayed systemic inflammation. The Th2 markers C-C motif chemokine (CCL)17 and CCL13 (also known as monocyte chemotactic protein 4) were the top differentially expressed proteins in both very severe CHENO_AD and moderate-to-severe AD, showing a higher fold change and significance in AD. CCL17 and CCL13 levels further correlated positively with disease severity in both CHENO_AD and AD. Systemic Th2-driven inflammation is shared between very severe CHE with no history of AD, and moderate-to-severe AD, suggesting that Th2 cell targeting could be effective in several CHE subtypes.


Clinical and genetic characteristics of childhood-onset myotonic dystrophy.
Myotonic dystrophy type 1 (DM1) is caused by a CTG (cytosine-thymine-guanine) trinucleotide repeat expansion. Congenital DM (CDM) presents in the first month of life, whereas individuals with infantile and juvenile DM1 have later onset of symptoms. We performed a retrospective chart review of patients with childhood-onset DM1 seen at one of three locations in Dallas, Texas between 1990 and 2018. Symptoms, disease course, cognitive features, and family history were reviewed. Seventy-four patients were included; CDM was diagnosed in 52 patients. There was maternal inheritance in 74% of patients. CTG repeat number ranged from 143 to 2300. Neuropsychiatric and cognitive deficits were common. Over half of the patients had GI disturbances, and orthopedic complications were common. Myotonic dystrophy type 1 in children requires a multidisciplinary approach to management. Presenting symptoms vary, and repeat expansion size does not necessarily directly relate to severity of symptoms. A consensus for outcome measures is required.


Potency of pertussis component in the DTP vaccine--an overview of three decade study in Poland.
In Poland, similar to many highly immunized Western countries, a recent increase in cases of pertussis has been observed. This study aims to evaluate the level of potency fluctuations of the pertussis component of Polish-produced DTP vaccine due to the changes having occurred in production and potency testing procedures. We compared the potency of the pertussis component of DTP vaccine lots produced and evaluated in similar periods and with similar production and testing procedures. Records of Kendrick test results performed over a 30-year period were available for analysis. This study confirms the role of different manufacturers, changes in vaccine strain compositions, in-house reference preparations used as reference vaccines in the Kendrick tests, and in mice of single strain sources in the potency values obtained. In addition, the comparisons performed revealed a downtrend in potency levels since 1992. Potency decrease in vaccine lots produced during 1992-1997 has been positively correlated to the lowering of the number of IOU/dose. Strain compositions of the DTP vaccine pertussis component and in-house references have been found to be associated with the fluctuation in potency estimations, and confirmed their crucial role in ensuring vaccine efficacy. Our study reveals that relative efficacy of the DTP vaccine produced in 1992-1997 might be lower than that of vaccines produced in other periods. This might in turn explain the increase in pertussis cases among children aged 5-15 years which is presently being observed in Poland.


Hypnotic suggestion alters the state of the motor cortex.
Hypnosis often leads people to obey a suggestion of movement and to lose perceived voluntariness. This inexplicable phenomenon suggests that the state of the motor system may be altered by hypnosis; however, objective evidence for this is still lacking. Thus, we used transcranial magnetic stimulation of the primary motor cortex (M1) to investigate how hypnosis, and a concurrent suggestion that increased motivation for a force exertion task, influenced the state of the motor system. As a result, corticospinal excitability was enhanced, producing increased force exertion, only when the task-motivating suggestion was provided during hypnotic induction, showing that the hypnotic suggestion actually altered the state of M1 and the resultant behavior.


Characterization of ZnO Nanoparticles using Superconducting Tunnel Junction Cryodetection Mass Spectrometry.
Zinc oxide (ZnO) nanoparticles coated with either n-octylamine (OA) or α-amino poly(styrene-co-acrylonitrile) (PSAN) ligands (L) have been analyzed using laser desorption/ionization and matrix assisted laser desorption/ionization (MALDI) time-of-flight (TOF) superconducting tunnel junction (STJ) cryodetection mass spectrometry. STJ cryodetection has the advantage of high m/z detection and allows for the determination of average molecular weights and dispersities for 500-600 kDa ZnO-L nanoparticles. The ability to detect the relative energies deposited into the STJs has allowed for investigation of ZnO-L metastable fragmentation. ZnO-L precursor ions gain enough internal energy during the MALDI process to undergo metastable fragmentation in the flight tube. These fragments produced a lower energy peak, which was assigned as ligand-stripped ZnO cores whereas the individual ligands were at too low of an energy to be observed. From these STJ energy resolved peaks, the average weight percentage of inorganic material making up the nanoparticle was determined, where ZnO-OA and ZnO-PSAN nanoparticles are comprised of ~62% and ~68% wt ZnO, respectively. In one example, grafting densities were calculated based on the metastable fragmentation of ligands from the core to be 16 and 1.1 nm-2 for ZnO-OA and ZnO-PSAN, respectively, and compared with values determined by thermogravimetric analysis (TGA) and transmission electron microscopy (TEM). Graphical Abstract .


River water contaminated with perfluorinated compounds potentially posing the greatest risk to young children.
Although, humans are exposed to perflourinated compounds (PFCs) from various media, water consumption could be an important source for the residents living near to contaminated areas. Since comprehensive multimedia exposure model has not been developed for PFCs, assessment of the potential risk due to exposure to PFCs through direct water consumption could be a conservative estimate. The human health risks derived from the exposure to PFCs through water consumption were assessed for different age groups of general population in Taiwan using probabilistic approach. Based on available data on concentrations of PFCs in river water, exposure to PFOS, PFOA and PFDA via water consumption for different age groups were calculated using deterministic and probabilistic risk assessment methods. The oral non-cancer risks from PFOS, PFOA and their combination, expressed as a Hazard Index (HI), was determined by comparing oral exposure dose (through water intake) with the oral Reference Dose (RfD). The average exposure to PFOS, PFOA and PFDA via water consumption for adults ranged from 0.16 to 220.15, 0.43 to 12.5 and 0.43 to 2.36 ng kg-bw(-1) d(-1) and for children 0.13-354.3, 0.35-20.17 and 0.35-3.79 ng kg-bw(-1) d(-1), respectively. Probabilistic values of total HIs for all age groups reside near to Keya River exceed the RfD 2.4-4.8 times, corresponding mainly to PFOS with a percentage of 97%. In conclusions, children aged 1-3 years old and the residents reside near to Keya River are at the highest risk of exposure to PFCs via water consumption.


