Painless destructive thyroiditis in a patient with resistance to thyroid hormone: a case report.
Resistance to thyroid hormone (RTH) usually features a syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH) without suppression of the typical high thyroid hormone levels. However, some patients with RTH show thyroid-stimulating hormone (TSH) suppression due to thyrotoxicosis. We report a case of painless thyroiditis in a patient with RTH that was misdiagnosed as Graves' disease because of TSH-suppressed thyrotoxicosis. A sixteen-year-old boy consulted a local general physician for fatigue. He had a goiter, and biochemical analysis showed TSH < 0.1 μIU/mL, free triiodothyronine (FT3) of 2.70 pg/mL, and free thyroxine (FT4) of 3.6 ng/dL. He was diagnosed with Graves' disease and was treated with 20 mg thiamazole. One year later, he was referred to the department of endocrinology because of SITSH. He was finally diagnosed with RTH due to the finding of a heterozygous missense mutation (methionine 334 threonine) in the thyroid hormone receptor β gene. Three years after cessation of thiamazole, his hyperthyroxinemia showed marked exacerbation with TSH suppression. We diagnosed him with painless destructive thyroiditis because of low technetium-99 m (Tc-99 m) uptake in the thyroid. Extreme hyperthyroxinemia was ameliorated, with a return to the usual SITSH levels, within 1 month without any treatment. The present case demonstrates that diagnosing RTH is difficult when patients show hyperthyroxinemia with complete suppression of TSH to undetectable levels, and the data lead to misdiagnosis of RTH as Graves' disease. The initial diagnosis is important, and Tc-99 m scintigraphy is useful for the differential diagnosis of thyrotoxicosis accompanying RTH.


Characterization and regional distribution of peptides derived from the vasoactive intestinal peptide precursor in the normal human brain.
To study the biosynthetic processing of the precursor for vasoactive intestinal peptide (prepro-VIP) in the human brain, we have developed antisera against the five functional domains of the precursor molecule: prepro-VIP 22-79, peptide histidine methionine (PHM), prepro-VIP 111-122, VIP, and prepro-VIP 156-170. The antisera were used in radioimmunoassays in combination with HPLC to identify and quantify the peptides in regions of the human brain. All five peptides were expressed, but mainly in nonequimolar ratios. In only three regions were the same amounts of VIP and PHM found; in the remaining areas the concentration of PHM was two-thirds that of VIP. The concentrations of prepro-VIP 22-79, prepro-VIP 111-122, and prepro-VIP 156-170 were considerably lower than the corresponding VIP concentrations, and the relative concentration of prepro-VIP 111-122 differed between cortical and subcortical areas. A small proportion of the VIP precursor followed a pathway in which the dibasic conversion site after PHM is not cleaved, as evidenced by the presence of a C-terminally extended form of PHM. Finally, it was found that the C-terminal lysine residue of prepro-VIP is not removed during processing. The findings indicate that differences in the posttranslational processing of prepro-VIP exist in subpopulations of neurons in the human brain.


[Pelger-Huet leukocyte anomaly. A clinical case of acquired and transient anomaly].
A survey of the relevant literature is followed by the presentation of a case of transient, acquired Pelger-Huët anomaly observed in a patient operated for Crohn's disease.


Effect of a forced diuresis on the distribution and excretion (via urine and bile) of 195mplatinum when given as 195mplatinum cis-dichlorodiammineplatinum(II).
195mPlatinum cis-dichlorodiammineplatinum(II) (195mPt cis-DDP) was injected iv with furosemide or mannitol into male Sprague-Dawley rats. The effect of such a diuresis on the distribution, excretion, and retention of cis-DDP was measured. The mannitol-treated animals had a significant increase in the urinary excretion of 196mPt over control animals for the first five 15-minute collection times and for the 24-hour cumulative urine for the 0.01-mg/kg dose. At the 6-mg/kg dose, only the first three 15-minute and 24-hour cumulative urine collections were significant. This increased excretion, however, did not affect tissue or blood concentrations of this agent. Furosemide did not affect the excretion of 195mPt. A biliary excretion of 195mPt given as 195mPt cis-DDP is documented. The excretion is biphasic, with a rapid phase followed by a slower protracted phase. Forced diuresis, if it affords renal protection, does so during the first 90 minutes of urinary excretion.


Semicarbazide-sensitive amine oxidase (SSAO) of the rat aorta. Interactions with some naturally occurring amines and their structural analogues.
The influence of a number of naturally occurring amines and their structural analogues has been examined on the metabolism of radiolabelled benzylamine (BZ) by the membrane bound semicarbazide-sensitive amine oxidase (SSAO) of the rat aorta. Only primary monoamines were effective in reducing the deamination of BZ. In the phenylethylamine series, addition of hydroxyl groups to the benzene ring decreased their potency as inhibitors while addition of a hydroxyl group at the beta position increased the inhibitory potency. Stereoselectivity of action was shown with octopamine, the L-isomer being the more active form. Kinetic analysis of these interactions showed predominantly competitive inhibition and kynuramine had the lowest Ki of 5.4 microM. The aliphatic monoamines, isoamylamine and isobutylamine both competed with BZ. 5-Hydroxytryptamine (5-HT) was the only amine that inhibited non-competitively. Direct evidence for metabolism by SSAO of some of the competing amines such as isoamylamine, phenylethylamine, tyramine and tryptamine was obtained by fluorimetric or radiochemical assays. The inhibitors clorgyline and (E)-2-(3',4'-dimethoxyphenyl)-3-fluoroallylamine (MDL 72145) were used to characterise the amine oxidase activity responsible for the deamination. Octopamine and phenylethanolamine (PeOH) were not SSAO substrates and inhibited BZ metabolism in the fluorimetric assay. It is possible that the activity of SSAO is controlled by octopamine released from sympathetic nerve endings or 5-HT released from platelets.


The surface antigens of Campylobacter sputorum subspecies mucosalis.
Campylobacter sputorum subsp mucosalis is the vibrio associated with a group of porcine enteropathies in which it is believed the primary lesion is that of adenomatosis. The surface antigens of mucosalis were investigated and individual factor sera were produced; these were used to examine a range of field strains from adenomatosis, necrotic enteritis, regional ileitis and proliferative haemorrhagic enteropathy. Neither these not sequential isolants from the same farm showed any distinctive antigenic pattern and it is suggested that changes in the surface antigens take place during the intracellular existence of the organism.


Ouabain potentiation of Ca release from fragmented cardiac sarcoplasmic reticulum from isolated cat heart.
The present study was performed to determine the effect of ouabain on Ca release from fragmented sarcoplasmic reticulum (FSR) isolated from cat cardiac muscles. The results clearly demonstrate that ouabain potentiates the Ca release from FSR by changing the ionic environment.


Author Correction: Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR.
The version of this paper originally published cited a preprint version of ref. 12 instead of the published version (Proc. Natl. Acad. Sci. USA 115, 5594-5599; 2018), which was available before this Nature Methods paper went to press. The reference information has been updated in the PDF and HTML versions of the article.


Paradoxical effects of oxytocin and vasopressin on basal prolactin secretion and the estrogen-induced prolactin surge.
The roles of oxytocin (OT) and vasopressin (AVP) on both basal and estrogen-induced prolactin (PRL) secretion were examined. Adult female Sprague-Dawley rats that were ovariectomized for 3 weeks and received estrogen treatment for 1 week were used. Intravenous administration of hormones and serial blood sampling were accomplished through indwelling intraatrial catheters which were implanted two days before. Plasma PRL levels were measured by radioimmunoassay. Oxytocin at a dose of 20 micrograms/rat stimulated a moderate PRL release in the morning and lower doses (5 and 10 micrograms) were without effect. Vasopressin was most effective at a dose of 5 micrograms/rat in stimulating PRL release, while consecutive injections of higher doses (10 and 20 micrograms) were less effective. In contrast, TRH, ranging from 1 to 8 micrograms/rat, induced a dose-dependent increases in PRL secretion. Using the effective dosages determined from the morning studies, repeated injections of either OT, AVP or their specific antagonists MPOMeOVT [( 1-(beta-mercapto-beta, beta-cyclopentamethylene propanoic acid), 2-(O-methyl)tyrosine, 8-ornithine]-vasotocin) and d (CH2)5Tyr(Me)AVP ([1-(beta-mercapto-beta, beta-cyclo-pentamethylene propionic acid), 2-(O-methyl)tyrosine, 8-arginine]-vasopressin), were given hourly between 1300 to 1800 h and blood samples were obtained hourly from 1100 to 1900 h. It was found that either OT or AVP significantly reduced the afternoon PRL surge, while their antagonists were not as effective. When OT or AVP were administered together with their specific antagonists, the inhibitory effects of either hormone on PRL surge were reversed. Thus it is concluded that both OT and AVP assume a non-specific stress-like effect on PRL release, in which basal secretion is stimulated and surge secretion is inhibited.


Establishment of a simple living donor liver transplantation dog model using a two-step nonvenous bypass hepatectomy.
Dogs are an ideal model for studying living donor liver transplantation (LDLT). However, due to their poor tolerance to congestion and acidosis during portal vein blockage, current LDLT dog models with long operation times have high mortality. To address the issue, we designed a novel simplified operation with two-step nonvenous bypass (NVB) hepatectomy. Eighty dogs were evenly randomized to the living liver donor (LLD) or the recipient (LLR) groups. A standard lobectomy of I, II, and III lobes was performed in the LLD group. In the LLR group, first only I, II, and III lobes were resected using NVB; the residual lobes were resected off just after donor lobes were implanted. For the LLD group, the operation time was 172.67 ± 20.98 minutes, amount of blood loss was 71.39 ± 13.59 mL, and 2-week survival rate was 85.00%. For the LLR group, the operation time was 251.61 ± 22.87 minutes, amount of blood loss was 220.00 ± 96.40 mL, amount of blood transfusion was 163.89 ± 44.74 mL, and 48-hour survival rate was 77.14%. In the LLR group, the mean arterial and central venous pressures decreased after organ implantion, but gradually recovered to normal levels after surgery. The liver function biochemical parameters recovered to preoperational levels after 14 days in the LLD group; in the LLR group, they gradually increased during 48 hours after operation. The present method with two-step NVB hepatectomy can be used efficiently and safely for establishing LDLT dog model.


