Halothane and enflurane attenuate pulmonary vasodilation mediated by adenosine triphosphate-sensitive potassium channels compared to the conscious state.
Adenosine triphosphate (ATP)-sensitive potassium (k+ATP) channels play an important role in pulmonary vasoregulation. However, the effects of volatile anesthetics on k+ATP channel-mediated pulmonary vasoregulation have not been elucidated. The purpose of the present study was to investigate the effects of halothane and enflurane anesthesia on the pulmonary vasodilator response to the selective k+ATP channel agonist lemakalim (BRJ38227) compared with that measured in the conscious state. The authors also investigated the extent to which endogenous neurohumoral vasoconstrictor mechanisms modulate the vasodilator response to k+ATP channel activation. Nineteen conditioned, male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relationship. LPQ plots were generated by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during gradula (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. After preconstriction with the thromboxane analog, U46619 (9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha), the pulmonary vascular dose-response relationship for the k+ATP agonist lemakalim was assessed in the conscious and halothane-anesthetized states and also in the conscious and enflurane-anesthetized states. This protocol was repeated in conscious and halothane-anesthetized dogs after combined neurohumoral block with antagonists of sympathetic alpha 1 adrenoreceptors, arginine vasopressin V1-receptors, and angiotensin II receptors. The effect of the k+ATP antagonist glybenclamide on the baseline LPQ relationship and on the lemakalim dose-response relationship also was assessed in conscious dogs. Compared with the conscious state, halothane, enflurane and glybenclamide had no net effect on the baseline LPQ relationship. In contrast, halothane and enflurane attenuated (P < 0.05) the pulmonary vasodilator response to lemakalim compared with the conscious state. Glybenclamide also caused a rightward shift (P < 0.05) in the lemakalim dose-response relationship. Combined neurohumoral block did not modulate the vasodilator response to lemakalim in the conscious state. The halothane-induced attenuation of the vasodilator response to lemakalim was apparent after combined neurohumoral block. These results indicate that halothane and enflurane act to reduce the magnitude of K+ATP channel-mediated pulmonary vasodilation. Reflex pulmonary vasoconstriction resulting from K+ATP mediated systematic hypotension does not alter the magnitude of the pulmonary vasodilator response to lemakalim nor is it responsible for the attenuated response to K+ATP channel activation during halothane anesthesia.


Early executive and school functioning: Protective roles of home environment by income.
This study used data from the Family Life Project (N=1,227), a longitudinal study of child development. We tested a three-way interaction in which positive parenting and learning materials in the home from age 6-36 months and family income predicted children's executive functioning (EF) at 58 months. We also tested whether this interaction predicted early school functioning, specifically behavioral and academic skills in the 1st grade. The interactive effects of positive parenting and learning materials differed by family income. For children in families of lower income, more learning materials and positive parenting predicted better EF, and in turn, better early school functioning. For children in families of higher income, only positive parenting significantly predicted EF, which in turn, predicted better early school functioning. Findings suggest that more targeted policy and program support for enrichment and positive parenting may bolster efforts to combat poverty.


A historical review of surgery for peritonitis secondary to acute colonic diverticulitis: from Lockhart-Mummery to evidence-based medicine.
The management of patients with colonic diverticular perforation is still evolving. Initial lavage with or without simple suture and drainage was suggested in the late 19th century, replaced progressively by the three-stage Mayo Clinic or the two-stage Mickulicz procedures. Fears of inadequate source control prompted the implementation of the resection of the affected segment of colon with formation of a colostomy (Hartman procedure) in the 1970's. Ensuing development of the treatment strategies was driven by the recognition of the high morbidity and mortality and low reversal rates associated with the Hartman procedure. This led to the wider use of resection and primary anastomosis during the 1990's. The technique of lavage and drainage regained popularity during the 1990's. This procedure can also be performed laparoscopically with the advantage of faster recovery and shorter hospital stay. This strategy allows resectional surgery to be postponed or avoided altogether in many patients; and higher rates of primary resection and anastomosis can be achieved avoiding the need for a stoma. The three recent randomized controlled trials comparing laparoscopic peritoneal lavage alone to resectional surgery reported inconsistent outcomes. The aim of this review is to review the historical evolution and future reflections of surgical treatment modalities for diffuse purulent and feculent peritonitis. In this review we classified the various surgical strategies according to Krukowski et al. and Vermeulen et al. and reviewed the literature related to surgical treatment separately for each period.


[Cytogenetic instability, the ability to produce interferon and immunoreactivity of blood lymphocytes in patients with schizophrenia].
In schizophrenia patients, the level of T-lymphocytes with cytogenetic aberrations is elevated, and the ability of these cells for PGA-blast-transformation and the interferon synthesis is reduced. The elevation of the lymphocytes ability for blast-transformation in the presence of the native preparation of DNA and for lysis of the erythrocytes proper is marked in these patients. The observed changes were especially marked in schizophrenia with an interrupted course.


The Gly82Ser mutation in AGER contributes to pathogenesis of pulmonary fibrosis in combined pulmonary fibrosis and emphysema (CPFE) in Japanese patients.
The dominant pathogenesis underlying the combined pulmonary fibrosis and emphysema (CPFE) remains unresolved. The receptor for advanced glycation end-products (RAGE) is highly expressed in lung tissues and interacts with distinct multiple ligands, implicating it in certain lung diseases. To elucidate the pathogenesis of CPFE, we genotyped three single nucleotide polymorphisms (SNPs: rs2070600, rs1800625, and rs2853807) of the gene encoding RAGE (AGER) in 111 CPFE patients and 337 chronic obstructive pulmonary disease (COPD) patients of Japanese by using StepOne Real-Time PCR System for SNP genotyping assay. Serum levels of soluble RAGE (sRAGE) were measured by ELISA. We found that the allele frequency of rs2070600 was significantly different between the two groups [corrected P (Pc) = 0.015]. In addition, the minor allele was associated with CPFE patients relative to COPD patients in a dominant effect model (Odds Ratio = 1.93; Pc = 0.018). Moreover, the serum sRAGE level was significantly lower in the CPFE group than the COPD group (P = 0.014). The rs2070600 minor allele was significantly associated with reduced sRAGE level in CPFE patients and independently affected sRAGE level reduction in this group (P = 0.020). We concluded that the AGER rs2070600 minor allele (Gly82Ser mutation) is associated with the pathogenesis of pulmonary fibrosis in CPFE in Japanese patients.


Endovascular management of spontaneous carotid artery dissection.
Despite medical therapy, a subset of patients with spontaneous carotid artery dissection (SCD) experience recurrent or progressive symptoms. In this study, we assessed the safety and efficacy of endovascular stent angioplasty in the treatment of SCD. Seven consecutive patients with SCD underwent endovascular stent angioplasty of a total of 12 vessels. Indications included the presence of a large or enlarging pseudoaneurysm, a contraindication to anticoagulation, failure of anticoagulation, and compromised cerebral blood flow. Five patients had fibromuscular dysplasia. All patients tolerated the procedure well, with no adverse clinical events. All patients showed symptomatic improvement on clinical follow-up except for one patient, who had hemorrhagic conversion of a pre-existing large ischemic stroke 13 days after intervention; he made an eventual recovery to baseline. All stents have remained patent on radiologic follow-up. This study provides additional evidence that endovascular stent angioplasty is a safe and effective treatment for SCD in patients for whom medical treatment is not adequate.


Effects of Occupational Therapy Program Based on Active Meditation on Hair Cortisol Levels in Undergraduate Healthcare Students.
Undergraduate students from the University of Chile's health careers were divided at random into control (n = 7) and treated groups (n = 15). The treated group participated in an active meditation program once a week for three months. This treatment included different techniques such as Chakra Sounds, Nataraj, Mandala, Kundalini, Devavani, Gourishankar, and Nadabrahma. Hair samples were taken before and after the treatment period to measure cortisol. The control group increased cortisol level 168.9 ± 76.8 pg/mg compared with initial levels. The treated group shows a decrease of initial cortisol values in 28.5 ± 12.8 pg/mg after meditation protocol application. Blending active meditation in students' daily routine through occupational therapy intervention might prevent undergraduate students' stress in healthcare careers.


Improved outcomes of patients with end-stage cystic fibrosis requiring invasive mechanical ventilation for acute respiratory failure.
The aim of this study was to determine the effects of an antibiotic strategy with intravenous (IV) continuous infusion of a β-lactam (CIBL) antibiotic and high-dose extended-interval (HDEI) tobramycin upon outcomes in patients with cystic fibrosis (CF) requiring invasive mechanical ventilation (IMV) for acute respiratory failure. The study was a retrospective review from June 1, 2006, to December 1, 2010, of patients at a university hospital with an adult CF center. The study population included adult CF patients requiring IMV. A total of 15 hospitalizations with IMV episodes were reviewed, involving 10 adult (31.4 ± 11.1 years) CF patients with end-stage lung disease (FEV(1) = 23.6 ± 7.8% predicted) and malnutrition (body mass index = 20.5 ± 3.1). Each patient survived to discharge and to follow-up 6 months later without the need for lung transplantation during the study period. A novel antibiotic strategy with a CIBL antibiotic and HDEI tobramycin improved survival in a small cohort of critically ill CF patients with end-stage lung disease and malnutrition requiring IMV.


Curing and induction of the Fels 1 and Fels 2 prophages in the Ames mutagen tester strains of Salmonella typhimurium.
A method is described for curing the Ames Salmonella mutagen tester strains of their Fels 1 and Fels 2 prophages with the aid of the antitumor drug daunorubicin. Non-lysogenic derivatives corresponding to TA100 and TA1535 were isolated and designated TAQ100 and TAQ1535 respectively. In addition, the Fels 1 monolysogens TAQ100F1 and TAQ1535F1, as well as the Fels 2 monolysogens TAQ100F2 and TAQ1535F2, were obtained. Finally, strains corresponding to TA98 and TA1538 cured of Fels 2, but retaining a cryptic Fels 1 (F1d) prophage were isolated and designated TAQ98F1d and TAQ1538F1d respectively. The various cured derivatives were identified by colony hybridization with 32P-labeled probes of Fels 1 and Fels 2 DNA. Southern blot hybridizations confirmed that phage-specific Fels DNA sequences were missing from the cured strains. The Fels 2-cured strains were resistant to Fels 2, but Fels 1 grew, albeit poorly, on the Fels 1-cured strains. Strains TAQ100F1, TAQ1535F1, TAQ100F2 and TAQ1535F2 were used in prophage induction assays, in the presence of rat-liver extract where necessary. Daunorubicin, bleomycin, mitomycin C, aflatoxin B1, 2-amino-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) were found to induce Fels 1 and/or Fels 2 in at least one of these strains. The induction of the Fels prophages in the TAQ monolysogens may provide a useful complement to the Ames test for the detection of DNA-damaging agents and potential carcinogens.