Automatic quantification and classification of microplastics in scanning electron micrographs via deep learning.
Microplastics quantification and classification are demanding jobs to monitor microplastic pollution and evaluate the potential health risks. In this paper, microplastics from daily supplies in diverse chemical compositions and shapes are imaged by scanning electron microscopy. It offers a greater depth and finer details of microplastics at a wider range of magnification than visible light microscopy or a digital camera, and permits further chemical composition analysis. However, it is labour-intensive to manually extract microplastics from micrographs, especially for small particles and thin fibres. A deep learning approach facilitates microplastics quantification and classification with a manually annotated dataset including 237 micrographs of microplastic particles (fragments or beads) in the range of 50 μm-1 mm and fibres with diameters around 10 μm. For microplastics quantification, two deep learning models (U-Net and MultiResUNet) were implemented for semantic segmentation. Both significantly outmatched conventional computer vision techniques and achieved a high average Jaccard index over 0.75. Especially, U-Net was combined with object-aware pixel embedding to perform instance segmentation on densely packed and tangled fibres for further quantification. For shape classification, a fine-tuned VGG16 neural network classifies microplastics based on their shapes with high accuracy of 98.33%. With trained models, it takes only seconds to segment and classify a new micrograph in high accuracy, which is remarkably cheaper and faster than manual labour. The growing datasets may benefit the identification and quantification of microplastics in environmental samples in future work.


Immunoglobulin E levels and antisperm antibody titers in infertile couples.
Immunoglobulin E (IgE) levels and antisperm antibody titers were determined in samples of serum and seminal plasma from 25 fertile men (Group A), 18 infertile men without measurable immunity to sperm (Group B), and 42 infertile men autoimmune to sperm (Group C), and in samples of serum and cervical and vaginal secretions from 25 fertile women (Group D), 28 infertile women without measurable immunity to sperm (Group E), and 32 infertile women isoimmune to sperm (Group F). Among the men, IgE levels in the serum, measured in international units per milliliter, were elevated in Group C (230 +/- 41, mean +/- SEM) as compared with Groups B (94 +/- 33, P less than 0.05) and A (55 +/- 8, P less than 0.001). In contrast, IgE levels in the seminal plasma in Group C (180 +/- 44) were not significantly different from those in Group B (48 +/- 21), but were higher than those in Group A (8 +/- 2, P less than 0.05). In the women, serum IgE levels were higher (P less than 0.001) in Group F, with isoimmunity to sperm (472 +/- 55), than in Groups E (219 +/- 32) and D (76 +/- 16). Wives of autoimmune husbands had somewhat, though not significantly, higher serum IgE levels (406 +/- 55), than had wives of nonautoimmune husbands (247 +/- 97). These results provide evidence for an elevated IgE response in subjects with significantly elevated antisperm antibody titers.


Red blood cell transfusions can induce proinflammatory cytokines in preterm infants.
The risk of developing red blood cell (RBC) transfusion-associated necrotizing enterocolitis (TANEC) in preterm infants has recently been emphasized. Our aim was to assess changes in cytokine serum levels after RBC transfusions in a cohort of very preterm infants to evaluate their possible proinflammatory effect. We carried out a prospective observational study. One transfusion event was studied in infants less than 32 weeks' gestation and more than 7 days old (n = 20) admitted to a tertiary neonatal intensive care unit. Interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, interferon-γ (IFN-γ), IL-17, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule serum levels were measured in enrolled patients within 120 minutes before (T0 ) the RBC transfusion and then within 120 minutes (T1 ), 12 ± 3 hours (T2 ), 24 ± 6 hours (T3 ), and 48 ± 6 hours (T4 ) after the end of RBC transfusion. Infants received 19.8 ± 3.0 mL of RBCs at the mean age of 50 ± 18 days. Their hematocrit level increased from 24.1 ± 1.2% to 39.4 ± 2.9%. IL-1β, IL-8, IFN-γ, IL-17, MCP-1, IP-10, and ICAM-1 increased significantly after RBC transfusions. Proinflammatory cytokines are increased after RBC transfusion. These findings may contribute to explaining the pathogenesis of TANEC and suggest the opportunity of adopting wise transfusion guidelines that would help to avoid detrimental risks of transfusion-related immunomodulation and of undertransfusion.


Endoscopic management of foreign body in the upper gastrointestinal tract: a tertiary care center experience.
Foreign body (FB) in the upper gastrointestinal tract (UGIT) is a common clinical problem in endoscopic practice. At present, many physicians recommend endoscopy for both diagnosis and treatment. To date, few have report endoscopic findings and management of FB in UGIT. To report the authors' experience and outcome of the endoscopic management of foreign body ingestion at Siriraj Hospital. Medical records of patients with FB ingestion in the UGIT, who underwent endoscopic management between January 2004 and January 2008 at Siriraj Hospital, were reviewed. The analysis included 34 patients of which 58.82% were men. The mean age of the group was 18.26 years (range 10 months - 86 years). 58.82% of patients were younger than 5 years. Esophagogastroduodenoscopy (EGD) was performed in 100% of cases, under general anesthesia (GA) in 85.29%, and under transintravenous anesthesia (TIVA) in 14.71%. Endoscopic management was successful in all cases. The extractions were done with rat-tooth forceps, polypectomy snare, dormia basket, or tripods. There were no procedure related complications. The ingested FB varied widely according to the underlying medical condition and age. In a tertiary care center endoscopic removal of FB in UGIT could be safely performed with a very good result.