Free energy calculations applied to membrane proteins.
Selected applications of free energy calculations to the realm of membrane proteins are reviewed. The theoretical underpinnings of these calculations are described, focusing on free energy perturbation and the use of thermodynamic integration to determine free energy changes along well-delineated order parameters. Current strategies for improving the reliability of free energy calculations, while making them somewhat more affordable are outlined. Application of the free energy methodology to understand the structure and function of membrane proteins is illustrated in three concrete examples: The binding of an agonist ligand to a G protein-coupled receptor, the assisted transport of a small permeant through a membrane channel, and the recognition and association of transmembrane alpha-helical domains.


Metabolic characteristics and urine albumin excretion rate in relation to pubertal maturation in Type 1 diabetes.
The objective of this study was to assess the impact of pubertal maturation on urinary albumin excretion rate (AER) and persistent microalbuminuria, and to identify possible factors affecting urinary AER in adolescents with Type 1 diabetes. One hundred patients aged 9.1-19.0 years with a duration of diabetes of >2 years out of 138 eligible adolescents with Type 1 diabetes from an outpatient diabetes clinic participated in the study, together with 100 healthy controls. A timed overnight urine sample was collected in the hospital, where all the adolescents stayed for 22-24 h, and microalbuminuria was confirmed with at least one consecutive positive sample (AER 20-200 microg/min). The prevalence of persistent microalbuminuria was 6%. All the patients affected were girls: one prepubertal (T I), one in late puberty (T IV) and three postpubertal (T V). These patients had significantly higher HbA(1c) levels than did the normoalbuminuric girls with Type 1 diabetes. Neither duration of diabetes nor age differed significantly between the two groups. AER increased more conspicuously with pubertal maturation in the boys with Type 1 diabetes than in the control boys, while the girls with diabetes had significantly higher body mass index (BMI) and serum total and LDL cholesterol than did the control girls. HbA(1c) was independently associated with AER in a multiple regression model. Diastolic blood pressure (BP) was elevated in both girls and boys with Type 1 diabetes as compared with healthy adolescents, while no difference was observed between the patients with microalbuminuria and normoalbuminuria. Persistent microalbuminuria was mainly observed in late puberty and after puberty among adolescents with Type 1 diabetes. Female sex and poor metabolic control predispose such adolescents to this condition during pubertal maturation.


Voiding function improves under long-term testosterone treatment (TTh) in hypogonadal men, independent of prostate size.
Functional hypogonadism is a condition in which some, but not all, older men have low testosterone levels. Rather than chronological age per se, the causality of hypogonadism includes obesity and impaired general health (e.g., metabolic syndrome). An association between testosterone deficiency and lower urinary tract symptoms (LUTS) has been reported, yet due to prostate safety concerns, men with severe LUTS (IPSS score > 19) have invariably been excluded from entering testosterone trials. Irrespective, exogenous testosterone has not been demonstrated to cause de novo or worsen mild to moderate LUTS. This study investigated whether long-term testosterone therapy (TTh) could have a protective effect on improving the symptoms of LUTS in hypogonadal men. However, the exact mechanism by which testosterone exerts is beneficial effect remains uncertain. In this study 321 hypogonadal patients with an average age of 58.9 ± 9.52 years received testosterone undecanoate in 12-week intervals for 12 years. One hundred and forty-seven of these males had the testosterone treatment interrupted for a mean of 16.9 months before it was resumed. Total testosterone, International Prostate Symptom Scale (IPSS), post-voiding residual bladder volume and aging male symptoms (AMS) were measured over the study period. Prior to TTh interruption, it was observed that testosterone stimulation improved the men's IPSS, AMS and post-voiding residual bladder volume, while their prostate volume significantly increased. During the TTh interruption, there was a significant worsening in these parameters, although the increase in prostate volume continued. When TTh was resumed, these effects were reversed, implying that hypogonadism may require lifelong treatment.


Effect of surfactant-associated protein-A (SP-A) on the activity of lipid extract surfactant.
The properties of natural bovine surfactant and its lipid extract have been examined with a pulsating bubble surfactometer which assesses the ability of surfactant lipids to adsorb to the air/liquid interface and reduce the surface tension to near 0 dynes/cm during dynamic compression. Studies conducted at 1 mg/ml phospholipid revealed that the surface activity (i.e., the ability to produce low surface tensions) of lipid extracts could be enhanced by incubating the sample at 37 degrees C for 120 min or by addition of CaCl2. In contrast, incubation at 37 degrees C only slightly improved the biophysical activity of natural surfactant and the addition of CaCl2 had a more modest effect than with lipid extracts. With 20 mM CaCl2, the surfactant activity of lipid extract surfactant was similar to that of natural surfactant. Incubation with EDTA reduced the biophysical activity of natural surfactant. Experiments in which increasing amounts of lipid extract were replaced by natural surfactant revealed that small amounts of natural surfactant enhanced the surfactant activity of lipid extract. The biophysical activity of lipid extract surfactant was also increased by the addition of soluble surfactant-associated protein-A (SP-A) (28-36 kDa) purified from natural bovine surfactant. These results indicate that SP-A (28-36 kDa) improves the surfactant activity of lipid extracts by enhancing the rate of adsorption and/or spreading of phospholipid at the air/liquid interface resulting in the formation of a stable lipid monolayer at lower bulk concentrations of either phospholipid or calcium.


Inflammatory response and blood hypercoagulable state induced by low level co-exposure with silica nanoparticles and benzo[a]pyrene in zebrafish (Danio rerio) embryos.
Given the severe situation of world-wide particulate matter air pollution, it is urgent to explore the combined effects of particulate matter components on cardiovascular system. Using zebrafish model, this study was aimed to determine whether the low level co-exposure to silica nanoparticles (SiNPs) and benzo[a]pyrene (B[a]P) had a pronounced cardiovascular toxicity than the single exposure to either SiNPs or B[a]P alone. The FTIR and TGA analysis showed that the co-exposure system possessed of high absorption and thermal stability. Embryos exposed to SiNPs or B[a]P alone did not show cardiac toxicity phenotype at the NOAEL level. However, embryos co-exposed to SiNPs and B[a]P exhibited pericardial edema and bradycardia. While ROS generation remained unaffected, the co-exposure induced significant neutrophil-mediated inflammation and caused erythrocyte aggregation in caudal vein of embryos. Microarray analysis and STC analysis were performed to screen the cardiovascular-related differential expression genes and the expression trend of genes in each group. The co-exposure of SiNPs and B[a]P significantly enhanced the expression of proinflammatory and procoagulant genes. Moreover, the co-exposure markedly increased the phosphorylated AP-1/c-Jun and induced TF expression, but not NF-κB p65. This study for the first time demonstrated the inflammatory response and blood hypercoagulable state were triggered by the combination of SiNPs and B[a]P at low level exposure.


Role of leukotrienes in hydrochloric acid-induced gastric lesions in rats.
This study was designed to clarify the role of leukotrienes (LTs) in 0.6 N hydrochloric acid (HCl)-induced gastric lesions. In rats given 1 ml of 0.6 N HCl intragastrically, severe hemorrhagic lesions were observed in the gastric corpus mucosa 15 min, and 1, 3, and 5 hr after HCl administration. In the control rats treated with physiological saline, LTs in gastric mucosa were not observed throughout the experiments. Peptide LT contents (sum of LTC4 and LTD4) after 1 or 3 hr were increased to 13.2 +/- 2.9 ng/g tissue and 6.3 +/- 1.9, respectively, although peptide-LTs were not observed 15 min and 5 hr after HCl administration. Premedication with AA-861, a lipoxygenase inhibitor, decreased dose-dependently peptide LT contents 1 hr after HCl administration. Furthermore, gastric lesions caused by 0.6 N HCl were significantly prevented by 300 mg/kg of AA-861 3 hr after HCl administration, although the dose of AA-861 did not significantly prevent gastric lesions 1 hr after HCl administration. Administration of YM-638, a peptide LT antagonist, showed similar protective effects to AA-861 except inhibition of increase in LT levels after HCl administration. These results suggest that peptide LTs contribute to persistence of gastric lesions, although they might not participate in the onset of 0.6 N HCl-induced gastric lesions.


["Functional and anatomical organization of associative" cortical areas 7, 21 and 22 in monkeys. A study of the cortical projections from the pulvinar by means of HRP tracing technique (author's transl)].
The thalamic projections to the parietal and temporal associative areas (Brodmann's areas 7, 21 and 22) have been revealed by means of the retrograde axonal transport of horseradish peroxidase (HRP). The medial pulvinar (PM) was found to send afferents to the three studied areas. Labelled neurones of the PM appeared to be grouped in terms of their cortical target; indeed, neurones of origin of projection fibres to areas 7, 21 and 22 were respectively localized in the dorso-lateral, ventro-lateral and ventro-medial part of the PM. Although the multimodal sensory nature of the PM has been demonstrated by electrophysiological works, the function of PM neurones and the significance of their topographical repartition remain unknown. However PM could be involved in the transmission of specific sensory informations to the three associative areas 7, 21 and 22. Such an hypothesis is discussed according to the hitherto available data.


Race, ABO blood group, and venous thromboembolism risk: not black and white.
The rate of venous thromboembolism (VTE) has been reported to be higher in blacks compared to whites. Non-O blood groups have also been associated with a significantly higher VTE risk. Given that a higher proportion of blacks have O blood group, one might have expected that black individuals would have fewer VTEs. In this study, we analyzed race, sex, age, ABO or Rh blood group, and VTE risk in 60,982 black and white patients admitted over a span of 10 years. The overall occurrence of VTEs was 7.6%, higher in males (8.7% males vs. 7.2% females), higher in non-O blood groups (8.5% non-O vs. 6.9% O blood group), and increased with age (5.8% <65 years, 11.3% ≥65 years). No difference in VTE rate was noted with Rh antigen positivity. When stratified by age, VTE rate was consistently higher in blacks and non-O blood groups. No difference was detected among the various non-O blood groups. To assess the potential confounder of comorbidities, we stratified patients according to Charlson comorbidity score. In a subgroup of healthy patients with age-independent Charlson comorbidity scores of 0 (n = 28,387), blacks still had an increased VTE risk and this risk was still higher with increasing age and in those with non-O blood groups. We conclude that black race and non-O blood groups have increased VTE risk when stratified for age and that associated comorbidities do not explain these differences.