[The differential diagnosis of lung ossifications].
In addition to the well-known secondary ossification of pulmonary depositions of calcium, and interstitial ossification in the case of mitral valve disease, there is also a rare idiopathic ramifying ossification in the lungs, the pathomorphology of which is reported in this case history.


L-arginine causes whereas L-argininosuccinic acid inhibits endothelium-dependent vascular smooth muscle relaxation.
This study examined the actions of L-arginine, a putative precursor of endothelium-derived nitric oxide, and arginine analogs on endothelium-dependent relaxation of isolated rings of bovine pulmonary artery. L-Arginine did not consistently relax arterial rings unless rings were first rendered refractory to endothelium-dependent relaxation by pretreatment with 1 microM A23187 for 45 min. L-Arginine-elicited relaxation was endothelium-dependent, antagonized by oxyhemoglobin or methylene blue, and unaffected by indomethacin. L-Argininosuccinic acid caused endothelium-dependent contractions and irreversible inhibition of endothelium-dependent but not nitroglycerin-elicited relaxation, which was not overcome by addition of L-arginine. Inhibition of endothelium-dependent relaxation by L-NG-monomethyl arginine, however, was reversible and overcome by L-arginine. Therefore, endothelium-dependent relaxants may cause arginine depletion in endothelial cells and endogenous argininosuccinic acid may modulate the biosynthesis of endothelium-derived nitric oxide from arginine.


Enrollment of reproductive age women in community-based health insurance: An evidence from 2019 Mini Ethiopian Demographic and Health Survey.
Universal health coverage (UHC) is aimed at ensuring that everyone has access to high-quality healthcare without the risk of financial ruin. Community-based health insurance (CBHI) is one of the essential means to achieve the sustainable development goals (SDGs) global health priority of UHC. Thus, this study assessed health insurance enrollment and associated factors among reproductive age women in Ethiopia. We computed the health insurance enrollment of reproductive-age women using secondary data from the recent Ethiopian Mini Demographic and Health Surveys (EMDHS) 2019. The EMDHS was a community-based cross-sectional study carried out in Ethiopia from March 21 to June 28, 2019. Cluster sampling with two stages was employed for the survey. The study comprised 8885 (weighted) reproductive-age women. STATA 14 was used for data processing and analysis. Bivariate and multivariable logistic regression analyses were conducted. Adjusted odds ratio (AOR) with 95% confidence interval (CI) was reported and statistical significance was set at a value of p < 0.05. Of the 8,885 study participants, 3,835 (43.2, 95% CI; 42.1, 44.2%) of women had health insurance. Women aged 20-24 years, 25-29 years, and 30-34 years less likely to enroll in health insurance compared to their younger counterparts (15-19 years). Women living in rural areas, had greater than five family sizes, living with a female household head, and having more than five living children were negatively associated with enrollment in health insurance. Besides, health insurance enrollment among reproductive-age women is significantly affected by region and religious variation. The overall CBHI enrolment among reproductive-age women in Ethiopia was low. To achieve the SDGs of reducing maternal mortality ratio and neonatal mortality, improving reproductive-age women's access to health insurance is essential. The national, regional, and local officals, policymakers, NGOs, program planners, and other supporting organizations working on improving health insurance enrollment of reproductive age women need to create awareness and support them based on these significant factors.


Elevated levels of gonadotrophins but not sex steroids are associated with musculoskeletal pain in middle-aged and older European men.
The aim of this study was to determine the association of hormone levels with the occurrence of musculoskeletal pain. Men ages 40 to 79 years were recruited from population registers in 8 European centres. Subjects were asked to complete a postal questionnaire, which enquired about lifestyle and the occurrence of musculoskeletal pain over the past month. Total testosterone (T), oestradiol (E2), luteinising hormone (LH), and follicle-stimulating hormone (FSH) were assayed from a fasting blood sample. The association between pain status and hormone levels was assessed using multinomial logistic regression with results expressed as relative risk ratios (RRR) and 95% confidence intervals (CI). A total of 3206 men had complete data on pain status. Of these, 8.7% reported chronic widespread pain (CWP), whereas 50% had some pain although not CWP and were classified as having some pain. T and E2 were not associated with musculoskeletal pain, whereas significant differences in LH and FSH levels were found between pain groups. After adjustment for age and other possible confounders, the association between pain status and both LH and FSH persisted. Compared with those in the lowest tertile of LH, those in the highest tertile were more likely to report some pain (vs no pain, RRR=1.28; 95% CI 1.09 to 1.50) and also CWP (vs no pain, RRR=1.51; 95% CI 1.10 to 2.07). Similar results were found for FSH. Gonadotrophins, but not sex steroid hormone levels, are associated with musculoskeletal pain in men.


alpha N-acetyl derivatives of beta-endorphin-(1-31) and -(1-27) regulate the supraspinal antinociceptive activity of different opioids in mice.
alpha N-acetyl human beta-endorphin-(1-31) injected icv to mice antagonized the analgesic activity of beta-endorphin-(1-31) and morphine whereas the analgesia evoked by DADLE and DAGO was enhanced by this treatment. The modulatory activity of alpha N-acetyl beta-endorphin-(1-31) was exhibited at remarkable low doses (fmols) reaching a maximum that persisted even though the dose was increased 100,000 times. The regulatory effect of a single dose of the acetylated neuropeptide lasted for 24h. The activity of alpha N-acetyl human beta-endorphin-(1-31) was partially retained by the shorter peptide alpha N-acetyl human beta-endorphin-(1-27) and to a lesser extent by beta-endorphin-(1-27), beta-endorphin-(1-31) lacked this regulatory activity on opioid analgesia. Acetylated beta-endorphin-(1-31) displayed a biphasic curve when competing with 5 pM [125I]-Tyr27 human beta-endorphin-(1-31) specific binding, the first step (20 to 30% of the binding) was abolished with an apparent IC50 of 0.35 nM, and the rest with an IC50 of 200 nM. It is suggested that alpha N-acetyl beta-endorphin-(1-31) changed the efficiency of the opioid analgesics by acting upon a specific substrate that is functionally coupled to the opioid receptor, presumably the guanine nucleotide binding regulatory proteins Gi/Go.


Optimality in the standard genetic code is robust with respect to comparison code sets.
The genetic code and its evolution have been studied by many different approaches. One approach is to compare the properties of the standard genetic code (SGC) to theoretical alternative codes in order to determine how optimal it is and from this infer whether or not it is likely that it has undergone a selective evolutionary process. Many different properties have been studied in this way in the literature. Less focus has been put on the alternative code sets which are used as a comparison to the standard code. Each implicitly represents an evolutionary hypothesis and the sets used differ greatly across the literature. Here we determine the influence of the comparison set on the results of the optimality calculation by using codes based upon different sub-structures of the SGC. With these results we can generalize the results to different evolutionary hypotheses. We find that the SGC's optimality is very robust, as no code set with no optimised properties is found. We therefore conclude that the optimality of the SGC is a robust feature across all evolutionary hypotheses. Our results provide important information for any future studies on the evolution of the standard genetic code. We also studied properties of the SGC concerning overlapping genes, which have recently been found to be more widespread than often believed. Although our results are not conclusive yet we find additional intriguing structures in the SGC that need explanation.


Noninvasive venous testing in the diagnosis of pulmonary embolism: the impact on decisionmaking.
To characterize the use and utility of lower extremity noninvasive venous testing (NIVT) in the diagnosis of pulmonary embolism (PE). The study is a retrospective case series of consecutive patients in whom PE was suspected who were referred to a large, urban tertiary care center for NIVT. The main outcome measures of the study were the rate of positive results of NIVT, the amount of new information provided by NIVT, and the frequency of management changes that were attributable to NIVT. Forty-one of 450 patients (9%) had deep venous thrombosis (DVT) by NIVT. The prevalence of DVT by NIVT among patients not evaluated by ventilation/perfusion (V/Q) scanning was 8%. The prevalence of DVT by NIVT among patients with a high-probability V/Q scan result before NIVT was 39%, but no management decisions in this group were based on a positive NIVT result and only two decisions were based on negative NIVT results. The prevalence of DVT according to NIVT among patients who had a negative "diagnostic" (low, or very low probability, or normal) result of V/Q scan before NIVT was 2%. The overall frequency of management changes attributed to NIVT was only 2.5%. In the remaining 97% of patients, management was determined by the result of V/Q scanning or of subsequent pulmonary arteriography. In patients in whom PE is suspected, results of NIVT are usually negative for acute DVT. Management decisions are almost always based on V/Q scan or results of pulmonary arteriography and not on NIVT. The utility of NIVT to identify DVT in these patients appears limited, and a more selective approach to its application for the diagnosis of PE should be considered.


Microdevice immunoassay with conjugated magnetic nanoparticles for rapid anti-cyclic citrullinated peptide (anti-CCP) detection.
Anti-cyclic citrullinated peptide IgG antibodies (anti-CCP) are produced as an immune response in the presence of post-translational modified peptides known as cyclic citrullinated peptides (CCP). Anti-CCP have been considered as specific biomarkers for the diagnosis of rheumatoid arthritis (RA), and due to their high specificity, it is possible to make a differential diagnosis of other rheumatic diseases. These autoantibodies can be detected in the early stages of RA and even up to 10 years before presenting the first symptoms of the disease opening a window of opportunity for timely treatment. In this work, a simple straight channel microdevice and CCP conjugated magnetic nanoparticles (MNPs-CCP) as solid support was developed for quantifying anti-CCP. An additional microdevice with an optical flow Z cell design coupled with optical fibers was used to perform the spectrophotometric detection. The dynamic range of concentrations was determined between 0.70 and 2000 U mL-1 with a limit of detection of 0.70 U mL-1. The developed microdevice immunoassay was probed using a positive control and a negative control of plasma employing only 6 μL of both samples and reagents. The results showed that the proposed microdevice was almost nine times faster than using a commercial anti-CCP ELISA kit obtaining equivalent results and being 16 times more sensitive. The microdevice immunoassay, with conjugated MNPs-CCP is a simple method for anti-CCP quantification being cheaper, faster, and more sensitive than the ELISA kit.