Graph theoretical analysis of structural and functional connectivity MRI in normal and pathological brain networks.
Graph theoretical analysis of structural and functional connectivity MRI data (ie. diffusion tractography or cortical volume correlation and resting-state or task-related (effective) fMRI, respectively) has provided new measures of human brain organization in vivo. The most striking discovery is that the whole-brain network exhibits "small-world" properties shared with many other complex systems (social, technological, information, biological). This topology allows a high efficiency at different spatial and temporal scale with a very low wiring and energy cost. Its modular organization also allows for a high level of adaptation. In addition, degree distribution of brain networks demonstrates highly connected hubs that are crucial for the whole-network functioning. Many of these hubs have been identified in regions previously defined as belonging to the default-mode network (potentially explaining the high basal metabolism of this network) and the attentional networks. This could explain the crucial role of these hub regions in physiology (task-related fMRI data) as well as in pathophysiology. Indeed, such topological definition provides a reliable framework for predicting behavioral consequences of focal or multifocal lesions such as stroke, tumors or multiple sclerosis. It also brings new insights into a better understanding of pathophysiology of many neurological or psychiatric diseases affecting specific local or global brain networks such as epilepsy, Alzheimer's disease or schizophrenia. Graph theoretical analysis of connectivity MRI data provides an outstanding framework to merge anatomical and functional data in order to better understand brain pathologies.


Lacrimal sac lymphoproliferative lesion: case report.
The case is presented of a 51 year-old woman with a firm mass at the medial canthus of the right eye of five years onset. A low-grade lymphoproliferative lesion (reactive lymphoid hyperplasia) was diagnosed from an excisional biopsy Lacrimal sac tumors are rare, with a peak incidence in the fifth decade of life. The initial clinical features are epiphora and medial canthus swelling. As it mimics nasolacrimal duct obstruction, up to 40% of these tumors are misdiagnosed until undergoing surgery.


Optimization of eco-friendly novel amendments for sustainable utilization of Fly ash based on growth performance, hormones, antioxidant, and heavy metal translocation in chickpea (Cicer arietinum L.) plant.
The present study has focused on the evaluation of the maximum amount of flyash (FA) utilization augmentation in the acidic soil (pH 6.1) with the manure during the growth performance and impact of toxic heavy metals under the pot experiment. The 15 days pre-incubated 40% FA treated combination (T16) significantly (P < 0.05) influenced growth performance of chickpea plant after 60 days. The dry weight as well as the contents of N, P, and K increased from 38.8 to 78.53%, 118 to 86%, 148 to 115%, and 95.8 to 95%, respectively, over control in T15 combination after 30 and 60 days. T15 and T16 both treatments induced a significant rise in IAA and GB from 76 to 75.5% and 50%-45%, respectively, after 60 days. The significant increase in the activities of SOD, APX, CAT, and GR with 47%, 56%, 42%, and 28%, respectively, over control was observed in T16 treated combination after 60 days. The significant (P < 0.05) influence in the antioxidant activities, levels of GB, Proline, TSS, and RS were observed across the treatments and durations. The levels of BCF and TF both were <1 in T16 treated plants for toxic heavy metals (Pb, Mo, Cd, and Al), which indicated a negligible extent of translocation from root to shoot and shoot to edible parts in the plants. The results demonstrated that 40% FA supplementation with manure could induce the growth of chickpea in slightly acidic soil and reduce the translocation of toxic metals in the edible parts of the plant.


Migrant General Practitioners' Experiences of Using Interpreters in Health-care: a Qualitative Explorative Study.
According to the UNHCR, 250 million people currently live outside their country of birth. The growing multicultural population poses a major challenge to healthcare professionals who aim to provide individualized, holistic care, which respects the individual's autonomy. To ensure basic rights, healthcare interventions should be guided by the value of benefiting others; individuals should be treated honestly, equally, and impartially. To investigate immigrant doctors' experiences of using interpreters in the Swedish health-care system. Twenty-eight doctors, 12 men and 16 women from Bosnia and Herzegovina, Croatia, Macedonia and Serbia participated in four focus group interviews (FGI). The interviews were audio recorded, transcribed and analyzed using content analysis method. The best results in the present study were achieved in situations where a professional interpreter was involved. In some cases, the doctors were forced to use relatives or a colleague to interpret, which in many cases proved to be a mistake. The consequences of poor interpretation routines included payment by mistake, a patient paying an interpreter who refused to interpret, time spent waiting for another interpreter, as well as disturbances to the daily work schedule. Finding someone who could replace an interpreter who did not show up caused time shortage and increased stress. Improved routines and more effective cooperation between interpreting services and health-care centers are needed in order to ensure that using professional interpreters guarantees appropriate, high quality care. Improvements are needed to provide satisfactory health-care to people with limited language skills. In order to achieve this, better education of interpreters is needed, especially regarding cultural diversity and medical terminology. These improvements present complex challenges, deserving empirical and critical reflection in order to improve the work situation for doctors.


Substantial decrease in CO2 emissions from Chinese inland waters due to global change.
Carbon dioxide (CO2) evasion from inland waters is an important component of the global carbon cycle. However, it remains unknown how global change affects CO2 emissions over longer time scales. Here, we present seasonal and annual fluxes of CO2 emissions from streams, rivers, lakes, and reservoirs throughout China and quantify their changes over the past three decades. We found that the CO2 emissions declined from 138 ± 31 Tg C yr-1 in the 1980s to 98 ± 19 Tg C yr-1 in the 2010s. Our results suggest that this unexpected decrease was driven by a combination of environmental alterations, including massive conversion of free-flowing rivers to reservoirs and widespread implementation of reforestation programs. Meanwhile, we found increasing CO2 emissions from the Tibetan Plateau inland waters, likely attributable to increased terrestrial deliveries of organic carbon and expanded surface area due to climate change. We suggest that the CO2 emissions from Chinese inland waters have greatly offset the terrestrial carbon sink and are therefore a key component of China's carbon budget.