One-year patient outcomes based on lung morphology in acute respiratory distress syndrome: secondary analysis of LIVE trial.
Acute respiratory distress syndrome (ARDS) has different phenotypes and distinct short-term outcomes. Patients with non-focal ARDS have a higher short-term mortality than focal ones. The aim of this study was to assess the impact of the morphological phenotypes of ARDS on long-term outcomes. This was a secondary analysis of the LIVE study, a prospective, randomised control trial, assessing the usefulness of a personalised ventilator setting according to lung morphology in moderate-to-severe ARDS. ARDS was classified as focal (consolidations only in the infero-posterior part of the lungs) or non-focal. Outcomes were assessed using mortality and functional scores for quality of life at the 1-year follow-up. A total of 124 focal ARDS and 236 non-focal ARDS cases were included. The 1-year mortality was higher for non-focal ARDS than for focal ARDS (37% vs. 24%, p = 0.012). Non-focal ARDS (hazard ratio, 3.44; 95% confidence interval, 1.80-6.59; p < 0.001), age, McCabe score, haematological cancers, SAPS II, and renal replacement therapy were independently associated with 1-year mortality. This difference was driven by mortality during the first 90 days (28 vs. 16%, p = 0.010) but not between 90 days and 1 year (7 vs. 6%, p = 0.591), at which point only the McCabe score was independently associated with mortality. Morphological phenotypes had no impact on patient-reported outcomes. Lung morphologies reflect the acute phase of ARDS and its short-term impact but not long-term outcomes, which seem only influenced by comorbidities. NCT02149589; May 29, 2014.


Implication of inhaled nitric oxide for the treatment of critically ill COVID-19 patients with pulmonary hypertension.
This study aims to analyse whether inhaled nitric oxide (iNO) was beneficial in the treatment of coronavirus disease 2019 (COVID-19) patients with pulmonary hypertension. Five critically ill COVID-19 patients with pulmonary hypertension designated Cases 1-5 were retrospectively included. Clinical data before and after iNO treatment were serially collected and compared between patients with or without iNO treatment. The five cases experienced pulmonary artery systolic pressure (PASP) elevation (≥50 mmHg) at 30, 24, 33, 23, and 24 days after illness onset (d.a.o), respectively. Cases 1-3 received iNO treatment on the 24th, 13th, and 1st day after the first elevation of PASP, with concentrations varied from 10 to 20 ppm based on the changes of PASP and blood pressure for 10, 9, and 5 days, respectively. Upon iNO treatment, PASP of Cases 1 and 2 returned to normal on the 10th day and 1st day, and maintained between 50 and 58 mmHg in Case 3. Pa02 /Fi02 increased from 88 to 124, 51 to 118, and 146 to 244, respectively. SPO2 increased from 91% to 97% for Case 1 and maintained a high level above 97% for Case 2. Cardiac function remained normal in the three patients after treatment. Moreover, Cases 1 and 3 survived from severe acute respiratory syndrome coronavirus 2 infection, while Case 2 finally died on the 36th day after the first elevation of PASP due to severe complications. Both cases who did not receive iNO treatment experienced a sudden decrease of PASP and Pa02 /Fi02 due to right heart failure and then died. Inhaled nitric oxide treatment was beneficial in reducing and stabilizing the PASP and might also reduce the risk of right heart failure in COVID-19 with pulmonary hypertension.


Generalized pruritus preceding paraneoplastic neuropathy.
Paraneoplastic syndromes are a group of rare disorders involving non-metastatic systemic effects accompanying malignancies, and occur remotely from the tumor itself. Chronic pruritus lasting more than 6 weeks can be from paraneoplastic origin. A 65-year-old woman was admitted for generalized pruritus lasting for 1 month, despite treatment with prednisolone, levocetirizine and hydroxyzine. General examination was normal. Biological data and gastroscopy were normal. One month later, the patient was readmitted for worsening of her pruritus and walking impairment, revealing a severe sensory neuropathy. Blood anti-Hu antibodies returned positive at a level of 400 (normal <100). Bronchoscopy and bronchial biopsies revealed small-cell lung carcinoma. To our knowledge, the association of generalized pruritus and paraneoplastic neuropathy has been rarely reported. Our observation raises the question of a pathophysiological continuum between pruritus and neuropathy in a paraneoplastic context.


Replication study of the insulin receptor gene in migraine with aura.
We performed the first replication study for the reported association of the insulin receptor gene (INSR) with migraine with aura (MA). Two of 35 SNPs (rs1052371 and rs2860174) reached borderline significance (best uncorrected allelic p value of 0.052 for rs2860174) in stage 1 of our study (270 MA patients, 280 controls). As rs2860174 was 1 of the 5 SNPs with prior evidence of association, we also genotyped this SNP in our stage 2 sample (679 MA patients, 368 controls), and it was nonsignificant (allelic p value 0.478). The combined analysis of our samples showed just a nonsignificant trend for rs2860174 (p=0.1). However, the joint analysis of our study and the initial study reporting an association-including 1278 Caucasian MA patients and 1337 Caucasian controls altogether-displayed a significant allelic p value of 0.005. In conclusion, further association studies for rs2860174 with even larger numbers of individuals are required to exclude or confirm definitely a small effect of this SNP on migraine susceptibility.


The effect of varying sea salt concentration in the growth medium on the chemical composition of a purified membrane fraction from Planococcus citreus Migula.
Membrane preparations were prepared from cells of Planococcus citreus grown in the presence of three final concentrations of sea salt in a basic growth medium. The concentration of salt in the medium affects the amount of membrane in the cell. The three preparations were subjected to chemical analysis and no significant changes in chemical composition were seen as the salt concentration in the medium was increased. Values for the various components generally were within normal ranges and were similar to those of non-halophiles rather than extreme halophiles. The protein levels were slightly higher and it it cellular ion balance. Atomic absorption analysis of the major cations associated with the membranes showed that divalent ions were present in a 2:1 ratio with ...


Prenatal Depression: Screening and Referral for Women Who Are Low Income during Antenatal Care.
This study uses prenatal clinical chart reviews of 245 women who were screened for depression while receiving antenatal care services at an urban hospital-based clinic in Syracuse, New York. The results indicate that more than one half of the mothers who screened positive are not being adequately referred and followed-up on to ensure they are receiving proper treatment. Among the mothers who are not being successfully referred are women who are non-English speaking, facing multiple life stressors, and inadequately insured. Recommendations for colocating services that may ease the ongoing burdens of new motherhood are addressed.


Rhinomanometry in children.
During the period January 1982 to December 1985 nasal resistance (NR) was measured by computer-assisted 'head-out' plethysmography in 986 patients aged 4-18 years referred to the Airflow Laboratory at the Hospital for Sick Children, Toronto. Nasal resistance was found to decline with increasing age, and it was elevated in the presence of mucosal swelling, adenoid enlargement and other significant nasal pathology. Studies of variance on the equipment used indicated that in the assessment of NR results of the head-out volume displacement plethysmographic method of active posterior rhinometry were highly reproducible.


Epiphytic proliferation of Zymoseptoria tritici isolates on resistant wheat leaves.
The wheat pathogen Zymoseptoria tritici is capable of a long period of pre-invasive epiphytic growth. Studies have shown that virulent isolates vary in the extent, duration and growth form of this epiphytic growth, and the fungus has been observed to undergo behaviours such as asexual reproduction by budding and vegetative fusion of hyphae on the leaf surface. This epiphytic colonisation has been investigated very little during interactions in which an isolate of Z. tritici is unable to colonise the apoplast, as occurs during avirulence. However, avirulent isolates have been seen to undergo sexual crosses in the absense of leaf penetration, and it is widely accepted that the main point of distinction between virulent and avirulent isolates occurs at the point of attempted leaf penetration or attempted apoplastic growth, which fails in the avirulent case. In this work, we describe extensive epiphytic growth in three isolates which are unable or have very limited ability to invade the leaf, and show that growth form is as variable as for fully virulent isolates. We demonstrate that during certain interactions, Z. tritici isolates rarely invade the leaf and form pycnidia, but induce necrosis. These isolates are able to achieve higher epiphytic biomass than fully virulent isolates during asymptomatic growth, and may undergo very extensive asexual reproduction on the leaf surface. These findings have implications for open questions such as whether and how Z. tritici obtains nutrients on the leaf surface and the nature of its interaction with wheat defences.


Climate and genetic data enhancement using deep learning analytics to improve maize yield predictability.
Despite efforts to collect genomics and phenomics ('omics') and environmental data, spatiotemporal availability and access to digital resources still limit our ability to predict plants' response to changes in climate. Our goal is to quantify the improvement in the predictability of maize yields by enhancing climate data. Large-scale experiments such as the Genomes to Fields (G2F) are an opportunity to provide access to 'omics' and climate data. Here, the objectives are to: (i) improve the G2F 'omics' and environmental database by reducing the gaps of climate data using deep neural networks; (ii) estimate the contribution of climate and genetic database enhancement to the predictability of maize yields via environmental covariance structures in genotype by environment (G×E) modeling; and (iii) quantify the predictability of yields resulting from the enhancement of climate data, the implementation of the G×E model, and the application of three trial selection schemes (i.e. randomization, ranking, and precipitation gradient). The results show a 12.1% increase in predictability due to climate and 'omics' database enhancement. The consequent enhancement of covariance structures evidenced in all train-test schemes indicated an increase in maize yield predictability. The largest improvement is observed in the 'random-based' approach, which adds environmental variability to the model.


First Constraints on Nuclear Coupling of Axionlike Particles from the Binary Neutron Star Gravitational Wave Event GW170817.
Light axion fields, if they exist, can be sourced by neutron stars due to their coupling to nuclear matter, and play a role in binary neutron star mergers. We report on a search for such axions by analyzing the gravitational waves from the binary neutron star inspiral GW170817. We find no evidence of axions in the sampled parameter space. The null result allows us to impose constraints on axions with masses below 10^{-11} eV by excluding the ones with decay constants ranging from 1.6×10^{16} to 10^{18} GeV at a 3σ confidence level. Our analysis provides the first constraints on axions from neutron star inspirals, and rules out a large region in parameter space that has not been probed by the existing experiments.


Root plasma membrane transporters controlling K+/Na+ homeostasis in salt-stressed barley.
Plant salinity tolerance is a polygenic trait with contributions from genetic, developmental, and physiological interactions, in addition to interactions between the plant and its environment. In this study, we show that in salt-tolerant genotypes of barley (Hordeum vulgare), multiple mechanisms are well combined to withstand saline conditions. These mechanisms include: (1) better control of membrane voltage so retaining a more negative membrane potential; (2) intrinsically higher H(+) pump activity; (3) better ability of root cells to pump Na(+) from the cytosol to the external medium; and (4) higher sensitivity to supplemental Ca(2+). At the same time, no significant difference was found between contrasting cultivars in their unidirectional (22)Na(+) influx or in the density and voltage dependence of depolarization-activated outward-rectifying K(+) channels. Overall, our results are consistent with the idea of the cytosolic K(+)-to-Na(+) ratio being a key determinant of plant salinity tolerance, and suggest multiple pathways of controlling that important feature in salt-tolerant plants.