Aspiration technique for percutaneous endovascular retrieval of contraceptive device embolized to the pulmonary vasculature.
Contraceptive implant migration into the pulmonary circulation is an uncommon, but potentially serious complication. We describe an "aspiration" technique for percutaneous retrieval of a contraceptive implant from a subsegmental pulmonary artery, using a Penumbra Neuron MAX 088 guiding catheter and a Merit Medical VacLok Vacuum Pressure Syringe, as an alternative to the previously described snare technique. Our patient had an uneventful recovery and was discharged home on the same day.


Nasolabial morphology after Le Fort I osteotomies. Effect of alar base suture.
This paper describes the effect of an alar base suture in an attempt to gain control of the alar base flaring associated with maxillary advancement and/or maxillary impaction. The suture did reduce alar flaring but it also increased the nasolabial angle. The suture did not significantly influence nasal tip projection.


Fast heating induced impulse halogenation of refractory sample components in electrothermal atomic absorption spectrometry by direct injection of a liquid halogenating agent.
A novel electrothermal atomic absorption spectrometry (ETAAS) method was developed for the halogenation of refractory sample components (Er, Nd and Nb) of lithium niobate (LiNbO(3)) and bismuth tellurite (Bi(2)TeO(5)) optical single crystals to overcome memory effects and carry-over. For this purpose, the cleaning step of a regular graphite furnace heating program was replaced with a halogenation cycle. In this cycle, after the graphite tube cooled to room temperature, a 20 μL aliquot of liquid carbon tetrachloride (CCl(4)) was dispensed with a conventional autosampler into the graphite tube. The CCl(4) was partially dried at 80°C under the mini-flow (40 cm(3) min(-1)) condition of the Ar internal furnace gas (IFG), then the residue was decomposed (pyrolyzed) by fast furnace heating at 1900-2100°C under interrupted flow of the IFG. This step was followed by a clean-out stage at 2100°C under the maximum flow of the IFG. The advantage of the present method is that it does not require any alteration to the graphite furnace gas supply system in contrast to most of the formerly introduced halogenation techniques. The effectiveness of the halogenation method was verified with the determination of Er and Nd dopants in the optical crystals. In these analyses, a sensitivity decrease was observed, which was likely due to the enhanced deterioration of the graphite tube surface. Therefore, the application of mathematical correction (resloping) of the calibration was also required. The calibration curves were linear up to 1.5 and 10 μmol L(-1) for Er and Nd, respectively. Characteristic masses of 18 and 241 pg and the limit of detection (LOD) values of 0.017 and 0.27 μmol L(-1) were found for Er and Nd, respectively. These LOD data correspond to 0.68 μmol mol(-1) Er and 11 μmol mol(-1) Nd in solid bismuth tellurite samples. The analytical results were compared with those obtained by a conventional ETAAS method and validated with X-ray fluorescence spectrometry analysis.


Effect of carbon nanotubes on the isotropic to nematic and the nematic to smectic- A phase transitions in liquid crystal and carbon nanotubes composites.
A high-resolution ac-calorimetric study on the weakly first-order isotropic to nematic (I -N) and the continuous nematic to smectic-A (N -SmA) phase transitions of the liquid crystal octyl-cyanobiphenyl (8CB) doped with well-dispersed multiwall carbon nanotubes (CNTs) as a function of CNT concentrations is reported. Thermal scans were performed for all samples having CNT weight fraction from Φ(w) = 0.0005 to 0.0060 over a wide temperature range well above and below the two transitions in pure 8CB. Both the I -N and the N -SmA transitions evolve in character and have their transition temperatures qualitatively offset by ∼ 1.10 K lower as compared to that in pure 8CB for all 8CB+CNTs samples. The enthalpy change associated with each phase transition is essentially the same as that of pure 8CB and remains unchanged with increasing Φ(w). However, there is an evidence that the thermal transport properties of the composites differ from the pure LC upon cooling below a Φ(w)-dependent temperature within the nematic phase. In addition, a new C(p) feature is resolved for intermediate Φ(w) samples that appears to be correlated to this onset temperature.


Reliability of measurements of energy expenditure and substrate oxidation using whole-room indirect calorimetry.
This analysis aimed to measure the intraparticipant reliability-the intraclass correlation coefficient-of all the components of daily energy expenditure (EE) (24-hour EE, sleep EE, resting EE, basal EE, and thermic effect of food) over a period of 3 consecutive days in 35 study participants. The components of daily EE and substrate use (respiratory exchange ratio) were measured over 3 consecutive days before and after a 3-week 1,000-kcal/d caloric restriction/weight-loss intervention. There was a high degree of reliability for sleep EE (96.8%), 24-hour EE (97.8%), basal EE (90.6%), and resting EE (93.2%) during the run-in period. The intraclass correlation coefficient for the follow-up period after weight loss (3.67 ± 1.10 kg) remained high for sleep EE (95.6%), 24-hour EE (100%), basal EE (96.1%), and resting EE (92.5%). The minimal detectable differences in EE were reduced by 30% for both 24-hour EE and sleep EE when comparing 2 days versus 1 day spent in the whole-room indirect calorimeter. The reliability of the daily components of EE is very high both prior to and after a weight-loss intervention. We here provide instrumental data for investigators to adequately power studies investigating energy metabolism using whole-room indirect calorimetry.


Central cardiovascular effects of physostigmine in anesthetized cats.
The central cardiovascular effects of a cholinesterase inhibitor, physostigmine, were studied in alpha-chloralose- and urethane-anesthetized cats, to determine the underlying site and mechanism of action. Intravenous injection of physostigmine produced a dose-dependent fall in blood pressure and heart rate. These responses were blocked by intravenous injection of atropine; however, the peripheral antimuscarinic agent, methscopolamine, failed to inhibit the depressor response. In decerebrated cats, physostigmine elicited similar responses in blood pressure and heart rate as in intact animals. In spinal cats, physostigmine failed to evoke any response. Physostigmine significantly reduced sympathetic nervous activity, as measured by renal sympathetic nerve discharges, indicating that the fall in blood pressure was due to a decrease in sympathetic tone. These results demonstrate that physostigmine, which crosses the blood-brain barrier, produces a depressor response through stimulation of muscarinic cholinergic receptors, located in the medullary region and that the effect is mediated by a decrease in sympathetic activity.


Comparative Analysis of Patch Angioplasty Versus Selective Primary Closure during Carotid Endarterectomy Performed at a Single Vascular Center in China.
One of the ongoing debates about carotid endarterectomy (CEA) is the closure technique of arterial wall in the operation. Current guidelines recommend routine patch closure (PAC); this recommendation is based on the evidence reported 10-20 years ago. Therefore, the exact role of PAC and primary closure (PRC) remains uncertain. The objectives of this study were to compare the perioperative and long-term outcomes of patients who underwent CEA with different closure techniques. From January 2013 and December 2018, one senior vascular surgeon performed CEA for 126 patients in the First Affiliated Hospital, Sun Yat-sen University. The closure technique (PAC or PRC) was determined on the characteristics (diameter and level) of carotid arteries. Patient demographics and clinical data were retrospectively collected by two research fellows by reviewing the hospital medical records and relevant radiologic studies, as were carotid duplex reports, indications, intraoperative data, closure technique, and perioperative complications. Data of long-term outcomes were gathered by reviewing outpatient clinic visits and associated supplementary examinations. PRC was performed in 78 operations (61.9%), and PAC was performed in 48 operations (38.1%). There were no statistical differences in demographic and clinical data between the two groups. Carotid clamp time (P < 0.001) and operating time (P < 0.001) were significantly longer when performing PAC (P < 0.001), and intraoperative blood loss was significantly more when performing PAC than that of PRC (P < 0.001). The postoperative outcome and the follow-up results showed that there was no significant difference in the short-term and middle-term overall survival rate and restenosis-free survival rate between the two groups. There are no differences in postoperative and middle-term outcomes between PAC and selective PRC, whereas PRC technique can save operation time and shorten the intraoperative carotid clamp time. PRC can be safely applied in patients with a greater than 5 mm internal carotid artery (ICA).


Controlled growth of ordered monolayers of N-heterocyclic carbenes on silicon.
N-Heterocyclic carbenes (NHCs) are promising modifiers and anchors for surface functionalization and offer some advantages over thiol-based systems. Because of their strong binding affinity and high electron donation, NHCs can dramatically change the properties of the surfaces to which they are bonded. Highly ordered NHC monolayers have so far been limited to metal surfaces. Silicon, however, remains the element of choice in semiconductor devices and its modification is therefore of utmost importance for electronic industries. Here, a comprehensive study on the adsorption of NHCs on silicon is presented. We find covalently bound NHC molecules in an upright adsorption geometry and demonstrate the formation of highly ordered monolayers exhibiting good thermal stability and strong work function reductions. The structure and ordering of the monolayers is controlled by the substrate geometry and reactivity and in particular by the NHC side groups. These findings pave the way towards a tailor-made organic functionalization of silicon surfaces and, thanks to the high modularity of NHCs, new electronic and optoelectronic applications.


Soil properties mediate ecosystem intrinsic water use efficiency and stomatal conductance via taxonomic diversity and leaf economic spectrum.
The interactions between plants and soils lead to complex feedbacks that regulate intrinsic water use efficiency (iWUE) and stomatal conductance (gs) at ecosystem level and reflect water constraints on plant productivity. However, the relationships among soil properties, biodiversity, and leaf functional traits contributing to the variability in ecosystem iWUE and gs remain largely unknown. To elucidate these relationships, we used principal component analysis to reduce soil properties to a fertility spectrum and a limiting-resource spectrum across grassland, and early-, mid- and late-successional forests in a karst catchment. Leaf functional traits at community level were calculated based on leaf biomass, and were reduced to an economic spectrum and a limiting-resource spectrum. Leaf carbon (δ13C) and oxygen (δ18O) stable isotopes at community levels were used as proxies for ecosystem iWUE and gs. The effects of soil properties, biodiversity (taxonomic, functional and phylogenetic diversity) and leaf traits on δ13C and δ18O were evaluated using structural equation models. Our results showed that variability in ecosystem iWUE and gs was determined overwhelmingly by indirect effects of soil properties via two different pathways: the soil fertility spectrum, determining the number of coexisting species (taxonomic diversity) and turnover of species (leaf economic spectrum), and the soil limiting-resource spectrum, shaping the specific phylogenetic lineages (phylogenic diversity). In addition, δ13C and δ18O were constrained by the interactive effects of leaf economic spectrum, and taxonomic and phylogenic diversity; total effects of biodiversity on δ13C and δ18O were larger than those of leaf economic spectrum. Our study highlighted the critical role of the evaluating interaction relationships between leaf functional traits, biodiversity metrics and soil properties in understanding the mechanisms of ecosystem function responding to environmental change.