Immunohistochemical comparison of p53, Ki-67, CD68, vimentin, α-smooth muscle actin and alpha-1-antichymotry-psin in oral peripheral and central giant cell granuloma.
Giant cell lesions are characterised histologically by multinucleated giant cells in a background of ovoid to spindle-shaped mesenchymal cells. There is a major debate whether these lesions are separate entities or variants of the same disease. Our aim was to study the nature of multinucleated and mononuclear cells from peripheral giant cell granuloma (PGCG), and central giant cell granuloma (CGCG) and giant cell tumor (GCT) of long bones using immunohistochemistry evaluation and to determine whether there is a correlation between recurrence and the markers used. Ki-67, p53, Vimentin, smooth muscle specific actin, CD68 and alpha-1-antichymotrypsin were used to study 60 giant cell lesions. These included 26 CGCG, 28 PGCG, and 6 GCT cases using an avidin-biotin-complex immunohistochemistry standard method. All studied cases showed the same results except the percentage of Ki-67 positive mononuclear cells in PGCG was significantly higher than that of both CGCG and GCT (p<0.05). Interestingly, no statistical correlation between recurrence and the markers used was found. Our results may suggest that these lesions have the same histogenesis. The mononuclear stromal cells, both histiocytic and myofibroblastic, are thought to be responsible for the behavior of these lesions whereas the multinucleated cells are considered as reactive. This might support the argument that PGCG, CGCG and GCT are different variants for the same disease. Further studies using molecular techniques are required to elucidate why some of these lesions behave aggressively than others.


Samuelsia mundiveteris sp. nov. from Thailand.
Samuelsia mundiveteris is described as the first member of the genus from the Old World tropics.


Tracheal epithelium in culture: a model for toxicity testing of inhaled molecules.
Rabbit trachea primary cultures have been developed as a model to evaluate the toxicity of noxious airborne pollutants. A mucociliary epithelium has been restored in vitro on collagen gel. Several general cytotoxicity assays (viability and growth inhibition) permit a first assessment for the acute toxicity of the tested molecules. More specific criteria such as measurement of the integrity of the epithelial barrier and inhibition of ciliary beat frequency allow to determine a specific impact of xenobiotics on the mucociliary epithelium in culture.


Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis.
Exposure to particulate silica (most crystalline polymorphs) causes a persistent inflammation sustained by the release of oxidants in the alveolar space. Reactive oxygen species (ROS), which include hydroxyl radical, superoxide anion, hydrogen peroxide, and singlet oxygen, are generated not only at the particle surface, but also by phagocytic cells attempting to digest the silica particle. Two distinct kinds of surface centers-silica-based surface radicals and poorly coordinated iron ions-generate O(2)(*)(-) and HO(*) in aqueous solution via different mechanisms. Crystalline silica is also a potent stimulant of the respiratory burst in phagocytic cells with increased oxygen consumption and production of O(*)(-), H(2)O(2), and NO leading to acute inflammation and HO(*) generation in the lung. Oxidative stress elicited by crystalline silica is also evidenced by increased expression of antioxidant enzymes such as manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase, and the enzyme inducible nitric oxide synthase (iNOS). Generation of oxidants by crystalline silica particles and by silica-activated cells results in cell and lung injury, activation of cell signaling pathways to include MAPK/ERK kinase (MEK), and extracellular signal-regulated kinase (ERK) phosphorylation, increased expression of inflammatory cytokines (e.g., tumor necrosis factoralpha [TNFalpha], interleukin-1 [IL-1]), and activation of specific transcription factors (e.g., NFkappaB, AP-1). Silica can also initiate apoptosis in response to oxygen- and nitrogen-based free radicals, leading to mitochondrial dysfunction, increased gene expression of death receptors, and/or their ligands (TNFalpha, Fas ligand [FasL]).


Duramycin radiosensitization of MCA-RH 7777 hepatoma cells through the elevation of reactive oxygen species.
The objective of this study is to explore the radiosensitization effects of duramycin against the liver cancer hepatoma cells and relationship to reactive oxygen species (ROS) generation. MCA-RH 7777 cells were treated with various combinations of duramycin concentrations and radiation doses. After the treatment, cell viabilities were determined by a cell proliferation assay; intracellular ROS levels were detected with the flow cytometric method. MCA-RH 7777 cell viability was found significantly reduced after combining duramycin and radiation exposure (comparing to that of either treatment alone). Increased intracellular ROS levels were observed in cells treated with combinations of duramycin and radiation. Duramycin increased the intracellular ROS generation and also increased the radiosensitivity of MCA-RH 7777 cells.


Effect of vinblastine in vivo on ultrastructure and insulin releasing capacity of the B-cell following sulphonylurea and isopropyl-noradrenaline.
The effect of vinblastine in vivo on ultrastructure and insulin releasing capacity of the B-cell was studied in mice. Treatment with vinblastine (1.1 mumole/mouse) resulted in a 75% decrease of the amount of normal microtubules and the appearance of characteristic paracrystals. Basal plasma immunoreactive insulin levels were depressed to about 60% of the control level. The dose-response pattern for insulin release (first phase) following two chemically unrelated insulin secretagogues, the potent sulphonyl-urea derivative, glibenclamide, and the beta-adrenegic agonist L-isopropylnoradrenaline, (L-IPNA), was tested with and without vinblastine pretreatment. The dose-response curves for L-IPNA-induced insulin release in vinblastine-treated and control animals did not deviate significantly from each other, whereas insulin release following glibenclamide was almost totally suppressed by vinblastine except at the lowest dose level. Injection of maximal doses of glibenclamide or L-IPNA did not alter the ultrastructural changes induced by vinblastine in the B-cells. It is suggested that the microtubular system of the B-cell might play a minor role for certain insulin-releasing processes and/or that vinblastine might have other important effects on the insulin secretory machinery.