Altered Structural and Functional Connectivity of Salience Network in Patients with Classic Trigeminal Neuralgia.
Classic trigeminal neuralgia (CTN) is a neuropathic pain disorder displaying spontaneously stabbing or electric shock-like paroxysms in the face. Previous research suggests structural and functional abnormalities in brain regions related to sensory and cognitive-affective dimensions of pain contribute to the pathophysiology of CTN. However, few studies to date have investigated how changes in whole-brain functional networks and white matter connectivity are related to CTN. We performed an independent component analysis to examine abnormalities in resting state functional connectivity of large-scale networks in 48 patients with CTN compared to 46 matched healthy participants. Then, diffusion tensor tractography was performed to test whether these alterations of functional connectivity in intrinsic networks were associated with impairment of the white matter tracts connecting them. Distinct patterns of functional connectivity were detected within default mode network, somatosensory network, and salience network (SN) in the CTN group when compared with healthy controls. Furthermore, abnormality of SN was negatively correlated with pain severity. In support of aberrant functional connectivity within SN, structural disintegration was observed in the white matter tract from left anterior insula (aIns) to left anterior cingulate cortex (ACC) in CTN. These results suggest that altered structural and functional connectivity between aIns and ACC may underpin the aberrant SN in patients with CTN and provide an alternative target for clinical interventions. PERSPECTIVE: This article presents distinctive abnormalities of functional and structural connectivity from aIns to ACC in the patients with CTN, which is associated with pain ratings. This measure could potentially provide an alternative target for clinicians to alleviate this type of intermittent and refractory pain.


Association between household conditions and diarrheal diseases among children in Turkey: a cohort study.
This aim of the present study was to estimate the frequency of diarrheal diseases among children as well as investigating the relationship between diarrheal diseases and household conditions and other factors. The study was performed over 12 month period in Binevler Health Center, Gaziantep, Turkey. Five health stations were selected by using a sampling technique with probability proportional to size, and all households with children under the age of 5 years were visited. A questionnaire on diarrhea, household conditions, socioeconomic status of the family and individual characteristics of the children was applied to the mothers by doctors. Three composite indices, including household conditions, socioeconomic status of the family and individual status of the children, were prepared and a classification was made as good, mild or poor in order to better evaluate the results of the study. Daily recordings of diarrheal disease symptoms were made by the parents and these records were collected every month for 1 year. The annual mean incidence of diarrheal diseases was found to be 1.09 per child per year (median = 1). The mean was higher in children with poor household conditions (1.48 +/- 0.12) and with poor individual status (1.48 +/- 0.14), compared with good household conditions (0.76 +/- 0.07) and good individual status (0.71 +/- 0.08). The mean was also higher in children aged between 6 and 11 months (1.51 +/- 0.18), whose father graduated from primary school or lower (1.34 +/- 0.09) and with parents having no habit of washing their hands before taking care of the child (2.00 +/- 0.33). Person-month and case-month incidence rates of diarrhea were calculated to be 8.56 and 9.12%, respectively. Household conditions, individual status, age, education level of fathers and parents' habit of washing hands before taking care of the child were major factors affecting the incidence of diarrhea.


Stoichiometry of bacterial anaerobic oxidation of elemental sulfur by ferric iron.
The conventional stoichiometry of the oxidation of elemental sulfur by ferric iron in Acidithiobacillus ferrooxidans was not in agreement with our experimental data in terms of ferrous iron and proton formation. Reaction modelling under the actual conditions of bacterial activity resulted in a different stoichiometry, where additional iron species participate in the process to affect the number of released protons. The suggested reaction equation may more accurately predict the intensity of environmental acidification during the anaerobic bioprocess.


Effects of a teen resident camp leadership program on changes in dimensions of self-control and interpersonal functioning, and their theory-based relationships.
Camp leadership programs have the potential of improving important psychosocial factors in teens who might eventually become counselors. Accepted behavioral theory might increase understandings of those changes so program training architectures can be improved. As part of larger-scale longitudinal research, participants (N = 129; 64 % female, Mage = 14.6 years, SD = 0.6) were selected by senior camp administrators for a structured leadership training program that required in-person conferences, viewing training videos every 2 weeks, obtaining ongoing mentoring from senior camp staff, and attending several weeks of summer camp where further training was provided. Validated surveys of proposed dimensions of self-control and interpersonal functioning were administered twice over 6 months to assess training program-associated changes. There were significant improvements in total self-control, self-control specifically related to coping, and family-related functioning. Although no demographic factor was associated with score change, baseline score was a significant predictor across measures. After controlling for baseline scores, stepwise multiple regression analyses indicated that higher self-control scores (i.e., planful behavior, coping efficacy, affective thought management) significantly predicted improvements in general, family, and peer-related functioning. Theory-based relationships between changes in self-control and interpersonal functioning enabled the identification of training program areas that might be targeted for improvement.


When Time Shifts the Boundaries: Isolating the Role of Forgetting in Children's Changing Category Representations.
In studies of children's categorization, researchers have typically studied how encoding characteristics of exemplars contribute to children's generalization. However, it is unclear whether children's internal cognitive processes alone, independent of new information, may also influence their generalization. Thus, we examined the role that one cognitive process, forgetting, plays in shaping children's category representations by conducting three experiments. In the first two experiments, participants (NExp1=37, Mage=4.02 years; NExp2=32, Mage=4.48 years) saw a novel object labeled by the experimenter and then saw five new objects with between one and five features changed from the learned exemplar. The experimenter asked whether each object was a member of the same category as the exemplar; children saw the five new objects either immediately or after a five-minute delay. Children endorsed category membership at higher rates at immediate test than at delayed test, suggesting that children's category representations became narrower over time. In Experiment 3, we investigated forgetting as a key mechanism underlying the narrowing found in Experiments 1 and 2. We showed participants (NExp3=34, Mage=4.20 years) the same exemplars used in Experiments 1 and 2; then, either immediately or after a five-minute delay, we showed children seven individual object features and asked if each one had been part of the exemplar. Children's accuracy was lower after the delay, showing that they did indeed forget individual features. Taken together, these results show that forgetting plays an important role in changing children's newly-learned categories over time.


'With this study, we have hope that something is coming': community members' perceptions of HIV cure-related research in Durban, South Africa - a qualitative focus group study.
Developing a cure for HIV remains a global scientific priority. In 2022, the Females Rising through Education, Support and Health (FRESH) cohort launched an HIV cure-related trial involving an analytical treatment interruption (ATI) in Durban, South Africa. To explore community perspectives about HIV cure-related research. Between July-August 2022, we conducted three focus groups with community members. We transcribed audio recordings verbatim and used content analysis to analyze the data. Twenty community members (13 women and 7 men) participated in three focus groups (HIV status not included). Participants viewed HIV cure-related research as a way to address the issue of defaulting on (not taking) HIV treatment. Participants expressed hesitancy around ATIs, since these contradict longstanding treatment adherence messages. Participants shared concerns around the risk of side effects from experimental interventions balanced against potential efficacy. They advocated for trial participants to have the right to decide whether to inform their sex partners about their HIV status and ATI participation, rather than research teams making disclosure mandatory. Focus group participants also emphasized the importance of using simple language to explain HIV cure-related research. With HIV cure trials set to launch across Africa in the future, there is a critical need to better understand and respond to local community needs and preferences and to adopt this as standard practice prior to regional trial implementation.


High mobility group box 1 and homocysteine as preprocedural predictors for contrast-induced acute kidney injury after percutaneous coronary artery intervention.
High mobility group box 1 (HMGB1) and homocysteine (Hcy) play important roles in contrast-induced acute kidney injury (CI-AKI). We compared HMGB1 to Hcy as preprocedural predictors for CI-AKI in coronary artery disease (CAD) patients after percutaneous coronary artery intervention (PCI). We included 257 eligible patients who were categorized into CI-AKI ( +) and CI-AKI ( -) group. The differences in clinical characteristics and biochemical indexes between two groups were analyzed. We observed that thirty-eight (14.8%) of 257 eligible CAD patients developed CI-AKI. HMGB1 (14.65 [11.13-24.89] vs 10.88 [7.94-13.23], p < 0.001) and Hcy (14.07 [12.07-17.31] vs 12.09 [10.71-13.47], p < 0.001) increased significantly in CI-AKI ( +) group. Both age (r = 0.210, p = 0.001), serum creatinine (r = 0.509, p < 0.001), eGFR (r = - 0.459, p < 0.001) and Hcy (r = 0.531, p < 0.001) were significantly correlated with HMGB1. Among all patients, HMGB1 (OR 1.181, 95% CI 1.081-1.290, p < 0.001) and Hcy (OR 1.260, 95% CI 1.066-1.489, p = 0.007) were independent predictors for the development of CI-AKI. We built the propensity score matching (PSM) using 38 pairs of patients. After adjustment, HMGB1 (OR 1.169, 95% CI 1.035-1.322, p = 0.012) and Hcy (OR 1.457, 95% CI 1.064-1.997, p = 0.019) were also independent predictors for the development of CI-AKI. Both HMGB1 (AUC: 0.704, 95% CI: 0.588-0.819, p = 0.002) and Hcy (AUC: 0.708, 95% CI: 0.593-0.823, p = 0.002) had predictive values for CI-AKI. There is a significant positive association between HMGB1 and Hcy in CAD patients. Both HMGB1 and Hcy are potential preprocedural predictors of CI-AKI after PCI.


Circulating sclerostin and estradiol levels are associated with inadequate response to bisphosphonates in postmenopausal women with osteoporosis.
The biological mechanisms associated with an inadequate response to treatment with bisphosphonates are not well known. This study investigates the association between circulating levels of sclerostin and estradiol with an inadequate clinical outcome to bisphosphonate therapy in women with postmenopausal osteoporosis. This case-control study is based on 120 Spanish women with postmenopausal osteoporosis being treated with oral bisphosphonates. Patients were classified as adequate responders (ARs, n=66, mean age 68.2±8 years) without incident fractures during 5 years of treatment, or inadequate responders (IRs, n=54, mean age 67±9 years), with incident fractures between 1 and 5 years of treatment. Bone mineral density (DXA), structural analysis of the proximal femur and structural/fractal analysis of the distal radius were assessed. Sclerostin concentrations were measured by ELISA and 17β-estradiol levels by radioimmunoassay based on ultrasensitive methods. In the ARs group, sclerostin serum levels were significantly lower (p=0.02) and estradiol concentrations significantly higher (p=0.023) than in the IRs group. A logistic regression analysis was performed, including as independent variables in the original model femoral fracture load, 25 hydroxyvitamin D, previus history of fragility fracture, sclerostin and estradiol. Only previous history of fragility fracture (OR 14.04, 95% CI 2.38-82.79, p=0.004) and sclerostin levels (OR 1.11, 95% CI 1.02-1.20, p=0.011), both adjusted by estradiol levels remained associated with IRs. Also, sclerostin concentrations were associated with the index of resistance to compression (IRC) in the fractal analysis of the distal radius, a parameter on bone microstructure. Sclerostin and estradiol levels are associated with the response to bisphosphonate therapy in women with postmenopausal osteoporosis.