Application of Doehlert design in optimizing the solid-state hydrogenogenic stage augmented with biomass fly ash in a two-stage biohythane production process.
This study aimed to optimize the solid-state hydrogenogenic stage supplemented with biomass fly ash in a two-stage anaerobic digestion (AD) process for biohythane production from the organic fraction of municipal solid waste (OFMSW). Doehlert's experimental design was used to obtain the optimal set of two investigated variables, namely total solids (TS) content and biomass fly ash dosage in the defined ranges of 0-20 g/L and 20-40%, respectively. Applying the optimal conditions of TS content (29.1%) and fly ash dosage (19.2 g/L) in the first stage led not only to a total H2 yield of 95 mL/gVSadded, which was very close to the maximum H2 yield predicted by the developed model (97 mL/gVSadded), but also to a high CH4 yield of 400 mL/gVSadded (76% of the theoretical CH4 yield). Moreover, the biohythane obtained from the optimized two-stage process met the standards of a biohythane fuel with an H2 content of 19% v/v.


Pathogenic mosaic variants in congenital hypogonadotropic hypogonadism.
Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder resulting in absent puberty and infertility. The genetic architecture is complex with multiple loci involved, variable expressivity, and incomplete penetrance. The majority of cases are sporadic, consistent with a disease affecting fertility. The current study aims to investigate mosaicism as a genetic mechanism for CHH, focusing on de novo rare variants in CHH genes. We evaluated 60 trios for de novo rare sequencing variants (RSV) in known CHH genes using exome sequencing. Potential mosaicism was suspected among RSVs with altered allelic ratios and confirmed using customized ultradeep sequencing (UDS) in multiple tissues. Among the 60 trios, 10 probands harbored de novo pathogenic variants in CHH genes. Custom UDS demonstrated that three of these de novo variants were in fact postzygotic mosaicism-two in FGFR1 (p.Leu630Pro and p.Gly348Arg), and one in CHD7 (p.Arg2428*). Statistically significant variation across multiple tissues (DNA from blood, buccal, hair follicle, urine) confirmed their mosaic nature. We identified a significant number of de novo pathogenic variants in CHH of which a notable number (3/10) exhibited mosaicism. This report of postzygotic mosaicism in CHH patients provides valuable information for accurate genetic counseling.


Twenty years of experience in vascular reconstructions associated with resection of malignant neoplasms in a single cancer center.
Vascular invasion is no longer considered to be an absolute contraindication to tumor removal, and complex reconstructions are part of the daily activity of vascular surgeons in specialized cancer centers. Our aim was to report a single-center experience of complex vascular reconstructions involving en bloc resection of tumors and patients' long-term survival and graft patency outcomes. To the best of our knowledge, this is the largest report of vascular reconstructions published to date, with the longest follow-up. Between September 1997 and January 2016, there were 91 patients who underwent 92 arterial and 47 venous reconstruction procedures in this retrospective cohort study. Long-term survival and patency outcomes were analyzed for all study patients and individually assessed in different body segments (head and neck, thorax, upper limbs, abdomen, and lower limbs). The estimated mean and median follow-up times were 112.66 and 100 months, respectively. The 24- and 60-month survival estimates for the patients overall were 55.3% and 31.1%, respectively. Survival estimates were significantly lower in the head and neck cases compared with the other body segments. The primary arterial patency rates at 24 and 60 months were 96.7% and 84.9%, respectively, and they were similar in all body segments. The venous patency rates were 71.4% and 64.2% at 24 and 60 months, respectively. Seven cases (7.6%) of arterial vascular complications were observed. Vascular reconstruction performed in conjunction with oncologic resection is a feasible treatment option for tumors with vessel involvement. When surgery is performed in specialized centers, low perioperative morbidity and long-term patency rates are expected irrespective of the vascular territory undergoing intervention.


Congenital retinal arteriovenous communication associated with a full-thickness macular hole.
We present here a patient suffering from an unilateral retinal arteriovenous communication, belonging to group 2 in Archer classification, associated to a homolateral vascular malformation into the ophthalmic artery area, and a full-thickness macular hole. This is the first case with such an association reported in the literature.


Are bicuspid aortic valves a limitation for aortic valve repair?
To compare the mid-term results after aortic valve (AV) repair in bicuspid AVs with those in tricuspid AVs. Between 2000 and 2010, 100 patients (mean age 47.2 years) underwent AV repair procedures for insufficient bicuspid AV (n=43) and tricuspid AV (n=57). Aortic regurgitation (AR) more than moderate was present in 31/43 and 21/57 patients in the bicuspid AV and the tricuspid AV group, respectively. Concomitant root replacement by either the reimplantation or the remodeling technique was performed in 42 patients (bicuspid AV 17/43, tricuspid AV 25/57). All patients were prospectively studied with postoperative and further annual clinical assessment and echocardiography. Follow-up was 99% complete with a mean follow-up time of 22 months. Three patients died during the initial hospitalization, all due to postoperative cardiac failure. Overall actuarial 3 years' survival was 93±4.2% without significant differences between the two groups. Overall actuarial 3 years' freedom from AV-related reoperation was 86±5.1% without significant differences between the groups (85±9.7% for bicuspid AV, 86±6.0% for tricuspid AV; log-rank test: p=0.98). Overall actuarial 3 years' freedom from recurrent AR≥moderate was 100% and AR>trace was 71.3±8.2% without significant differences between the groups (76.5±11.7% for bicuspid AV, 71.4±9.4 for tricuspid AV; log-rank test: p=0.97). The mid-term outcome in terms of survival, freedom from reoperation or recurrent AR is similar for both groups of patients after AV repair procedures. Therefore, we advocate valve repair also in patients presenting with an insufficient bicuspid AV.


Adrenal masses in children.
Adrenal tumors include those of neural and cortical origin. Although most neuroblastomas present as abdominal masses, pheochromocytomas and cortical tumors usually present with endocrine dysfunction. Although imaging may not be able to differentiate benign lesions from malignant tumors, or whether they arise in the adrenal medulla or cortex, imaging is useful in determining the extent of the lesion and its relation to surrounding anatomic structures, particularly to vessels. Regardless of what imaging modality is used, meticulous attention to technique is required.


Self Nano-Emulsifying Curcumin (SNEC30) attenuates arsenic-induced cell death in mice.
Several precedents have confirmed numerous infirmities caused by arsenic poisoning, including immune suppression and cancer. Exposure to arsenic leads to alterations of the cellular machinery and eventually cell death, depending on the dose and duration of exposure. Oxidative stress induced by arsenic is the major mechanism by which it inflicts cellular toxicity, challenging the survival-support - autophagy and culminating in apoptosis in the thymus and spleen of mice. Curcumin, a potent dietary anti-oxidant with known anti-apoptotic and anti-inflammatory properties, was assessed for therapeutic benefits. However, the major caveat of this polyphenol is its low water solubility and limited bioavailability. Therefore, Self Nano-Emulsifying Curcumin (SNEC30) was used to treat mice exposed to arsenic. When administered, SNEC30 effectively ameliorated the adverse effects of arsenic in mice, by restoring structural alterations and reducing ROS-mediated cell death, thereby endorsing the importance of nutraceuticals in counteracting heavy metal-induced cellular toxicity.


Non-invasive tests for liver disease severity and the hepatocellular carcinoma risk in chronic hepatitis B patients with low-level viremia.
We tested whether non-invasive tests for liver disease severity can stratify hepatocellular carcinoma (HCC) risk in chronic hepatitis B virus (HBV)-infected patients showing low-level viremia (LLV, HBV DNA <2000 IU/mL). A retrospective cohort of 1006 chronic hepatitis B patients showing persistently LLV, defined by at least two consecutive assessments in the year before enrolment, was assessed for HCC development. Two non-invasive serum biomarkers, the aspartate aminotransferase to platelet ratio index (APRI) and the Fibrosis-4 (FIB-4), were tested. Cirrhosis was defined with ultrasonography. During a median 5.1 years of follow-up, HCC developed in 36 patients. HCC incidence rate at 5 years was significantly higher for cirrhotic patients (19/139, 13.7%), but was not null for non-cirrhotic patients (17/867, 2.0%, P<.001). APRI at a cut-off of 0.5 was more specific but less sensitive for HCC development, and FIB-4 at a cut-off of 1.45 was more sensitive but less specific. When both APRI and FIB-4 were used to group patients, the 5-year cumulative HCC incidence rate was 13.9%, 1.4% and 1.2% for both high, any high, and both low APRI and FIB-4 score among all patients (n=1006, P<.001), respectively, and was 11.4%, 1.5% and 0.4% in the same respective order among non-cirrhotic patients (n=867, P<.001). The combined use of two non-invasive serum biomarkers (APRI and FIB-4) could stratify HCC risk for chronic HBV-infected patients with LLV.


High-resolution HLA-A, -B and -DRB1 allele and haplotype frequencies in 7823 Han marrow donors of Liaoning province, China.
The human leukocyte antigen (HLA) system is the most polymorphic gene cluster in humans. High-resolution donor-recipient matching for HLA genes improves patient survival after unrelated hematopoietic stem cell transplantation. In this study, we analyzed the high-resolution allele and haplotype frequencies at the HLA-A, -B and -DRB1 loci in the Liaoning Han population and analyzed its relationships with other populations. The 3 most frequent alleles at the HLA-A, -B and -DRB1 loci were A*24:02, A*02:01:01G, A*11:01; B*13:02, B*46:01, B*40:01:01G; DRB1*09:01, DRB1*15:01 and DRB1*07:01, respectively. The most frequent 2-locus haplotypes were A*30:01-B*13:02 and B*13:02-DRB1*07:01. A*30:01-B*13:02-DRB1*07:01 was determined to be the predominant 3-locus haplotype. Hot maps and multiple correspondence analyses based on the frequencies of HLA specificities, which allow statistical visualization of dependent and independent relationships among variables, indicate that the Liaoning Han population is closely related to Northern populations of China and shows relative close relationships with Asian populations. These data will provide an outline of the HLA characteristics of healthy individuals in our region and help bone marrow transplantation patients find suitable HLA-matched donors.