Human papillomavirus vaccination coverage among Greek higher education female students and predictors of vaccine uptake.
One of the biggest public health measures to prevent HPV infection, and consequently, cervical cancer, is the HPV vaccine. Greece introduced HPV vaccines to its National Vaccination Program in 2008. The aims of this study were to estimate HPV vaccination coverage among female Greek students in higher education and to identify uptake predictors. We conducted a cross-sectional study. Data was collected through a self-completed questionnaire. The sample size included 3153 women with an 87% participation rate. Overall 25.8% of students reported they had received three doses of the HPV vaccine. Positive predictors of vaccine uptake were: younger age, higher educational level (own and parents), ever previous visit(s) to the gynecologist, always use of condoms, not smokers, not being in a stable relationship and easy access to Health Care Services. Vaccine compliance was unacceptably low despite the fact that the vaccination is free-of-charge. Interventions on college campuses should stress vaccination as a normative behavior.


A Rapid Review and Narrative Synthesis of the Consequences of Non-Inclusive Sex Education in UK Schools on Lesbian, Gay, Bisexual, Transgender and Questioning Young People.
Relationships and Sex Education (RSE) in schools are predominantly heterocentric. Consequently, lesbian, gay, bisexual, transgender, and questioning young people have reported feeling excluded. This exclusion results in feelings of being "different" and "other," which in turn leads to further disengagement in the sex education classroom, contributing to poor sexual health literacy, greater risk of abusive relationships, and higher rates of sexually transmitted infections. A rapid review was undertaken to identify the impact of non-inclusive sex education. The review makes recommendations for policy and practice, which includes the provision of training courses to school teaching staff with an emphasis on inclusive RSE, appropriate online resources for lesbian, gay, bisexual transgender, and questioning (LGBTQ) young people, as well as offering 1:1 emotional health support for LGBTQ young people as they begin to question their sexual orientation.


Pancreatic resection without routine intraperitoneal drainage.
Most surgeons routinely place intraperitoneal drains at the time of pancreatic resection but this practice has recently been challenged. Evaluate the outcome when pancreatic resection is performed without operatively placed intraperitoneal drains. In all, 226 consecutive patients underwent pancreatic resection. In 179 patients drains were routinely placed at the time of surgery and in 47 no drains were placed. Outcomes for these two cohorts were recorded in a prospective database and compared using the χ(2) - /Fisher's exact test for categorical variables, and Wilcoxon's test for continuous variables. Demographic, surgical and pathological details were similar between the two cohorts. Elimination of routine intraperitoneal drainage did not increase the frequency or severity of serious complications. However, when all grades of complications were considered, the number of patients that experienced any complication (65% vs. 47%, P= 0.020) and the median complication severity grade (1 vs. 0, P= 0.027) were increased in the group that had drains placed at the time of surgery. Eliminating intra-operative drains was associated with decreased delayed gastric emptying (24% vs. 9%, P= 0.020) and a trend towards decreased wound infection (12% vs. 2%, P= 0.054). The readmission rate (9% vs. 17% P= 0.007) and number of patients requiring post-operative percutaneous drains (2% vs. 11%, P= 0.001) was higher in patients who did not have operatively placed drains but there was no difference in the re-operation rate (4% vs. 0%, P= 0.210). Abandoning the practice of routine intraperitoneal drainage after pancreatic resection may not increase the incidence or severity of severe post-operative complications.


Clinical Skills Passport: A Method to Increase Participation in Clinical Skills by Medical Students During a Surgery Clerkship.
To prospectively evaluate the effect of introducing a clinical skills "passport" on medical students' reporting of their experience with basic clinical skills. A prospective longitudinal intervention study was conducted. Medical students were administered a questionnaire at the conclusion of their 12-week surgery clerkship regarding their experience with 15 clinical skills, inquiring whether they had "learned on surgery clerkship", "learned before surgery clerkship", or "not learned". Preintervention baseline data were obtained for 2 consecutive academic years (n = 213 students). In the third year, students (n = 124) were given a clinical skills passport to document performance of 8 of the 15 skills under the supervision of a surgical resident or faculty member. After excluding from analysis those students who learned a skill before their surgery clerkship, the fraction of students who reported learning clinical skills during their surgery clerkship before and after the introduction of the clinical skills passport was compared using Fisher exact test and chi-squared test, where appropriate (p ≤ 0.003 was considered significant; Bonferroni correction for multiple comparisons). Washington University School of Medicine. A total of 337 medical students completing the junior surgery clerkship over a 3-year period were included in the study. All 337 students completed a survey. Considering each skill individually, survey response rate was 5045/5055 (99.8%). Combining all responses for all skills, the fraction of students reporting that skills were learned on the surgery clerkship increased after the introduction of the clinical skills passport (1498/1938 [77%] preintervention vs. 974/1109 [88%] postintervention, p < 0.0001, chi square). After the introduction of the clinical skills passport, the fraction of students reporting that a skill was "learned on surgery clerkship" significantly increased for the 8 skills listed on the passport (1026/1699 [83%] preintervention vs. 685/714 [96%] postintervention, p < 0.0001, chi square), but did not increase for the 7 skills not listed on the passport (472/695 [68%] preintervention vs. 289/395 [73%] postintervention, p = 0.08, chi square). Considering each skill individually, after the introduction of the clinical skills passport, the fraction of students reporting that a skill was "learned on surgery clerkship" significantly increased for 4/15 skills (all listed on the clinical passport) and decreased for 0/15 skills (p < 0.003, Fisher exact test, 2 tailed). Institution of a clinical skills passport system during a surgery clerkship increased medical student reporting of their performance of basic clinical skills.


Injury and death on the farm: improving prevention through improved surveillance.
Work-related injury data suggest that agricultural workers in North Carolina are experiencing high rates of injury and death compared with workers in other occupations. However, current occupational injury data sources are insufficient to calculate accurate injury and mortality rates. We propose recommendations to improve existing farm injury surveillance, to guide prevention.