Complete genome sequence of the archetype bile acid 7α-dehydroxylating bacterium, Clostridium scindens VPI12708, isolated from human feces, circa 1980.
Clostridium scindens strain VPI12708 serves as model organism to study bile acid 7α-dehydroxylating pathways. The closed circular genome of C. scindens VPI12708 was obtained by PacBio sequencing. The genome is composed of 3,983,052 bp, with 47.59% G + C, and 3,707 coding DNA sequences are predicted.


Filter performance of n99 and n95 facepiece respirators against viruses and ultrafine particles.
The performance of three filtering facepiece respirators (two models of N99 and one N95) challenged with an inert aerosol (NaCl) and three virus aerosols (enterobacteriophages MS2 and T4 and Bacillus subtilis phage)-all with significant ultrafine components-was examined using a manikin-based protocol with respirators sealed on manikins. Three inhalation flow rates, 30, 85, and 150 l min(-1), were tested. The filter penetration and the quality factor were determined. Between-respirator and within-respirator comparisons of penetration values were performed. At the most penetrating particle size (MPPS), >3% of MS2 virions penetrated through filters of both N99 models at an inhalation flow rate of 85 l min(-1). Inhalation airflow had a significant effect upon particle penetration through the tested respirator filters. The filter quality factor was found suitable for making relative performance comparisons. The MPPS for challenge aerosols was <0.1 mum in electrical mobility diameter for all tested respirators. Mean particle penetration (by count) was significantly increased when the size fraction of <0.1 mum was included as compared to particles >0.1 mum. The filtration performance of the N95 respirator approached that of the two models of N99 over the range of particle sizes tested ( approximately 0.02 to 0.5 mum). Filter penetration of the tested biological aerosols did not exceed that of inert NaCl aerosol. The results suggest that inert NaCl aerosols may generally be appropriate for modeling filter penetration of similarly sized virions.


Genome-scale definition of the transcriptional programme associated with compromised PU.1 activity in acute myeloid leukaemia.
Transcriptional dysregulation is associated with haematological malignancy. Although mutations of the key haematopoietic transcription factor PU.1 are rare in human acute myeloid leukaemia (AML), they are common in murine models of radiation-induced AML, and PU.1 downregulation and/or dysfunction has been described in human AML patients carrying the fusion oncogenes RUNX1-ETO and PML-RARA. To study the transcriptional programmes associated with compromised PU.1 activity, we adapted a Pu.1-mutated murine AML cell line with an inducible wild-type PU.1. PU.1 induction caused transition from leukaemia phenotype to monocytic differentiation. Global binding maps for PU.1, CEBPA and the histone mark H3K27Ac with and without PU.1 induction showed that mutant PU.1 retains DNA-binding ability, but the induction of wild-type protein dramatically increases both the number and the height of PU.1-binding peaks. Correlating chromatin immunoprecipitation (ChIP) Seq with gene expression data, we found that PU.1 recruitment coupled with increased histone acetylation induces gene expression and activates a monocyte/macrophage transcriptional programme. PU.1 induction also caused the reorganisation of a subgroup of CEBPA binding peaks. Finally, we show that the PU.1 target gene set defined in our model allows the stratification of primary human AML samples, shedding light on both known and novel AML subtypes that may be driven by PU.1 dysfunction.


Pharmacologic, nonhormonal treatment of impotence. Evaluation of associated factors.
A group of impotent patients previously treated with Strychiomel was evaluated. Strychiomel is a compound of three drugs, yohimbine, thioridazine (Mellaril), and strychnine sulfate, each of which has a specific effect. The results suggest that the compound drug may be beneficial in the majority of patients (66.7%) when impotence occurs without hormonal or severe vascular or psychologic problems. Other factors such as age or presence of other simultaneous diseases do not appear to be significant when treatment with this multiaction drug (Strychiomel) is utilized.


The acromiohumeral distance and the subacromial clearance are correlated to the glenoid version.
The acromiohumeral distance (ACHD) is a radiographic parameter for evaluating the presence of a rotator cuff rupture. Previous investigations have demonstrated that several factors may influence the magnitude of the acromiohumeral distance, but glenoid version has not yet been considered. Our hypothesis was that there is a direct correlation between glenoid version and acromiohumeral distance as well as subacromial clearance. Four right glenohumeral joints from adult fresh cadavers were anatomically dissected to the level of the rotator cuff. After fixation to a board and positioning of the humeral head in neutral position, an osteotomy of the glenoid neck was carried out and the version was altered in steps of 5°. The ACHD as well as the subacromial clearance (SAC) were measured for every degree of glenoid version. The ACHD increased with increased anteversion and consistently decreased with increased retroversion of the glenoid. The SAC also depended on glenoid version. Neutral version was associated with a minimal clearance under the anterior third of the acromion, retroversion transferred the minimal SAC posteriorly and anteversion transferred minimal SAC under the coracoacromial ligament. Our results indicate that glenoid version correlates directly with the magnitude of ACHD and SAC. Therefore, variations of glenoid version can lead to false interpretations of cuff integrity. Biomechanical investigation. Not possible to define.


Design, synthesis and pharmacological evaluation of hybrid molecules out of quinazolinimines and lipoic acid lead to highly potent and selective butyrylcholinesterase inhibitors with antioxidant properties.
A set of hybrid molecules were synthesized out of lipoic acid, alpha,omega-diamines of different lengths serving as spacers, and cholinesterase (ChE) inhibiting [2,1-b]quinazolinimines. Depending on the length of the alkylene spacer the amide hybrids are inhibitors of acetylcholinesterase (AChE) with inhibitory activities of 0.5-4.6microM and inhibitors of butyrylcholinesterase (BChE) with activities down to 5.7nM, therefore greatly exceeding the inhibitory activities of the parent quinazolinimines by factors of up to 1000. Due to increasing activity at BChE with increasing length of the alkylene spacer approximately 100-fold selectivity toward BChE is reached with a hepta- and an octamethylene spacer. Kinetic measurements reveal competitive and reversible inhibition of both ChEs by the hybrids. Furthermore, cell viability and antioxidant activity (using the ORAC-fluorescein assay) of several hybrids were evaluated, showing cytotoxicity at concentrations from 3.7 to 10.2microM and antioxidant properties are in the range of 0.4-0.8 Trolox equivalents (lipoic acid=0.6).


After "Hello" with a wounded warrior: A student journey.
The article describes the journey of a terror-stricken student growing into an adept healthcare provider; representing courageous personal and professional growth after a "Hello" in a nursing school immersion experience. The journey includes the student's emotional maturity and courage, recognizing the uniqueness of military culture, realizing the magnitude of the patient's losses, ascertaining patient concerns, personal recovery goals and long-term support network. Together recovery milestones are recognized and achieved. The article underscores the importance of nurse education in facilitating student's effective nurse-patient communication techniques considering diverse cultural elements, and consistently applying these theoretical concepts into practice. Assignments geared toward a holistic patient perspective can serve to develop student leadership progress toward becoming informed and engaged citizens, enlarging worldviews and a heightened awareness of relevant global issues, and spark passion related to national policy reform. Commitment to professional ownership of personal and professional growth throughout nursing school leads to positive transitions as a seasoned healthcare provider.


Chronic Lymphocytic Leukemia in the Elderly: Epidemiology and Proposed Patient-Related Approach.
Chronic lymphocytic leukemia (CLL) occurs primarily in the elderly, and the majority of deaths attributable to CLL occur in persons 65 years of age or older. The greater number of comorbidities and reduced functionality associated with aging have also made successful treatment of CLL in the elderly more difficult. The authors reviewed current epidemiology and guidelines for treatment of CLL, as well as recently approved therapies and studies of physiological aging. Determination of physiological age and performance of a thorough geriatric assessment play critical roles in the selection of optimal therapeutic approaches for older patients diagnosed with CLL. Older age, expressed via a frailty index, is a prognostic factor for poorer outcome in patients with CLL. However, several novel treatment options may result in reduced mortality and lessened treatment-related toxicity in older CLL patients.


Expression of heme oxygenase gene in rat and human liver.
Developmental changes of microsomal heme oxygenase were studied. In human fetal liver, the enzyme activity was 8 times higher than that detected in the adult liver. On the other hand, adult livers contained 4 times more cytochrome P450 than fetal livers. Elevated heme oxygenase activity in fetal liver was not due to modulators present in the microsomes. Similar to human, rat fetal liver also contained high enzyme activity which appeared to be regulated at the transcriptional level. Hybridization analysis of rat liver RNAs with cDNA for rat heme oxygenase revealed that the level of mRNA for the enzyme was 3-fold higher in the fetus than in the adult. The low cytochrome P450 content may be due in part to the high heme oxygenase activity in fetal livers.


Elicitation of sorbitol accumulation in cultured human proximal tubule cells by elevated glucose concentrations.
The human proximal tubule (HPT) is the characteristic site within the kidney that mediates absorption of glucose. This study was designed to determine whether cultured HPT cells would respond to a hyperglycemic environment through activation of the polyol pathway. The results of this study clearly indicate that exposure of the HPT cells to an extracellular glucose concentration greater than or equal to 11 mM results in substantial intracellular accumulation of sorbitol. This accumulation is inhibited by approximately 70% by treatment with 100 microM sorbinil. When cells growing 24 h on 27.5 mM glucose were changed to medium containing 5.5 mM glucose, sorbitol concentration returned to the control level within 12 h. The activity of aldose reductase was increased by a factor of 1.6 by exposure to elevated glucose concentrations, and the relative reactivity of the enzyme with glucose as substrate was approximately 0.1 compared with that of glyceraldehyde as substrate. Together, these results indicate that cultured cells derived from the HPT undergo activation of the polyol pathway when exposed to a hyperglycemic environment.