Synthetic modeling of the structure and function of the rare-earth dependent methanol dehydrogenase cofactor.
Historically, rare-earth ions have been considered irrelevant to biology. Recently, the active sites of certain methanol dehydrogenase (MDH) enzymes have been shown to contain a redox-inactive, rare-earth (RE) cation coordinated by the redox-active pyrroloquinoline quinone (PQQ) cofactor. Importantly, it was demonstrated that rare earths were essential for the growth of certain methylotrophs that incorporated the XoxF-MDH. In this chapter, we summarize the optimized synthesis of a previously published rare-earth complex that serves as a model of the active site of this RE-containing MDH enzyme. The structure and reactivity of the metalated complex, [La(LQQ)(NO3)3] are also discussed. [La(LQQ)(NO3)3] catalytically oxidizes the test alcohol substrate, p-methylbenzyl alcohol, 4MeBnOH, to p-methylbenzaldehyde, 4MePhCHO, in the presence of a base (2,6-lutidine) and a terminal oxidant (ferrocenium hexafluorophosphate) with ~17 turnovers. By studying this synthetic model, we have developed a body of evidence about both the reactivity and the mechanism of dehydrogenation of alcohols as a molecular analogue to a native, rare-earth dependent enzyme.


N-terminal pro-brain natriuretic peptide and coronary collateral formation in patients undergoing primary percutaneous coronary intervention.
There is insufficient information on the relationship between the N-terminal pro-brain natriuretic peptide (NT-proBNP) level and collateral circulation (CC) formation after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction. We analyzed 857 patients who underwent primary PCI. The serum NT-proBNP levels were measured on the day of admission, and the CC was scored according to Rentrop's classification. Log-transformed NT-proBNP levels were significantly higher in patients with good CC compared to those with poor CC (6.13 ± 2.01 pg/mL versus 5.48 ± 1.97 pg/mL, p < 0.001). The optimum cutoff value of log NT-proBNP for predicting CC was 6.04 pg/mL. Log NT-proBNP ≥ 6.04 pg/mL (odds ratio 2.23; 95% confidence interval 1.51-3.30; p < 0.001) was an independent predictor of good CC. CC development was higher in patients with a pre-TIMI flow of 0 or 1 than those with a pre-TIMI flow of 2 or 3 (22.6% versus 8.8%, p = 0.001). The incidence of left ventricular (LV) dysfunction (< 50%) was greater in patients with a pre-TIMI flow of 0 or 1 (49.8% versus 35.5%, p < 0.001). The release of NT-proBNP was greater in patients with LV dysfunction (34.3% versus 15.6%, p < 0.001). The incidence of good CC was greater in patients with log NT-proBNP levels ≥ 6.04 pg/ml (16.8% versus 26.2%, p = 0.003). The association between NT-proBNP and collateral formation was not influenced by pre-TIMI flow and LV function. NT-proBNP appears to reflect the degree of collateral formation in the early phase of STEMI and might have a new role as a useful surrogate biomarker for collateral formation in patients undergoing primary PCI.


The role of peripheral capacitance and resistance vessels in hypotension following hemodialysis.
The arterial pressure (AP) response to hemodialysis was studied with echocardiography and strain gauge plethysmography in 17 patients with end-stage renal disease; mean AP was unchanged in seven (group A) and was reduced by more than 10 mm Hg in 10 patients (group B). Following dialysis, body weight decreased and heart rate increased equally in both groups. Ejection fraction did not change in the two groups. Left ventricular end-diastolic volume fell by 13 +/- 10% in group A and by 24 +/- 16% in group B. Cardiac index (CI) fell in group B, but remained unchanged in group A. Systemic vascular resistance (SVR) did not change in both groups. The change in mean AP before and after dialysis was significantly correlated with that in Cl (r = 0.49, p less than 0.05), but not with that in SVR. Calf venous pressure-volume curves were not different between the two groups before dialysis. Hemodialysis shifted the curve toward the volume axis for group B but not for group A. These results suggest that hypotension following dialysis is mainly due to the fall in cardiac output, in which increases in venous distensibility play an important role.


A Shakespearean Dilemma in Breast Augmentation: to Use Drains or not? a Systematic Review : Drains in Breast Augmentation.
Breast augmentation is one of the most commonly requested and performed plastic surgery procedures. In order to prevent early postoperative complications such as seroma or hematoma, surgical drains could be useful. The aim is to perform a systematic review of the literature on the use of surgical drains in primary breast augmentation. This review was performed following the PRISMA guidelines. PubMed, SCOPUS, Web of Science and Cochrane Library databases were queried in search of clinical studies describing the use of surgical drains in women undergoing primary breast augmentation with implants and documenting seroma and/or hematoma formation rate and/or infection rate. Initial search identified 2596 studies, and 162 were found relevant. Full-text review and application of our inclusion criteria to all retrieved papers produced 38 articles that met inclusion criteria. Among the included studies, 16 papers reported the use of surgical drains in breast augmentation, while in the remaining 22 articles drains were not used. Only 5 studies specifically investigated the role and effectiveness of surgical drains in augmentation mammaplasty and its possible relationship with complication rate such as seroma, hematoma or infection. Despite similar complication rates emerged from the analyzed articles, because of the heterogeneity of the studies, we were not able to demonstrate specifically whether drain use affects the rate of early postoperative complications such as seroma, hematoma and infection. Additional randomized controlled trials are strongly advocated in order to provide the necessary scientific evidence. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Evaluating the impact of direct and indirect contact on the mental health stigma of pharmacy students.
Contact with mental health consumers has shown to be a promising strategy to address mental health stigma, particularly in the context of pharmacy education. This research aimed to compare the effectiveness of a direct (face-to-face) contact intervention with an indirect (film based) contact intervention in reducing the mental health stigma of pharmacy students. A two-group, non-randomized, comparative study was conducted with third year pharmacy students (n = 198) allocated to the direct contact arm and fourth year pharmacy students (n = 278) allocated to the indirect contact arm. Baseline and immediate post-intervention data were collected using a validated 39 item survey instrument to assess the impact of the interventions on mental health stigma as well as attitudes towards providing mental health pharmaceutical services. Participants in the direct contact group showed a significant improvement in 37 out of 39 survey items and participants in the indirect contact group showed a significant improvement in 27 out of 39 items (P < 0.05). While direct contact had a stronger impact than indirect contact for 22 items (P < 0.05), for numerous key measures of mental health stigma the impact of the two contact interventions was equivalent. Both indirect and direct contact may positively impact mental health stigma. While the strength of the stigma-change process may be heightened by face-to-face interactions, the largely positive impact of indirect contact suggests that stigma reduction may depend less on the medium of contact but more on the transcendent messages contributed by the consumers facilitating the contact experience.


Hormesis effects of sulfoxaflor on Aphis gossypii feeding, growth, reproduction behaviour and the related mechanisms.
Sulfoxaflor, an important alternative insecticide in integrated pest management (IPM) strategies, can effectively control sap-feeding insect pests such as Aphis gossypii. Although the side effects of sulfoxaflor have recently attracted widespread attention, its toxicological characteristics and mechanisms are still largely undefined. Therefore, the biological characteristics, life table and feeding behaviour of A. gossypii were studied to evaluate the hormesis effect of sulfoxaflor. Then, the potential mechanisms of induced fecundity associated with the vitellogenin (Ag. Vg) and vitellogenin receptor (Ag. VgR) genes were investigated. Although the LC10 and LC30 concentrations of sulfoxaflor significantly reduced the fecundity and net reproduction rate (R0) of the directly exposed sulfoxaflor-resistant and susceptible aphids, hormesis effects on fecundity and R0 were observed in the F1 generation of Sus A. gossypii when the parental generation was exposed to the LC10 of sulfoxaflor. Moreover, the hormesis effects of sulfoxaflor on phloem feeding were observed in both A. gossypii strains. Additionally, enhanced expression levels and protein content of Ag. Vg and Ag. VgR were observed in progeny generations when F0 was subjected to the trans- and multigenerational sublethal sulfoxaflor exposure. Therefore, sulfoxaflor-induced resurgence might occur in A. gossypii after exposure to sublethal concentrations. Our study could contribute to a comprehensive risk assessment and provide convincing reference to optimize sulfoxaflor in IPM strategies.


Promising effects of β-glucans on gelation in protein-based products: A review.
Gel property is one of the most important abilities to endow protein-based food products with a unique texture and higher overall acceptability. Cereal β-glucan (BG) is widely applied in protein-based products to improve the stability of the protein gel by increasing water holding capacity, storage modulus (G'), loss modulus (G") and linking with protein through more exposed sites, making it easier to form a stronger three-dimensional gel network. In addition, BG may be cross-linked with proteins, or physically embedded and covered in protein network structures, interacting with proteins mainly through non-covalent bonds including hydrogen bonding and electrostatic interaction. Furthermore, the transition of the α-helix to the β-form in the protein secondary structure also contributes to the stability of the protein gel. The practical applications of BG from different cereals in protein-based products are summarized, and the rheological properties, microstructure of protein as well as the underlying interaction mechanisms between BG and protein are discussed. In conclusion, cereal BG is a promising polysaccharide in developing nutritional protein-based products with better sensory properties.


Developments and perspectives in allergology.
Allergology is a key part of dermatological care. This paper reviews current pathophysiological, diagnostic and therapeutic developments in immediate-type allergies. Type-2 inflammation is involved in several allergological diseases such as allergic rhinitis and asthma. Allergen immunotherapy as an important therapeutic procedure is regulated in Germany by an official legal directive (Therapieallergene-Verordnung). Therapeutically, several biologics are already available that target interleukin (IL)-4, -5, -13, -33, or TSLP (thymic stromal lymphopoietin). Collateral efficacy may result in simultaneous treatment of allergological comorbidities. In mast cell mediated diseases (urticaria, anaphylaxis), there is increasing understanding of mast cell activation pathways. Several mast cell receptors such as MRGPRX2 (mas-related G protein coupled receptor X2) and Siglec-8 (sialinic acid binding Ig like lectin-8) as well as intracellular signaling pathways have recently been identified. Clinical trials are underway with drugs acting on mast cell receptors and intracellular signaling, i.e., Bruton's tyrosine kinase inhibitors. Further perspectives on biomarkers, novel therapeutics and unmet needs for future research activities are presented.