Histamine H1 receptor antagonism by cetirizine in isolated guinea pig tissues: influence of receptor reserve and dissociation kinetics.
We characterised histamine H(1) receptor antagonism by cetirizine and its enantiomers on isolated guinea pig ileum and trachea. Competitive or mixed (competitive and apparent noncompetitive) antagonism profiles were observed. The order of potency was: chlorpheniramine> or =mepyramine>levocetirizine>cetirizine> or =terfenadine>loratadine>dextrocetirizine. The inhibitory effects of cetirizine, levocetirizine, terfenadine and loratadine were slowly reversible compared to those of dextrocetirizine or mepyramine. Cetirizine and its enantiomers were inactive on L-type Ca(2+) channels. Reduction of the histamine H(1) receptor reserve by dibenamine in the ileum (100-fold higher than in the trachea) showed a gradual change from the competitive profile of dextrocetirizine and mepyramine to a mixed profile. The present results show that cetirizine and levocetirizine are selective competitive but slowly reversible histamine H(1) receptor antagonists. Their mixed antagonism profile observed in the trachea can be explained by the small receptor reserve present in this tissue compared to the ileum and their very slow dissociation rate from the histamine H(1) receptor.


Molecular cloning, expression analysis of the IgT gene and detection of IgT+ B cells in the half-smooth tongue sole (Cynoglossus semilaevis).
IgT is a specific Ig isotype in teleosts, which plays extremely important roles in the mucosal immunity of fish. In the present study, the membrane-bound and secretory IgT of the half-smooth tongue sole (Cynoglossus semilaevis) were identified for the first time. The V-D-J-C structure of two forms of csIgT are translated by the same Cτ gene, and the secretory tail and transmembrane domain were encoded through alternative splicing at the 3' end of the Cτ4. The CH regions of csIgT had high similarity with that of other flatfish (P. olivaceus and S. maximus). In healthy C. semilaevis, sIgT and mIgT were mainly expressed in mucus related tissues such as skin, intestine and gill. The transcript levels of sIgT and mIgT mRNA showed a significant induction in the immune-related tissues upon Vibrio Harveyi infection. A polyclonal rabbit anti-csIgT was successfully prepared using the csIgT heavy chain recombinant protein. Using this antibody, we detected the native IgT with the molecular mass at 220 kDa in skin total protein under non-reducing SDS-PAGE condition. Immunofluorescence analysis indicated that IgT+ B lymphocytes were intensively located in the skin, gill, intestine, and head kidney of C. semilaevis. These results suggest that IgT may participate in the immune response of C. semilaevis, which will facilitate the investigations of the immunoglobulins of marine fish.


The influence of positioning in urination: an electromyographic and uroflowmetric evaluation.
We conducted a cross-sectional study to evaluate whether the different positions during urination influence the electrical activity of the abdominal and perineal musculature, as well as the uroflowmetric parameters of children with lower urinary tract dysfunction (LUTD). Ninety-four children between the ages of 3 and 14 years with symptoms of LUTD were evaluated. All underwent uroflowmetry and electromyography tests (abdominal and perineal) in two different positions: oriented position (trunk bent slightly forward and feet flat) and atypical position (standing on toes for boys and buttocks not in contact with the lavatory seat and legs flexed in girls). We excluded nine patients due to suspicions of outside interference or elements complicating the analysis of charts. Among patients evaluated 55 (64.7%) were girls and 30 (35.3%) were boys with an average age of 8.5 years. Children urinating in atypical position showed higher levels of perineal electrical activity than when they were in normal position (p=0.018). However, there was no difference in the pattern of the curve if normal or abnormal when comparing the two groups (p=0.824). When evaluated separately, the boys demonstrated no difference between positions, in relation to perineal electrical activity (p=0.412) or abdominal electrical activity (p=0.202). The electrical activity of the pelvic floor musculature is decreased in the oriented position when compared to atypical positions in female children. Our data suggest that special attention should be given to adopting an adequate posture during urination for girls with LUTD.


A UK nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID-19.
To investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission. Retrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression. In total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment. Hospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA.


VAST 2020 Contest Challenge: GraphMatchMaker-Visual Analytics for Graph Comparison and Matching.
We report on the process and design of our visual analytics graph analysis challenge winning entry. Specifically, our team addressed the IEEE VAST 2020 Mini-Challenge 1 that asked participants to identify a group of people that accidentally caused an internet outage. To identify this group, we were given a network profile and a large multivariate social network to search in. Our approach involved statistical and graphical analysis as well as the design of three custom visual analytics tools. The submitted solution and visualizations are available at https://graphletmatchmaker.github.io/.


Factors Influencing Patient Decision-Making Concerning Treatment Escalation in Raynaud's Phenomenon Secondary to Systemic Sclerosis.
To explore patient priorities and ranking of factors influencing patient decision-making concerning treatment escalation in the management of Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). Patients with SSc were invited to participate in an online survey disseminated through patient-led organizations and social media platforms. Responses from 747 individuals with self-reported SSc-RP were evaluable with broad international representation. The mean ± SD age (54.7 ± 12.1 years), clinical phenotype, and disease subsets distribution (limited cutaneous SSc [402 of 747, 53.8%], diffuse cutaneous SSc [260 of 747, 34.8%], and overlap disease [85 of 747, 11.4%]) were consistent with expected demographic information. Around one-half (56.3%) of patients reported that their SSc-RP symptoms were adequately controlled. The 5 highest ranked factors (of 13) that would prompt treatment escalation for SSc-RP were as follows: 1) inability to use the fingers properly; 2) emergence of new digital ulcer on ≥1 fingers; 3) worsening pain or discomfort from RP; 4) more severe attacks; and 5) if it may help with internal problems. Despite symptoms not being adequately controlled, 47.1% were concerned about potential treatment side effects and were more likely to accept mild (~20-40%) versus severe (2%) side effects. Patients were open to different management strategies for uncontrolled RP that included adding new treatment in combination with existing treatment (52.8%), drug substitution (40.9%), increasing the current dose (28.8%), or focusing on nonpharmacologic approaches (29.7%). We have identified the relative importance of different factors influencing patient preferences for treatment decision-making regarding SSc-RP. Side-effect profiles influence acceptability of drug treatments, and many patients report a preference for nonpharmacologic management of SSc-RP.