Exogenous Pseudomonas endophthalmitis: a cause of lens enucleation.
Pseudomonas aeruginosa eye infection, although uncommon, may be a devastating disease if not recognised and treated appropriately, especially in premature infants. The case is presented of a premature baby who lost her right eye from invasive exogenous Ps aeruginosa eye infection.


A randomised study of the effects of osmolality and heparin with hydrocortisone on thrombophlebitis in peripheral intravenous nutrition.
Intravenous nutrition administered via the central route incurs both the risks of catheter insertion and catheter related sepsis. Peripheral intravenous nutrition avoids these risks but is associated with a high risk of thrombophlebitis. We undertook a study to look at the incidence of thrombophlebitis caused by the infusion of a) a 'ready to use' mixture (Vitrimix KV) with an osmolality of 1130 mOsmol/kg, b) Vitrimix KV plus heparin and hydrocortisone, and c) a feed, with an osmolality of 700 mOsmol/kg, with heparin and hydrocortisone, to investigate the effects of the addition of heparin and hydrocortisone and the effect of osmolality on the incidence of thrombophlebitis. The addition of heparin (500 u/l) and hydrocortisone (5 mg/l) to Feed A significantly reduced the daily risk of thrombophlebitis from 0.43 to 0.11 episodes per patient, p < 0.01. A reduction in the osmolality resulted in a further fall in the incidence of thrombophlebitis to 0.04 episodes per patient with a significant increase in the median life span of the cannula from 26 h to 86 h, p < 0.02. Our data show that a low incidence of thrombophlebitis can be achieved by the use of a low osmolality feed with heparin and hydrocortisone. It is recommended that peripheral intravenous nutrition be used in patients who require nutritional support for less than 10 days.


The catadromous teleost Anguilla japonica has a complete enzymatic repertoire for the biosynthesis of docosahexaenoic acid from α-linolenic acid: Cloning and functional characterization of an Elovl2 elongase.
The Japanese eel Anguilla japonica is a catadromous fish species with considerable farming scale. Previous studies showed that dietary α-linolenic acid (18:3n-3) and linoleic acid (18:2n-6) satisfied essential fatty acid requirements in eel, which suggested that Japanese eel should have a complete pathway for the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFA). However, existing knowledge was insufficient to explain the molecular basis of LC-PUFA biosynthetic capacity in eel. In order to further characterize this pathway in eel, a full-length cDNA of a putative fatty acyl elongase was isolated, with the ORF encoding a protein with 294 amino acids. The putative elongase displayed high homology to Elovl2 of other teleosts. Functional characterization by heterologous expression in yeast showed the protein product of the cDNA had high activity towards C20 and C22 PUFA substrates and low activity towards C18 PUFA substrates, characteristic of Elovl2 elongases. Tissue distribution of the elovl2 mRNA showed highest expression in brain and eyes, which was different from freshwater and anadromous species. This may reflect an important role for this enzyme in the in situ endogenous biosynthesis of docosahexaenoic acid (DHA) in neural tissues in eel. This is the first report of an Elovl2 in a catadromous teleost and demonstrates that Japanese eel has a complete enzyme repertoire required for the endogenous biosynthesis of DHA via the Sprecher pathway. These data have increased our knowledge of the diversity of LC-PUFA biosynthesis in vertebrates, and provided further insight into the regulatory mechanisms of LC-PUFA biosynthesis in teleost fish.


High-resolution anatomic, diffusion tensor, and magnetization transfer magnetic resonance imaging of the optic chiasm at 3T.
To evaluate techniques for anatomical and physiological imaging of the intracranial optic nerve (ON), optic chiasm (OC), and optic tract (OT) at 3T with the aim of visualizing axonal damage in multiple sclerosis (MS). Imaging was performed on a 3T scanner employing a custom-designed head coil that consisted of a coil array with four coils (30 x 30 cm(2)). Oblique fast spin echo (FSE) images, magnetization transfer (MT)-enhanced 3D gradient-echo (GRE) time-of-flight (TOF) images, and line scan diffusion images (LSDI) were obtained. Full diffusion tensor (DT) analysis was performed, and apparent diffusion coefficient (ADC), fractional anisotropy (FA), and fiber direction maps were obtained. FSE anatomic images were obtained with an in-plane resolution of 0.39 x 0.52 mm(2). The in-plane resolution of the MT and LSDI images was 0.78 x 0.78 mm(2). The OC, intracranial ON, and OT can be seen on these images. The dominant fiber orientations in the OC, ON, and OT, as derived from the DT images, are displayed. This study shows that by using 3T and a custom-designed, four-channel head coil, it is possible to acquire high-resolution anatomical and physiological images of the OC, ON, and OT. The pilot results presented here pave the way for imaging the anterior visual pathway in patients with MS.


Comparative study between topical tranexamic acid alone versus its combination with autologous platelet rich plasma for treatment of melasma.
Tranexamic acid is a promising drug for melasma treatment, but its topical formulation has limited efficacy. Its use as liposome based cream or in combination with other modalities might help to achieve better results. Comparing efficacy of topical tranexamic acid 5% in liposome base alone versus its combination with intradermal platelet rich plasma (PRP) for melisma treatment. Forty female patients with melasma were divided randomly into 2 equal groups who were treated with topical tranexamic acid 5% cream twice daily for 12 weeks and group B received additional intradermal injections of PRP every 3 weeks throughout the treatment period. Evaluation was done through modified MASI score and patient satisfaction after one month from the end of treatment. Both groups showed significant improvement of modified MASI score after treatment. Significantly better treatment response and patient satisfaction were detected in patients of group B (p = .024, .029). The side effects of PRP were mild and tolerable and tranexamic acid was well tolerated. 5% topical tranexamic acid in liposome base is thought to be safe and effective modality for treatment of melasma. PRP is advisable as an autologous safe elixir which boosts the therapeutic effect of tranexamic acid.


Depressive Symptoms in Youth With Type 1 or Type 2 Diabetes: Results of the Pediatric Diabetes Consortium Screening Assessment of Depression in Diabetes Study.
To evaluate the frequency of depressive symptoms and the diagnosis and management of depression in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) enrolled in the Pediatric Diabetes Consortium T1D and T2D registries. The Children's Depression Inventory (CDI) 2 Self-Report (Short) version was completed by 261 T1D and 339 T2D youth aged 10-17 years. Symptoms of depression were identified in 13% of T1D and 22% of T2D (P = 0.007) participants; of these, only 4% of T1D and 9% of T2D youth were treated by a therapist within the prior 12 months. Depressive symptoms were associated with lower family income (P = 0.006) and obesity (P = 0.002) in T1D but not T2D youth. Depressive symptoms are more frequent than diagnosed depression in youth with T1D or T2D. These results underscore the need for regular depression screening and appropriate referral for youth with diabetes.


Aging and motor inhibition: a converging perspective provided by brain stimulation and imaging approaches.
The ability to inhibit actions, one of the hallmarks of human motor control, appears to decline with advancing age. Evidence for a link between changes in inhibitory functions and poor motor performance in healthy older adults has recently become available with transcranial magnetic stimulation (TMS). Overall, these studies indicate that the capacity to modulate intracortical (ICI) and interhemispheric (IHI) inhibition is preserved in high-performing older individuals. In contrast, older individuals exhibiting motor slowing and a declined ability to coordinate movement appear to show a reduced capability to modulate GABA-mediated inhibitory processes. As a decline in the integrity of the GABA-ergic inhibitory processes may emerge due to age-related loss of white and gray matter, a promising direction for future research would be to correlate individual differences in structural and/or functional integrity of principal brain networks with observed changes in inhibitory processes within cortico-cortical, interhemispheric, and/or corticospinal pathways. Finally, we underscore the possible links between reduced inhibitory functions and age-related changes in brain activation patterns.


Valorization of olive mill wastewater by its incorporation in building bricks.
This investigation deals with the possibility of incorporating the effluent resulting from olive oil extraction activity, known as olive oil mill wastewater (OMW), in the brick-making process. It was undertaken at an important Tunisian brickworks company. In this study, the OMW was mixed with clays following the same brick-making procedure used at the collaborative brickworks in Tunisia. The samples containing OMW were found to be comparable in forming/extrusion performance to a control product that used fresh water. The experimental products produced were tested for their comparative physical properties (volume shrinkage, water absorption, tensile strength of bricks, after firing at 920 degrees C and paste plasticity) in the unfired and fired states against a control representing the commercial product in the same factory. The results showed a significant increase in the volume shrinkage (10%) and the water absorption (12%), while the tensile strength remained constant. The maximum plasticity index value was found when incorporating 23% of OMW. This rate either maintained the physical and mechanical properties of bricks or improved them. The incorporation of OMW in bricks can represent a promising way to valorize this effluent, to rid the environment of a highly polluting wastewater and to save huge and precious amounts of water in a country where water shortage is a serious problem. This newly-prepared material has a double positive impact: it protects the environment and allows water economy.


Correlation of tetracycline and sulfonamide antibiotics with corresponding resistance genes and resistant bacteria in a conventional municipal wastewater treatment plant.
Antibiotics and corresponding resistance genes and resistant bacteria have been considered as emerging pollutants worldwide. Wastewater treatment plants (WWTPs) are potential reservoirs contributing to the evolution and spread of antibiotic resistance. In this study, total concentrations of tetracycline and sulfonamide antibiotics in final effluent were detected at 652.6 and 261.1ng/L, respectively, and in treated sludge, concentrations were at 1150.0 and 76.0μg/kg dry weight (dw), respectively. The quantities of antibiotic resistance genes and antibiotic resistant bacteria in final effluent were quantified in the range of 9.12×10(5)-1.05×10(6) gene abundances /100mL (genomic copies/100mL) and 1.05×10(1)-3.09×10(3)CFU/mL, respectively. In treated sludge, they were quantified at concentrations of 1.00×10(8)-1.78×10(9) gene abandances/100mL and 7.08×10(6)-1.91×10(8)CFU/100mL, respectively. Significant reductions (2-3 logs, p<0.05) of antibiotic resistance genes and antibiotic resistant bacteria were observed between raw influent and final effluent. The gene abundances of tetO and tetW normalized to that of 16S rRNA genes indicated an apparent decrease as compared to sulI genes, which remained stable along each treatment stage. Significant correlations (R(2)=0.75-0.83, p<0.05) between numbers of resistant bacteria and antibiotic concentrations were observed in raw influent and final effluent. No significance (R(2)=0.15, p>0.05) was found between tet genes (tetO and tetW) with concentration of tetracyclines identified in wastewater, while a significant correlation (R(2)=0.97, p<0.05) was observed for sulI gene and total concentration of sulfonamides. Correlations of the quantities of antibiotic resistance genes and antibiotic resistant bacteria with corresponding concentrations of antibiotics in sludge samples were found to be considerably weak (R(2)=0.003-0.07).