Low-intensity pulsed ultrasound increases the fracture callus strength in diabetic BB Wistar rats but does not affect cellular proliferation.
Type I diabetes mellitus (DM) is associated with impaired fracture healing. Specifically, DM affects multiple phases of fracture healing including early cellular proliferation and late phases resulting in inferior biomechanical properties. Recent studies demonstrated the utility of pulsed low-intensity ultrasound (US) to facilitate fracture healing. The current study evaluated the effects of daily application of US on mid-diaphyseal femoral fractures in DM and non-DM BB Wistar rats. Immunohistochemical staining for PCNA was used to evaluate cellular proliferation at 2, 4, and 7 days post-fracture. In concordance with previous findings. DM fracture callus demonstrated decreased cellular proliferation. Importantly, the application of US did not significantly alter the proliferation in either DM or control groups. However, mechanical testing revealed significantly greater torque to failure and stiffness in US-treated DM versus non-US-treated DM groups at six weeks post-fracture. Despite the inability of US to affect the early proliferative phase of fracture healing, its application clearly results in improved mechanical properties during the late phases of healing. These findings suggest a potential role of US as an adjunct for DM fracture treatment.


Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesial temporal lobe epilepsy and unilateral hippocampal sclerosis.
Several studies have demonstrated the positive effect of resective epilepsy surgery in drug-resistant temporal lobe epilepsy (TLE). However, it is still a matter of debate whether selective amygdalohippocampectomy (SAH) or standard temporal lobectomy (STL) are the most effective approaches concerning seizure outcome, quality of life and memory. In each of the two centers participating in this study either SAH or STL was the neurosurgical standard procedure irrespective of contextual aspects. Thus, with this postoperative assessment of resected patients we sought to avoid any selection bias that usually impaired comparative trials of both surgical approaches. We finally identified and studied 95 adult patients who had undergone either SAH (n=46) or STL (n=49) between 1999 and 2009 and fulfilled the inclusion criteria, namely drug-resistant unilateral mesial TLE with hippocampal sclerosis without any further structural lesions. We assessed the postoperative seizure outcome according to the ILAE criteria and postoperative quality of life by means of standardized questionnaires. Finally, we compared postoperative neuropsychological performance in 60 completely seizure-free patients (n=27 after SAH, n=33 after STL) prior to, one year after surgery and at a long-term follow-up with a mean of seven years. 78.2% of SAH and 85.7% of STL were seizure-free at the last observation. Quality of life had improved in 95.6% of the SAH patients and 89.8% of the STL patients. These differences were not statistically significant. Left-sided TLE patients had a significantly worse verbal memory outcome irrespective of the surgical method. However, SAH patients had a significantly better outcome concerning visual encoding, verbal and visual short-term memory and visual working memory. In this study, seizure outcome and quality of life did not differ depending on the surgical approach. However, a more selective resection led to better neuropsychological performances.


A new balance equation of reducing equivalents for data consistency check and bioprocess calculation.
The reducing equivalent (RE) balance is a basic equation for data consistency check and calculations of bioprocesses. The macroscopic approach is often used because it does not require detailed knowledge of metabolic pathways. In this work, the conventional Minkevich-Eroshin balance equation is examined with data of anaerobic glycerol conversion by Klebsiella pneumoniae and Clostridium butyricum as examples. It is shown that the Minkevich-Eroshin equation is very insensitive to measurement errors in products of less dominance and/or with relatively low reductance degree. Relatively large deviations from experimental values are encountered when the Minkevich-Eroshin equation is used for the calculations of these products. To overcome some of these shortcomings an improved RE balance equation is proposed that is based on 'reductance equations' of substrate conversion into the individual carbon containing products (including biomass). The proposed new equation significantly improves the performance of the RE balance equation for data consistency check and for the calculations of unknown variables with relatively low reductance degree. The rationale for this is that it considers merely the REs that really participate in the bioreactions. The use of the proposed method requires no detailed knowledge of metabolic pathways and is therefore of macroscopic nature. It can be reduced to the pathway balance equation if the pathways are known.


Drug-resistant pandemic (H1N1) 2009, South Korea.
Eleven patients with drug-resistant pandemic (H1N1) 2009 were identified in South Korea during May 2009-January 2010. Virus isolates from all patients had the H275Y mutation in the neuraminidase gene. One isolate had the I117M mutation. Of the 11 patients, 6 were ≥ 59 months of age, and 5 had underlying immunosuppressive conditions.


O-Glycoproteomic analysis of engineered heavily glycosylated fusion proteins using nanoHILIC-MS.
Recombinant protein engineering design affects therapeutic properties including protein efficacy, safety, and immunogenicity. Importantly, glycosylation modulates glycoprotein therapeutic pharmacokinetics, pharmacodynamics, and effector functions. Furthermore, the development of fusion proteins requires in-depth characterization of the protein integrity and its glycosylation to evaluate their critical quality attributes. Fc-fusion proteins can be modified by complex glycosylation on the active peptide, the fragment crystallizable (Fc) domain, and the linker peptides. Moreover, the type of glycosylation and the glycan distribution at a given glycosite depend on the host cell line and the expression system conditions that significantly impact safety and efficacy. Because of the inherent heterogeneity of glycosylation, it is necessary to assign glycan structural detail for glycoprotein quality control. Using conventional reversed-phase LC-MS methods, the different glycoforms at a given glycosite elute over a narrow retention time window, and glycopeptide ionization is suppressed by co-eluting non-modified peptides. To overcome this drawback, we used nanoHILIC-MS to characterize the complex glycosylation of UTI-Fc, a fusion protein that greatly increases the half-life of ulinastatin. By this methodology, we identified and characterized ulinastatin glycopeptides at the Fc domain and linker peptide. The results described herein demonstrate the advantages of nanoHILIC-MS to elucidate glycan features on glycotherapeutics that fail to be detected using traditional reversed-phase glycoproteomics.


Colony expansions underlie the evolution of army ant mass raiding.
The mass raids of army ants are an iconic collective phenomenon, in which many thousands of ants spontaneously leave their nest to hunt for food, mostly other arthropods. While the structure and ecology of these raids have been relatively well studied, how army ants evolved such complex cooperative behavior is not understood. Here, we show that army ant mass raiding has evolved from a different form of cooperative hunting called group raiding, in which a scout directs a small group of ants to a specific target through chemical communication. We describe the structure of group raids in the clonal raider ant, a close relative of army ants in the subfamily Dorylinae. We find evidence that the coarse structure of group raids and mass raids is highly conserved and that all doryline ants likely follow similar behavioral rules for raiding. We also find that the evolution of army ant mass raiding occurred concurrently with expansions in colony size. By experimentally increasing colony size in the clonal raider ant, we show that mass raiding gradually emerges from group raiding without altering individual behavioral rules. This suggests that increasing colony size can explain the evolution of army ant mass raids and supports the idea that complex social behaviors may evolve via mechanisms that need not alter the behavioral interaction rules that immediately underlie the collective behavior of interest.


Thermalization and possible signatures of quantum chaos in complex crystalline materials.
Analyses of thermal diffusivity data on complex insulators and on strongly correlated electron systems hosted in similar complex crystal structures suggest that quantum chaos is a good description for thermalization processes in these systems, particularly in the high-temperature regime where the many phonon bands and their interactions dominate the thermal transport. Here we observe that for these systems diffusive thermal transport is controlled by a universal Planckian timescale [Formula: see text] and a unique velocity [Formula: see text] Specifically, [Formula: see text] for complex insulators, and [Formula: see text] in the presence of strongly correlated itinerant electrons ([Formula: see text] and [Formula: see text] are the phonon and electron velocities, respectively). For the complex correlated electron systems we further show that charge diffusivity, while also reaching the Planckian relaxation bound, is largely dominated by the Fermi velocity of the electrons, hence suggesting that it is only the thermal (energy) diffusivity that describes chaos diffusivity.


Synthesis and characterization of metal nanoparticles templated chitosan-SiO2 catalyst for the reduction of nitrophenols and dyes.
Different metal nanoparticles (MNPs) templated on chitosan-silica (CH-SiO2) nanocomposite fiber were prepared via simple and fast method of the metal ions uptake by fiber and their subseqent reduction using strong reducing agent. The performance difference of CH-SiO2 templated with Cu, Co, Ag and Ni nanoparticles for both reduction of 4-nitroaniline (4-NA) and decolorization of congo red (CR) was investigated. The Cu nanoparticles loaded CH-SiO2 (Cu/CH-SiO2), showed high catalytic efficiencies in the reduction of 4-NA and CR, as compared to other loaded MNP fibers. The apparent rate constants of 6.17 × 10-3 s-1 and 1.68 × 10-2 s-1 and turnover frequencies (TOF) of 4.693 h-1 and 3.965 h-1 were observed for the reduction of 4-NA and CR, respectively. In addition, the catalytic activity of Cu/CH-SiO2 catalyst was also examined and found efficient in the reduction of nitrophenols (2-NP, 3-NP and 4-NP), and other dyes. Thus, Cu/CH-SiO2 with excellent catalytic activity can also be employed for other applications.


[Antitumor effects of soluble TRAIL in human hepatocellular carcinoma].
To investigate therapeutic potential of soluble TRAIL (sTRAIL) in hepatocellular carcinoma (HCC). Expression of TRAILR was determined by in situ hybridization in 60 samples of resected hepatocellular carcinoma, 20 samples of normal liver tissue near the margin of benign tumor and 2 HCC cell lines of HepG2 and SMMC-7721. The clinical data of the patients were analyzed as well as cellular effects of sTRAIL in promoting apoptosis on HCC cell lines HepG2 and SMMC-7721 (p53 gene mutated) after exposure to different concentrations of recombinant protein. High death receptor (DR) expression and low DcR expression in HCC tissue differed from low DR expression and high DcR expression in the normal hepatic tissue with statistical significance. DR5, DR4, and DcR2 but not DcR1 were expressed in both cell lines. The expression of DR was closely correlated with HCC differentiation, with the weak expression in poor differentiation. The positive rate of DR expression in 32 cases of grade III-IV was significantly lower than that in 28 cases of grade I-II (P < 0.05). Cell apoptosis rates were 10%, 70% and 50% of HCC cells, Jurkat cells and human cholangiocarcinoma cell line QBC939 24 h after recombinant of TRAIL alone. TRAILR expression is prevalent in HCC, with different receptor types existing. HCC is resistant to TRAIL-mediated apoptosis. The treatment of TRAIL alone only has a limited effect on inducing apoptosis on HCC cell lines of HepG2 and SMMC-7721.