Electrical impedance tomography applied to assess matching of pulmonary ventilation and perfusion in a porcine experimental model.
Electrical impedance tomography (EIT) can be used to measure impedance changes related to the thoracic content of air and blood. Few studies, however, have utilised EIT to make concurrent measurements of ventilation and perfusion. This experimental study was performed to investigate the feasibility of EIT to describe ventilation/perfusion (V/Q) matching after acute changes of pulmonary perfusion and aeration. Six mechanically ventilated, anaesthetised pigs in the supine position were studied at baseline, after inflation of a balloon in the inferior caval vein (Binfl) to reduce cardiac output and after an increased positive end-expiratory pressure (PEEP) of 20 cmH2O (PEEP20) to increase pulmonary aeration. EIT measurements were performed at the mid-thoracic level to measure the amplitude of impedance changes related to ventilation (ZV) and perfusion (ZQ), both globally and in four defined regions of interest (ROI) extending from the ventral to dorsal distance. A largely parallel distribution of ZV and ZQ in all four ROIs during baseline conditions corresponded to a bell-shaped frequency distribution of ZV/ZQ ratios with only moderate scatter. Binfl and PEEP20 with unchanged tidal volumes significantly increased the mismatch of regional ZV and ZQ, the scatter of ZV/ZQ ratios and the heterogeneity of the ZV/ZQ frequency distribution. Significant positive and negative correlations were demonstrated between fractional alveolar dead space (r2 = 0.63 [regression coefficient]) and venous admixture (r2 = 0.48), respectively, and the global ZV/ZQ ratio. EIT may be used to monitor the distribution of pulmonary ventilation and perfusion making detailed studies of V/Q matching possible.


Socioeconomic deprivation and asthma prevalence and severity in young adolescents.
This study used the international study of asthma and allergies in childhood (ISAAC) to investigate the association between asthma and socioeconomic deprivation among young adolescents in Cape Town, South Africa. The completed ISAAC written and video questionnaires of 4,706 13-14-yr-old school pupils were used. The prevalence of asthma symptoms was analysed by a local index of socioeconomic deprivation, based on residential location and defined on a 10-category scale from least to most deprived. Linear trends were examined visually and the prevalence odds ratio was used to summarize overall trends. In general, the least socioeconomically deprived pupils reported higher prevalences of asthma symptoms "ever" and "in the last 12 months". In contrast, the most socioeconomically deprived pupils reported higher asthma-symptom occurrence monthly or more frequently in the previous 12 months. A subgroup of pupils from low-income areas commuting to better-off schools showed the highest symptom prevalences. The findings are consistent with a model in which an increase in the incidence of asthma is driven by factors associated with improved social circumstances, whereas severity is determined by factors associated with poverty. The impact of social mobility on asthma, including reporting of symptoms, deserves closer study.


Therapeutic effects of glucosides of Cheanomeles speciosa on collagen-induced arthritis in mice.
To investigate the therapeutic effect of the glucosides of Cheanomeles speciosa (GCS) on the collagen-induced arthritis (CIA) in mice. Mice were divided randomly into six groups, including normal, CIA, CIA+GCS (60, 120, and 240 mg/kg) and CIA plus glucosides of Tripterygium wilfordii (GTW) groups. CIA model was based on mice. The effect of GCS in CIA mice was measured by paw-swelling, arthritis scores, and histopathological assessment of synovium. Indices of thymus and spleens were measured. Thymocytes and splenocytes proliferation, activity of interleukin-1 (IL-1), and interleukin-2 (IL-2) were assayed by MTT and [(3)H]TdR method. The level of anti-collagen type II (CII) antibody in serum and prostaglandin E (PGE) in ankle were assayed by ELISA and ultraviolet spectrophotometer method, respectively. The onset of paw-swelling was on d 24 after injection of emulsion. The peak of secondary inflammation appeared on d 36 and then declined after d 40. GCS and GTW significantly reduced paw-swelling and arthritis scores, reduced the increase of spleen indices of CIA mice, suppressed the ConA or LPS-induced thymocyte or spleen cell proliferation, and the production of IL-1 and IL-2 in CIA mice. GCS reduced the level of anti-CII antibody and PGE. Histological pathology analysis demonstrated that the synovium of CIA mice was hyperplastic, pannus was formed, and inflammatory cells infiltrated into synovium. The pathological changes were significantly reduced by GCS. GCS had anti-inflammatory effect on CIA mice, which might be related to the modification of the abnormal immunological function of CIA mice.


Cycloaddition reactions of polyenic donor-π-acceptor systems with an electron-rich alkyne: access to new chromophores with second-order optical nonlinearities.
The formal [2 + 2] cycloaddition-cycloreversion (CA-CR) between 4-ethynyl-N,N-dimethylaniline and polyenic Donor-π-Acceptor (D-π-A) systems takes place to yield compounds bearing two donors and one acceptor. Structural, linear and second-order nonlinear optical (NLO) properties of the new molecules reveal the stronger polarization of these systems when compared to analogous merocyanines lacking the dimethylaminophenyl (DMA) ring.


Multicenter study of the safety and effects of magnetic resonance imaging in patients with coronary sinus left ventricular pacing leads.
Magnetic resonance imaging (MRI) in patients with left ventricular (LV) leads may cause tissue or lead heating, dislodgment, venous damage, or lead dysfunction. The purpose of this study was to determine the safety of MRI in patients with LV pacing leads. Prospective data on patients with coronary sinus LV leads undergoing clinically indicated MRI at 3 institutions were collected. Patients were not pacemaker-dependent. Scans were performed under pacing nurse, technician, radiologist, and physicist supervision using continuous vital sign, pulse oximetry, and ECG monitoring and a 1.5-T scanner with specific absorption rate <1.5 W/kg. Devices were interrogated pre- and post-MRI, programmed to asynchronous or inhibition mode with tachyarrhythmia therapies off (if present), and reprogrammed to their original settings post-MRI. MRI scans (n = 42) were performed in 40 patients with non-MRI conditional LV leads between 2005 and 2013 (mean age 67 ± 9 years, n = 16 [40%] women, median lead implant duration 740 days with interquartile range 125-1173 days). MRIs were performed on the head/neck/spine (n = 35 [83%]), lower extremities (n = 4 [10%]), chest (n = 2 [5%]), and abdomen (n = 1 [2%]). There were no overall differences in pre- and post-MRI interrogation LV lead sensing (12.4 ± 6.2 mV vs 12.9 ± 6.7 mV, P = .38), impedance (724 ± 294 Ω vs 718 ± 312 Ω, P = .67), or threshold (1.4 ± 1.1 V vs 1.4 ± 1.0 V, P = .91). No individual LV lead changes required intervention. MRI scanning was performed safely in non-pacemaker-dependent patients with coronary sinus LV leads who were carefully monitored during imaging without clinically significant adverse effect on LV lead function.