Efficacy and safety of different subsequent therapies after fertility preserving surgery for endometriosis: A systematic review and network meta-analysis.
Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases, laparoscopic fertility preservation surgery is considered a common treatment for EMT. The present study aimed to evaluate the efficacy and safety of dienogest, leuprolide, danazol, gestrinone, mifepristone and levonorgestrel intrauterine system (LNG-IUS) in relieving symptoms and delaying the recurrence of EMT cysts after fertility protection surgery. We searched PubMed, the Cochrane Library, Web of Science, EMBase, China National Knowledge Infrastructure, VIP Database, China Biology Medicine disc, WanFang Data databases to collect randomized controlled trials (RCT) related to dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS as a follow-up treatment after fertility preserving surgery for EMT. After literature screening, data extraction and quality evaluation, effective rate, recurrence rate, pregnancy rate and adverse reaction rate were used as outcome indicators to evaluate the efficacy and safety of drugs. Evidence networks included in the study were drawn and publication bias was assessed. The drugs most likely to be the best postoperative treatment were explored through mixed comparison of different drugs and efficacy ranking. Effective rate: dienogest, leprerelin, gestrinone and LNG-IUS were better than placebo after EMT fertility preservation surgery; dienogest was superior to mifepristone and danazol. LNG-IUS is superior to danazol. LNG-IUS has the highest potential for improving the effectiveness of EMT symptoms. Recurrence rate: the application of dienogest, leuprolide, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was lower than that of placebo; dienogest and LNG-IUS were lower than danazol. The recurrence rate of dinorgestrel was the last place with the highest performance. Pregnancy rate: in the cases with fertility requirements, dienogest and,leuprolide were better than placebo after EMT fertility preservation surgery; dienogest was superior to danazol, gestrinone and mifepristone. Leuprolide is superior to danazol and gestrinone. The first rank of dienogest pregnancy rate was the highest. Adverse reaction rate: the application of dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was higher than that of placebo. After placebo, LNG-IUS had the highest adverse reaction rate. For patients after fertility preserving surgery for EMT, the recurrence rate of dienogest was the last place with highest preference. The first rank of dienogest pregnancy was the highest.


Evaluation of surgical staples for ligation of the renal pedicle during nephrectomy.
A mechanical stapling instrument was evaluated for ligation of the renal pedicle during nephrectomy in nine healthy sheep. Two forms of disposable loading unit, from which stainless steel surgical staples could be dispensed in double or triple staggered row configuration, were assessed for their proper function when applied across the renal pedicle singularly or in series. The response of the sheep to surgery was assessed by physical, hematological, and serum chemistry evaluations. Tissue healing was determined by gross and histopathological examinations. Ligation and transection of the pedicle took 2 to 4 minutes. The vessels of the pedicle ranged in diameter from 3 to 12 mm. In two sheep, overzealous stripping of perivascular tissue from the renal pedicle prior to placement of a triple staggered row of staples resulted in mild hemorrhage from the renal stump. This was controlled by placing a second triple staggered row of staples proximal to the first. It was concluded that ligation of the renal pedicle could be performed rapidly, effectively, and safely in healthy sheep using the correctly applied mechanical stapler. It is inferred that a similar technique would be applicable to other species including man.


Flow Diversion for Treatment of Acutely Ruptured Intracranial Aneurysms : A Single Center Experience from 45 Consecutive Cases.
Reports about the use of flow diverter stents (FDS) in the acute setting of subarachnoid hemorrhage (SAH) are limited. This article presents a single center experiences based on 45 consecutive cases with emphasis on complication rates and clinical and radiologic outcomes. A prospectively maintained database of all cases treated with FDS as a stand-alone or adjunct device was retrospectively reviewed. All patients treated within 30 days of SAH were included. Records were made of clinical presentation, details of endovascular treatment, procedural complications, clinical outcome, and degree of occlusion on follow-up. In this study 45 patients (48.9% females; mean age 58.8 ± 12.4 years) were included. Flow diversion was performed after a median of 4 days. The procedural complication rate was 13.3% resulting in 2.2% permanent morbidities and 4.4% mortalities. No major hemorrhagic complications related to antiplatelet therapy were recorded. Immediate complete occlusion was achieved in 13.3%. Among survivors, complete occlusion was achieved in 94.6%. Excellent clinical outcome was recorded in 68.9% and 81.6% of the total population and survivors, respectively. There were no records of rebleeding from the target lesions. Flow diversion is an attractive alternative strategy for management of acutely ruptured aneurysms with high rates of delayed complete occlusion and acceptable complication rates.


Characteristics of Online Crowdfunding Campaigns for Urological Cancers in the United States.
We examined the characteristics and financial outcomes of online crowdfunding campaigns for patients with major urological cancers in the U.S. This cross-sectional study analyzed publicly available data from GoFundMe, the largest online medical crowdfunding service, via automated web scraping. Online campaigns from 2010 to 2018 with the following primary cancer types were included: kidney, prostate, bladder and testicular. Financial outcomes were compared using Kruskal-Wallis and Wilcoxon rank-sum tests. Multivariable analyses were utilized to identify predictors of campaign financial outcomes. Kidney cancers were the most frequent online campaign type (478), followed by prostate (379), bladder (202) and testicular (175) malignancies. Urological cancer campaign recipients frequently requested funding for medical expenses (71%) during active treatment (57%). After adjustment, testicular cancer and children's cancer campaigns generated more donations than other urological and adult cancer campaigns (p <0.05). Family and friend-authored campaigns generated more donations and average donation amounts than self-authored campaigns (p <0.05). Campaign narratives focused on disheartening circumstances received fewer donations than narratives focused on the recipient's high moral character or contributions to society (p <0.05), and unclear narratives received the smallest donation amounts (p <0.05). Urological cancer crowdfunding in the U.S. is primarily used to finance uncovered costs associated with medical care during active treatment. Crowdfunding financial outcomes are likely related to the campaign recipient's age, malignancy type, social network and primary appeal of the narrative. Urologists should be aware of trends in medical crowdfunding in order to better understand the financial burden this patient population faces.


Healthcare utilization during the first two waves of the COVID-19 epidemic in South Africa: A cross-sectional household survey.
Healthcare utilization surveys contextualize facility-based surveillance data for burden estimates. We describe healthcare utilization in the catchment areas for sentinel site healthcare facilities during the first year of the COVID-19 pandemic. We conducted a cross-sectional healthcare utilization survey in households in three communities from three provinces (KwaZulu-Natal, Western Cape and North West). Field workers administered structured questionnaires electronically with the household members reporting influenza-like illness (ILI) in the past 30 days or severe respiratory illness (SRI) since March 2020. Multivariable logistic regression was used to identify factors associated with healthcare utilization among individuals that reported illness. From November 2020 through April 2021, we enrolled 5804 households and 23,003 individuals. Any respiratory illness was reported by 1.6% of individuals; 0.7% reported ILI only, 0.8% reported SRI only, and 0.1% reported both ILI and SRI. Any form of medical care was sought by 40.8% (95% CI 32.9% - 49.6%) and 71.3% (95% CI 63.2% - 78.6%) of individuals with ILI and SRI, respectively. On multivariable analysis, respiratory illness was more likely to be medically attended for individuals at the Pietermaritzburg site (aOR 3.2, 95% CI 1.1-9.5, compared to Klerksdorp), that were underweight (aOR 11.5, 95% CI 1.5-90.2, compared to normal weight), with underlying illness (aOR 3.2, 95%CI 1.2-8.5), that experienced severe illness (aOR 4.8, 95% CI 1.6-14.3) and those with symptom duration of ≥10 days (aOR 7.9, 95% CI 2.1-30.2, compared to <5 days). Less than half of ILI episodes and only 71% of SRI episodes were medically attended during the first two COVID-19 waves in South Africa. Facility-based data may underestimate disease burden during the COVID-19 pandemic.


Hypericum erectum alcoholic extract inhibits Toxoplasma growth and Entamoeba encystation: an exploratory study on the anti-protozoan potential.
Hypericum erectum is an important ethnobotanical medicine in East Asian tradition. To explore the anti-parasitic potential of H. erectum, inhibitory effects on the growth of intracellular parasite Toxoplasma and on the encystation of intestinal parasite Entamoeba were examined. The constituents in H. erectum alcoholic extracts and fractions separated by solvent-partitioning were analysed by high resolution LC-MS. Toxoplasma gondii growth inhibition assay was performed using GFP-labelled T. gondii strain PTG-GFP by measuring the fluorescence intensity. Anti-Toxoplasma drug pyrimethamine was used as a positive control. T. gondii-induced immune reaction was assessed by quantitative PCR and fluorescence microscopy, using co-culture of PTG-GFP and monocyte-macrophage cell line Raw264. The inhibitory effect on the encystation of Entamoeba invadens was measured by flow-cytometry, where paromomycin was used as a positive control. H. erectum methanol (MeOH) extract (50 µg/mL) and ethyl acetate (EtOAc) fraction (50 µg/mL) inhibited the growth of T. gondii, while 50%MeOH extract and hydrophilic fractions were ineffective. Co-culture with T. gondii reduced the viability of macrophages, however macrophages were protected in the presence of H. erectum MeOH extract or EtOAc fraction (above 10 µg/mL). The MeOH extract and EtOAc fraction also effectively suppressed the encystation of E. invadens at 1 mg/mL. Hypericine, a major constituent in MeOH extract and EtOAc fraction, inhibited T. gondii growth and E. invadens encystation. Our results demonstrated that H. erectum effectively inhibited Toxoplasma growth and Entamoeba encystation. These activities are partly mediated by hypericin. In addition, it was suggested the extract and fraction may protect innate immune cells from Toxoplasma-induced damages, thereby enhancing parasite clearance. Further investigation is warranted to address the in vivo effectiveness of H. erectum as an anti-protozoal medicine.