Mepolizumab and dupilumab as a replacement to systemic glucocorticoids for the treatment of Chronic Eosinophilic Pneumonia and Allergic Bronchopulmonary Aspergillosis - Case series, Almoosa specialist hospital.
In this case series, we present four patients who had asthma and blood eosinophilia. Two patients were diagnosed with Chronic Eosinophilic Pneumonia (CEP) and the other two with Allergic Bronchopulmonary Aspergillosis (ABPA). Laboratory findings revealed profound peripheral eosinophilia with abnormal chest radiography (alveolar shadows, segmental atelectasis, and cystic changes). Initial improvement (clinical, laboratory, and radiological) occurred with traditional asthma therapy, including systemic corticosteroids. The patients did not tolerate corticosteroid therapy because of weight gain, uncontrolled diabetes, bone fractures, and psychological adverse effects. Mepolizumab (administered to two CEP cases and one ABPA case) and Dupilumab (administered to one ABPA case) were initiated as steroid-sparing agents, resulting in successful therapy without relapse or adverse effects. Mepolizumab, and Interleukin-5 (IL-5) antagonist, targets diseases mediated by eosinophil activity and proliferation. Dupilumab blocks the Interleukin-4/Interleukin-13 pathway and suppresses Type 2 inflammation, including Immunoglobulin E (IgE). Dupilumab resulted in up to 70% drop in total IgE levels from baseline and reduced eosinophil-mediated lung inflammation, despite the presence of normal or increased blood eosinophil counts.


Enlargement of subarachnoid spaces and lateral ventricles in pediatric patients undergoing chemotherapy.
This retrospective study investigated the possible adverse effects of cancer therapy on the brain. Cranial computed tomographic scans of 76 patients with non-central nervous system malignancies and 25 patients with leukemia had enlarged lateral ventricles and/or cortical sulci in 19% and 40%, respectively. Leukemic patients, especially those with meningeal involvement, had the most frequent and most severe abnormalities.


Mitral regurgitation severity at left ventricular assist device implantation is associated with distinct myocardial transcriptomic signatures.
We examined for differences in pre-left ventricular assist device (LVAD) implantation myocardial transcriptome signatures among patients with different degrees of mitral regurgitation (MR). Between January 2018 and October 2019, we collected left ventricular (LV) cores during durable LVAD implantation (n = 72). A retrospective chart review was performed. Total RNA was isolated from LV cores and used to construct cDNA sequence libraries. The libraries were sequenced with the NovaSeq system, and data were quantified using Kallisto. Gene Set Enrichment Analysis (GSEA) and Gene Ontology analyses were performed, with a false discovery rate <0.05 considered significant. Comparing patients with preoperative mild or less MR (n = 30) and those with moderate-severe MR (n = 42), the moderate-severe MR group weighted less (P = .004) and had more tricuspid valve repairs (P = .043), without differences in demographics or comorbidities. We then compared both groups with a group of human donor hearts without heart failure (n = 8). Compared with the donor hearts, there were 3985 differentially expressed genes (DEGs) for mild or less MR and 4587 DEGs for moderate-severe MR. Specifically altered genes included 448 DEGs for specific for mild or less MR and 1050 DEGs for moderate-severe MR. On GSEA, common regulated genes showed increased immune gene expression and reduced expression of contraction and energetic genes. Of the 1050 genes specific for moderate-severe MR, there were additional up-regulated genes related to inflammation and reduced expression of genes related to cellular proliferation. Patients undergoing durable LVAD implantation with moderate-severe MR had increased activation of genes related to inflammation and reduction of cellular proliferation genes. This may have important implications for myocardial recovery.


Real-World Effectiveness and Safety of Apixaban versus Warfarin in Patients with Acute Venous Thromboembolism: Experience of a Large Tertiary Hospital in Saudi Arabia.
The main objective of this study was to evaluate the effectiveness and safety of apixaban versus warfarin in patients with venous thromboembolism (VTE) in a "real-world" setting. A retrospective cohort study was conducted using data from a large tertiary hospital in Saudi Arabia. Patients were included if they were adults (≥18 years), diagnosed with VTE, and treated with either apixaban or warfarin between January 2016 and September 2018. Patients who had received anticoagulation therapy within three months of the date of the index event were excluded. The effectiveness outcomes were incidence of VTE recurrence (ie, deep vein thrombosis DVT or pulmonary embolism [PE]), while the safety outcome was incidence of any major bleeding (MB) event within 90 days of follow-up. Among the 492 patients included for study, 212 (43.1%) received apixaban and 280 (56.1%) received warfarin. The mean age of patients was 53.6±19.1 years and 62% of the cohort was female. Comparable rates of VTE recurrence were observed for apixaban and warfarin treatment groups during follow-up (adjusted odds ratio (AOR) =0.95; 95% CI 0.53-1.68), including DVT (AOR=1.06; 95% CI 0.52-2.17) and PE (AOR=0.78; 95% CI 0.31-1.96). However, apixaban was associated with significantly fewer MB events than warfarin (AOR=0.18; 95% CI 0.04-0.83). The use of apixaban for the treatment of Saudi patients with acute VTE is associated with a VTE recurrence rate comparable to that of warfarin, with significantly fewer MB events.


[Bridging sectoral barriers with integrative care].
In an international comparison, Germany is in the top group for health care. Not only since the economic burdens of the corona pandemic, however, has there been agreement of the necessity of exploiting the considerable efficiency and effectiveness reserves that also exist in this area. Particularly in the interface area between outpatient and inpatient care, increasingly divergent development paths are beeing discusssed. Despite scientific findings to the contrary, integrative cooperative structures threaten to fall behind.


Effects of phenylbutazone and oxyphenbutazone on acidic drug detection in high performance thin layer chromatographic systems.
Interference or "masking" in thin layer chromatography occurs when the presence of one drug on a thin layer plate physically obscures or interferes with the detection of another drug. We investigated the ability of phenylbutazone and oxyphenbutazone to mask or interfere with the detection of acidic drugs of high performance thin layer chromatography. Of 20 acidic drugs called "positive" since 1981 by laboratories affiliated with the Association of Official Racing Chemists, 16 did not comigrate with phenylbutazone or oxyphenbutazone and could not, therefore, be masked by these agents. Three medications (diclofenac, fenoprofen, ibuprofen) were potentially masked by phenylbutazone and one (sulindac) was potentially masked by oxyphenbutazone. These agents were therefore administered to horses to determine whether or not their metabolites would allow their detection. In each case, metabolites of these agents were detectable for at least 24 hr after drug administration and detection was not interfered with by phenylbutazone or oxyphenbutazone. These results suggest that these 20 acidic drugs should be readily detectable in postrace urines of horses in the presence of phenylbutazone either as the parent drug or by virtue of the easily distinguishable metabolites that each agent possesses. There is, therefore, no reason to believe that the agents tested in this study can be effectively masked or interfered with by phenylbutazone or its metabolites in equine urine.


Psychiatric genetics: recent advances and clinical implications.
To present an overview on current progress and future directions in psychiatric genetics. The review of studies that have demonstrated a genetic contribution to a wide range of psychopathology using family, twin, adoption studies and exploration of the methods and limitations of molecular genetic studies. Single gene disorders has been the area that is most straightforward with striking advances in disorders such as Huntington Disease and early onset familial Alzheimer disease. Complex phenotypes such as schizophrenia and affective disorder have presented greater difficulties but late onset Alzheimer disease and dyslexia are examples where replicated molecular genetic findings suggest that gene identification is feasible even for multifactorial disorders. The combination of increasingly complete information on the genome together with accessibility to this on the internet provide the essential tools for the search for susceptibility genes. Another essential requirement in trying to identify genes of small effect is well characterized large scale collections of cases and this demands the interaction of epidemiological and clinical researchers. Advances in genomics will also allow tailoring of pharmaceuticals pointing at treatment response and side effects. Hopefully all this perspectives together, will improve our understanding of the neurobiological pathogenesis of diseases such as Schizophrenia, Depression and Bipolar disorder 'legitimizing' them in the public view.


Comparative study of the effects of ceftazidime compared with tobramycin plus cefamandole in the treatment of gall bladder empyema.
Fifty patients with empyema of the gall bladder took part in a prospective comparative study. One treatment group received ceftazidime 2 g bd, while the other received combined therapy with cefamandole 2 g tds and tobramycin 80 mg bd. The intraoperative administration of the antibiotic was started immediately after a sample had been obtained for culture, by puncture of the gall bladder. Results with ceftazidime monotherapy in severe infections were superior to the combined therapy. No septic complications of wound healing were observed.


Birth complications and the distribution of handedness.
In an attempt to clarify the relationship between self-reported birth complications and handedness, the handedness distributions of 181 college students who reported birth complications and 1320 students who reported no complications were compared. The results suggest a clear but modest shift in the birth complications group away from the dextral end of the continuum. However these data did not validate the hypothesis that left-handedness results from birth complications.


Mimosine mitigates oxidative stress in selenium deficient seedlings of Vigna radiata--Part I: Restoration of mitochondrial function.
Mimosine, a non-protein plant amino acid found in Mimosa pudica and certain species of Leucaena, was beneficial for the growth of seedlings of Vigna radiata germinated under selenium-deficient stressed condition (-Se stressed) despite the recognized toxicity of the allelochemical. Exposure of mimosine at 0.1 mM (Mim-0.1) promoted the growth of the seedlings and significantly enhanced mitochondrial functional efficiency. Growth-related parameters including root and shoot lengths and dry weight were increased by 44-58% in the Mim-0.1 group compared to that of the -Se-stressed group. Oxygen uptake by mitochondria of Mim-0.1 group, studied with different substrates, revealed enhanced State 3 respiratory rates with regulated State 4 rates, resulting in high respiratory control ratio (RCR) of 3.4 to 3.9 indicative of a high degree of oxidative coupling. Specific activities of mitochondrial electron transport enzymes, nicotinamide adenine dinucleotide (reduced form) (NADH)-cytochrome (cyt) c oxidoreductase, succinate dehydrogenase, and cyt c oxidase in the Mim-0.1 group were enhanced by 53% to threefold over those of the Se-stressed group. Marked decreases in the extent of mitochondrial lipid peroxidation ensued upon mimosine exposure, indicative of its antioxidant function. Mitochondrial 45Ca2+ uptake was notably augmented twofold in the Mim-0.1 group, compared to the Se-stressed group. Detailed kinetic analyses of Ca2+ uptake revealed positive cooperative interactions in both -Se-stressed group and Mim-0.1 groups with Hill coefficient (nH) values of 1.7 and 2, respectively. The present study establishes the beneficial effects of mimosine exposure at 0.1 mM on the growth and mitochondrial function of the seedlings grown under selenium-deficient stressed condition and a significant physiological role can be ascribed to mimosine.