Similar within-utterance loci of dysfluency in acquired neurogenic and persistent developmental stuttering.
Although the underlying neural mechanisms remain unknown for both persistent developmental stuttering (PSD) and acquired neurogenic stuttering (ANS), few studies have examined similarities/differences between these two disorders. We evaluated in both PDS (n = 35) and ANS (n = 5) phonetic, word class, word length, and word position variables that are widely believed to influence at which loci within utterances PDS speakers' stuttering is most likely to occur. For both groups, (a) word weights based on the combination of variables were greater for stuttered vs. fluent words, and (b) stuttered words were loaded more by individual variables. However, contrary to long-standing views regarding PDS, greater loading for stuttered words was not found for the position variable. Findings suggest similar loci of stuttering in adults with PDS and ANS, and, for both groups, the probability of stuttering on a given word was more influenced by motor production variables than language variables.


[Reactive oxygen species produced by the addition of sepiolite and vermiculite (expanded or not) to suspensions of human polymorphonuclear phagocytes and bovine alveolar macrophages].
We have studied a sample of commercial sepiolite and two samples of commercial vermiculite, which are clay minerals advised to replace asbestos. We have in vitro tested their abilities to produce reacting oxygen species (ROS) after they have been added to suspension of human polymorphonuclear leukocytes and bovine alveolar macrophages. The behaviour of sepiolite and vermiculite have been compared with those of asbestos fibres given by Unione Internationale contre le Cancer (UICC) and with kaolin and illite. Sepiolite was not able to induce ROS production, while vermiculite was able to induce a relevant ROS generation, even if the values were always lower than that obtained from chrysotile. Kaolin was able to generate a high ROS production.


Racial/Ethnic and Gender Differences in Risk of Injury and Life-Course Drinking Patterns: Data from US National Alcohol Surveys.
To estimate risk of injury associated with frequency of drinking and heavy drinking (5+ drinks on occasion) by gender and race/ethnicity in the US population. Data were from a merged sample of two National Alcohol Surveys (telephone and web-based) (2014-2015 and 2019-2020) on 16,639 respondents, and analyzed using Cox proportional hazards models with age as the timescale in a retrospective cohort design. Life-course drinking was determined by age of onset and questions on any drinking and heavy drinking by decade of life. The outcome measure was having had an injury from a serious accident at a certainage. Frequent heavy drinking (5+ daily, weekly and monthly) was significantly predictive of injury with hazard ratios (HRs) of 2.40, 1.81 and 1.50, respectively, while frequent light drinking (alcohol at least weekly and 5+ yearly or less) was also significant for women (HR = 1.73). For White respondents, 5+ at least weekly was significant for both men (HR = 1.74) and women (HR = 2.42). Among Hispanic respondents, 5+ at least weekly and 5+ monthly were both significant for men (HR = 2.81 and 2.49, respectively) and women (HR = 2.81 and 3.48, respectively). Among Black women, risk was significant for 5+ monthly (HR = 2.90) and for any alcohol ≥ weekly (HR = 2.72), but neither frequency of any drinking or 5+ was significant for Blackmen. Data suggest a greater risk of injury from a serious accident for frequent heavy drinkers among all White and Hispanic respondents, and Black women, but not for Blackmen.


Partners of wild type Grb7 and a mutant lacking its calmodulin-binding domain.
Growth factor receptor bound protein 7 (Grb7) is a mammalian adaptor protein participating in signaling pathways implicated in cell migration, metastatic invasion, cell proliferation and tumor-associated angiogenesis. We expressed tagged versions of wild type Grb7 and the mutant Grb7Δ, lacking its calmodulin-binding domain (CaM-BD), in human embryonic kidney (HEK) 293 cells and rat glioma C6 cells to identify novel binding partners using shot-gun proteomics. Among the new identified proteins, we validated the ubiquitin-ligase Nedd4 (neural precursor cell expressed developmentally down-regulated protein 4), the heat-shock protein Hsc70/HSPA8 (heat shock cognate protein 70) and the cell cycle regulatory protein caprin-1 (cytoplasmic activation/proliferation-associated protein 1) in rat glioma C6 cells. Our results suggest a role of Grb7 in pathways where these proteins are implicated. These include protein trafficking and degradation, stress-response, chaperone-mediated autophagy, apoptosis and cell proliferation.


Similar cleavage efficiencies of an oligoribonucleotide substrate and an mdr1 mRNA segment by a hammerhead ribozyme.
Hammerhead ribozymes (Rz) can specifically recognize and cleave target RNAs in trans. This makes them attractive in antisense RNA approaches for specific gene inactivation in vivo. A severe limitation is the poor cleavage efficiency of large RNA substrates, in contrast to the high activities observed with small oligoribonucleotides (oligos) as model substrates. It was suggested that the low efficiency is caused by poor accessibility of the target sequence in the structure of the long RNA substrates. This means it should be possible to overcome this limitation by judicious choice of the target sequence, although experimental proof was lacking. We observed similar cleavage efficiencies of small and large RNA substrates with a hammerhead Rz directed against multidrug resistance-encoding mdr1 mRNA. Accordingly, large RNAs can also be good substrates, if an optimal target sequence is selected.