Trends and prevalence of suicide 2017-2021 and its association with COVID-19: Interrupted time series analysis of a national sample of college students in the United States.
Suicide is among the leading causes of death for college students. We aimed to assess the impact of the pandemic on trends in suicidal thoughts and behaviors among college students, and whether suicidal thoughts and behaviors were associated with COVID-19 infection and psychosocial factors. We analyzed 2017-2021 data from 4 waves of Healthy Minds Study including a random sample of college students (N = 354,473) from 286 U.S. institutions. We performed interrupted time series analysis to model the effect of the pandemic on trends in suicidal ideation (SI), plan (SP), and attempt (SA). At the peripandemic assessment, we utilized multivariable logistic regression to examine the association of SI, SP, and SA with COVID-19 infection and psychosocial factors. We observed significant decreases in SI, SP, and SA among college students from 2017 to 2021. The pandemic was significantly associated with a 1.33 percentage points reduction in SI and a 0.85 percentage points reduction in SP but was not associated with a significant reduction in SA. Adjusted associations of SI, SP, and SA with risk factors showed the significant odds ratio (OR) for suspected COVID-19 infection (SI: 1.33, SP: 1.22, SA: 1.32), severe depression (SI: 6.39, SP: 6.63, SA: 5.63), severe anxiety (SI: 3.66, SP: 3.62, SA: 3.60), COVID-19-related financial stress (SI: 1.35, SP: 1.34, SA: 1.48), food insecurity (SI: 2.12, SP: 2.13, SA: 2.79), and academic impairment (SI: 2.07, SP: 2.05, SA: 2.14) but not for test-confirmed COVID-19. Certain COVID-19 mitigation strategies might have protected college students from suicidal thoughts/behaviors.


Efficacy and safety of budesonide administered by pressurized metered-dose inhaler in children with asthma.
Budesonide is approved for delivery using a nebulized solution and dry-powder inhaler, but its use through a pressurized metered-dose inhaler (pMDI) in pediatric patients with asthma has not been determined. To examine the efficacy and safety of 160 μg twice daily of budesonide through a pMDI vs placebo in children 6 to younger than 12 years with asthma and a demonstrated need for inhaled corticosteroids. A 6-week, international, multicenter, double-blinded, parallel-group, phase 2 study randomized 304 pediatric patients (mean age, 9 years; 21.7% <8 years) 1:1 to 160 μg (80 μg × 2 inhalations) twice daily of budesonide through a pMDI or placebo after a 7- to 21-day run-in period. The primary efficacy end point was change from baseline in morning peak expiratory flow (PEF); safety end points included adverse events, vital signs, and discontinuations. Budesonide treatment significantly improved morning PEF vs placebo; mean treatment effect (budesonide vs placebo) was 13.6 L/min (P < .0001). Budesonide also showed significant improvements vs placebo for forced expiratory volume in 1 second, evening PEF, forced expiratory flow at 25% to 75% of pulmonary volume, reliever medication use, nighttime awakenings, awakenings with reliever use, and percentage of patients with at least 15- and at least 30-L/min increase in morning PEF from baseline. The numbers of patients experiencing adverse events and discontinuations were smaller in the budesonide than in the placebo group. No serious adverse events were reported. Budesonide at 160 μg twice daily through a pMDI was generally well tolerated and significantly improved lung function, symptoms, rescue medication use, and nighttime awakenings vs placebo in children 6 to younger than 12 years with asthma and a demonstrated need for inhaled corticosteroids.


[Burns].
The therapy for burn injuries has established a definable management: percentage of the body surface area burned and thickness are important for the method of treatment (ambulant, on ward, intensive burn center). Open and close wound care with different bandages, in combination with primary surgery, has increased the probability of survival. A special problem is the aesthetics and function of the head and neck area. Hypertrophy and keloid scars may be disturbing, especially in children who have had a scald accident (41.2% of cases were children up to 5 years of age). The possibilities of correction are multiple: conservative therapy (bandages, ointment treatment, physical therapy) or surgical intervention with free skin transplantation or difficult flaps (pedicle flap, free graft, expanded flap, and microvascular anastomosed flap). The aim of research is also to cover large defects with skin culture from small donor areas. It is necessary to establish maxillofacial and plastic surgery from the beginning of the treatment for aesthetic and functionally acceptable results.


Cholinesterase activities in the autonomic nervous system of rabbits with experimental allergic neuritis: a biochemical study.
Utilizing a colorimetric method with acetylthiocholine iodide (AThCh) as substrate and eserine and ethopropazine as inhibitors, the activities of AThCh-splitting enzymes, acetylcholinesterase (AChE) and non-specific esterase (psi ChE) were determined in different structures of the autonomic nervous system (ANS) from the left and from the right sides of rabbits with experimental allergic neuritis (EAN) and controls. The total activity of AThCh-splitting enzymes showed a highly significant decrease in the ganglion nodosum and in the ganglia of the thoracal and abdominal paravertebral sympathetic chain in rabbits with clinical symptoms of ANS-involvement. Lesser but still significant changes were found in EAN-rabbits with motor symptoms but without ANS symptoms. No definite changes could be found in the superior cervical ganglia, the cervical sympathetic trunk or the interganglionic portions of the abdominal and thoracal paravertebral sympathetic chains. In samples with decreased total enzyme activities, both AChE and psi ChE appeared to decrease to approximately the same extent. This study demonstrates that the activities of AThCh-splitting enzymes are decreased in EAN in parts of ANS innervating the heart, abdominal and pelvic organs, and suggests that enzyme activities not derived from the myelin sheath may be involved in the pathogenesis of this demyelinating disease.


Nature, nurture, or chance: stochastic gene expression and its consequences.
Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to cell-to-cell variations in mRNA and protein levels. This variation appears in organisms ranging from microbes to metazoans, and its characteristics depend both on the biophysical parameters governing gene expression and on gene network structure. Stochastic gene expression has important consequences for cellular function, being beneficial in some contexts and harmful in others. These situations include the stress response, metabolism, development, the cell cycle, circadian rhythms, and aging.


Comparison of embolic effect between water-in-oil emulsion and microspheres in transarterial embolization for rat hepatocellular carcinoma model.
To compare two different embolic materials, water-in-oil (W/O) emulsion followed by gelatin particles and microspheres in transarterial embolization (TAE), using a rat hepatocellular carcinoma model. Twenty rats bearing N1S1 cells were divided into the W/O emulsion group and Microsphere group. Water-in-oil emulsion was created by a glass membrane emulsification device. The tumor vascularity was measured by contrast-enhanced ultrasonography 24 h before and 10 min and 48 h after TAE. Tumor necrosis, hepatic infarction ratio surrounding the tumor, and locations of the embolic materials 48 h after TAE were assessed. The changes of serum liver enzymes were also evaluated. Statistical significance was determined by using either the Mann-Whitney U-test or Fisher's exact test. The tumor vascularity 48 h after TAE was significantly higher in the Microsphere group (20.1 vs. 3.76%, P = 0.016). The overflow of Lipiodol into the portal veins surrounding the tumor was seen, whereas microspheres were seen only in the artery. The percentage of necrotic area and complete response ratio in the W/O emulsion group was significantly higher (99.9 vs. 87.6%, P = 0.029 and 87.5 vs. 28.6%, P = 0.041, respectively). Serum aspartate aminotransferase and serum alanine aminotransferase levels 48 h after TAE were significantly higher in the W/O emulsion group (P < 0.01). The embolization using W/O emulsion followed by gelatin particles showed stronger antitumor effects with the occlusion of both the tumor feeding artery and the portal vein compared with microspheres, which occluded only the arteries.


Retracted: Construction and Immunogenicity of DNA Vaccines Encoding Fusion Protein of Porcine IFN-λ1 and GP5 Gene of Porcine Reproductive and Respiratory Syndrome Virus.
[This retracts the article DOI: 10.1155/2013/318698.].


Sequence and task analysis of instrument use in common laparoscopic procedures.
In the area of instrument evaluation, one aspect that still requires objective assessment is the dynamics of instrument maneuver and exchange. If we could gain a better understanding of these phenomena, we could improve the design of the instruments themselves. A total of 29 laparoscopic procedures were videotaped and reviewed using time motion analysis. Instrument multifunctionality was determined using a standardized list of laparoscopic maneuvers. State transition diagrams were utilized to document the sequence of instrument exchanges. The curved dissector, atraumatic grasper, and cautery scissors were identified as the most multifunctional instruments; each was able to perform five distinct maneuvers. Instrument sequences were found to consist of a three-part dissect --> clip --> cut cycle and a two-part dissect --> suction cycle of instrument exchange. This study demonstrated that laparoscopic instruments are often used to perform a variety of maneuvers in addition to their primary function. Furthermore, there are common patterns in instrument exchange that provide a potential source of design parameters for improved surgical efficiency.


Competitive displacement and predation between introduced and native mud snails.
Experimental field and laboratory studies indicate that Cerithidea californica, a native mud snail, is restricted to only a portion of its normal habitat range in San Francisco Bay as a result of direct interactions with an introduced ecological equivalent, Ilyanassa obsoleta. The native snail typically inhabits marsh pans, tidal creeks and mudflats in estuaries along the Pacific coast. However, in San Francisco Bay it is confined to pans for most of the year, while the non-native snail inhabits the creeks and mudflats. Experiments and field monitoring demonstrate that this abnormal distribution pattern is caused by 1) interference competition for space in the form of an adult-adult behavioral avoidance by C. californica in the presence of invading I. obsoleta, and 2) predation by I. obsoleta on the eggs and juveniles of C. californica. The competitive exclusion of C. californica by I. obsoleta has not led to the extinction of the native snail because of the existence of a refuge for C. californica in pan habitats, beyond the physiological tolerances of I. obsoleta. As a consequence of the seasonal migrations of both species and changes in abiotic factors along the habitat gradient, repeated competitive displacements, rather than a one-time competitive exclusion, are observed between these two species. This is the first documented case of the competitive displacement of an endemic marine intertidal species by an introduced ecological equivalent.


A case of retractable helix lead auto-retraction: A possible cause of deep septal lead dislodgement.
This paper explains the phenomenon where the helix lead automatically retracts because of residual torque during deep septal pacing.


Inverse relationship between serum erythropoietin and blood lead concentrations in Kathmandu tricycle taxi drivers.
Kathmandu tricycle taxi drivers, whose environmental lead (Pb) exposure is ascribable mainly to vehicular exhaust, were studied to examine a dose-response relationship between blood Pb (Pb-B) and serum erythropoietin (sEPO) concentrations. Subjects were 27 drivers and 9 non-drivers. They were non-anemic healthy men with normal renal function. Pb-B was measured by an atomic absorption spectrometer with a graphite furnace, and sEPO was determined with a sandwich-type enzyme-linked immunosorbent assay. sEPO levels in drivers were lower than those of non-drivers, while Pb-B levels in drivers were higher than those of non-drivers. There was an inverse relationship between Pb-B and sEPO. The data suggest that Pb inhibits renal EPO production in a dose-dependent manner in persons with subclinical Pb toxicity. sEPO may serve as an early biochemical marker of subclinical Pb toxicity.