Histoplasmosis Following Systemic Immunomodulatory Therapy for Ocular Inflammation.
Histoplasmosis is a known complication of systemic immunosuppressive therapy, particularly among patients who are receiving tumor necrosis factor α inhibitors. There are limited data on the development of disseminated or pulmonary histoplasmosis among patients who are receiving systemic immunosuppressive medication for noninfectious ocular inflammation. Retrospective case series. We reviewed all patients with uveitis or scleritis who subsequently developed pulmonary or disseminated histoplasmosis at the Mayo Clinic in Rochester, Minnesota between September 1, 1994 and July 1, 2017, with a 3:1 age- and sex-matched control cohort who did not develop histoplasmosis. This was a single institutional study examining patients that developed histoplasmosis after the initiation of systemic immunomodulatory therapy (IMT). Patients had to develop either disseminated or pulmonary histoplasmosis while receiving systemic immunosuppressive therapy and have an ophthalmic examination at Mayo Clinic Rochester. The control group was comprised of patients who received systemic IMT for ocular inflammation but did not develop histoplasmosis. Nine cases of histoplasmosis were identified: 2 disseminated and 7 pulmonary. Both patients with disseminated histoplasmosis were taking tumor necrosis factor α inhibitors. Seven of the 9 patients received systemic antifungal medication, including both disseminated cases. Over a median follow-up of 4.4 years, none of the patients died, and there were no recurrences of histoplasmosis. When compared to the control cohort, there was no correlation between length of time on IMT and the risk of histoplasmosis. Ocular inflammation patients on systemic immunomodulatory therapy may develop pulmonary or disseminated histoplasmosis. Most cases require treatment with systemic antifungal medication, but it might not be necessary to stop systemic immunomodulatory medication for ocular inflammation. Ophthalmologists should be aware that patients receiving systemic immunomodulatory therapy have a higher risk of developing Histoplasma infections. Prompt diagnosis and treatment using the expertise of an infectious diseases specialist may ensure low mortality for these patients.


Glutamate and dopamine receptors contribute to the lateral spread of epileptiform discharges in rat neocortical slices.
The effects of AMPA-type glutamate receptor as well as dopamine D1 and D2 receptors on the lateral propagation of epileptiform field potentials (EFP) were studied across adjacent areas of rat neocortical tissues. Epileptiform burst discharges were induced by superfusion of Mg(2+)-free artificial cerebrospinal fluid. Simultaneous field potential recordings of EFP were obtained from four microelectrodes placed 2-3 mm apart across coronal slices in the third layer of the neocortex. The effects of AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), dopamine D1 receptor agonist SKF 81297, and dopamine D2 receptor agonist quinpirole on lateral propagation of burst discharges were investigated. CNQX, applied focally between recording sites, blocked rapid propagation across treated areas and resulted in the emergence of spatially separate, independent pacemakers. Focal application of SKF 81297 between recording sites increased the repetition rate of EFP, but reduced the amplitude as well as the duration of epileptic discharges. However, addition of SKF 81297 to the bath medium abolished EFP. Both local and systemic applications of quinpirole irreversibly enhanced repetition rate of epileptiform burst discharges. The results indicate the prerequisite of AMPA synaptic transmission for synchronized lateral propagation of Mg(2+)-free ACSF-induced epileptic activity and the modulatory effects of dopamine D1 and D2 receptors on both EFP initiation and propagation in epileptic tissues.


Comparison Theorems for Stochastic Chemical Reaction Networks.
Continuous-time Markov chains are frequently used as stochastic models for chemical reaction networks, especially in the growing field of systems biology. A fundamental problem for these Stochastic Chemical Reaction Networks (SCRNs) is to understand the dependence of the stochastic behavior of these systems on the chemical reaction rate parameters. Towards solving this problem, in this paper we develop theoretical tools called comparison theorems that provide stochastic ordering results for SCRNs. These theorems give sufficient conditions for monotonic dependence on parameters in these network models, which allow us to obtain, under suitable conditions, information about transient and steady-state behavior. These theorems exploit structural properties of SCRNs, beyond those of general continuous-time Markov chains. Furthermore, we derive two theorems to compare stationary distributions and mean first passage times for SCRNs with different parameter values, or with the same parameters and different initial conditions. These tools are developed for SCRNs taking values in a generic (finite or countably infinite) state space and can also be applied for non-mass-action kinetics models. When propensity functions are bounded, our method of proof gives an explicit method for coupling two comparable SCRNs, which can be used to simultaneously simulate their sample paths in a comparable manner. We illustrate our results with applications to models of enzymatic kinetics and epigenetic regulation by chromatin modifications.


N6-methyladenosine demethylase FTO promotes growth and metastasis of gastric cancer via m6A modification of caveolin-1 and metabolic regulation of mitochondrial dynamics.
Gastric cancer (GC) is the fifth most common tumor and the third most deadly cancer worldwide. N6-methyladenosine (m6A) modification has been reported to play a regulatory role in human cancers. However, the exact role of m6A in GC remains largely unknown, and the dysregulation of m6A on mitochondrial metabolism has never been studied. In the present study, we demonstrated that FTO, a key demethylase for RNA m6A modification, was up-regulated in GC tissues, especially in tissues with liver metastasis. Functionally, FTO acted as a promoter for the proliferation and metastasis in GC. Moreover, FTO enhanced the degradation of caveolin-1 mRNA via its demethylation, which regulated the mitochondrial fission/fusion and metabolism. Collectively, our current findings provided some valuable insights into FTO-mediated m6A demethylation modification and could be used as a new strategy for more careful surveillance and aggressive therapeutic intervention.


Internal fixation or primary arthrodesis for Lisfranc complex joint injuries? A meta-analysis of comparative studies.
Though uncommon, Lisfranc complex joint injuries constitute a therapeutic challenge. Two surgical methods are commonly used to treat such injuries: open reduction and internal fixation (ORIF) and primary arthrodesis (PA). The aim of this meta-analysis is to look for significant differences in the outcomes between these two techniques. A comprehensive search of databases including PubMed, Embase, Cochrane Library and Google Scholar was planned. Only studies with comparative design using ORIF/PA techniques were included. One randomized trial, one quasi-randomized trial and four of retrospective comparative studies met the inclusion criteria. Proportion meta-analysis was used to look for weighted frequencies of outcomes. Risk difference rate meta-analysis was conducted to look for significant differences between proportion rates. The pooled sample included 269 patients [269 surgical procedures: 176 (65.4%) ORIF vs. 93 (34.6%) PA] with a mean follow-up period of 31.85 ± 16.14 months. Besides a similar radiological healing failure rate, meta-analytical results yielded better outcomes in favour of PA: lesser implant removal rate (P < 0.0001), better rate of return to full activities (P = 0.01) and satisfaction rate (P = 0.052). A double rate of revision for non-healing following ORIF was found but did not reach significance (P = 0.1). This meta-analysis demonstrated that even with a similar union rate, PA could be a better option in treating Lisfranc complex joint injuries when compared to ORIF. There is a need for larger controlled sampled studies to research on this type of injuries.


Adrenal glands in beta-thalassemia major: magnetic resonance (MR) imaging features and correlation with iron stores.
This study aimed at describing the magnetic resonance (MR) imaging features of the adrenal glands in beta-thalassemic patients and at investigating the relation between adrenal and hepatic siderosis. Adrenal signal intensity (SI) was retrospectively assessed on abdominal MR studies of 35 patients with beta-thalassemia major undergoing quantification of hepatic siderosis and 12 healthy controls, using T1-(120/4/90), intermediate-(120/4/20), and T2*-(120/15/20) weighted GRE sequences. Adrenal SI was graded as grade 0 (normal SI on all sequences), grade 1 (hypointensity on T2* alone), or grade 2 (hypointensity on at least T2*). Adrenal size was measured in the thalassemic patients and compared with normative data. Liver-to-muscle (L/M) SI ratios, expressing hepatic siderosis, were estimated on each sequence. Serum ferritin levels were recorded. Adrenal hypointensity (grades 1 and 2) was noted in 24/35 (68.6%) patients. L/M ratios correlated significantly with adrenal SI in all sequences. Patients with grade 1 and grade 2 adrenal SI had significantly decreased L/M ratios compared with grade 0. Serum ferritin correlated significantly with L/M values but not with adrenal SI. Adrenal size was within normal limits. Diffuse hypointensity in normal-sized adrenals is a common MR finding in beta-thalassemic patients and correlates with the degree of hepatic siderosis.


Antidromically evoked facial nerve response.
Facial nerve electrodiagnostic tests that are currently available indirectly assess the severity of injury to the intratemporal facial nerve. Antidromic conduction testing is an alternate approach that, if feasible, could provide direct and immediate assessment of proximal facial nerve function. This possibility was tested in a guinea pig model, in which near-field (intracranial) and far-field (extradural) recording techniques were used to assess antidromically evoked facial nerve activity. Response characteristics, topographical distribution, and lesion effects suggest that the recorded potentials represent antidromic activation of the facial nerve. If response amplitude and/or latency can be correlated with the functional state of the nerve, antidromic testing may provide a useful means of assessing proximal facial nerve function in pathologic states.


Follow-up effects of a medical school course in human sexuality.
The effects of a course in human sexuality for a class of second-year male medical students are described. The course consists of two interacting components: a 2-day seminar and a 2-week didactic presentation. The purpose of the seminar is to develop humanistic understanding and tolerance of one's own and others' sexuality. The didactic presentation focuses on factual information. A variety of evaluation instruments were used, and students were tested precourse, postcourse, and at the end of 6 and 12 months. Results show a significant pre-post increase in tolerance in attitude and amount of knowledge. There appears to be some moderation in level of attitude and knowledge gain at the 6-months point, and significant increases from the precourse level to the 12-months point persist. Participants almost uniformly report personal benefit, with a significant number described greater satisfaction in their own sexual behaviour.